US 201401.00249A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0100249 A1 Sears et al. (43) Pub. Date: Apr. 10, 2014

(54) THERAPEUTIC TREATMENT A63/37 (2006.01) A613 L/45 (2006.01) (71) Applicants: Douglas Sears, Oak Park, CA (US); A613 L/4458 (2006.01) Michael Reilly, Oak Park, CA (US) (52) U.S. Cl. CPC ...... A61K 45/06 (2013.01); A61 K3I/451 (72) Inventors: Douglas Sears, Oak Park, CA (US); (2013.01): A613 L/4458 (2013.01); A61 K Michael Reilly, Oak Park, CA (US) 3 1/137 (2013.01); A61 K31/165 (2013.01) USPC ...... S14/325 (21) Appl. No.: 14/046,528 (57) ABSTRACT (22) Filed: Oct. 4, 2013 This invention discloses a treatment for a patient receiving O O medication to treat an attention deficit disorder Such as Related U.S. Application Data ADHD wherein the treatment results in a loss of appetite and (60) Provisional application No. 61/744,948, filed on Oct. impairment of the patient's attentiveness. The treatment com 9, 2012, now abandoned. bines a treatment for an attention deficit disorder with an appetite stimulant, wherein the appetite stimulant increases Publication Classification the caloric intake of a patient, which can increase the patients attentiveness. The combination treatment can be given for an (51) Int. Cl. indefinite, including, without limitation, life-long, to allow a A6 IK 45/06 (2006.01) patient to maintain normal caloric intake during treatment for A6 IK3I/65 (2006.01) an attention deficit disorder.

8aasaias: Patent Application Publication Apr. 10, 2014 Sheet 1 of 22 US 2014/010O249 A1

Figure i: improvement in Atiention with increased Caiotic intake

8aakast Patent Application Publication Apr. 10, 2014 Sheet 2 of 22 US 2014/010O249 A1

Figure 2: Impact of Combination Treatment of Weight

Mean Slope with combination tx " a 13.97 g/day

& Faie A & Patients & Pace Xie

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's, 8:3 •. ate :- year Siope before combination tx at 3,46 gfday &

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Figure 3: Impact of Combination Treatinent or Height

in pact of Cypra on height -35%. --

X-Sesses. x8x serias S. Sees: s:xx-x-Series:

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Figure 4: Change in Weight and ieight for Patiant A

338 18% f8. 18% 338 M8-3age is ti:isit

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Figure 5: ADID Sensitivity (CGE-S} for Patient A

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figure 6: Change in Height and Weight of Patient B

x Cage it waight x8x{iage in height.

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Figure 7: Ai f: E Sensitivity (CG-S) for Patient A

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Figure 8. Change in Height and Weight for Patient C

8

8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 a

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Figure 9: ADHD Sensitivity (CGi-S) for Patient C

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Figure : ). Change in Weight and Height of Patient C

x8:::::ge is: weight

3 SC a: s: 83 38 2. : 83 Patent Application Publication Apr. 10, 2014 Sheet 11 of 22 US 2014/010O249 A1

Figure it: AIEEE Sensitivity (CGi-S) for Patient D

8. 283 8. S8. 8 88: 3.3 33 8. Patent Application Publication Apr. 10, 2014 Sheet 12 of 22 US 2014/010O249 A1

Figure 2: Change in hieight and Weight of Patient E

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Figure 3: Ai iD Sensitivity (CGI-S for Patient E

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Figure 4: Change in Weight atti Eeight if Patient F

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s S. : RS: S. &B treatset sy Patent Application Publication Apr. 10, 2014 Sheet 15 of 22 US 2014/010O249 A1

Figure 5: ADHD Sensitivity (CG1-S for Patient F

:------8 S3 383 S38 88: s 3:33 Patent Application Publication Apr. 10, 2014 Sheet 16 of 22 US 2014/010O249 A1

Figure 6: Weight and Height Change of Patient G

X Charge: weig: x Chaige ::::gigit

reatnet sy Patent Application Publication Apr. 10, 2014 Sheet 17 of 22 US 2014/010O249 A1

Figure 7: AID}} E Sensitivity (CGi-S) for Patient G

83 8 388 3. 88: 883 88 83 Patent Application Publication Apr. 10, 2014 Sheet 18 of 22 US 2014/010O249 A1

Figure 8: Weight aris Height Change of Patient H

X sixarge is weig: 8x88&tige it i:ight Patent Application Publication Apr. 10, 2014 Sheet 19 of 22 US 2014/010O249 A1

Figure 9: ADHD Sensitivity (CGI-S) for Patient H

treatest Easy Patent Application Publication Apr. 10, 2014 Sheet 20 of 22 US 2014/010O249 A1

Figure 20; impact Of Combination Treatment or AIDHB Severty (CG-S)

gss s: s : i.e. & Sier *:::Rie: 3 38: 83

s: treatinert Day retative to Etitiatio of Corioitatio 3'x Patent Application Publication Apr. 10, 2014 Sheet 21 of 22 US 2014/010O249 A1

Figure 2 : impact of Treatment on ADHD Severity (CGi-S)

3. 8.

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Figure 22: impact of Treatment on improvement in ADHR (CGi-I)

impact of Treatmenton improvementin ADHD (CG-I)

& 88: 888:38.3: 3 & US 2014/010O249 A1 Apr. 10, 2014

THERAPEUTIC TREATMENT impulsively, reduced salary, poorer work performance scores, more frequent job changes, three times more likely to be 0001. This application claims the benefit of priority to unemployed, lower occupational attainment than patient IQ U.S. Provisional Patent Application 61/744.948, filed on Oct. would predict. Other functional impacts include a two times 4, 2012, which is hereby incorporated by reference in its more likely chance to be arrested, three times more likely to entirety. be convicted, fifteen times more likely to be incarcerated, a greater tendency toward antisocial/criminal behaviour, a BACKGROUND lower household income, higher accident claims and higher 0002 To treat psychological and/or neurological disor cost of accidents. (Goodman D. W. Primary Psychiatry: 17, 2 ders, including without limitation, attention deficit disorder, 2010) migrane, anti-serotonergic side effects, narcolepsy, excessive 0006 Various drugs and methods have been used to treat sleepiness associated with shift work, obstructive sleep apnea ADHD, including amphetamine and methylphenidate based as an adjunct to continuous positive airways pressure drugs. While these drugs are generally effective in treating (“CPAP), exogenous obesity, disruptive behaviour disorder ADHD, the side effects suffered by the children taking them including oppositional defiant disorder (“ODD) and conduct can include loss of appetite resulting in weight loss, insomnia, disorder (“CD), obesity, depression, neural insult, fatigue, drug dependence and loss of attentiveness. lethargy, binge eating disorder, Schizophrenia, sleep cycle 0007. With regard to treatments for ADHD, one option disorder, disease related fatigue in depression and fibromy generally followed by clinicians is to prescribe the use of algia, cocaine addiction, Parkinson's Disease, combat and short-acting stimulants. These are often used as an initial non-combat related PTSD, tic, and any other psychological treatment in small children (<16 kg), but these drugs have the and/or neurological syndrome it is common to prescribe to a disadvantage of requiring that they be administered twice a patient a therapeutic regimen that includes an amphetamine day (“b.i.d.) or three times a day (“t.i.d.) to provide control and/or methylphenidate. An attention deficit disorder for over a child’s ADHD symptoms throughout day. Longer act which these therapeutics are generally prescribed is attention ing stimulants offer greater convenience, confidentiality, and deficit hyperactivity disorder, also known as ADHD. ADHD compliance with single daily dosing, but the side effects is one of the most common childhood psychiatric conditions. Suffered with these once a day drugs by children taking them It has been diagnosed in approximately 8.4% of all children is frequently more severe than the b.i.d. or t.i.d. ones. aged 3-17 years old (Center for Disease Control and Preven 0008 But there are significant problems with therapeutic tion). Although scientists and clinicians debate the best way use of amphetamines and methylphenidates for the treatment to diagnose and treat ADHD, there is no debate among com of any neurological or psychological syndrome. For ADHD. petent and well-informed health care professionals that the drugs are reported to be associated with loss of appetite in ADHD is a valid neurobiological condition that causes sig roughly 35% of patients as well as weight loss in approxi nificant impairment to children who suffer from it. mately 15% of patients. In practice, it is not unusual to find 0003. The clinical practice parameters followed by doc that the frequency of appetite reduction and the amount of tors inform them that ADHD is a chronic condition that will weight loss is actually greater than what has been reported in most likely to persist into adulthood. The current standard of the scientific literature. (Sears clinical observation). While care recommendations state treatment should be 7 days a this effect is perceived as positive by patients who are taking week, 12 months a year with no drug holidays. (see, for amphetamines as a weight loss medication, it can be detri example, AACAP 2007). Untreated ADHD is to known to mental to the health and proper development of children have significant long-term consequences including loss of taking medications for ADHD and other psychiatric disor academic performance, Social performance, and more aber ders. rant behaviors including Substance abuse, teen pregnancies 0009. It is widely recognized in ADHD patients, and espe and imprisonment. cially in children, that there is a documented link between 0004 Among the functional impacts of ADHD in children patients missing meals and learning impairment. For and adolescents are a higher risk of injury, including, without instance, overnight and morning fasting among Schoolchil limitation bicycle/pedestrian injury, head injury and multiple dren was found to have a deleterious effect on the children's injuries that require admission to an intensive care unit. Other memory, attention, performance in academic pursuits and functional impacts of ADHD include a higher rate of failure in ability to interact with other children socially. (Pollitt et al., School, higher risk of expulsion or dropout, higher rate of 1998; Pollitt and Gorman, 1994). This correlates with the associated learning disability and lower rates of high School finding that regularity in breakfast consumption has been or college completion. Additionally, functional impacts of linked with improvement in academic performance and psy ADHD include a lack of friendships, less liked by their peers chosocial functioning as well as cognition among children. compared to non-ADHD peers, difficulty retaining peer sta (Benton, 2001; Bellisle, 2004). tus, a two times higher risk for tobacco Smoking, a two and a 0010. It has been widely recognized that there is a docu halftime higher risk for alcohol abuse, a two times higher risk mented link between missing meals and learning impairment for Substance abuse, are four times more likely to contract an for ADHD patients as well as patients suffering from a neu STD, a ten times higher risk for unplanned pregnancy, a two rological or psychological syndrome. A possible reason for to six times higher rate of suspended or revoked driver's this link may be a drop in glucose levels resulting from license, more traffic violations and speeding tickets, more missing a meal, since the Supply of glucose to the brain is motor vehicle accidents and greater vehicular damage. believed to impact upon memory, mood and attentiveness. (Goodman D. W. Primary Psychiatry: 17, 2 2010) Research Suggests that when engaging in cognitively 0005 Among the function impacts of ADHD in adults are demanding tasks, such as Schoolwork, repeated Supplies of similar to those found in children and adolescents, but also glucose to the brain enhances cognitive functioning and include a higher likelihood of being fired or quitting a job improves memory, mood and attentiveness. Research on the US 2014/010O249 A1 Apr. 10, 2014

immediate effects of glucose on cognition demonstrated that 0014. An example of an appetite enhancement drug is the ability of the brain to fully function appears to be sensitive cyproheptadine hydrochloride (4-(5H-dibenzoa.dcyclo to short-term fluctuations in glucose supply. (Bellisle, 2004). hepten-5-ylidene)-1-methylpiperidine hydrochloride) Patients with nutritional deficiencies are particularly suscep ("cyproheptadine'). This drug has been used as oral mono tible to the short-term fluctuations in glucose Supply that therapy for allergy under the tradename PeriactinR). It is impact upon cognitive ability, attentiveness and performance known to reach peak plasma levels in 1-3 hours after admin of the brain. Maintaining adequate levels of glucose through istration and has a half-life of 8 hours. (Gunja, 2004). In the out the day contributes to optimizing cognition and attentive 1960s, it was recognized that this drug had several side effects ness, Suggesting that nutritional intake should be designed to that made it a suboptimal allergy treatment. Among the side Sustain an adequate level of glucose by minimizing fluctua effects were weight gain and drowsiness. tions in food intake during the day. 0015 While weight gain was a side effect that made 0011. One way to overcome issues with appetite in cyproheptadine a poor antihistamine, this side effect is desir patients with ADHD is for the parents, spouse or other car able in children suffering weight loss due to loss of appetite egiver to actively monitor a patient's food intake. However, from use of amphetamines or methylphenidates to treat this generally only works when the patient is not resistant to ADHD. Cyproheptadine has been shown to cause weight gain eating, for instance, due to loss of appetite. Moreover, par in studies that used either non-human animals or humans. ents, spouse, or other caregiver cannot generally spend all day (Orthen-Gambill 1988). It has also been studied for its ability with a patient. This is particularly true when a majority of to promote weight gain in clinical trials for cancer cachexia. patients spend at least a portion of their day at School or work (Coulris). Other areas where there is interest in cyprohepta where they eat lunch. dine to promote weight gain are tuberculosis, anorexia ner 0012 Clinical guidelines for ADHD have tried to cope Vosa, cystic fibrosis, migrane, attention deficit disorder, with appetite reduction and ADHD medication. (See for migrane, anti-serotonergic side effects, underweight chil example, AACAP 2007). Particularly, where a patient suffers dren, narcolepsy and any other psychological and/or neuro deleterious effects resulting from a loss of appetite including logical syndrome. (Coulris, Halm, Kardinal). slower growth in their height, a slowing in their weight gain 0016. In ADHD, there is anecdotal evidence that a com and a loss in the child's attentiveness. The general standard is bination of an amphetamine or a methylphenidate and cypro that if a patient has a change in height or weight that crosses heptadine as a treatment for children suffering from ADHD two percentile lines, then this suggests an aberrant growth can result in weight gain and excessive sleep. (Daviss 2004). trajectory. In these cases the general response is for the child In the report, a number of children were administered their to stop taking the drug used to treat ADHD during weekends ADHD drug along with 4-8 mg of cyproheptadine at night or during a patient's vacation or Summer break if in School in before they went to sleep. While this report suggests that there order to attempt to mitigate the harm suffered by the patient. may be a benefit of using cyproheptadine in ADHD children One problem with this approach is that it can lead to the who are Suffering weight loss as a result of taking an amphet marked impairment of attentiveness by a patient during the amine or methylphenidate drug, it did not identify whether periods of time when their ADHD medication is removed. the resultant weight gain was due to the child eating over a One option available to a clinician is to switch the patient to a regular eating cycle, for instance, breakfast, lunch and/or different ADHD medication. However, as these drugs are also dinner or due to eating over a short period of time during often eitheran amphetamine or a methylphenidate, it is likely which the cyproheptadine affects the child’s appetite, fol that the patient will suffer from the same side effects. Know lowed by hunger during the day after the effect of the effects ing both the benefits and side effects of current treatment of the cyproheptadine have worn off. Nor did the report iden regimens, in making a treatment decision, it is incumbent tify whether the administration of cyproheptadine had an upon a clinician to carefully balance the benefits of medica effect on a child's attentiveness and ability to function cog tion treatment with the risks of reductions in height and nitively and socially. Additionally, the report did not analyze weight gain and the loss of attentiveness resulting from a lack the impact on height. Based on the 8 hour half-life of cypro of appetite. heptadine and its administration before bed in Daviss, it is not 0013 Therefore it would be preferable to treat the side likely that children receiving the appetite stimulant had their effects such as appetite reduction that prevent the proper use appetites stimulated in a manner that would result in their and optimal levels of amphetamine and/or methylphenidate eating food during their waking hours. Thus, though it is not therapy that are necessary to meet the treatment guidelines to reported in Daviss, it is likely that while the children gained treat ADHD or other neurological or psychological Syn weight, they did not see a cyproheptadine-related improve drome. One way to do this is through the use of appetite ment in attentiveness during the day, particularly, while stimulants. These include, but are not limited to, a diverse attending School. group of medications given to patients to prevent undesired 0017. It is an aim of the present invention to provide a weight loss in the elderly and in patients Suffering from Such pharmaceutical composition wherein a patient Suffering from diseases as AIDS and cancer, diseases often associated with a psychological and/or neurological disorder, including, the wasting of the body's muscle tissue as well as overall without limitation, attention deficit disorder (including, with weight loss. The medical term for these drugs is orexigenic, out limitation ADHD), migrane, anti-serotonergic side which is derived from the Greek word for “appetite' or effects, narcolepsy, excessive sleepiness associated with shift "desire” and includes various drugs, including, without limi work, obstructive sleep apnea as an adjunct to continuous tation, hormones, vitamins or other compounds known to positive airways pressure (“CPAP), exogenous obesity, dis increase appetite. This can include a naturally occurring neu ruptive behaviour disorder including oppositional defiant dis ropeptide hormone such as ghrelin, orexin or neuropeptide Y. order (“ODD) and conduct disorder (“CD), obesity, depres or a drug or compound that increases hunger and therefore sion (including, without limitation, augmentation of enhances food consumption. antidepressants in treating refractory depression and cancer US 2014/010O249 A1 Apr. 10, 2014 related depression), neural insult, fatigue (including, without obesity, disruptive behaviour disorder including oppositional limitation, disease-related fatigue in patients with HIV. defiant disorder (“ODD) and conduct disorder (“CD), obe advanced cancer, multiple Sclerosis, myotonic dystrophy, sity, depression (including, without limitation, augmentation depression, fibromyalgia and hepatitis C), lethargy, binge of antidepressants in treating refractory depression and can eating disorder, Schizophrenia, sleep cycle disorder, cocaine cer-related depression), neural insult, fatigue (including, addiction, Parkinson's Disease, combat and non-combat without limitation, disease-related fatigue in patients with related PTSD, tic, and any other psychological and/or neuro HIV, advanced cancer, multiple Sclerosis, myotonic dystro logical syndrome is provided an amphetamine and/or a meth phy, depression fibromyalgia and hepatitis C), lethargy, binge ylphenidate drug and a drug that promotes an increase in eating disorder, Schizophrenia, sleep cycle disorder, cocaine addiction, Parkinson's Disease, combat and non-combat appetite. It is a further aim of the present invention to provide related PTSD, tic, and any other psychological and/or neuro a pharmaceutical composition wherein a patient Suffering logical syndrome is provided an amphetamine and/or meth from a psychological and/or neurological disorder, including, ylphenidate drug and a drug that promotes an increase in without limitation, attention deficit disorder (including, with appetite during the day that results in the maintenance or an out limitation ADHD), migrane, anti-serotonergic side increase in the attentiveness by the patient during the day effects, narcolepsy, excessive sleepiness associated with shift while at school, work or other situation where the patient work, obstructive sleep apnea as an adjunct to continuous learns, works or interacts with other people as compared to a positive airways pressure (“CPAP), exogenous obesity, dis patient not receiving the appetite stimulant. It is a further aim ruptive behaviour disorder including oppositional defiant dis of the present invention to provide a pharmaceutical compo order (“ODD) and conduct disorder (“CD), obesity, depres sition wherein a patient Suffering from a psychological and/or sion (including, without limitation, augmentation of neurological disorder, including, without limitation, attention antidepressants in treating refractory depression and cancer deficit disorder (including, without limitation ADHD), related depression), neural insult, fatigue (including, without migrane, anti-serotonergic side effects, narcolepsy, excessive limitation, disease-related fatigue in patients with HIV. sleepiness associated with shift work, obstructive sleep apnea advanced cancer, multiple Sclerosis, myotonic dystrophy, as an adjunct to continuous positive airways pressure depression, fibromyalgia and hepatitis C), lethargy, binge (“CPAP), exogenous obesity, disruptive behaviour disorder eating disorder, Schizophrenia, sleep cycle disorder, cocaine including oppositional defiant disorder (“ODD) and conduct addiction, Parkinson's Disease, combat and non-combat disorder (“CD), obesity, depression (including, without related PTSD, tic, and any other psychological and/or neuro limitation, augmentation of antidepressants in treating refrac logical syndrome is provided an amphetamine and/or meth tory depression and cancer-related depression), neural insult, ylphenidate drug and a drug that promotes an increase in fatigue (including, without limitation, disease-related fatigue appetite, while maintaining or increasing the attentiveness by in patients with HIV, advanced cancer, multiple Sclerosis, the patient when compared to a patient not receiving the myotonic dystrophy, depression, fibromyalgia and hepatitis appetite stimulant. It is an additional aim of the present inven C), lethargy, binge eating disorder, Schizophrenia, sleep cycle tion to provide a pharmaceutical composition wherein a disorder, cocaine addiction, Parkinson's Disease, combat and patient Suffering from a psychological and/or neurological non-combat related PTSD, tic, and any other psychological disorder, including, without limitation, attention deficit dis and/or neurological syndrome is provided an amphetamine order (including, without limitation ADHD), migrane, anti and/or methylphenidate drug and a drug that promotes an serotonergic side effects, narcolepsy, excessive sleepiness increase in appetite during the day that results in an increase associated with shift work, obstructive sleep apnea as an in the height of the patient taking Such medication versus the adjunct to continuous positive airways pressure (“CPAP), same patient if such medication is not taken. By following exogenous obesity, disruptive behaviour disorder including Such a therapeutic regimen, a patient will Suffer fewer side oppositional defiant disorder (“ODD) and conduct disorder effects resulting from appetite loss that can reduce treatment (“CD), obesity, depression (including, without limitation, Success and compliance, while maintaining a reasonable augmentation of antidepressants intreating refractory depres degree of attentiveness during the day, including, without sion and cancer-related depression), neural insult, fatigue limitation maintaining a reasonable degree of cognition and (including, without limitation, disease-related fatigue in social ability. patients with HIV, advanced cancer, multiple Sclerosis, myo tonic dystrophy, depression, fibromyalgia and hepatitis C), lethargy, binge eating disorder, Schizophrenia, sleep cycle SUMMARY OF THE INVENTION disorder, cocaine addiction, Parkinson's Disease, combat and 0018 Aspects of the present specification disclose a non-combat related PTSD, tic and any other psychological method of treating an individual with a psychological and/or and/or neurological syndrome is provided an amphetamine neurological disorder, including, without limitation, an atten and/or methylphenidate drug and a drug that promotes an tion deficit disorder, the method comprises the step of admin increase in appetite during the day that results in the mainte istering to an individual in need thereof a pharmaceutical nance oran increase in the attentiveness by the patient during composition which comprises administration of a therapeutic the day when compared to a patient not receiving the appetite compound to treat the attention deficit disorder and a thera stimulant. It is a further aim of the present invention to pro peutic compound to treat a reduction in appetite. Aspects of vide a pharmaceutical composition wherein a patient Suffer the present specification further disclose a pharmaceutical ing from a psychological and/or neurological disorder, composition comprising a therapeutic compound for a psy including, without limitation, attention deficit disorder (in chological and/or neurological disorder, including, without cluding, without limitation ADHD), migrane, anti-serotoner limitation, an attention deficit disorder and atherapeutic com gic side effects, narcolepsy, excessive sleepiness associated pound for a disorder associated with a reduction in appetite, with shift work, obstructive sleep apnea as an adjunct to wherein the pharmaceutical composition reduces a symptom continuous positive airways pressure ("CPAP), exogenous of a psychological and/or neurological disorder, including, US 2014/010O249 A1 Apr. 10, 2014

without limitation, a disorder associated with an attention at least 10 mg/kg/day, at least 15 mg/kg/day, at least 20 deficit disorder. Aspects of the present specification disclose mg/kg/day, at least 25 mg/kg/day, at least 30 mg/kg/day, at treatments that can result in an increase in attentiveness, least 35 mg/kg/day, at least 40 mg/kg/day, at least 45 mg/kg/ weight and/or height of the individual, thereby treating the day, or at least 50 mg/kg/day or in the range of about 0.001 individual. mg/kg/day to about 100 mg/kg/day or in the range of about 0019 Aspects of the present specification dislose a treat 0.001 mg/kg/day to about 10 mg/kg/day, about 0.001 mg/kg/ ment for a neurological and/or psychological disorder, day to about 15 mg/kg/day, about 0.001 mg/kg/day to about including without limitation, attention deficit disorder, and 20 mg/kg/day, about 0.001 mg/kg/day to about 25 mg/kg/day, further without limitation, Attention Deficit Hyperactivity about 0.001 mg/kg/day to about 30 mg/kg/day, about 0.001 Disorder (ADHD) are treated in an individual with an mg/kg/day to about 35 mg/kg/day, about 0.001 mg/kg/day to amphetamine or a methylphenidate. about 40 mg/kg/day, about 0.001 mg/kg/day to about 45 0020 Aspects of the present specification disclose, with mg/kg/day, about 0.001 mg/kg/day to about 50 mg/kg/day, out limitation, that an amphetamine or methylphenidate can about 0.001 mg/kg/day to about 75 mg/kg/day, or about 0.001 be selected from the group consisting of OROS methylpheni mg/kg/day to about 100 mg/kg/day. date (Concerta), dextroamphetamine immediate? sustained 0023 Aspects of the present specification disclose, with release (Adderall/Adderall XR), dexmethylphenidate (Foca out limitation, a therapeutic compound to treat the disorder is lin), Focalin XR, Metadate CD, Metadate ER, NWP09, administered to an individual topical, Sublingual, rectal, vagi Dexedrine, dextroamphetamine (Dexedrine), Dexedrine nal, trancutaneous, oral, inhaled, intranasal. Subcutaneous, SpanSules, Methylin ER (Ritalin SR), methylphenidate (Ri intravenous, enteral or parenteral. Aspects of the present talin), and methylphenidate CR, Ritalin, Ritalin LA, SD-483, specification disclose, without limitation a therapeutic com SPD-503, Ritalin SR, Intuniv ER, Intuniv, Methylin, Day pound to treat the attention deficit disorder is administered as trana, Equasym, Dixirit, KapVay, Daytrana Patch, Methylin a liquid, a Solid, a semi-solid or an aerosol and a therapeutic chewable, Methylin liquid, Dextrostat, Strattera, Tenex, Cat compound is formulated as a tablet, lozenge, orally dissolved apres, Catapres TTS patch, Prozac, Serefam, Zoloft, Luvox, strip, capsule, syrup, oral Suspension, emulsion, granule, Paxil, Paxil CR, Pexeva, Celexa, Lexapro, Tofranil, Nor sprinkle or pellet. pamin, Elavil, Pamelor, Sinequan, Anafranil, Wellbutrin, 0024 Aspects of the present specification disclose, with Wellbutrin SR, Wellbutrin XL, Effexor, Effexor XR, out limitation, a therapeutic compound is a long acting, Sus Remeron, Cymbalta, Nardil, Parnate, Emsam patch, Haldol, tained release, extended release, immediate release, slow Orap, Prolixin, Mellaril, Thorazine, Stelazine, Moban, Loxi release, or controlled release therapeutic compound and the tane, Risperdal, Zyprexa, Seroguel, Geodon, Abilify, Cloz therapeutic compound is released over a period of about 3 aril, Xanax, Xanax XR, Klonopin, Ativan, Buspar, Ambien days after administration, about 7 days after administration, CR, Ambien, Lunesta, Sonata, Rozerem, Lithiu, Lithobid, about 10 days after administration, about 15 days after admin Eskalith, Depakote, Tegretol, Carbatrol, Trileptal, Lamictal, istration, about 20 days after administration, about 25 days Topamax, Neurontin and the therapeutic compounds identi after administration, about 30 days after administration, fied in Table 1. about 45 days after administration, about 60 days after admin 0021 Aspects of the present specification disclose that the istration, about 75 days after administration, or about 90 days symptoms associated with attention deficit disorder is after administration or is released over a period of at least 3 reduced by at least 10%, at least 15%, at least 20%, at least days after administration, at least 7 days after administration, 25%, at least 30%, at least 35%, at least 40%, at least 45%, at at least 10 days after administration, at least 15 days after least 50%, at least 55%, at least 60%, at least 65%, at least administration, at least 20 days after administration, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or 25 days after administration, at least 30 days after adminis at least 95% and the severity associated with attention deficit tration, at least 45 days after administration, at least 60 days disorder is reduced by at least 10%, at least 15%, at least 20%, after administration, at least 75 days after administration, or at least 25%, at least 30%, at least 35%, at least 40%, at least at least 90 days after administration or is released over a 45%, at least 50%, at least 55%, at least 60%, at least 65%, at period of about 1 day after administration, about 2 days after least 70%, at least 75%, at least 80%, at least 85%, at least administration, about 3 days after administration, about 4 90%, or at least 95%. Aspects of the present specification days after administration, about 5 days after administration, disclose the symptoms associated with attention deficit dis about 6 days after administration or about 7 days or more after order is reduced by about 10% to about 100%, about 20% to administration. about 100%, about 30% to about 100%, about 40% to about 0025 Aspects of the present specification disclose, with 100%, about 50% to about 100%, about 60% to about 100%, out limitation, a pharmaceutical composition that includes about 70% to about 100%, about 80% to about 100%, about pharmaceutical acceptable components and the pharmaceu 10% to about 90%, about 20% to about 90%, about 30% to tical acceptable components is selected from the group con about 90%, about 40% to about 90%, about 50% to about sisting of a salt, a Surfactant, an amino acid, a stabilizer or a 90%, about 60% to about 90%, about 70% to about 90%, buffer and the salt is selected from the group consisting of about 10% to about 80%, about 20% to about 80%, about 30% citric acid, sodium chloride, potassium chloride, Sodium Sul to about 80%, about 40% to about 80%, about 50% to about fate, potassium nitrate, sodium phosphate monobasic or 80%, or about 60% to about 80%, about 10% to about 70%, Sodium phosphate dibasic, wherein the Surfactant can be a about 20% to about 70%, about 30% to about 70%, about 40% polysorbate and the polysorbate is selected from the group to about 70%, or about 50% to about 70%. consisting of Tween 20, Tween 80, F68, F88, sorbitain esters, 0022 Aspects of the present specification disclose a dose lipids, fatty acids or fatty esters. ofatherapeutic compound to treat the disorder is in the range 0026. Aspects of the present specification disclose, with of at least 0.001 mg/kg/day, at least 0.01 mg/kg/day, at least out limitation, a therapeutic compound to treat a appetite 0.1 mg/kg/day, at least 1.0 mg/kg/day, at least 5.0 mg/kg/day, reduction is an orexigenic drug and the orexigenic drug can be US 2014/010O249 A1 Apr. 10, 2014

selected from the group of alcohol, GHB, and other sedatives least 50%, at least 55%, at least 60%, at least 65%, at least Such as some benzodiazepine and nonbenzodiazepine tran 70%, at least 75%, at least 80%, at least 85%, at least 90% or quilizers and sleeping pills, anti-depressants (some SSRIs, at least 95% and/or the severity associated with reduction in Mianserin, etc.). 5-HT, receptor antagonists/inverse ago appetite is reduced by about 10% to about 100%, about 20% nists (e.g., mirtazapine, mianserin, olanzapine, quetiapine, to about 100%, about 30% to about 100%, about 40% to about risperidone, amitriptyline, imipramine, cyproheptadine, 100%, about 50% to about 100%, about 60% to about 100%, etc.), H receptor antagonists/inverse agonists (e.g., bucliz about 70% to about 100%, about 80% to about 100%, about ine, mirtazapine, mianserin, olanzapine, quetiapine, n-3 fatty 10% to about 90%, about 20% to about 90%, about 30% to acids, amitriptyline, chlorpheniramine maleate, etc.), D/D about 90%, about 40% to about 90%, about 50% to about receptor antagonists (e.g., haloperidol, chlorpromazine, olan 90%, about 60% to about 90%, about 70% to about 90%, Zapine, risperidone, quetiapine, etc.), Marinol, Megace, about 10% to about 80%, about 20% to about 80%, about 30% Megace ES, C-adrenergic receptor antagonists (such as dox to about 80%, about 40% to about 80%, about 50% to about aZosin, carvedilol, propanolol, colonidine), Serefam, C2-adr 80%, or about 60% to about 80%, about 10% to about 70%, energic receptor agonists (e.g., clonidine, guanfacine, etc.). about 20% to about 70%, about 30% to about 70%, about 40% Some beta blockers such as propanolol, natural or synthetic to about 70%, or about 50% to about 70% and/or the treat CB, receptor agonists (e.g., THC or dronabinol (found in ment for appetite reduction results in an increase in weight by Cannabis), tetrahydrocannibinol, diphenydramine, promet at least 10%, at least 15%, at least 20%, at least 25%, at least hazine, B vitamin supplements, nabilone, JWH-018 etc.), 30%, at least 35%, at least 40%, at least 45%, at least 50%, at Corticosteroids (e.g. prednisone or dexamethasone), Sodium least 55%, at least 60%, at least 65%, at least 70%, at least valproate (Depakote), Megestrol, Pregabalin, Sulfonylurea 75%, at least 80%, at least 85%, at least 90% or at least 95% antidiabetic drugs such as glibenclamide and chlorpropam and/or the treatment for appetite reduction results in an ide, Steroids (including, without limitation, boldenone, increase in weight by about 10% to about 100%, about 20% to oxymetholone, dexamethasone, or methandrostenolone, about 100%, about 30% to about 100%, about 40% to about prednisone, hydrocortisone, Oxandrolone, nandrolone, test 100%, about 50% to about 100%, about 60% to about 100%, osterone), some kappa opioid receptoragonists such as tiflua about 70% to about 100%, about 80% to about 100%, about dom, hormones such as mederoxyprogesteronemirtazapine 10% to about 90%, about 20% to about 90%, about 30% to (Remeron), a tetracyclic antidepressant, cyproheptadine (Pe about 90%, about 40% to about 90%, about 50% to about riactin), an antihistamine; nandrolone, oxymetholone, and 90%, about 60% to about 90%, about 70% to about 90%, oxandrolone (Anadrol-50. Durabolin, Hybolin, anti-IL6 anti about 10% to about 80%, about 20% to about 80%, about 30% body, selective androgen receptor modulator (“SARM), to about 80%, about 40% to about 80%, about 50% to about Oxandrin, and other brand names), VT-122 (a coadministra 80%, or about 60% to about 80%, about 10% to about 70%, tion of propranolol and etodolac), type 4 melanocortin recep about 20% to about 70%, about 30% to about 70%, about 40% tor antagonis, IL6 antagonist, synthetic ghrelin, myostatin to about 70%, or about 50% to about 70% and/or the treat decoy receptor, fast skeletal muscle troponin-activating Sub ment for appetite reduction results in an increase in height by stance, anticatabolic/anabolic transforming agent MT-102, at least 10%, at least 15%, at least 20%, at least 25%, at least celecoxib, testosterone, vitamin D, OHR/AVR118, soluble 30%, at least 35%, at least 40%, at least 45%, at least 50%, at version of the ActRIIB receptor, 5-HT, antagonists, Cox-2 least 55%, at least 60%, at least 65%, at least 70%, at least inhibitor, thalidomide, omega-3 fatty acids, anticyclooxyge 75%, at least 80%, at least 85%, at least 90% or at least 95% nase-2 drugs and megestrol acetate (Megace). In addition to and/or the treatment for appetite reduction results in an these prescription drugs, fish oil (eicosapentaenoic acid or increase in weight by at least 0.5 pounds, at least 1 pound, at EPA), EATMOR, other vitamins and natural or artificial least 1.5 pounds, at least 2 pounds, at least 2.5 pounds, at least appetite stimulants and cyproheptadine hydrocholoride. 3 pounds, at least 3.5 pounds, at least 4 pounds, at least 4.5 0027 Aspects of the present specification disclose symp pounds, at least 5 pounds, at least 5.5 pounds, at least 6 toms associated with appetite reduction is reduced by at least pounds, at least 6.5 pounds, at least 7 pounds, at least 7.5 10%, at least 15%, at least 20%, at least 25%, at least 30%, at pounds, at least 8 pounds, at least 8.5 pounds, at least 9 least 35%, at least 40%, at least 45%, at least 50%, at least pounds, at least 9.5 pounds, at least 10 pounds, at least 10.5 55%, at least 60%, at least 65%, at least 70%, at least 75%, at pounds, at least 11 pounds, at least 11.5 pounds, at least 12 least 80%, at least 85%, at least 90%, or at least 95% and/or pounds, at least 12.5 pounds, at least 13 pounds, at least 13.5 the symptoms associated with appetite reduction is reduced pounds, at least 14 pounds, at least 14.5 pounds, at least 15 by about 10% to about 100%, about 20% to about 100%, pounds, at least 20 pounds, at least 25 pounds, at least 30 about 30% to about 100%, about 40% to about 100%, about pounds, at least 50 pounds. In another embodiment, a thera 50% to about 100%, about 60% to about 100%, about 70% to peutic compound disclosed herein for the treatment of appe about 100%, about 80% to about 100%, about 10% to about tite reduction results in an increase in weight by, e.g., from 0.5 90%, about 20% to about 90%, about 30% to about 90%, pounds to 50 pounds, from 0.5 pounds to 30 pounds, from 0.5 about 40% to about 90%, about 50% to about 90%, about 60% pounds to 25 pounds, from 0.5 pounds to 20 pounds, from 0.5 to about 90%, about 70% to about 90%, about 10% to about pounds to 15 pounds, from 0.5 pounds to ten pounds, from 0.5 80%, about 20% to about 80%, about 30% to about 80%, pounds to 7.5 pounds, from 0.5 pounds to 5 pounds, from 1 about 40% to about 80%, about 50% to about 80%, or about pound to 15 pounds, from 1 pound to 10 pounds, from 1 60% to about 80%, about 10% to about 70%, about 20% to pound to 7.5 pounds, form 1 pound to 5 pounds, from 2 about 70%, about 30% to about 70%, about 40% to about pounds to ten pounds, from 2 pounds to 7.5 pounds. 70%, or about 50% to about 70% and/or the symptoms asso 0028 Aspects of the present specification disclose a treat ciated with reduction in the severity of appetite reduction is ment for appetite reduction increases the attentiveness of a reduced by at least 10%, at least 15%, at least 20%, at least patient by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at 25%, at least 30%, at least 35%, at least 40%, at least 45%, at US 2014/010O249 A1 Apr. 10, 2014

least 50%, at least 55%, at least 60%, at least 65%, at least 10% to about 70%, about 20% to about 70%, about 30% to 70%, at least 75%, at least 80%, at least 85%, at least 90% or about 70%, about 40% to about 70%, or about 50% to about at least 95% and/or increases the attentiveness of a patient by 70%. about 10% to about 100%, about 20% to about 100%, about 0031 Aspects of the present specification disclose, with 30% to about 100%, about 40% to about 100%, about 50% to out limitation, an increase in attentiveness by an individual is about 100%, about 60% to about 100%, about 70% to about measured by CGI-I wherein, wherein the CGI-I scale is from 100%, about 80% to about 100%, about 10% to about 90%, 1 to 7 and a measurement of 7 identifies an individual that is about 20% to about 90%, about 30% to about 90%, about 40% very much worse, 6 identifies an individual that is much to about 90%, about 50% to about 90%, about 60% to about worse, 5 identifies an individual that is minimally worse, 4 90%, about 70% to about 90%, about 10% to about 80%, identifies an individual that is no change, 3 identifies an about 20% to about 80%, about 30% to about 80%, about 40% individual that is minimally improved, 2 identifies an indi to about 80%, about 50% to about 80%, or about 60% to about vidual that is much improved and a measurement of 1 iden 80%, about 10% to about 70%, about 20% to about 70%, tifies an individual that is very much improved and, wherein about 30% to about 70%, about 40% to about 70%, or about the increase in attentiveness measured CGI-I is by a reduction 50% to about 70%. in the score by 1 or more as compared to a patient not receiv 0029. Aspects of the present specification disclose a dose ing a therapeutic compound to treat a reduction in appetite ofatherapeutic compound to treat the reduction in appetite is and further, wherein the patients CGI-S score is reduced by in the range of at least 0.001 mg/kg/day, at least 0.01 mg/kg/ at least 10%, at least 15%, at least 20%, at least 25%, at least day, at least 0.1 mg/kg/day, at least 1.0 mg/kg/day, at least 5.0 30%, at least 35%, at least 40%, at least 45%, at least 50%, at mg/kg/day, at least 10 mg/kg/day, at least 15 mg/kg/day, at least 55%, at least 60%, at least 65%, at least 70%, at least least 20 mg/kg/day, at least 25 mg/kg/day, at least 30 mg/kg/ 75%, at least 80%, at least 85%, at least 90% or at least 95% day, at least 35 mg/kg/day, at least 40 mg/kg/day, at least 45 and further, wherein the patients CGI-S score is reduced by mg/kg/day, or at least 50 mg/kg/day and/or the dose of the about 10% to about 100%, about 20% to about 100%, about therapeutic compound to treat reduction in appetite is in the 30% to about 100%, about 40% to about 100%, about 50% to range of about 0.001 mg/kg/day to about 100 mg/kg/day about 100%, about 60% to about 100%, about 70% to about and/or the dose of the therapeutic compound to treat the 100%, about 80% to about 100%, about 10% to about 90%, reduction in appetite is in the range of about 0.001 mg/kg/day about 20% to about 90%, about 30% to about 90%, about 40% to about 10 mg/kg/day, about 0.001 mg/kg/day to about 15 to about 90%, about 50% to about 90%, about 60% to about mg/kg/day, about 0.001 mg/kg/day to about 20 mg/kg/day, 90%, about 70% to about 90%, about 10% to about 80%, about 0.001 mg/kg/day to about 25 mg/kg/day, about 0.001 about 20% to about 80%, about 30% to about 80%, about 40% mg/kg/day to about 30 mg/kg/day, about 0.001 mg/kg/day to to about 80%, about 50% to about 80%, or about 60% to about about 35 mg/kg/day, about 0.001 mg/kg/day to about 40 80%, about 10% to about 70%, about 20% to about 70%, mg/kg/day, about 0.001 mg/kg/day to about 45 mg/kg/day, about 30% to about 70%, about 40% to about 70%, or about about 0.001 mg/kg/day to about 50 mg/kg/day, about 0.001 50% to about 70%. mg/kg/day to about 75 mg/kg/day, or about 0.001 mg/kg/day 0032. Aspects of the present specification disclose an to about 100 mg/kg/day. increase in attentiveness by an individual is measured by, 0030 Aspects of the present specification disclose, with without limitation, the pacademic performance rating scale, out limitation, that the increase in attentiveness by an indi ADD evaluation scale-3rd edition (ADDES-3), ADHD rating vidual is measured by CGI-S, wherein the CGI-S scale is scale-IV (ADHD-RS-IV), youth self report (broadband from 1 to 7 and a measurement of 7 identifies an individual instrument), Conners parent rating scale-revised (CPRS-R), that is extremely ill, 6 identifies an individual that is severely Conners teacher rating scale-revised (CTRS-R), Conners 3 ill, 5 identifies an individual that is markedly ill, 4 identifies an self-reporting scale (Conner 3-SR: ages 8-18 y), home situa individual that is moderately ill, 3 identifies an individual that tions questionnaire-revised, inattention/overactivity with is mildly ill, 2 identifies an individual that is borderline ill and aggression (IOWA) Conners teacher's rating scale, Swanson a measurement of 1 identifies an individual that is normal and Nolan and Pelham IV scale (SNAP-IV), Swanson Kotkin wherein, the increase in attentiveness measured by CGI-S is Agler M-Flynn and Pelham (SKAMP), Vanderbilt ADHD by a reduction in the score by 1 or more as compared to a diagnostic parent rating scale (VADPRS), Vanderbilt ADHD patient not receiving a therapeutic compound to treata appe diagnostic teacher rating scale (VADTRS), behavior assess tite reduction and wherein, a patients CGI-S score is reduced ment system for children-2nd edition (BASC-2) or the Con by at least 10%, at least 15%, at least 20%, at least 25%, at ners rating scale long version. least 30%, at least 35%, at least 40%, at least 45%, at least 0033 Aspects of the present specification disclose that a 50%, at least 55%, at least 60%, at least 65%, at least 70%, at psychological and/or neurological disorder can be selected least 75%, at least 80%, at least 85%, at least 90% or at least from, without limitation, the group of migrane, anti-seroton 95%. Another aspecit of the present specification discloses a ergic side effects, narcolepsy, excessive sleepiness associated patients CGI-S score is reduced by about 10% to about with shift work, obstructive sleep apnea as an adjunct to 100%, about 20% to about 100%, about 30% to about 100%, continuous positive airways pressure ("CPAP), exogenous about 40% to about 100%, about 50% to about 100%, about obesity, disruptive behaviour disorder including oppositional 60% to about 100%, about 70% to about 100%, about 80% to defiant disorder (“ODD) and conduct disorder (“CD), obe about 100%, about 10% to about 90%, about 20% to about sity, depression (including, without limitation, augmentation 90%, about 30% to about 90%, about 40% to about 90%, of antidepressants in treating refractory depression and can about 50% to about 90%, about 60% to about 90%, about 70% cer-related depression), neural insult, fatigue (including, to about 90%, about 10% to about 80%, about 20% to about without limitation, disease-related fatigue in patients with 80%, about 30% to about 80%, about 40% to about 80%, HIV, advanced cancer, multiple Sclerosis, myotonic dystro about 50% to about 80%, or about 60% to about 80%, about phy, depression, fibromyalgia and hepatitis C), lethargy, US 2014/010O249 A1 Apr. 10, 2014 binge eating disorder, Schizophrenia, sleep cycle disorder, (“CD), obesity, depression (including, without limitation, cocaine addiction, Parkinson's Disease, combat and non augmentation of antidepressants intreating refractory depres combat related PTSD and/or tic. sion and cancer-related depression), neural insult, fatigue 0034 Aspects of the present specification disclose a kit (including, without limitation, disease-related fatigue in comprising a pharmaceutical composition to treat a disorder. patients with HIV, advanced cancer, multiple Sclerosis, myo tonic dystrophy, depression, fibromyalgia and hepatitis C), BRIEF DESCRIPTION OF THE DRAWINGS lethargy, binge eating disorder, Schizophrenia, sleep cycle 0035 FIG.1 depicts improvement in attention of individu disorder, cocaine addiction, Parkinson's Disease, combat and als, for example children, with increased caloric intake. non-combat related PTSD, tic, and any other psychological 0036 FIG. 2 depicts the impact of combination treatment and/or neurological disorder. In an embodiment, the present on weight. invention discloses the treatment of an attention deficit dis 0037 FIG.3 depicts the impact of combination treatment order, wherein the attention deficit disorder is any disorder on height. that a patient suffers from an attention deficit. In an embodi 0038 FIG. 4 depicts the change in weight and height for ment, the attention deficit disorder can manifest as inatten Patient A. tiveness, hyperactivity, impulsiveness, distractibility, disor 0039 FIG.5 depicts the ADHD sensitivity for Patient Aas ganization, procrastination, forgetfulness, lethargy, fatigue or measured by CGI-S. any other type of attention deficit disorder. In another 0040 FIG. 6 depicts the change in weight and height for embodiment, the attention deficit disorder is Attention Deficit Patient B. Hyperactivity Disorder or ADHD. 004.1 FIG.7 depicts the ADHD sensitivity for Patient Bas 0058. In an embodiment, the present invention discloses measured by CGI-S. the use of a pharmaceutical composition for the treatment of 0042 FIG. 8 depicts the change in weight and height for a psychological and/or neurological disorder. In an embodi Patient C. ment, the present invention discloses the use of a pharmaceu 0043 FIG.9 depicts the ADHD sensitivity for Patient Cas tical composition to treat a psychological and/or neurological measured by CGI-S. disorder, including without limitation, attention deficit disor 0044 FIG. 10 depicts the change in weight and height for der, migrane, anti-serotonergic side effects, narcolepsy, Patient D. excessive sleepiness associated with shift work, obstructive 004.5 FIG. 11 depicts the ADHD sensitivity for Patient D sleep apnea as an adjunct to continuous positive airways as measured by CGI-S. pressure ("CPAP), exogenous obesity, disruptive behaviour 0046 FIG. 12 depicts the change in weight and height for disorder including oppositional defiant disorder (“ODD) Patient E. and conduct disorder (“CD), obesity, depression (including, 0047 FIG. 13 depicts the ADHD sensitivity for Patient E without limitation, augmentation of antidepressants in treat as measured by CGI-S. ing refractory depression and cancer-related depression), 0048 FIG. 14 depicts the change in weight and height for neural insult, fatigue (including, without limitation, disease Patient F. related fatigue in patients with HIV, advanced cancer, mul 0049 FIG. 15 depicts the ADHD sensitivity for Patient F tiple Sclerosis, myotonic dystrophy, depression, fibromyalgia as measured by CGI-S. and hepatitis C), lethargy, binge eating disorder, Schizophre 0050 FIG. 16 depicts the change in weight and height for nia, sleep cycle disorder, cocaine addiction, Parkinson's Dis Patient G. ease, combat and non-combat related PTSD, tic, and any 0051 FIG. 17 depicts the ADHD sensitivity for Patient G other psychological and/or neurological disorder. as measured by CGI-S. 0059. In an embodiment, the present invention discloses 0052 FIG. 18 depicts the change in weight and height for the use of a pharmaceutical composition for the treatment of Patient H. ADHD in a patient suffering from ADHD. In a further 0053 FIG. 19 depicts the ADHD sensitivity for Patient H embodiment, a pharmaceutical composition treats ADHD in as measured by CGI-S. a patient suffering from ADHD and results in weight gain by 0054 FIG. 20 depicts the impact of combination treatment a patient suffering from ADHD. In another embodiment, a on the severity of ADHD as measured by CGI-S). pharmaceutical composition treats ADHD in a patient suffer 0055 FIG. 21 depicts the impact of treatment on the sever ing from ADHD and results in the maintenance or an increase ity of ADHD as measured by CGI-S. of the patient's attentiveness as compared to an individual not 0056 FIG. 22 depicts the impact of treatment on the Suffering from ADHD and not taking a pharmaceutical com improvement of ADHD as measured by CGI-I. position to treat ADHD. 0060 Definitions: In describing and claiming the present DETAILED DESCRIPTION OF THE INVENTION invention, the following terminology will be used in accor 0057. In an embodiment, the present invention discloses dance with the definitions described below. the treatment of a psychological and/or neurological disorder. 0061 “Pharmacologically effective amount,” “physi In an embodiment, the present invention discloses the treat ologically effective amount, and “therapeutically effective ment of a psychological and/or neurological disorder, includ amount are used interchangeably herein to mean the amount ing without limitation, attention deficit disorder, migrane, of a drug or drug-combination that is needed to provide a anti-serotonergic side effects, narcolepsy, excessive sleepi desired level of drug in the bloodstream or in the target tissue. ness associated with shift work, obstructive sleep apnea as an The precise amount will depend upon numerous factors, e.g., adjunct to continuous positive airways pressure (“CPAP), the particular drug or drugs employed, the components and exogenous obesity, disruptive behaviour disorder including physical characteristics of the therapeutic composition, oppositional defiant disorder (“ODD) and conduct disorder intended patient population, individual patient consider US 2014/010O249 A1 Apr. 10, 2014

ations, and the like, and can readily be determined by one tion, disease-related fatigue in patients with HIV, advanced skilled in the art, based upon the information provided herein. cancer, multiple Sclerosis, myotonic dystrophy, depression, 0062 “Substantially” or “essentially’ means nearly fibromyalgia and hepatitis C), lethargy, binge eating disorder, totally or completely, for instance, 95% or greater of some Schizophrenia, sleep cycle disorder, cocaine addiction, Par given quantity. For example, a Substantial elimination of one kinson's Disease, combat and non-combat related PTSD, tic, or more symptoms or clinical indicators, means a reduction in while stimulating the same patient’s appetite. The first step in severity of 95% or more of a symptom, as assessed by any current treatment of a psychological and/or neurological dis clinically acceptable method, or an improvement of at least order, including, without limitation, attention deficit disorder 95% of a given clinical indicator. (including, without limitation ADHD), migrane, anti-sero 0063 A“diminution of one or more symptoms or clinical tonergic side effects, narcolepsy, excessive sleepiness asso indicators, means a measurable reduction in the severity of ciated with shift work, obstructive sleep apnea as an adjunct Such one or more symptoms, as assessed by any clinically to continuous positive airways pressure (“CPAP), exog acceptable method, or a measurable improvement of a given enous obesity, disruptive behaviour disorder including oppo clinical indicator, as assessed by a skilled clinician. sitional defiant disorder (“ODD) and conduct disorder 0064. The term “patient,” refers to a living organism suf (“CD), obesity, depression (including, without limitation, fering from or prone to a condition that can be prevented or augmentation of antidepressants intreating refractory depres treated by administration of a drug or combination of drugs of sion and cancer-related depression), neural insult, fatigue the invention, and includes both humans and animals. (including, without limitation, disease-related fatigue in 0065 “Optional” or “optionally” means that the subse patients with HIV, advanced cancer, multiple Sclerosis, myo quently described circumstance may or may not occur, so that tonic dystrophy, depression, fibromyalgia and hepatitis C), the description includes instances where the circumstance lethargy, binge eating disorder, Schizophrenia, sleep cycle occurs and instances where it does not. disorder, cocaine addiction, Parkinson's Disease, combat and 0066 Aspects of the present specification disclose, in part, non-combat related PTSD, tic, is to usually treat a patient with a pharmaceutical composition. As used herein, the term a short acting stimulant, including, but not limited to an “pharmaceutical composition' is synonymous with “pharma amphetamine and/or a methylheptadine, or introduce a long ceutically acceptable composition' and refers to a therapeu acting stimulant, including, but not limited to a long acting tically effective concentration of an active ingredient, such as, version of an amphetamine or methylheptadine. If there is e.g., any of the therapeutic compounds disclosed herein. A insufficient improvement, the dose is generally titrated up pharmaceutical composition disclosed herein is useful for and/or a long-acting stimulant is initiated in patients not medical and Veterinary applications. A pharmaceutical com receiving along-acting stimulant. If there are side-effects, the position may be administered to an individual alone, or in dosage can be titrated down or the patient can be taken off the combination with other Supplementary active ingredients, treatment. One of the principal side-effects of amphetamine agents, drugs or hormones. and methylphenidate usage is loss of appetite by a patient 0067 Aspects of the present specification disclose, in part, taking Such medicine. This can have adverse effects on the a therapeutic compound. A therapeutic compound is a com patient, including, but not limited to, loss of weight, slower or pound that provides pharmacological activity or other direct reduced growth in height, reduced attentiveness resulting in a effect in the diagnosis, cure, mitigation, treatment, or preven reduction in cognition and an inability to interact socially. To tion of disease, or to affect the structure or any function of the overcome this it is an aspect of the present invention to pro body of man or animals. Any Suitable form of a therapeutic vide a method of treatment wherein a patient suffering from a compound may be chosen. A therapeutic compound dis psychological and/or neurological disorder, including, with closed herein may be used in the form of a pharmaceutically out limitation, attention deficit disorder (including, without acceptable salt, Solvate, or Solvate of a salt, e.g. the hydro limitation ADHD), migrane, anti-serotonergic side effects, chloride. Additionally, therapeutic compound disclosed narcolepsy, excessive sleepiness associated with shift work, herein may be provided as racemates, or as individual enan obstructive sleep apnea as an adjunct to continuous positive tiomers, including the R- or S-enantiomer. Thus, the thera airways pressure (“CPAP), exogenous obesity, disruptive peutic compound disclosed herein may comprise an R-enan behaviour disorder including oppositional defiant disorder tiomer only, a S-enantiomer only, or a combination of both a (“ODD) and conduct disorder (“CD), obesity, depression R-enantiomer and a S-enantiomer of a therapeutic com (including, without limitation, augmentation of antidepres pound. Atherapeutic compound disclosed herein may also be sants in treating refractory depression and cancer-related provided as prodrug or active metabolite. depression), neural insult, fatigue (including, without limita 0068. The present specification discloses combinations of tion, disease-related fatigue in patients with HIV, advanced various therapeutic compounds that when combined produce cancer, multiple Sclerosis, myotonic dystrophy, depression, synergistic effects to treat a patient Suffering from a psycho fibromyalgia and hepatitis C), lethargy, binge eating disorder, logical and/or neurological disorder, including, without limi Schizophrenia, sleep cycle disorder, cocaine addiction, Par tation, attention deficit disorder (including, without limita kinson's Disease, combat and non-combat related PTSD, tic tion ADHD), migrane, anti-serotonergic side effects, is administered a pharmaceutical composition to treat the narcolepsy, excessive sleepiness associated with shift work, disorder and an appetite stimulant. Through Such treatment, a obstructive sleep apnea as an adjunct to continuous positive patient will generally gain weight, increase in height, and/or airways pressure (“CPAP), exogenous obesity, disruptive show improved attentiveness, resulting in an increase in cog behaviour disorder including oppositional defiant disorder nition and/or an ability to interact socially as compared to the (“ODD) and conduct disorder (“CD), obesity, depression same patient who does not take an appetite stimulant. (including, without limitation, augmentation of antidepres 0069. The present specification discloses combinations of sants in treating refractory depression and cancer-related various therapeutic compounds that when combined produce depression), neural insult, fatigue (including, without limita synergistic effects to treat a patient suffering from ADHD, US 2014/010O249 A1 Apr. 10, 2014 while stimulating the same patient’s appetite. The first step in including oppositional defiant disorder (“ODD) and conduct current treatment of ADHD is to usually treat a patient with a disorder (“CD), obesity, depression (including, without short acting stimulant, including, but not limited to an limitation, augmentation of antidepressants in treating refrac amphetamine and/or a methylheptadine, or introduce a long tory depression and cancer-related depression), neural insult, acting stimulant, including, but not limited to a long acting fatigue (including, without limitation, disease-related fatigue version of an amphetamine or methylheptadine. Within the in patients with HIV, advanced cancer, multiple Sclerosis, first month following treatment initiation, the patient is gen myotonic dystrophy, depression, fibromyalgia and hepatitis erally re-examined for impact of the treatment on attention C), lethargy, binge eating disorder, Schizophrenia, sleep cycle and treatment related side effects. If there is insufficient disorder, cocaine addiction, Parkinson's Disease, combat and improvement on attention, the dose is generally titrated up non-combat related PTSD, tic, and appetite reduction. In a and/or a long-acting stimulant is initiated in patients not further embodiment, a therapeutic compound treats ADHD receiving along-acting stimulant. If there are side-effects, the and a different therapeutic compound treats appetite reduc dosage can be titrated down or the patient can be taken off the tion. In another embodiment, one or more therapeutic com ADHD treatment. One of the principal side-effects of pounds treat a psychological and/or neurological disorder, amphetamine and methylphenidate usage is loss of appetite including, without limitation, attention deficit disorder (in by a patient taking Such medicine. This can have adverse cluding, without limitation ADHD), migrane, anti-serotoner effects on the patient, including, but not limited to, loss of gic side effects, narcolepsy, excessive sleepiness associated weight, slower or reduced growth in height, reduced atten with shift work, obstructive sleep apnea as an adjunct to tiveness resulting in a reduction in cognition and an inability continuous positive airways pressure ("CPAP), exogenous to interact Socially. To overcome this it is an aspect of the obesity, disruptive behaviour disorder including oppositional present invention to provide a method of treatment wherein a defiant disorder (“ODD) and conduct disorder (“CD), obe patient suffering from ADHD is administered a pharmaceu sity, depression (including, without limitation, augmentation tical composition to treat the ADHD and an appetite stimu of antidepressants in treating refractory depression and can lant. Through Such treatment, a patient will generally gain cer-related depression), neural insult, fatigue (including, weight, increase in height, and/or show improved attentive without limitation, disease-related fatigue in patients with ness, resulting in an increase in cognition and/oran ability to HIV, advanced cancer, multiple Sclerosis, myotonic dystro interact socially as compared to the same patient who does not phy, depression, fibromyalgia and hepatitis C), lethargy, take an appetite stimulant. binge eating disorder, Schizophrenia, sleep cycle disorder, 0070. In an embodiment, patient side effects are moni cocaine addiction, Parkinson's Disease, combat and non tored to identify side effects associated with the administra combat related PTSD, tic, and one or more different thera tion of amphetamines and/or methylphenidate to a patient. In peutic compounds treat appetite reduction. an embodiment, the side effects generally seen in patients, 0071. In an embodiment, patient side effects are moni include without limitation, appetite reduction, resulting in, tored to identify side effects associated with the administra without limitation, weight loss and/or reduced growth, tion of amphetamines and/or methylphenidate to a patient. In including without limitation, height, loss of attentiveness, an embodiment, the side effects generally seen in patients, including, without limitation, reduced cognition and reduced include without limitation, appetite reduction, resulting in, ability to interact socially. In a further embodiment, patients without limitation, weight loss and/or reduced growth, found to suffer from appetite reduction are provided a phar including without limitation, height, loss of attentiveness, maceutical composition comprising a therapeutic compound including, without limitation, reduced cognition and reduced to treat the patient’s a psychological and/or neurological dis ability to interact socially. In a further embodiment, patients order, including, without limitation, attention deficit disorder found to suffer from appetite reduction are provided a phar (including, without limitation ADHD), migrane, anti-sero maceutical composition comprising a therapeutic compound tonergic side effects, narcolepsy, excessive sleepiness asso to treat the patient’s ADHD and a therapeutic compound to ciated with shift work, obstructive sleep apnea as an adjunct treat the patient’s appetite reduction. In an embodiment, the to continuous positive airways pressure (“CPAP), exog therapeutic compound treats both ADHD and appetite reduc enous obesity, disruptive behaviour disorder including oppo tion. In a further embodiment, a therapeutic compound treats sitional defiant disorder (“ODD) and conduct disorder ADHD and a different therapeutic compound treats appetite (“CD), obesity, depression (including, without limitation, reduction. In another embodiment, one or more therapeutic augmentation of antidepressants intreating refractory depres compounds treat ADHD and one or more different therapeu sion and cancer-related depression), neural insult, fatigue tic compounds treat appetite reduction. (including, without limitation, disease-related fatigue in 0072 A pharmaceutical composition disclosed herein patients with HIV, advanced cancer, multiple Sclerosis, myo may comprise one or more therapeutic compounds disclosed tonic dystrophy, depression, fibromyalgia and hepatitis C), herein. In one embodiment, a pharmaceutical composition lethargy, binge eating disorder, Schizophrenia, sleep cycle disclosed herein may comprise only a single therapeutic com disorder, cocaine addiction, Parkinson's Disease, combat and pound that treats ADHD in a patient while stimulating the non-combat related PTSD, tic and a therapeutic compound to patient’s appetite and resulting in an increase in attentiveness. treat the patient’s appetite reduction. In an embodiment, the In another embodiment, a pharmaceutical composition dis therapeutic compound treats both a psychological and/or neu closed herein may comprise a plurality of therapeutic com rological disorder, including, without limitation, attention pounds wherein one or more of the therapeutic compounds deficit disorder (including, without limitation ADHD), treat ADHD in a patient, while one or more of the therapeutic migrane, anti-serotonergic side effects, narcolepsy, excessive compounds stimulates the patient’s appetite and results in an sleepiness associated with shift work, obstructive sleep apnea increase in attentiveness. In aspects of this embodiment, a as an adjunct to continuous positive airways pressure pharmaceutical composition disclosed herein comprises at (“CPAP), exogenous obesity, disruptive behaviour disorder least one therapeutic compound that treats ADHD in a patient US 2014/010O249 A1 Apr. 10, 2014 while stimulating the patient’s appetite resulting in an trana, Equasym, Dixirit, KapVay, Daytrana Patch, Methylin increase in attentiveness, at least two therapeutic compounds chewable, Methylin liquid, Dextrostat, Strattera, Tenex, Cat wherein one or more of the therapeutic compounds treats apres, Catapres TTS patch, Prozac, Serefam, Zoloft, Luvox, ADHD in a patient while one or more of the therapeutic Paxil, Paxil CR, Pexeva, Celexa, Lexapro, Tofranil, Nor compounds stimulates the patient’s appetite resulting in an pamin, Elavil, Pamelor, Sinequan, Anafranil, Wellbutrin, increase in attentiveness, at least three therapeutic com Wellbutrin SR, Wellbutrin XL, Effexor, Effexor XR, pounds wherein one or more of the therapeutic compounds Remeron, Cymbalta, Nardil, Parnate, Emsam patch, Haldol, treats ADHD in a patient while one or more of the therapeutic Orap, Prolixin, Mellaril, Thorazine, Stelazine, Moban, Loxi compounds stimulates the patient’s appetite resulting in an tane, Risperdal, Zyprexa, Seroquel, Geodon, Abilify, Cloz increase in attentiveness, or at least four therapeutic com aril, Xanax, Xanax XR, Klonopin, Ativan, Buspar, Ambien pounds wherein one or more of the therapeutic compounds CR, Ambien, Lunesta, Sonata, Rozerem, Lithiu, Lithobid, treats ADHD in a patient while one or more of the therapeutic Eskalith, Depakote, Tegretol, Carbatrol, Trileptal, Lamictal, compounds stimulates the patient’s appetite resulting in an Topamax, Neurontin and the therapeutic compounds identi increase in attentiveness. In other aspects of this embodiment, fied in Table 1. a pharmaceutical composition disclosed herein comprises at 0074. In another embodiment, a pharmaceutical composi most two therapeutic compounds wherein one or more of the tion disclosed herein to treat a patient Suffering from a psy therapeutic compounds treats ADHD in a patient while one or chological and/or neurological disorder, including without more of the therapeutic compounds stimulates the patients limitation, migrane, anti-serotonergic side effects and narco appetite resulting in an increase in attentiveness, at most three lepsy, excessive sleepiness associated with shift work, therapeutic compounds wherein one or more of the therapeu obstructive sleep apnea as an adjunct to continuous positive tic compounds treats ADHD in a patient while one or more of airways pressure (“CPAP), exogenous obesity, disruptive the therapeutic compounds stimulates the patient's appetite behaviour disorder including oppositional defiant disorder resulting in an increase in attentiveness, or at most fourthera (“ODD) and conduct disorder (“CD), obesity, depression peutic compounds wherein one or more of the therapeutic (including, without limitation, augmentation of antidepres compounds treats ADHD in a patient while one or more of the sants in treating refractory depression and cancer-related therapeutic compounds stimulates the patient's appetite depression), neural insult, fatigue (including, without limita resulting in an increase in attentiveness. In yet other aspects of tion, disease-related fatigue in patients with HIV, advanced this embodiment, a pharmaceutical composition disclosed cancer, multiple Sclerosis, myotonic dystrophy, depression, herein comprises one to three therapeutic compounds fibromyalgia and hepatitis C), lethargy, binge eating disorder, wherein one or more of the therapeutic compounds treats Schizophrenia, sleep cycle disorder, cocaine addiction, Par ADHD in a patient while one or more of the therapeutic kinson's Disease, combat and non-combat related PTSD, tic compounds stimulates the patient’s appetite resulting in an include, without limitation, amphetamines and/or meth increase in attentiveness, two to fourtherapeutic compounds ylphenidate. In an embodiment, a pharmaceutical composi wherein one or more of the therapeutic compounds treats tion disclosed herein to treat a patient Suffering from a psy ADHD in a patient while one or more of the therapeutic chological and/or neurological disorder, including without compounds stimulates the patient’s appetite resulting in an limitation, migrane, anti-serotonergic side effect and narco increase in attentiveness, two to five therapeutic compounds lepsy, excessive sleepiness associated with shift work, wherein one or more of the therapeutic compounds treats obstructive sleep apnea as an adjunct to continuous positive ADHD in a patient while one or more of the therapeutic airways pressure (“CPAP), exogenous obesity, disruptive compounds stimulates the patient’s appetite resulting in an behaviour disorder including oppositional defiant disorder increase in attentiveness, three to five therapeutic compounds (“ODD) and conduct disorder (“CD), obesity, depression wherein one or more of the therapeutic compounds treats (including, without limitation, augmentation of antidepres ADHD in a patient while one or more of the therapeutic sants in treating refractory depression and cancer-related compounds stimulates the patient’s appetite resulting in an depression), neural insult, fatigue (including, without limita increase in attentiveness, or two to three therapeutic com tion, disease-related fatigue in patients with HIV, advanced pounds wherein one or more of the therapeutic compounds cancer, multiple Sclerosis, myotonic dystrophy, depression, treats ADHD in a patient while one or more of the therapeutic fibromyalgia and hepatitis C), lethargy, binge eating disorder, compounds stimulates the patient’s appetite resulting in an Schizophrenia, sleep cycle disorder, cocaine addiction, Par increase in attentiveness. In aspects of this embodiment, a kinson's Disease, combat and non-combat related PTSD, tic therapeutic compound that treats ADHD in a patient and/or include, without limitation, OROS methylphenidate (Con stimulates the patients. certa), dextroamphetamine immediate/sustained release 0073. In another embodiment, a pharmaceutical composi (Adderall/Adderall XR), dexmethylphenidate (Focalin), tion disclosed herein to treat a patient suffering from ADHD Focalin XR, Metadate CD, dextroamphetamine (Dexedrine), include, without limitation, amphetamines and/or meth Dexedrine Spansules, Methylin ER (Ritalin SR), meth ylphenidate. In an embodiment, a pharmaceutical composi ylphenidate (Ritalin), and methylphenidate CR, Ritalin, tion disclosed herein to treat a patient suffering from ADHD Ritalin LA, Methylin chewable, Methylin liquid, Daytrana include, without limitation, OROS methylphenidate (Con Patch, SD-483, SPD-503, Ritalin SR, Intuniv ER, Intuniv, certa), dextroamphetamine immediate/sustained release Methylin, Daytrana, Equasym, Dixirit, Kapvay, Metadate (Adderall/Adderall XR), dexmethylphenidate (Focalin), ER, NWP09, Dexedrine, bupropion, Dextrostat, Strattera, Focalin XR, Metadate CD, Metadate ER, NWP09, Tenex, Catapres, Catapres TTS patch, Prozac, Serefam, Dexedrine, dextroamphetamine (Dexedrine), Dexedrine Zoloft, Luvox, Paxil, Paxil CR, Pexeva, Celexa, Lexapro, SpanSules, Methylin ER (Ritalin SR), methylphenidate (Ri Tofranil, Norpamin, Elavil, Pamelor, Sinequan, Anafranil, talin), and methylphenidate CR, Ritalin, Ritalin LA, SD-483, Wellbutrin, Wellbutrin SR, Wellbutrin XL, Effexor, Effexor SPD-503, Ritalin SR, Intuniv ER, Intuniv, Methylin, Day XR, Remeron, Cymbalta, Nardil, Parnate, Emsam patch, Hal US 2014/010O249 A1 Apr. 10, 2014 11 dol, Orap, Prolixin, Mellaril. Thorazine, Stelazine, Moban, TABLE 1-continued Loxitane, Risperdal, Zyprexa, Seroquel, Geodon, Abilify, CloZaril, Xanax, Xanax XR, Klonopin, Ativan, Buspar, Brand Name Generic Name** Ambien CR, Ambien, Lunesta, Sonata, Rozerem, Lithiu, Prolixin fluiphenazine Lithobid, Eskalith, Depakote, Tegretol, Carbatrol, Trileptal, Mellari thioridazine Thorazine chlorpromazine Lamictal, Topamax, Neurontin and the therapeutic com Stelazine trifluoperazine pounds identified in Table 1. Moban molindone LOXitane loxapine TABLE 1. Risperdal risperidone Zyprexa olanzapine Brand Name Generic Name** Seroquel quetiapine Geodon Ziprasidone Ritalin methylphenidate Abilify aripiprazole Ritalin SR Clozari clozapine Ritalin LA Xanax alprazolam Concerta Xanax XR Daytrana Klonopin clonazepam Equasym XL lorazepam Focalin buspirone Methylin Zolpidem Methylin Chewable Methylin Liquid eSzopiclone Metadate CD Sonata Zaleplon Metadate ER Rozerem ramelteon Lithium lithium Concerta methylphenidate Lithobid Focalin Eskalith Focalin XR Depakote divalproex Metadate CD valproate Ritalin LA Tegretol carbamazepine Daytrana Patch Carbatrol Dexedrine amphetamine Epitol Dexedrine SpanSule Tegretol XR Dextrostat Generics Adderall Tegretol SD-483 Equetro Adderall XR amphetamine salts Trileptal oxcarbazepine Strattera atomoxetine Lamictal lamotrigine Tenex guanfacine Topamax topiramate SPD-503 Neurontin gabapentin intuniv ER Lobeline active ingredient in the lobelia plant targets intuniv nicotinic receptors Catapres clonidine Unnamed Supplement Zinc, magnesium, vitamin B6 and vitamin C Catapres TTS patch Cylert central nervous system stimulant Dixirit CX-1739 ampakine Kapway CX-2O76 ampakine Prozac fluoxetine CX-516 ampakine Serefaim CX-546 ampakine Zoloft sertraline CX-614 ampakine LWOX fluvoxamine CX-717 ampakine Paxil paroxetine ABT-894 atomoxetine Strattera atomoxetine SONO216 bifemelane Celexa citalopram Alinert Lexapro escitallopram Celeport Tofrainil imipramine OPC-34712 Dopamine D2 receptor partial agonist Procentra dextroamphetamine Norpramin desipramine Vyvanse lisdexamfetamine Elavi amitryptyline lisdexamfetamine Pamelor nortriptyline Various melatonin Sinequan doxepin Namenda memantine Anafrainil clomipramine Desoxyn methamphetamine Wellbutrin bupropion Savella milnacipran Wellbutrin SR Attenace modafinil Wellbutrin XL Provigil Budeprion SR ABT-894 neuronal nicotinic receptor Budeprion XL AZD1446 Aplenzin AZD3480 Effexor venlafaxine TC-5619 Effexor XR venlafaxine ABTO89 Remeron mirtazapine TD-9855 norepinephrine (and serotonin) reuptake receptor Cymbalta dulloxetine LY2216684 Nardi phenelzine Desipramine norpramin Parnate tranylcypromine Pamelor nortriptyline Emsam patch Selegiline Cyclert pemoline Haldol haloperidol KP106 prodrug of d-amphetamine Orap pimozide Nuvigil R modafinil US 2014/01 00249 A1 Apr. 10, 2014

TABLE 1-continued ylidene)-1-methylpiperidine hydrochloride) ("Cyprohepta dine'). Cyproheptadine is used as an oral monotherapy for Brand Name Generic Name** allergy under the tradename Periactin R. Cyproheptadine Kuvan sapropterin reaches peak plasma levels in 1-3 hours and has a half-life of SGS-742 Selective GABA-B receptor antagonist 8 hours. (Gunja, 2004). In the 1960s, it was recognized that a Eltoprazine Serotonin 5-HT1A and 5-HT1B receptor agonist side-effect of Cyproheptadine was it could cause weight gain DOV-102 Serontoin-norepinephrine-dopamine reuptake DOV-677 inhibitor and drowsiness, which prompted the development of newer Zoloft sertraline anti-histamines with better side effect profiles. In an embodi Chantix varenicline ment, a pharmaceutical composition is comprised of a thera Orazinc Zinc peutic compound for the treatment of ADHD and Cyprohep Zinc sulfate IV tadine. In a further embodiment, a pharmaceutical Zine sulfate composition is comprised of an amphetamine and/or meth ylphenidate and Cyproheptadine. In another embodiment, a 0075 Atherapeutic compound disclosed herein may bean pharmaceutical compound is comprised of either Ritalin, orexigenic drug. As used herein, the term orexigenic drug Focalin or Concerta and Cyproheptadine. refers to a class of therapeutic compounds that have the ability 0078. The present specification discloses combinations of to stimulate a patient’s appetite. Examples of suitable orexi various therapeutic compounds that when combined produce genic drugs include, without limitation, alcohol, GHB, and synergistic effects in treating a patient suffering from ADHD other sedatives such as some benzodiazepine and nonbenzo and/or a psychological and/or neurological disorder, includ diazepine tranquilizers and sleeping pills, anti-depressants ing without limitation, migrane, anti-serotonergic side effects (some SSRIs, Mianserin, etc.), 5-HT, receptor antagonists/ and narcolepsy, excessive sleepiness associated with shift inverse agonists (e.g., mirtazapine, mianserin, olanzapine, work, obstructive sleep apnea as an adjunct to continuous quetiapine, risperidone, amitriptyline, imipramine, cypro positive airways pressure ("CPAP), exogenous obesity, dis heptadine, etc.), H receptor antagonists/inverse agonists ruptive behaviour disorder including oppositional defiant dis (e.g., buclizine, mirtazapine, mianserin, olanzapine, quetiap order (“ODD) and conduct disorder (“CD), obesity, depres ine, n-3 fatty acids, amitriptyline, chlorpheniramine maleate, sion (including, without limitation, augmentation of etc.). D/D receptor antagonists (e.g., haloperidol, chlorpro antidepressants in treating refractory depression and cancer mazine, olanzapine, risperidone, quetiapine, etc.), Marinol, related depression), neural insult, fatigue (including, without Megace, Megace ES, C.-adrenergic receptor antagonists limitation, disease-related fatigue in patients with HIV. (such as doxazosin, carvedilol, propanolol, colonidine), Sere advanced cancer, multiple sclerosis, myotonic dystrophy, fam, C2-adrenergic receptor agonists (e.g., clonidine, guan depression, fibromyalgia and hepatitis C), lethargy, binge facine, etc.), some beta blockers such as propanolol, natural eating disorder, schizophrenia, sleep cycle disorder, cocaine or synthetic CB, receptor agonists (e.g., THC or dronabinol addiction, Parkinson's Disease, combat and non-combat (found in Cannabis), tetrahydrocannibinol, diphenydramine, related PTSD, tic, while maintaining the patient’s appetite promethazine, B vitamin supplements, nabilone, JWH-018 and concomitant attentiveness. In addition, the present speci etc.). Corticosteroids (e.g. prednisone or dexamethasone), fication discloses that administration of the disclosed combi Sodium valproate (Depakote), Megestrol. Pregabalin, Sulfo nations of a therapeutic compound can be through inhalation, nylurea antidiabetic drugs such as glibenclamide and chlor oral administration, intravenous (“IV”), intranasal (IN). propamide, steroids (including, without limitation, bold sublingual, subcutaneous ("SC"), enteral, parenteral, inhaled, enOne, oxymetholone, dexamethasone, O transcutaneous TC (for example, without limitation, through methandrostenolone, prednisone, hydrocortisone, oxan a patch placed on the skin of an individual being treated). drolone, nandrolone, testosterone), some kappa opioid recep rectal and/or vaginal. tor agonists such as tifluadom, hormones such as mederoX 0079. In an embodiment, the patient is administered or yprogesterone. takes takes a serotonin-norepinephrine-dopamine reuptake 0076). Additional therapeutic compounds that are inhibitor (SNDR1), or triple reuptake inhibitor (TR1), one or examples of suitable orexigenic drugs, include, without limi more times a day. A SNDR1 or TR1 is a drug/ligand that tation, mirtazapine (Remeron), a tetracyclic antidepressant; simultaneously acts as a reuptake inhibitor for the monoam cyproheptadine (Periactin), an antihistamine; nandrolone, ine neurotransmitters, serotonin (5-HT), norepinephrine (no oxymetholone, and Oxandrolone (Anadrol-50. Durabolin, radrenaline, NA) and dopamine (DA). In an embodiment, a Hybolin, anti-IL6 antibody, selective androgen receptor SNDR1 or TR1 is, without limitation, EB-1020, which is modulator (“SARM), Oxandrin, and other brand names), catecholamine preferring TUI, is a triple reuptake inhibitor VT-122 (a coadministration of propranolol and etodolac), that modulates norepinephrine (NE), dopamine (DA) and type 4 melanocortin receptor antagonis, IL6 antagonist, syn serotonin (5-HT) in a ratio of 1 to 6 to 14, respectively. This thetic ghrelin, myostatin decoy receptor, fast skeletal muscle preferential NE with moderate DA reuptake inhibition pro troponin-activating substance, anticatabolic/anabolic trans file, with a small amount of 5-HT reuptake inhibition, has the forming agent MT-102, celecoxib, testosterone, Vitamin D. potential to be an effective treatment for ADHD in adults with OHR/AVR118, soluble version of the ActRIIB receptor, less risk of drug abuse liability and diversion than the stimu 5-HT antagonists, Cox-2 inhibitor, thalidomide, omega-3 lants used for ADHD today. fatty acids, anticyclooxygenase-2 drugs and megestrol 0080. In an embodiment, the patient is administered or acetate (Megace). In addition to these prescription drugs, fish takes a pharmaceutical composition two or more times per oil (eicosapentaenoic acid or EPA), EATMOR, other vita day, wherein the pharmaceutical composition comprises a mins and natural or artificial appetite stimulants. therapeutic compound for the treatment of ADHD and/or a 0077. In an embodiment, the orexigenic drug is cyprohep psychological and/or neurological disorder, including with tadine hydrochloride (4-(5H-dibenzoadcyclohepten-5- out limitation, migrane, anti-serotonergic side effects and US 2014/010O249 A1 Apr. 10, 2014 narcolepsy, excessive sleepiness associated with shift work, sion and cancer-related depression), neural insult, fatigue obstructive sleep apnea as an adjunct to continuous positive (including, without limitation, disease-related fatigue in airways pressure (“CPAP), exogenous obesity, disruptive patients with HIV, advanced cancer, multiple Sclerosis, myo behaviour disorder including oppositional defiant disorder tonic dystrophy, depression, fibromyalgia and hepatitis C), (“ODD) and conduct disorder (“CD), obesity, depression lethargy, binge eating disorder, Schizophrenia, sleep cycle (including, without limitation, augmentation of antidepres disorder, cocaine addiction, Parkinson's Disease, combat and sants in treating refractory depression and cancer-related non-combat related PTSD, tic and an appetite stimulant. In depression), neural insult, fatigue (including, without limita another embodiment, the patient is administered or takes a tion, disease-related fatigue in patients with HIV, advanced pharmaceutical composition in the afternoon, wherein the cancer, multiple Sclerosis, myotonic dystrophy, depression, pharmaceutical composition comprises a therapeutic com fibromyalgia and hepatitis C), lethargy, binge eating disorder, pound for the treatment of ADHD and/or a psychological Schizophrenia, sleep cycle disorder, cocaine addiction, Par and/or neurological disorder, including without limitation, kinson's Disease, combat and non-combat related PTSD, tic migrane, anti-serotonergic side effects and narcolepsy, exces and an appetite stimulant. In an embodiment, the patient is sive sleepiness associated with shift work, obstructive sleep administered or takes a pharmaceutical composition once a apnea as an adjunct to continuous positive airways pressure day, wherein the pharmaceutical composition comprises a (“CPAP), exogenous obesity, disruptive behaviour disorder therapeutic compound for the treatment of ADHD and/or a including oppositional defiant disorder (“ODD) and conduct psychological and/or neurological disorder, including with disorder (“CD), obesity, depression (including, without out limitation, migrane, anti-serotonergic side effects narco limitation, augmentation of antidepressants in treating refrac lepsy, excessive sleepiness associated with shift work, tory depression and cancer-related depression), neural insult, obstructive sleep apnea as an adjunct to continuous positive fatigue (including, without limitation, disease-related fatigue airways pressure (“CPAP), exogenous obesity, disruptive in patients with HIV, advanced cancer, multiple Sclerosis, behaviour disorder including oppositional defiant disorder myotonic dystrophy, depression, fibromyalgia and hepatitis (“ODD) and conduct disorder (“CD), obesity, depression C), lethargy, binge eating disorder, Schizophrenia, sleep cycle (including, without limitation, augmentation of antidepres disorder, cocaine addiction, Parkinson's Disease, combat and sants in treating refractory depression and cancer-related non-combat related PTSD, tic and an appetite stimulant. In depression), neural insult, fatigue (including, without limita another embodiment, the patient does not take a pharmaceu tion, disease-related fatigue in patients with HIV, advanced tical composition in the evening or before bed, wherein the cancer, multiple sclerosis, myotonic dystrophy, depression, pharmaceutical composition comprises a therapeutic com fibromyalgia and hepatitis C), lethargy, binge eating disorder, pound for the treatment of ADHD and/or a psychological Schizophrenia, sleep cycle disorder, cocaine addiction, Par and/or neurological disorder, including without limitation, kinson's Disease, combat and non-combat related PTSD, tic, migrane, anti-serotonergic side effects narcolepsy, excessive and an appetite stimulant. In an embodiment, the patient is sleepiness associated with shift work, obstructive sleep apnea administered or takes a pharmaceutical composition in the as an adjunct to continuous positive airways pressure morning or afternoon, wherein the pharmaceutical composi (“CPAP), exogenous obesity, disruptive behaviour disorder tion comprises a therapeutic compound for the treatment of including oppositional defiant disorder (“ODD) and conduct ADHD and/or a psychological and/or neurological disorder, disorder (“CD), obesity, depression (including, without including without limitation, migrane, anti-serotonergic side limitation, augmentation of antidepressants in treating refrac effects and narcolepsy, excessive sleepiness associated with tory depression and cancer-related depression), neural insult, shift work, obstructive sleep apnea as an adjunct to continu fatigue (including, without limitation, disease-related fatigue ous positive airways pressure ("CPAP), exogenous obesity, in patients with HIV, advanced cancer, multiple Sclerosis, disruptive behaviour disorder including oppositional defiant myotonic dystrophy, depression, fibromyalgia and hepatitis disorder (“ODD) and conduct disorder (“CD), obesity, C), lethargy, binge eating disorder, Schizophrenia, sleep cycle depression (including, without limitation, augmentation of disorder, cocaine addiction, Parkinson's Disease, combat and antidepressants in treating refractory depression and cancer non-combat related PTSD, tic and an appetite stimulant. In a related depression), neural insult, fatigue (including, without further embodiment, the patient taking a pharmaceutical limitation, disease-related fatigue in patients with HIV. composition comprising a therapeutic compound for the advanced cancer, multiple Sclerosis, myotonic dystrophy, treatment of ADHD and/or a psychological and/or neurologi depression, fibromyalgia and hepatitis C), lethargy, binge cal disorder, including without limitation, migrane, anti-Se eating disorder, Schizophrenia, sleep cycle disorder, cocaine rotonergic side effects and narcolepsy, excessive sleepiness addiction, Parkinson's Disease, combat and non-combat associated with shift work, obstructive sleep apnea as an related PTSD, tic and an appetite stimulant. In another adjunct to continuous positive airways pressure (“CPAP), embodiment, the patient is administered or takes a pharma exogenous obesity, disruptive behaviour disorder including ceutical composition in the morning, wherein the pharmaceu oppositional defiant disorder (“ODD) and conduct disorder tical composition comprises a therapeutic compound for the (“CD), obesity, depression (including, without limitation, treatment of ADHD and/or a psychological and/or neurologi augmentation of antidepressants intreating refractory depres cal disorder, including without limitation, migrane, anti-Se sion and cancer-related depression), neural insult, fatigue rotonergic side effects and narcolepsy, excessive sleepiness (including, without limitation, disease-related fatigue in associated with shift work, obstructive sleep apnea as an patients with HIV, advanced cancer, multiple Sclerosis, myo adjunct to continuous positive airways pressure (“CPAP), tonic dystrophy, depression, fibromyalgia and hepatitis C), exogenous obesity, disruptive behaviour disorder including lethargy, binge eating disorder, Schizophrenia, sleep cycle oppositional defiant disorder (“ODD) and conduct disorder disorder, cocaine addiction, Parkinson's Disease, combat and (“CD), obesity, depression (including, without limitation, non-combat related PTSD, tic and an appetite stimulant in the augmentation of antidepressants intreating refractory depres morning either maintains or increases their attentiveness US 2014/010O249 A1 Apr. 10, 2014

when compared to a patient taking only a therapeutic com severity of mental illness at the time of rating 1, normal, not at pound for the treatment of ADHD and/or a psychological all ill; 2, borderline mentally ill: 3, mildly ill; 4, moderately and/or neurological disorder, including without limitation, ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. In an migrane, anti-serotonergic side effects, narcolepsy, excessive embodiment, attentiveness is measured using the Clinical sleepiness associated with shift work, obstructive sleep apnea Global Impression-Improvement scale (“CGI-I). CGI-I is a as an adjunct to continuous positive airways pressure 7 point scale that requires the clinician to assess how much the (“CPAP), exogenous obesity, disruptive behaviour disorder patient’s illness has improved or worsened relative to a base including oppositional defiant disorder (“ODD) and conduct line state at the beginning of the intervention and rated as: 1. disorder (“CD), obesity, depression (including, without very much improved; 2, much improved; 3, minimally limitation, augmentation of antidepressants in treating refrac improved; 4, no change; 5, minimally worse; 6, much worse; tory depression and cancer-related depression), neural insult, or 7. Very much worse. In an embodiment, attentiveness is fatigue (including, without limitation, disease-related fatigue measured using the Clinical Global Impression-Efficacy in patients with HIV, advanced cancer, multiple Sclerosis, Index (“CGI-E). CGI-E is a 4 pointx4 point rating scale that myotonic dystrophy, depression, fibromyalgia and hepatitis assesses the therapeutic effect of the treatment as 1, C), lethargy, binge eating disorder, Schizophrenia, sleep cycle unchanged to worse; 2. minimal: 3, moderate; 4, marked by disorder, cocaine addiction, Parkinson's Disease, combat and side effects rated as none, do not significantly interfere with non-combat related PTSD and tic. In a further embodiment, patient’s functioning, significantly interferes with patients the patient taking a pharmaceutical composition comprising a functioning and outweighs therapeutic effect. therapeutic compound for the treatment of ADHD and/or a 0082 In a further embodiment, attentiveness is measured psychological and/or neurological disorder, including with using one or more of the following ADHD screening tools and out limitation, migrane, anti-serotonergic side effects and rating scales for children and adolescents, including, without narcolepsy, excessive sleepiness associated with shift work, limitation, academic performance rating scale, ADD evalua obstructive sleep apnea as an adjunct to continuous positive tion scale-3rd edition (ADDES-3), ADHD rating scale-IV airways pressure (“CPAP), exogenous obesity, disruptive (ADHD-RS-IV), youth self report (broadband instrument), behaviour disorder including oppositional defiant disorder Conners parent rating scale-revised (CPRS-R), Conners (“ODD) and conduct disorder (“CD), obesity, depression teacher rating scale-revised (CTRS-R), Connoers 3 self-re (including, without limitation, augmentation of antidepres porting scale (Conner 3-SR, ages 8-18 y), home situations sants in treating refractory depression and cancer-related questionnaire-revised, inattention/overactivity with aggres depression), neural insult, fatigue (including, without limita sion (IOWA) Conners teacher's rating scale, Swanson Nolan tion, disease-related fatigue in patients with HIV, advanced and Pelham IV scale (SNAP-IV), Swanson Kotkin Agler cancer, multiple Sclerosis, myotonic dystrophy, depression, M-Flynn and Pelham (SKAMP). Vanderbilt ADHD diagnos fibromyalgia and hepatitis C), lethargy, binge eating disorder, tic parent rating scale (VADPRS), Vanderbilt ADHD diag Schizophrenia, sleep cycle disorder, cocaine addiction, Par nostic teacher rating scale (VADTRS), behavior assessment kinson's Disease, combat and non-combat related PTSD, tic system for children-2nd edition (BASC-2). In an embodi and an appetite stimulant in the afternoon either maintains or ment, attentiveness is measured by the Conners rating scale increases their attentiveness when compared to a patient tak long version which includes without limitation, these sub ing only a therapeutic compound for the treatment of ADHD scales: and/or a psychological and/or neurological disorder, includ ing without limitation, migrane, anti-serotonergic side effects, narcolepsy, excessive sleepiness associated with shift Oppositional Social Problems work, obstructive sleep apnea as an adjunct to continuous Cognitive Problems. Inattention Psychosomatic positive airways pressure (“CPAP), exogenous obesity, dis Hyperactivity Conners Global Index ruptive behaviour disorder including oppositional defiant dis Anxious-Shy DSM-IV Symptom Subscale order (“ODD) and conduct disorder (“CD), obesity, depres Perfectionism ADHD Index sion (including, without limitation, augmentation of antidepressants in treating refractory depression and cancer I0083. In one embodiment, a therapeutic compound dis related depression), neural insult, fatigue (including, without closed herein is used for the treatment of ADHD and/or a limitation, disease-related fatigue in patients with HIV. psychological and/or neurological disorder, including with advanced cancer, multiple Sclerosis, myotonic dystrophy, out limitation, migrane, anti-serotonergic side effects, narco depression, fibromyalgia and hepatitis C), lethargy, binge lepsy, excessive sleepiness associated with shift work, eating disorder, Schizophrenia, sleep cycle disorder, cocaine obstructive sleep apnea as an adjunct to continuous positive addiction, Parkinson's Disease, combat and non-combat airways pressure (“CPAP), exogenous obesity, disruptive related PTSD and tic. behaviour disorder including oppositional defiant disorder 0081. In an embodiment, attentiveness is measured using (“ODD) and conduct disorder (“CD), obesity, depression the Clinical Global Impression rating scales to measure (including, without limitation, augmentation of antidepres symptom severity, treatment response and the efficacy of sants in treating refractory depression and cancer-related treatments in treatment studies of patients with mental disor depression), neural insult, fatigue (including, without limita ders (Guy, W., 1976). In an embodiment, attentiveness is tion, disease-related fatigue in patients with HIV, advanced measure using the Clinical Global Impression-Severity scale cancer, multiple Sclerosis, myotonic dystrophy, depression, (“CGI-S). In an embodiment, CGI-S is a 7-point scale that fibromyalgia and hepatitis C), lethargy, binge eating disorder, requires the clinician to rate the severity of the patients illness Schizophrenia, sleep cycle disorder, cocaine addiction, Par at the time of assessment, relative to the clinician’s past kinson's Disease, combat and non-combat related PTSD and experience with patients who have the same diagnosis. Con tic. In aspects of this embodiment, a therapeutic compound sidering total clinical experience, a patient is assessed on for the treatment of ADHD and/or a psychological and/or US 2014/010O249 A1 Apr. 10, 2014 neurological disorder, including without limitation, migrane, patients with HIV, advanced cancer, multiple Sclerosis, myo anti-serotonergic side effects and narcolepsy, excessive tonic dystrophy, depression, fibromyalgia and hepatitis C), sleepiness associated with shift work, obstructive sleep apnea lethargy, binge eating disorder, Schizophrenia, sleep cycle as an adjunct to continuous positive airways pressure disorder, cocaine addiction, Parkinson's Disease, combat and (“CPAP), exogenous obesity, disruptive behaviour disorder non-combat related PTSD and tic, by, e.g., about 10% to including oppositional defiant disorder (“ODD) and conduct about 100%, about 20% to about 100%, about 30% to about disorder (“CD), obesity, depression (including, without 100%, about 40% to about 100%, about 50% to about 100%, limitation, augmentation of antidepressants in treating refrac about 60% to about 100%, about 70% to about 100%, about tory depression and cancer-related depression), neural insult, 80% to about 100%, about 10% to about 90%, about 20% to about 90%, about 30% to about 90%, about 40% to about fatigue (including, without limitation, disease-related fatigue 90%, about 50% to about 90%, about 60% to about 90%, in patients with HIV, advanced cancer, multiple Sclerosis, about 70% to about 90%, about 10% to about 80%, about 20% myotonic dystrophy, depression, fibromyalgia and hepatitis to about 80%, about 30% to about 80%, about 40% to about C), lethargy, binge eating disorder, Schizophrenia, sleep cycle 80%, about 50% to about 80%, or about 60% to about 80%, disorder, cocaine addiction, Parkinson's Disease, combat and about 10% to about 70%, about 20% to about 70%, about 30% non-combat related PTSD and tic, reduces a symptom or set to about 70%, about 40% to about 70%, or about 50% to about of symptoms, including, without limitation, the CGI-S index 70%. associated with ADHD and/or a psychological and/or neuro logical disorder, including without limitation, migrane, anti I0084. In one embodiment, a therapeutic compound dis serotonergic side effects, narcolepsy, excessive sleepiness closed herein is used for the treatment of appetite reduction. associated with shift work, obstructive sleep apnea as an In aspects of this embodiment, a therapeutic compound for adjunct to continuous positive airways pressure (“CPAP), the treatment of ADHD and/or a psychological and/or neuro exogenous obesity, disruptive behaviour disorder including logical disorder, including without limitation, migrane, anti oppositional defiant disorder (“ODD) and conduct disorder serotonergic side effects and narcolepsy, excessive sleepiness (“CD), obesity, depression (including, without limitation, associated with shift work, obstructive sleep apnea as an augmentation of antidepressants intreating refractory depres adjunct to continuous positive airways pressure (“CPAP), sion and cancer-related depression), neural insult, fatigue exogenous obesity, disruptive behaviour disorder including (including, without limitation, disease-related fatigue in oppositional defiant disorder (“ODD) and conduct disorder patients with HIV, advanced cancer, multiple Sclerosis, myo (“CD), obesity, depression (including, without limitation, tonic dystrophy, depression, fibromyalgia and hepatitis C), augmentation of antidepressants intreating refractory depres lethargy, binge eating disorder, Schizophrenia, sleep cycle sion and cancer-related depression), neural insult, fatigue disorder, cocaine addiction, Parkinson's Disease, combat and (including, without limitation, disease-related fatigue in non-combat related PTSD and tic, by, e.g., at least 10%, at patients with HIV, advanced cancer, multiple Sclerosis, myo least 15%, at least 20%, at least 25%, at least 30%, at least tonic dystrophy, depression, fibromyalgia and hepatitis C), 35%, at least 40%, at least 45%, at least 50%, at least 55%, at lethargy, binge eating disorder, Schizophrenia, sleep cycle least 60%, at least 65%, at least 70%, at least 75%, at least disorder, cocaine addiction, Parkinson's Disease, combat and 80%, at least 85%, at least 90% or at least 95%. In other non-combat related PTSD and tic, reduces a symptom asso aspects of this embodiment, a therapeutic compound for the ciated with appetite reduction by, e.g., at least 10%, at least treatment of ADHD and/or a psychological and/or neurologi 15%, at least 20%, at least 25%, at least 30%, at least 35%, at cal disorder, including without limitation, migrane, anti-Se least 40%, at least 45%, at least 50%, at least 55%, at least rotonergic side effects and narcolepsy, excessive sleepiness 60%, at least 65%, at least 70%, at least 75%, at least 80%, at associated with shift work, obstructive sleep apnea as an least 85%, at least 90% or at least 95%. In other aspects of this adjunct to continuous positive airways pressure (“CPAP), embodiment, a therapeutic compound for the treatment of exogenous obesity, disruptive behaviour disorder including appetite reduction reduces a symptom associated with appe oppositional defiant disorder (“ODD) and conduct disorder tite reduction by, e.g., about 10% to about 100%, about 20% (“CD), obesity, depression (including, without limitation, to about 100%, about 30% to about 100%, about 40% to about augmentation of antidepressants intreating refractory depres 100%, about 50% to about 100%, about 60% to about 100%, sion and cancer-related depression), neural insult, fatigue about 70% to about 100%, about 80% to about 100%, about (including, without limitation, disease-related fatigue in 10% to about 90%, about 20% to about 90%, about 30% to patients with HIV, advanced cancer, multiple Sclerosis, myo about 90%, about 40% to about 90%, about 50% to about tonic dystrophy, depression fibromyalgia and hepatitis C), 90%, about 60% to about 90%, about 70% to about 90%, lethargy, binge eating disorder, Schizophrenia, sleep cycle about 10% to about 80%, about 20% to about 80%, about 30% disorder, cocaine addiction, Parkinson's Disease, combat and to about 80%, about 40% to about 80%, about 50% to about non-combat related PTSD and tic, reduces a symptom asso 80%, or about 60% to about 80%, about 10% to about 70%, ciated with ADHD and/or a psychological and/or neurologi about 20% to about 70%, about 30% to about 70%, about 40% cal disorder, including without limitation, migrane, anti-Se to about 70%, or about 50% to about 70%. rotonergic side effects and narcolepsy, excessive sleepiness I0085. In another embodiment, a therapeutic compound associated with shift work, obstructive sleep apnea as an disclosed herein for the treatment of ADHD reduces the adjunct to continuous positive airways pressure (“CPAP), severity of ADHD in a patient. In aspects of this embodiment, exogenous obesity, disruptive behaviour disorder including a therapeutic compound for the treatment of ADHD reduces oppositional defiant disorder (“ODD) and conduct disorder the severity of ADHD in a patient by, e.g., at least 10%, at least (“CD), obesity, depression (including, without limitation, 15%, at least 20%, at least 25%, at least 30%, at least 35%, at augmentation of antidepressants intreating refractory depres least 40%, at least 45%, at least 50%, at least 55%, at least sion and cancer-related depression), neural insult, fatigue 60%, at least 65%, at least 70%, at least 75%, at least 80%, at (including, without limitation, disease-related fatigue in least 85%, at least 90% or at least 95%. In other aspects of this US 2014/010O249 A1 Apr. 10, 2014

embodiment, a therapeutic compound for the treatment of least 65%, at least 70%, at least 75%, at least 80%, at least ADHD reduces the severity of ADHD in a patient by, e.g., 85%, at least 90% or at least 95%. In other aspects of this about 10% to about 100%, about 20% to about 100%, about embodiment, a therapeutic compound for the treatment of 30% to about 100%, about 40% to about 100%, about 50% to appetite reduction results in an increase in height by, e.g., about 100%, about 60% to about 100%, about 70% to about about 10% to about 100%, about 20% to about 100%, about 100%, about 80% to about 100%, about 10% to about 90%, 30% to about 100%, about 40% to about 100%, about 50% to about 20% to about 90%, about 30% to about 90%, about 40% about 100%, about 60% to about 100%, about 70% to about to about 90%, about 50% to about 90%, about 60% to about 100%, about 80% to about 100%, about 10% to about 90%, 90%, about 70% to about 90%, about 10% to about 80%, about 20% to about 90%, about 30% to about 90%, about 40% about 20% to about 80%, about 30% to about 80%, about 40% to about 90%, about 50% to about 90%, about 60% to about to about 80%, about 50% to about 80%, or about 60% to about 90%, about 70% to about 90%, about 10% to about 80%, 80%, about 10% to about 70%, about 20% to about 70%, about 20% to about 80%, about 30% to about 80%, about 40% about 30% to about 70%, about 40% to about 70%, or about to about 80%, about 50% to about 80%, or about 60% to about 50% to about 70%. 80%, about 10% to about 70%, about 20% to about 70%, I0086. In another embodiment, a therapeutic compound about 30% to about 70%, about 40% to about 70%, or about disclosed herein for the treatment of appetite reduction 50% to about 70% reduces the severity of appetite reduction in a patient. In I0089. In another embodiment, a therapeutic compound aspects of this embodiment, a therapeutic compound for the disclosed herein for the treatment of appetite reduction results treatment of appetite reduction reduces the severity of appe in an increase in weight by, e.g., at least 0.5 pounds, at least 1 tite reduction in a patient by, e.g., at least 10%, at least 15%, pound, at least 1.5 pounds, at least 2 pounds, at least 2.5 at least 20%, at least 25%, at least 30%, at least 35%, at least pounds, at least 3 pounds, at least 3.5 pounds, at least 4 40%, at least 45%, at least 50%, at least 55%, at least 60%, at pounds, at least 4.5 pounds, at least 5 pounds, at least 5.5 least 65%, at least 70%, at least 75%, at least 80%, at least pounds, at least 6 pounds, at least 6.5 pounds, at least 7 85%, at least 90% or at least 95%. In other aspects of this pounds, at least 7.5 pounds, at least 8 pounds, at least 8.5 embodiment, a therapeutic compound for the treatment of pounds, at least 9 pounds, at least 9.5 pounds, at least 10 appetite reduction reduces the severity of appetite reduction pounds, at least 10.5 pounds, at least 11 pounds, at least 11.5 in a patient by, e.g., about 10% to about 100%, about 20% to pounds, at least 12 pounds, at least 12.5 pounds, at least 13 about 100%, about 30% to about 100%, about 40% to about pounds, at least 13.5 pounds, at least 14 pounds, at least 14.5 100%, about 50% to about 100%, about 60% to about 100%, pounds, at least 15 pounds, at least 20 pounds, at least 25 about 70% to about 100%, about 80% to about 100%, about pounds, at least 30 pounds, at least 50 pounds. In another 10% to about 90%, about 20% to about 90%, about 30% to embodiment, a therapeutic compound disclosed herein for about 90%, about 40% to about 90%, about 50% to about the treatment of appetite reduction results in an increase in 90%, about 60% to about 90%, about 70% to about 90%, weight by, e.g., from 0.5 pounds to 50 pounds, from 0.5 about 10% to about 80%, about 20% to about 80%, about 30% pounds to 30 pounds, from 0.5 pounds to 25 pounds, from 0.5 to about 80%, about 40% to about 80%, about 50% to about pounds to 20 pounds, from 0.5 pounds to 15 pounds, from 0.5 80%, or about 60% to about 80%, about 10% to about 70%, pounds to ten pounds, from 0.5 pounds to 7.5 pounds, from about 20% to about 70%, about 30% to about 70%, about 40% 0.5 pounds to 5 pounds, from 1 pound to 15 pounds, from 1 to about 70%, or about 50% to about 70%. pound to 10 pounds, from 1 pound to 7.5 pounds, form 1 0087. In another embodiment, a therapeutic compound pound to 5 pounds, from 2 pounds to ten pounds, from 2 disclosed herein for the treatment of appetite reduction results pounds to 7.5 pounds. in an increase in weight by, e.g., at least 10%, at least 15%, at 0090. In another embodiment, a therapeutic compound least 20%, at least 25%, at least 30%, at least 35%, at least disclosed herein for the treatment of appetite reduction 40%, at least 45%, at least 50%, at least 55%, at least 60%, at increases the attentiveness of a patient being treated for least 65%, at least 70%, at least 75%, at least 80%, at least ADHD and/or a psychological and/or neurological disorder, 85%, at least 90% or at least 95%. In other aspects of this including without limitation, migrane, anti-serotonergic side embodiment, a therapeutic compound for the treatment of effects, narcolepsy, excessive sleepiness associated with shift appetite reduction results in an increase in weight by, e.g., work, obstructive sleep apnea as an adjunct to continuous about 10% to about 100%, about 20% to about 100%, about positive airways pressure (“CPAP), exogenous obesity, dis 30% to about 100%, about 40% to about 100%, about 50% to ruptive behaviour disorder including oppositional defiant dis about 100%, about 60% to about 100%, about 70% to about order (“ODD) and conduct disorder (“CD), obesity, depres 100%, about 80% to about 100%, about 10% to about 90%, sion (including, without limitation, augmentation of about 20% to about 90%, about 30% to about 90%, about 40% antidepressants in treating refractory depression and cancer to about 90%, about 50% to about 90%, about 60% to about related depression), neural insult, fatigue (including, without 90%, about 70% to about 90%, about 10% to about 80%, limitation, disease-related fatigue in patients with HIV. about 20% to about 80%, about 30% to about 80%, about 40% advanced cancer, multiple Sclerosis, myotonic dystrophy, to about 80%, about 50% to about 80%, or about 60% to about depression, fibromyalgia and hepatitis C), lethargy, binge 80%, about 10% to about 70%, about 20% to about 70%, eating disorder, Schizophrenia, sleep cycle disorder, cocaine about 30% to about 70%, about 40% to about 70%, or about addiction, Parkinson's Disease, combat and non-combat 50% to about 70%. related PTSD and tic. In aspects of this embodiment, a thera 0088. In another embodiment, a therapeutic compound peutic compound for the treatment of appetite reduction disclosed herein for the treatment of appetite reduction results increases the attentiveness of a patient being treated for in an increase in height by, e.g., at least 10%, at least 15%, at ADHD or a psychological and/or neurological disorder, least 20%, at least 25%, at least 30%, at least 35%, at least including without limitation, migrane, anti-serotonergic side 40%, at least 45%, at least 50%, at least 55%, at least 60%, at effects and narcolepsy, excessive sleepiness associated with US 2014/010O249 A1 Apr. 10, 2014 shift work, obstructive sleep apnea as an adjunct to continu tion, water, saline, glycine, hyaluronic acid and the like; Solid ous positive airways pressure ("CPAP), exogenous obesity, carriers such as, without limitation, mannitol, lactose, starch, disruptive behaviour disorder including oppositional defiant magnesium Stearate, sodium saccharin, talcum, cellulose, disorder (“ODD) and conduct disorder (“CD), obesity, glucose, Sucrose, magnesium carbonate, and the like; Sol depression (including, without limitation, augmentation of vents; dispersion media; coatings; antibacterial and antifun antidepressants in treating refractory depression and cancer gal agents; isotonic and absorption delaying agents; or any related depression), neural insult, fatigue (including, without other inactive ingredient. Selection of a pharmacologically limitation, disease-related fatigue in patients with HIV. acceptable carrier can depend on the mode of administration. advanced cancer, multiple Sclerosis, myotonic dystrophy, Except insofar as any pharmacologically acceptable carrier is depression, fibromyalgia and hepatitis C), lethargy, binge incompatible with the active ingredient, its use in pharmaceu eating disorder, Schizophrenia, sleep cycle disorder, cocaine tically acceptable compositions is contemplated. Non-limit addiction, Parkinson's Disease, combat and non-combat ing examples of specific uses of such pharmaceutical carriers related PTSD and tic, by, e.g., at least 10%, at least 15%, at can be found in Pharmaceutical Dosage Forms and Drug least 20%, at least 25%, at least 30%, at least 35%, at least Delivery Systems (Howard C. Ansel et al., eds., Lippincott 40%, at least 45%, at least 50%, at least 55%, at least 60%, at Williams & Wilkins Publishers, 7th ed. 1999); REMING least 65%, at least 70%, at least 75%, at least 80%, at least TON: THE SCIENCE AND PRACTICE OF PHARMACY 85%, at least 90% or at least 95%. In other aspects of this (Alfonso R. Gennaro ed., Lippincott, Williams & Wilkins, embodiment, a therapeutic compound for the treatment of 20th ed. 2000); Goodman & Gilman's The Pharmacological appetite reduction increases the attentiveness of a patient Basis of Therapeutics (Joel G. Hardman et al., eds., McGraw being treated for ADHD and/or a psychological and/or neu Hill Professional, 10th ed. 2001); and Handbook of Pharma rological disorder, including without limitation, migrane, ceutical Excipients (Raymond C. Rowe et al., APhA Publi anti-serotonergic side effects and narcolepsy, excessive cations, 4th edition 2003). These protocols are routine sleepiness associated with shift work, obstructive sleep apnea procedures and any modifications are well within the Scope of as an adjunct to continuous positive airways pressure one skilled in the art and from the teaching herein. (“CPAP), exogenous obesity, disruptive behaviour disorder 0092. In an embodiment, a pharmaceutical composition including oppositional defiant disorder (“ODD) and conduct disclosed herein can optionally include, without limitation, disorder (“CD), obesity, depression (including, without other pharmaceutically acceptable components (or pharma limitation, augmentation of antidepressants in treating refrac ceutical components), including, without limitation, buffers, tory depression and cancer-related depression), neural insult, preservatives, tonicity adjusters, salts, antioxidants, osmola fatigue (including, without limitation, disease-related fatigue lity adjusting agents, physiological Substances, pharmaco in patients with HIV, advanced cancer, multiple Sclerosis, logical Substances, bulking agents, emulsifying agents, wet myotonic dystrophy, depression, fibromyalgia and hepatitis ting agents, flavoring agents, coloring agents, and the like. In C), lethargy, binge eating disorder, Schizophrenia, sleep cycle an embodiment, various buffers and means for adjusting pH disorder, cocaine addiction, Parkinson's Disease, combat and can be used to prepare a pharmaceutical composition dis non-combat related PTSD and tic, by, e.g., about 10% to closed herein, provided that the resulting preparation is phar about 100%, about 20% to about 100%, about 30% to about maceutically acceptable. Such buffers include, without limi 100%, about 40% to about 100%, about 50% to about 100%, tation, acetate buffers, citrate buffers, phosphate buffers, about 60% to about 100%, about 70% to about 100%, about neutral buffered saline, phosphate buffered saline and borate 80% to about 100%, about 10% to about 90%, about 20% to buffers. It is understood that acids or bases can be used to about 90%, about 30% to about 90%, about 40% to about adjust the pH of a composition as needed. In an embodiment, 90%, about 50% to about 90%, about 60% to about 90%, pharmaceutically acceptable antioxidants include, without about 70% to about 90%, about 10% to about 80%, about 20% limitation, Sodium metabisulfite, Sodium thiosulfate, acetyl to about 80%, about 30% to about 80%, about 40% to about cysteine, butylated hydroxyanisole and butylated hydroxy 80%, about 50% to about 80%, or about 60% to about 80%, toluene. Useful preservatives include, without limitation, about 10% to about 70%, about 20% to about 70%, about 30% benzalkonium chloride, chlorobutanol, thimerosal, phenylm to about 70%, about 40% to about 70%, or about 50% to about ercuric acetate, phenylmercuric nitrate, a stabilized oxy 70%. chloro composition and chelants, such as, e.g., DTPA or 0091. In an embodiment, a pharmaceutical composition DTPA-bisamide, calcium DTPA, and CaNaDTPA-bisamide. disclosed herein may optionally include a pharmaceutically In an embodiment, tonicity adjustors useful in a pharmaceu acceptable carrier that facilitates processing of an active tical composition include, without limitation, salts such as, ingredient into pharmaceutically-acceptable compositions. e.g., sodium chloride, potassium chloride, mannitol or glyc As used herein, the term "pharmacologically-acceptable car erin and other pharmaceutically acceptable tonicity adjustor. rier is synonymous with “pharmacological carrier and In an embodiment, the pharmaceutical composition may be means any carrier that has substantially no long term or per provided as a salt and can beformed with many acids, includ manent detrimental effect when administered and encom ing but not limited to, hydrochloric, Sulfuric, acetic, lactic, passes terms such as “pharmacologically acceptable vehicle, tartaric, malic, Succinic, etc. Salts tend to be more soluble in stabilizer, diluent, additive, auxiliary or excipient.” Such a aqueous or other protonic solvents than are the corresponding carrier generally is mixed with an active compound or per free base forms. It is understood that these and other sub mitted to dilute or enclose the active compound and can be a stances known in the art of pharmacology can be included in Solid, semi-solid, or liquid agent. It is understood that the a pharmaceutical composition. active ingredients can be soluble or can be delivered as a 0093. In an embodiment, a therapeutic compound dis Suspension in the desired carrier or diluent. Any of a variety of closed herein, or a composition comprising Sucha therapeutic pharmaceutically acceptable carriers can be used including, compound, may be formulated for either local or systemic without limitation, aqueous media Such as, without limita delivery using topical, enteral or parenteral routes of admin US 2014/010O249 A1 Apr. 10, 2014

istration. In an additional embodiment, a therapeutic com 60% (w/v), 0.0001% (w/v) to about 50% (w/v), 0.0001% pound disclosed herein may be formulated by itself in a (w/v) to about 40% (w/v), 0.0001% (w/v) to about 30% (w/v), pharmaceutical composition, or may be formulated together 0.0001% (w/v) to about 20% (w/v), 0.0001% (w/v) to about with one or more other therapeutic compounds disclosed 10% (w/v), about 0.001% (w/v) to about 90.0% (w/v), herein in a single pharmaceutical composition. 0.001% (w/v) to about 80.0% (w/v), 0.001% (w/v) to about 0094. In an embodiment, a therapeutic compound dis 70.0% (w/v), 0.001% (w/v) to about 60.0% (w/v), 0.001% closed herein, or a composition comprising such atherapeutic (w/v) to about 0.0% (w/v), 0.001% (w/v) to about 40.0% compound, may be made into an inhaled formulation. In an (w/v), 0.001% (w/v) to about 30.0% (w/v), 0.001% (w/v) to embodiment, inhaled formulations suitable for enteral or about 20.0% (w/v), 0.001% (w/v) to about 10.0% (w/v) or parenteral administration include, without limitation, aero about 0.01% (w/v) to about 90.0% (w/v), about 0.01% (w/v) Sols, dry powders. In an additional embodiment, atherapeutic to about 80.0% (w/v), about 0.01% (w/v) to about 70.0% compound or composition disclosed herein intended for Such (w/v), about 0.01% (w/v) to about 60.0% (w/v), about 0.01% administration may be prepared according to any method (w/v) to about 50.0% (w/v), about 0.01% (w/v) to about known to the art for the manufacture of pharmaceutical com 40.0% (w/v), about 0.01% (w/v) to about 30.0% (w/v) about positions. 0.01% (w/v) to about 20.0% (w/v) or about 0.01% (w/v) to 0095. In an embodiment, such inhaled dosage forms, the about 10.0% (w/v). therapeutic compound may be prepared for delivery as an 0096. In an embodiment, a therapeutic compound dis aerosol in a liquid propellant for use in a pressurised (PDI) or closed herein, or a composition comprising Sucha therapeutic other metered dose inhaler (MDI). In an embodiment, pro compound, may be made into a solid formulation. In an pellants suitable for use in a PDI or MDI include, without embodiment, a solid formulations suitable for enteral or limitation, CFC-12, HFA-134a, HFA-227, HCFC-22 (difluo parenteral administration include, without limitation, cap rochloromethane), HFA-152 (difluoroethane and isobutane). Sules, tablets, pills, troches, lozenges, orally dissolving strips, In an embodiment, a therapeutic compound may also be powders and granules Suitable for inhalation or for reconsti delivered using a nebulisers or other aerosol delivery system. tution into sterile injectable solutions or dispersions. In an In an embodiment, a therapeutic compound may be prepared embodiment, each of the aforementioned formulations can for delivery as a dry powder for use in a dry powder inhaler include, without limitation, an immediate release formula (DPI). In an embodiment, a dry powder for use in the inhalers tion, a slow release formulation (including without limitation, will usually have a mass median aerodynamic diameter of a wax matrix), beaded (including, without limitation, a less than 100 pm, 90pm, 80 pm, 70 pm, 60 pm 50 pm, 40 pm, double beaded wherein a bead releases immediately followed 30 pm, 20 pm and 10 pm. In an embodiment, microparticles by another bead releasing at a later time), spheroidal oral drug having aerodynamic diameters in the range of about 5 pm to absorption system (“SODAS), an oral relase osmotic system about 0.5 pm will generally be deposited in the respiratory (“OROS), chewable tablet, a patch (including, without limi bronchioles, whereas Smaller particles, having aerodynamic tation, a delivery optimized thermodynamics (“DOT)), diameters in the range of about 2 pm to about 0.05 pm, are sprinkles, or a prodrug. In an embodiment, a therapeutic likely to be deposited in the alveoli. In an embodiment, a DPI compound or composition disclosed herein intended for Such may be a passive delivery mechanism, which relies on the administration may be prepared according to any method individuals inspiration to introduce the particles into the known to the art for the manufacture of pharmaceutical com lungs, or an active delivery mechanism, requiring a mecha positions. In an embodiment, Such solid dosage forms, the nism for delivering the powder to the individual. In an therapeutic compound may be admixed without limitation (a) embodiment, a therapeutically effective amount of a thera at least one inert customary excipient (or carrier). Such as peutic compound disclosed herein for an inhaled formulation without limitation, sodium citrate or dicalcium phosphate or may be between about 0.0001% (w/v) to about 90% (w/v), (b) fillers or extenders, as for example, without limitation, 0.0001% (w/v) to about 80% (w/v), 0.0001% (w/v) to about starch, lactose, Sucrose, glucose, mannitol, isomalt, and 70% (w/v), 0.0001% (w/v) to about 60% (w/v), 0.0001% silicic acid, (c) binders, such as, without limitation, car (w/v) to about 50% (w/v), 0.0001% (w/v) to about 40% (w/v), boxymethylcellulose, alignates, gelatin, polyvinylpyrroli 0.0001% (w/v) to about 30% (w/v), 0.0001% (w/v) to about done. Sucrose and acacia, (d) humectants, such as, e.g., glyc 20% (w/v), 0.0001% (w/v) to about 10% (w/v), about 0.001% erol, (e) disintegrating agents, such as, without limitation, (w/v) to about 90.0% (w/v), 0.001% (w/v) to about 80.0% agar-agar, calcium carbonate, corn starch, potato starch, tapi (w/v), 0.001% (w/v) to about 70.0% (w/v), 0.001% (w/v) to oca starch, alginic acid, certain complex silicates and sodium about 60.0% (w/v), 0.001% (w/v) to about 0.0% (w/v), carbonate, (f) solution retarders, such as, without limitation, 0.001% (w/v) to about 40.0% (w/v), 0.001% (w/v) to about paraffin, (g) absorption accelerators, such as, without limita 30.0% (w/v), 0.001% (w/v) to about 20.0% (w/v), 0.001% tion, quaternary ammonium compounds, (h) wetting agents, (w/v) to about 10.0% (w/v) or about 0.01% (w/v) to about Such as, without limitation, cetyl alcohol and glycerol 90.0% (w/v), about 0.01% (w/v) to about 80.0% (w/v), about monostearate, (i) adsorbents, such as, without limitation, 0.01% (w/v) to about 70.0% (w/v), about 0.01% (w/v) to kaolin and bentonite, () lubricants, such as, without limita about 60.0% (w/v), about 0.01% (w/v) to about 50.0% (w/v), tion, talc, Stearic acid, calcium Stearate, magnesium Stearate, about 0.01% (w/v) to about 40.0% (w/v), about 0.01% (w/v) Solid polyethylene glycols, sodium lauryl Sulfate or mixtures to about 30.0% (w/v) about 0.01% (w/v) to about 20.0% (w/v) thereof, and (k) buffering agents. In an embodiment, the or about 0.01% (w/v) to about 10.0% (w/v). In an embodi tablets may be uncoated or they may be coated by known ment, an inhaled formulations, a therapeutically effective techniques to delay disintegration and absorption in the gas amount of a therapeutic compound disclosed herein for an trointestinal tract and thereby provide a Sustained action over inhaled formulation may also be between 0.0001% (w/v) to a longer period. In an additional embodiment, without limi about 90% (w/v), 0.0001% (w/v) to about 80% (w/v), tation, a time delay material Such as glyceryl monostearate or 0.0001% (w/v) to about 70% (w/v), 0.0001% (w/v) to about glyceryl distearate may be employed. In an embodiment, in US 2014/010O249 A1 Apr. 10, 2014

solid formulations, a therapeutically effective amount of a (w/v), about 0.01% (w/v) to about 80.0% (w/v), about 0.01% therapeutic compound disclosed herein typically may be (w/v) to about 70.0% (w/v), about 0.01% (w/v) to about between about 0.0001% (w/v) to about 90% (w/v), 0.0001% 60.0% (w/v), about 0.01% (w/v) to about 50.0% (w/v), about (w/v) to about 80% (w/v), 0.0001% (w/v) to about 70% (w/v), 0.01% (w/v) to about 40.0% (w/v), about 0.01% (w/v) to 0.0001% (w/v) to about 60% (w/v), 0.0001% (w/v) to about about 30.0% (w/v) about 0.01% (w/v) to about 20.0% (w/v) 50% (w/v), 0.0001% (w/v) to about 40% (w/v), 0.0001% or about 0.01% (w/v) to about 10.0% (w/v). (w/v) to about 30% (w/v), 0.0001% (w/v) to about 20% (w/v), 0098. In an embodiment, a therapeutic compound dis 0.0001% (w/v) to about 10% (w/v), about 0.001% (w/v) to closed herein, or a composition comprising Sucha therapeutic about 90.0% (w/v), 0.001% (w/v) to about 80.0% (w/v), compound, may be made into a liquid formulation. In an 0.001% (w/v) to about 70.0% (w/v), 0.001% (w/v) to about embodiment, liquid formulations suitable for enteral or 60.0% (w/v), 0.001% (w/v) to about 0.0% (w/v), 0.001% parenteral administration include, without limitation, Solu (w/v) to about 40.0% (w/v), 0.001% (w/v) to about 30.0% tions, syrups, elixirs, dispersions, emulsions, and Suspen (w/v), 0.001% (w/v) to about 20.0% (w/v), 0.001% (w/v) to sions. In an embodiment, a therapeutic compound or compo about 10.0% (w/v) or about 0.01% (w/v) to about 90.0% sition disclosed herein intended for Such administration may (w/v), about 0.01% (w/v) to about 80.0% (w/v), about 0.01% be prepared, without limitation, according to any method (w/v) to about 70.0% (w/v), about 0.01% (w/v) to about known to the art for the manufacture of pharmaceutical com 60.0% (w/v), about 0.01% (w/v) to about 50.0% (w/v), about positions. In an embodiment, in Such liquid dosage forms, a 0.01% (w/v) to about 40.0% (w/v), about 0.01% (w/v) to therapeutic compound or composition disclosed herein may about 30.0% (w/v) about 0.01% (w/v) to about 20.0% (w/v) be admixed with, without limitation, (a) Suitable aqueous and or about 0.01% (w/v) to about 10.0% (w/v). nonaqueous carriers, (b) diluents, (c) solvents, such as, with 0097. In an embodiment, a therapeutic compound dis out limitation, water, ethanol, propylene glycol, polyethyl closed herein, or a composition comprising such atherapeutic eneglycol, glycerol, vegetable oils, such as, without limita compound, may be made into a semi-solid formulation. In an tion, rapeseed oil and olive oil, and injectable organic esters embodiment, a semi-solid formulations suitable for topical Such as ethyl oleate; and/or fluidity agents, such as, without administration include, without limitation, ointments, limitation, Surfactants or coating agents like lecithin. In the creams, Salves, and gels. In an embodiment, a therapeutic case of dispersions and Suspensions, fluidity can also be con compound or composition disclosed herein intended for Such trolled by maintaining aparticular particle size. In an embodi administration may be prepared according to any method ment, in liquid formulations, a therapeutically effective known to the art for the manufacture of pharmaceutical com amount of a therapeutic compound disclosed herein typically positions. In an embodiment, in semi-solid formulations, a may be between about 0.0001% (w/v) to about 90% (w/v), therapeutically effective amount of a therapeutic compound 0.0001% (w/v) to about 80% (w/v), 0.0001% (w/v) to about disclosed herein typically may be between about 0.0001% 70% (w/v), 0.0001% (w/v) to about 60% (w/v), 0.0001% (w/v) to about 90% (w/v), 0.0001% (w/v) to about 80% (w/v), (w/v) to about 50% (w/v), 0.0001% (w/v) to about 40% (w/v), 0.0001% (w/v) to about 70% (w/v), 0.0001% (w/v) to about 0.0001% (w/v) to about 30% (w/v), 0.0001% (w/v) to about 60% (w/v), 0.0001% (w/v) to about 50% (w/v), 0.0001% 20% (w/v), 0.0001% (w/v) to about 10% (w/v), about 0.001% (w/v) to about 40% (w/v), 0.0001% (w/v) to about 30% (w/v), (w/v) to about 90.0% (w/v), 0.001% (w/v) to about 80.0% 0.0001% (w/v) to about 20% (w/v), 0.0001% (w/v) to about (w/v), 0.001% (w/v) to about 70.0% (w/v), 0.001% (w/v) to 10% (w/v), about 0.001% (w/v) to about 90.0% (w/v), about 60.0% (w/v), 0.001% (w/v) to about 0.0% (w/v), 0.001% (w/v) to about 80.0% (w/v), 0.001% (w/v) to about 0.001% (w/v) to about 40.0% (w/v), 0.001% (w/v) to about 70.0% (w/v), 0.001% (w/v) to about 60.0% (w/v), 0.001% 30.0% (w/v), 0.001% (w/v) to about 20.0% (w/v), 0.001% (w/v) to about 0.0% (w/v), 0.001% (w/v) to about 40.0% (w/v) to about 10.0% (w/v) or about 0.01% (w/v) to about (w/v), 0.001% (w/v) to about 30.0% (w/v), 0.001% (w/v) to 90.0% (w/v), about 0.01% (w/v) to about 80.0% (w/v), about about 20.0% (w/v), 0.001% (w/v) to about 10.0% (w/v) or 0.01% (w/v) to about 70.0% (w/v), about 0.01% (w/v) to about 0.01% (w/v) to about 90.0% (w/v), about 0.01% (w/v) about 60.0% (w/v), about 0.01% (w/v) to about 50.0% (w/v), to about 80.0% (w/v), about 0.01% (w/v) to about 70.0% about 0.01% (w/v) to about 40.0% (w/v), about 0.01% (w/v) (w/v), about 0.01% (w/v) to about 60.0% (w/v), about 0.01% to about 30.0% (w/v) about 0.01% (w/v) to about 20.0% (w/v) (w/v) to about 50.0% (w/v), about 0.01% (w/v) to about or about 0.01% (w/v) to about 10.0% (w/v). 40.0% (w/v), about 0.01% (w/v) to about 30.0% (w/v) about 0099. In an embodiment, syrups and elixirs may be for 0.01% (w/v) to about 20.0% (w/v) or about 0.01% (w/v) to mulated, without limitation, Sweetening agents, for example about 10.0% (w/v). In an embodiment, in semi-solid formu glycerol, propylene glycol, Sorbitol or Sucrose. In an addi lations, a therapeutically effective amount of a therapeutic tional embodiment, such formulations may also contain, compound disclosed herein typically may also be between without limitation, a demulcent, a preservative, flavoring about 0.0001% (w/v) to about 90% (w/v), 0.0001% (w/v) to agents, and coloring agents. about 80% (w/v), 0.0001% (w/v) to about 70% (w/v), 0100. In an embodiment, liquid suspensions may be for 0.0001% (w/v) to about 60% (w/v), 0.0001% (w/v) to about mulated, without limitation, by Suspending a therapeutic 50% (w/v), 0.0001% (w/v) to about 40% (w/v), 0.0001% compound disclosed herein in admixture with excipients Suit (w/v) to about 30% (w/v), 0.0001% (w/v) to about 20% (w/v), able for the manufacture of aqueous Suspensions. In an 0.0001% (w/v) to about 10% (w/v), about 0.001% (w/v) to embodiment, such excipients are suspending agents, for about 90.0% (w/v), 0.001% (w/v) to about 80.0% (w/v), example, without limitation, sodium carboxymethylcellu 0.001% (w/v) to about 70.0% (w/v), 0.001% (w/v) to about lose, methylcellulose, hydroxypropylmethylcellulose, 60.0% (w/v), 0.001% (w/v) to about 0.0% (w/v), 0.001% Sodium alginate, pectin, polyvinyl pyrrolidone, polyvinyl (w/v) to about 40.0% (w/v), 0.001% (w/v) to about 30.0% alcohol, natural gum, agar, gum tragacanth and gum acacia: (w/v), 0.001% (w/v) to about 20.0% (w/v), 0.001% (w/v) to dispersing or wetting agents may be a naturally occurring about 10.0% (w/v) or about 0.01% (w/v) to about 90.0% phosphatide, for example lecithin, or condensation products US 2014/010O249 A1 Apr. 10, 2014 20 of an alkylene oxide with fatty acids, for example, without of the side residues. In an embodiment, if crosslinked, poly limitation, polyoxyethylene Stearate, or condensation prod mers are usually less than 75% crosslinked, 65% crosslinked, ucts of ethylene oxide with long-chain aliphatic alcohols, for 55% crosslinked, 45% crosslinked, 35% crosslinked, 25% example, without limitation, heptadecaethyleneoxycetanol, crosslinked, 15% crosslinked 5% crosslinked, usually less or condensation products of ethylene oxide with partial esters than 1% crosslinked. derived from fatty acids, for example, without limitation, 0105. In an embodiment, suitable polymers include, with polyoxyethylene Sorbitan monooleate. out limitation, alginates, aliphatic polyesters, polyalkylene 0101. In an embodiment, oily suspensions may be formu oxalates, polyamides, polyamidoesters, polyanhydrides, lated by Suspending a therapeutic compound disclosed herein polycarbonates, polyesters, polyethylene glycol, polyhy in admixture with (a) Vegetable oils, such as, without limita droxyaliphatic carboxylic acids, polyorthoesters, polyox tion, almond oil, arachis oil, avocado oil, canola oil, castor oil, aesters, polypeptides, polyphosphaZenes, polysaccharides, coconut oil, corn oil, cottonseed oil, grape seed oil, hazelnut and polyurethanes. In an embodiment, the polymer usually oil, hemp oil, linseed oil, olive oil, palm oil, peanut oil, comprises at least about 10% (w/w), at least about 20% rapeseed oil, rice bran oil, safflower oil, Sesame oil, soybean (w/w), at least about 30% (w/w), at least about 40% (w/w), at oil, soya oil, Sunflower oil, walnut oil, wheat germ oil, or a least about 50% (w/w), at least about 60% (w/w), at least combination thereof, (b) a saturated fatty acid, an unsaturated about 70% (w/w), at least about 80% (w/w), or at least about fatty acid, or a combination thereof. Such as, without limita 90% (w/w) of the drug delivery platform. In an embodiment, tion, palmitic acid, Stearic acid, oleic acid, linoleic acid, lino examples of biodegradable, bioerodible, and/or bioresorb lenic acid, or a combination thereof (c) mineral oil such as, able polymers and methods useful to make a drug delivery without limitation, liquid paraffin, (d) Surfactants or deter platform are described in, e.g., Drost, without limitation, gents. In an embodiment, the oily Suspensions may contain a Controlled Release Formulation, U.S. Pat. No. 4,756,911; thickening agent, for example beeswax, hard paraffin or cetyl Smith, et. al., Sustained Release Drug Delivery Devices, U.S. alcohol. In an embodiment, Sweetening agents, such as those Pat. No. 5,378.475; Wong and Kochinke, Formulation for set forth above, and flavoring agents may be added to provide Controlled Release of Drugs by Combining Hyrophilic and a palatable oral preparation. In an embodiment, these com Hydrophobic Agents, U.S. Pat. No. 7,048,946; Hughes, et. positions may be preserved by the addition of an antioxidant al., Compositions and Methods for Localized Therapy of the Such as ascorbic acid. Eye, U.S. Patent Publication 2005/0181017: Hughes, 0102. In an embodiment, dispersible powders and gran Hypotensive Lipid-Containing Biodegradable Intraocular ules suitable for preparation of an aqueous suspension by the Implants and Related Methods, U.S. Patent Publication 2005/ addition of water provide the combined therapeutic com 0244464; Altman, et al., Silk Fibroin Hydrogels and Uses pounds in admixture with a dispersing or wetting agent, Sus Thereof, U.S. Patent Publication 2011/0008437; each of pending agent and one or more preservatives. which is incorporated by reference in its entirety. 0103) In an embodiment, a therapeutic compound dis 0106. In an embodiment, a polymer composing the matrix closed herein may be in the form of oil-in-water emulsions. In is a polypeptide Such as, without limitation, silk fibroin, kera an embodiment, the oily phase may be a vegetable oil as tin, or collagen. In an additional embodiment, a polymer disclosed herein or a mineral oil as disclosed herein or mix composing the matrix is a polysaccharide such as, without tures thereof. In an additional embodiment, suitable emulsi limitation, cellulose, agarose, elastin, chitosan, chitin, or a fying agents may be naturally occurring gums, such as, with glycosaminoglycan like chondroitin Sulfate, dermatan Sul out limitation, gum acacia or gum tragacanth, naturally fate, keratan Sulfate, or hyaluronic acid. In yet another occurring phosphatides, for example Soya bean, lecithin, and embodiment, a polymer composing the matrix is a polyester esters or partial esters derived from fatty acids and hexitol Such as, without limitation, D-lactic acid, L-lactic acid, race anhydrides, for example, without limitation, Sorbitan mic lactic acid, glycolic acid, caprolactone, and combinations monooleate and condensation products of the said partial thereof. esters with ethylene oxide, for example polyoxyethylene sor 0107. One of ordinary skill in the art appreciates that the bitan monooleate. selection of a suitable polymer for forming a suitable dis 0104. In an embodiment, a therapeutic compound dis closed drug delivery platform depends on several factors. The closed herein, or a composition comprising such atherapeutic more relevant factors in the selection of the appropriate poly compound, may also be incorporated into a drug delivery mer(s), include, without limitation, compatibility of polymer platform in order to achieve a controlled release profile over with drug, desired release kinetics of drug, desired biodegra time. In an embodiment, such a drug delivery platform com dation kinetics of platform at implantation site, desired bio prises a therapeutic compound disclosed herein dispersed erodible kinetics of platform at implantation site, desired within a polymer matrix, typically, without limitation, a bio bioresorbable kinetics of platformat implantation site, in vivo degradable, bioerodible, and/or bioresorbable polymer mechanical performance of platform, processing tempera matrix. In an embodiment, as used herein, the term “polymer tures, biocompatibility of platform, and patient tolerance. refers to synthetic homo- or copolymers, naturally occurring Other relevant factors that, to some extent, without limitation, homo- or copolymers, as well as, without limitation, synthetic dictate the in vitro and in vivo behavior of the polymer include modifications or derivatives thereofhaving a linear, branched the chemical composition, spatial distribution of the constitu or star structure. In an embodiment, copolymers can be ents, the molecular weight of the polymer and the degree of arranged in any form, such as, without limitation, random, crystallinity. block, segmented, tapered blocks, graft, or triblock. In an 0108. In an embodiment, a drug delivery platform embodiment, polymers are generally condensation polymers. includes both a Sustained release drug delivery platform and In an embodiment, polymers can be further modified to an extended release drug delivery platform. In an embodi enhance their mechanical or degradation properties by intro ment, the term “sustained release' refers to the release of a ducing cross-linking agents or changing the hydrophobicity therapeutic compound or compounds disclosed herein over a US 2014/010O249 A1 Apr. 10, 2014

period of about seven days or more. In an embodiment, the after administration, about 60 days after administration, term “extended release' refers to the release of a therapeutic about 75 days after administration, or about 90 days after compound or compounds disclosed herein over a period of administration. In other aspects of this embodiment, a Sus time of less than about seven days. tained release drug delivery platform releases a therapeutic 0109. In an embodiment, a sustained release drug delivery compound or compounds disclosed herein with Substantially platform releases a therapeutic compound or compounds dis first order release kinetics over a period of, without limitation, closed herein with substantially Zero order release kinetics at least 3 days after administration, at least 7 days after admin over a period of, without limitation, about 3 days after admin istration, at least 10 days after administration, at least 15 days istration, about 7 days after administration, about 10 days after administration, at least 20 days after administration, at after administration, about 15 days after administration, least 25 days after administration, at least 30 days after about 20 days after administration, about 25 days after admin administration, at least 45 days after administration, at least istration, about 30 days after administration, about 45 days 60 days after administration, at least 75 days after adminis after administration, about 60 days after administration, tration, or at least 90 days after administration. about 75 days after administration, or about 90 days after 0112. In an embodiment, a drug delivery platform releases administration. In another embodiment, a Sustained release atherapeutic compound or compounds disclosed herein with drug delivery platform releases a therapeutic compound dis substantially zero order release kinetics over a period of, closed herein with substantially Zero order release kinetics without limitation, about 1 day after administration, about 2 over a period, without limitation, at least 3 days after admin days after administration, about 3 days after administration, istration, at least 7 days after administration, at least 10 days about 4 days after administration, about 5 days after admin after administration, at least 15 days after administration, at istration, about 6 days after administration or about 7 days or least 20 days after administration, at least 25 days after more after administration. In an additional embodiment, a administration, at least 30 days after administration, at least drug delivery platform releases a therapeutic compound or 45 days after administration, at least 60 days after adminis compounds disclosed herein with substantially Zero order tration, at least 75 days after administration, or at least 90 days release kinetics over a period of, without limitation, at most 1 after administration. day after administration, at most 2 days after administration, 0110. In an embodiment, an ADHD therapeutic com at most 3 days after administration, at most 4 days after pound and/or appetite stimulant therapeutic compound or administration, at most 5 days after administration, at most 6 compounds is in the form of a long acting composition that days after administration or at most 7 days or more after includes, without limitation, extended release compositions. administration. An embodiment includes, without limitation, an extended 0113. In an embodiment, a drug delivery platform releases release capsule, tablet or other solid or a liquid formulation atherapeutic compound or compounds disclosed herein with that provides the therapeutic compound or compounds to the substantially first order release kinetics over a period of, patient to whom it is administered over time. The long acting without limitation, about 1 day after administration, about 2 composition can provide activity of an ADHD therapeutic days after administration, about 3 days after administration, compound and/or appetite stimulant therapeutic compound about 4 days after administration, about 5 days after admin in a patient administered either or both therapeutic com istration, about 6 days after administration or about 7 days or pounds for 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 16 more after administration. In an additional embodiment, a hours, 20 hours, 24 hours, 28 hours, 30 hours, 32 hours, 34 drug delivery platform releases a therapeutic compound or hours, 36 hours, 40 hours, 48 hours, 3 days, 4 days, 5 days, 6 compounds disclosed herein with substantially first order days, 7 days, 2 weeks, 3 weeks or 4 weeks. The long acting release kinetics over a period of, e.g., at most 1 day after composition can provide activity of an ADHD therapeutic administration, at most 2 days after administration, at most 3 compound and/or appetite stimulant therapeutic compound days after administration, at most 4 days after administration, or compounds in a patient administered either or both thera at most 5 days after administration, at most 6 days after peutic compounds for as little as 4 hours or as long as 4 weeks, administration or at most 7 days or more after administration. for as little as 4 hours or as long as 3 weeks, for as little as 4 0114. In an embodiment of the present specification dis hours or as long as 2 weeks, for as little as 4 hours or as long close, in part, treating an individual Suffering from ADHD. As as 1 week, for as little as 4 hours or as long as 6 days, for as used herein, the term “treating refers to reducing or elimi little as 4 hours or as long as 5 days, for as little as 4 hours or nating in an individual a clinical symptom, set of symptoms, as long as 4 days, for as little as 4 hours or as long as 3 days, or clinical index for ADHD; or delaying or preventing in an for as little as 4 hours or as long as 2 days, for as little as 4 individual the onset of ADHD. In an embodiment, for hours or as long as 1 day, for as little as 4 hours or as long as example, without limitation, the term “treating can mean 20 hours, for as little as 4 hours or as long as 16 hours, for as reducing a symptom of a condition characterized by ADHD little as 4 hours or as long as 14 hours, for as little as 4 hours by, without limitation, at least 20%, at least 25%, at least 30%, or as long as 12 hours, for as little as 4 hours or as long as 10 at least 35%, at least 40%, at least 45%, at least 50%, at least hours, for as little as 4 hours or as long as 8 hours, for as little 55%, at least 60%, at least 65%, at least 70%, at least 75%, at as 4 hours or as long as 6 hours. least 80%, at least 85%, at least 90% at least 95%, or at least 0111. In an embodiment, a sustained release drug delivery 100%. In an embodiment, the actual symptoms associated platform releases a therapeutic compound or compounds dis with ADHD are well known and can be determined by a closed herein with substantially first order release kinetics person of ordinary skill in the art by taking into account over a period of, without limitation, about 3 days after admin factors well known, including, without limitation, missing istration, about 7 days after administration, about 10 days details, forgetting things, frequently switch from one activity after administration, about 15 days after administration, to another, having difficulty focusing, organizing, or complet about 20 days after administration, about 25 days after admin ing tasks, losing interest after only a few minutes unless they istration, about 30 days after administration, about 45 days are doing something they enjoy, having trouble with home US 2014/010O249 A1 Apr. 10, 2014 22

Work assignments, losing things (eg. pencils, toys, assign 20%, at least 25%, at least 30%, at least 35%, at least 40%, at ments), seeming to not listen when spoken to, daydreaming, least 45%, at least 50%, at least 55%, at least 60%, at least become easily confused, and moving slowly. having difficulty 65%, at least 70%, at least 75%, at least 80%, at least 85%, at processing information as quickly and accurately as others least 90% at least 95%, or at least 100%. do, struggling to follow instructions, fidgeting and Squirming 0117. In an embodiment, the present specification dis in their seats, talking nonstop, running around, touching or close, in part, treating an individual Suffering from reduced playing with anything and everything in sight, having trouble attentiveness. In an embodiment, as used herein, the term sitting still during, without limitation, meals, School, story “treating.” refers to reducing or eliminating in an individual a time, struggling to do quiet tasks or activities, being very clinical symptom for reduced attentiveness; or delaying or patient, blurting out inappropriate comments, showing emo preventing in an individual the onset of reduced attentiveness. tion without restraint, acting without regard for consequences In an embodiment, for example, without limitation, the term and/or interrupting conversations or other activities. In an “treating can mean reducing a symptom of a condition char embodiment, the actual symptoms associated with ADHD are acterized by reduced attentiveness by, e.g., at least 20%, at well known and can be determined by a person of ordinary least 25%, at least 30%, at least 35%, at least 40%, at least skill in the art by taking into account factors well known, 45%, at least 50%, at least 55%, at least 60%, at least 65%, at including, without limitation, often does not give close atten least 70%, at least 75%, at least 80%, at least 85%, at least tion to details or makes careless mistakes in work or other 90% at least 95%, or at least 100%. The actual symptoms activities, often has trouble keeping attention on tasks or play associated with reduced attentiveness are well known and can activities, often does not seem to listen when spoken to be determined by a person of ordinary skill in the art by taking directly, often does not follow instructions and fails to finish into account factors well known, including, without limita duties in the workplace, often has trouble organizing activi tion, lack of mental cognition, lack of ability to interact ties, often avoids, dislikes, or does not want to do things that Socially. take a lot of mental effort for a long period of time, often loses 0118. In an embodiment, a pharmaceutical composition things needed for tasks and activities, is often easily dis disclosed herein may comprise a therapeutic compound in a tracted, is often forgetful in daily activities, often fidgets or therapeutically effective amount. In an embodiment, as used squirms in seat, often gets up from seat when remaining herein, without limitation, the term “effective amount” is seated is expected, often feels very restless, often has trouble synonymous with “therapeutically effective amount”, “effec enjoying leisure activities quietly, is often on the go or often tive dose', or “therapeutically effective dose.” In an embodi acts as if driven by a motor, often talks impulsively, often ment, the effectiveness of a therapeutic compound disclosed blurts out answers before questions have been finished, often herein to treat ADHD, treat appetite reduction and/or treat a has trouble waiting one's turn and/or often interrupts or reduction in attentiveness can be determined, without limita intrudes on others. tion, by observing an improvement in an individual based 0115. In an embodiment, the present specification dis upon one or more clinical symptoms, and/or physiological close, in part, treating an individual Suffering from appetite indicators associated with the ADHD, appetite reduction and/ reduction. In an embodiment, the term “treating.” refers to or reduction in attentiveness. In an embodiment, an improve reducing or eliminating in an individual a clinical symptom ment in the symptoms associated with ADHD, appetite reduc for appetite reduction; or delaying or preventing in an indi tion and/or reduced attentiveness can be indicated by a vidual the onset of appetite reduction. In an embodiment, for reduced need for a concurrent therapy. example, without limitation, the term “treating can mean 0119. In an embodiment, the appropriate effective amount reducing a symptom of a condition characterized by appetite of a therapeutic compound disclosed herein to be adminis reduction by, without limitation, at least 20%, at least 25%, at tered to an individual for the treatment of ADHD and appetite least 30%, at least 35%, at least 40%, at least 45%, at least reduction can be determined by a person of ordinary skill in 50%, at least 55%, at least 60%, at least 65%, at least 70%, at the art by taking into account factors that are well known. In least 75%, at least 80%, at least 85%, at least 90% at least an additional embodiment, where repeated administration of 95%, or at least 100%. In an embodiment, the actual symp a therapeutic compound is used, an effective amount of a toms associated with appetite reduction are well known and therapeutic compound will further depend upon factors, can be determined by a person of ordinary skill in the art by including, without limitation, the frequency of administra taking into account factors well known, including without tion, the half-life of the therapeutic compound, or any com limitation, failure to eat a meal, failure to eat a Snack, or bination thereof. In an embodiment, it is known by a person of failure to eat food. ordinary skill in the art that an effective amount of a thera 0116. In an embodiment, the present specification dis peutic compound disclosed herein can be extrapolated from close, in part, treating an individual Suffering from weight in vitro assays and in vivo administration studies using animal loss resultant from appetite reduction. In an embodiment, for models prior to administration to humans. example, without limitation, an increase in weight following I0120 Wide variations in the necessary effective amount treatment with an appetite stimulant is by, without limitation, are to be expected in view of the differing efficiencies of the at least 20%, at least 25%, at least 30%, at least 35%, at least various routes of administration. For instance, without limi 40%, at least 45%, at least 50%, at least 55%, at least 60%, at tation, oral administration of a therapeutic compound dis least 65%, at least 70%, at least 75%, at least 80%, at least closed herein generally would be expected to require higher 85%, at least 90% at least 95%, or at least 100%. In an dosage levels than administration by inhalation. Similarly, embodiment, the present specification disclose, in part, treat without limitation, Systemic administration of a therapeutic ing an individual Suffering from a reduction in height result compound disclosed herein would be expected to require ant from appetite reduction. In an embodiment, for example, higher dosage levels than a local administration. Variations in without limitation, an increase in height following treatment these dosage levels, without limitation, can be adjusted using with an appetite stimulant is by, without limitation, at least standard empirical routines of optimization, which are well US 2014/010O249 A1 Apr. 10, 2014 known to a person of ordinary skill in the art. The precise antidepressants in treating refractory depression and cancer therapeutically effective dosage levels and patterns are pref related depression), neural insult, fatigue (including, without erably determined, without limitation, by the attending phy limitation, disease-related fatigue in patients with HIV. sician in consideration of the above-identified factors. One advanced cancer, multiple Sclerosis, myotonic dystrophy, skilled in the art will recognize that the condition of the depression, fibromyalgia and hepatitis C), lethargy, binge individual can be monitored, without limitation, throughout eating disorder, Schizophrenia, sleep cycle disorder, cocaine the course of therapy and that the effective amount of a addiction, Parkinson's Disease, combat and non-combat therapeutic compound disclosed herein that is administered related PTSD and tic, by, without limitation, about 10% to can be adjusted accordingly. about 100%, about 10% to about 90%, about 10% to about 0121. In an embodiment, a therapeutically effective 80%, about 10% to about 70%, about 10% to about 60%, amount ofatherapeutic compound disclosed herein reduces a about 10% to about 50%, about 10% to about 40%, about 20% symptom associated with ADHD and/or a psychological and/ to about 100%, about 20% to about 90%, about 20% to about or neurological disorder, including without limitation, 80%, about 20% to about 20%, about 20% to about 60%, migrane, anti-serotonergic side effects, narcolepsy, excessive about 20% to about 50%, about 20% to about 40%, about 30% sleepiness associated with shift work, obstructive sleep apnea to about 100%, about 30% to about 90%, about 30% to about as an adjunct to continuous positive airways pressure 80%, about 30% to about 70%, about 30% to about 60%, or (“CPAP), exogenous obesity, disruptive behaviour disorder about 30% to about 50%. including oppositional defiant disorder (“ODD) and conduct I0122. In an embodiment, a therapeutically effective disorder (“CD), obesity, depression (including, without amount ofatherapeutic compound disclosed herein reduces a limitation, augmentation of antidepressants in treating refrac symptom associated with appetite reduction by, without limi tory depression and cancer-related depression), neural insult, tation, at least 10%, at least 15%, at least 20%, at least 25%, fatigue (including, without limitation, disease-related fatigue at least 30%, at least 35%, at least 40%, at least 45%, at least in patients with HIV, advanced cancer, multiple Sclerosis, 50%, at least 55%, at least 60%, at least 65%, at least 70%, at myotonic dystrophy, depression, fibromyalgia and hepatitis least 75%, at least 80%, at least 85%, at least 90%, at least C), lethargy, binge eating disorder, Schizophrenia, sleep cycle 95% or at least 100%. In an additional embodiment, a thera disorder, cocaine addiction, Parkinson's Disease, combat and peutically effective amount of a therapeutic compound dis non-combat related PTSD and tic, by, without limitation, at closed herein reduces a symptom associated with appetite least 10%, at least 15%, at least 20%, at least 25%, at least reductionby, without limitation, at most 10%, at most 15%, at 30%, at least 35%, at least 40%, at least 45%, at least 50%, at most 20%, at most 25%, at most 30%, at most 35%, at most least 55%, at least 60%, at least 65%, at least 70%, at least 40%, at most 45%, at most 50%, at most 55%, at most 60%, 75%, at least 80%, at least 85%, at least 90%, at least 95% or at most 65%, at most 70%, at most 75%, at most 80%, at most at least 100%. In an additional embodiment, a therapeutically 85%, at most 90%, at most 95% or at most 100%. In a further effective amount of a therapeutic compound disclosed herein embodiment, a therapeutically effective amount of a thera reduces a symptom associated with ADHD and/or a psycho peutic compound disclosed herein reduces a symptom asso logical and/or neurological disorder, including without limi ciated with a appetite reduction by, without limitation, about tation, migrane, anti-serotonergic side effects, narcolepsy, 10% to about 100%, about 10% to about 90%, about 10% to excessive sleepiness associated with shift work, obstructive about 80%, about 10% to about 70%, about 10% to about sleep apnea as an adjunct to continuous positive airways 60%, about 10% to about 50%, about 10% to about 40%, pressure (“CPAP), exogenous obesity, disruptive behaviour about 20% to about 100%, about 20% to about 90%, about disorder including oppositional defiant disorder (“ODD) 20% to about 80%, about 20% to about 20%, about 20% to and conduct disorder (“CD), obesity, depression (including, about 60%, about 20% to about 50%, about 20% to about without limitation, augmentation of antidepressants in treat 40%, about 30% to about 100%, about 30% to about 90%, ing refractory depression and cancer-related depression), about 30% to about 80%, about 30% to about 70%, about 30% neural insult, fatigue (including, without limitation, disease to about 60%, or about 30% to about 50%. related fatigue in patients with HIV, advanced cancer, mul I0123. In an embodiment, a therapeutically effective tiple Sclerosis, myotonic dystrophy, depression, fibromyalgia amount ofatherapeutic compound disclosed herein reduces a and hepatitis C), lethargy, binge eating disorder, Schizophre symptom associated with loss of attentiveness by, without nia, sleep cycle disorder, cocaine addiction, Parkinson's Dis limitation, at least 10%, at least 15%, at least 20%, at least ease, combat and non-combat related PTSD and tic, by, with 25%, at least 30%, at least 35%, at least 40%, at least 45%, at out limitation, at most 10%, at most 15%, at most 20%, at least 50%, at least 55%, at least 60%, at least 65%, at least most 25%, at most 30%, at most 35%, at most 40%, at most 70%, at least 75%, at least 80%, at least 85%, at least 90%, at 45%, at most 50%, at most 55%, at most 60%, at most 65%, least 95% or at least 100%. In other aspects of this embodi at most 70%, at most 75%, at most 80%, at most 85%, at most ment, a therapeutically effective amount of a therapeutic 90%, at most 95% or at most 100%. In a further embodiment, compound disclosed herein reduces a symptom associated atherapeutically effective amount of a therapeutic compound with loss of attentiveness by, e.g., at most 10%, at most 15%, disclosed herein reduces a symptom associated with a ADHD at most 20%, at most 25%, at most 30%, at most 35%, at most and/or a psychological and/or neurological disorder, includ 40%, at most 45%, at most 50%, at most 55%, at most 60%, ing without limitation, migrane, anti-serotonergic side at most 65%, at most 70%, at most 75%, at most 80%, at most effects, narcolepsy, excessive sleepiness associated with shift 85%, at most 90%, at most 95% or at most 100%. In an work, obstructive sleep apnea as an adjunct to continuous additional embodiment, a therapeutically effective amount of positive airways pressure (“CPAP), exogenous obesity, dis atherapeutic compound disclosed herein reduces a symptom ruptive behaviour disorder including oppositional defiant dis associated with a loss of attentiveness by, without limitation, order (“ODD) and conduct disorder (“CD), obesity, depres about 10% to about 100%, about 10% to about 90%, about sion (including, without limitation, augmentation of 10% to about 80%, about 10% to about 70%, about 10% to US 2014/010O249 A1 Apr. 10, 2014 24 about 60%, about 10% to about 50%, about 10% to about the range of without limitation, about 0.01 mg/kg/day to 40%, about 20% to about 100%, about 20% to about 90%, about 10 mg/kg/day, about 0.01 mg/kg/day to about 15 about 20% to about 80%, about 20% to about 20%, about 20% mg/kg/day, about 0.01 mg/kg/day to about 20 mg/kg/day, to about 60%, about 20% to about 50%, about 20% to about about 0.01 mg/kg/day to about 25 mg/kg/day, about 0.01 40%, about 30% to about 100%, about 30% to about 90%, mg/kg/day to about 30 mg/kg/day, about 0.01 mg/kg/day to about 30% to about 80%, about 30% to about 70%, about 30% about 35 mg/kg/day, about 0.01 mg/kg/day to about 40 to about 60%, or about 30% to about 50%. mg/kg/day, about 0.01 mg/kg/day to about 45 mg/kg/day, 0.124. In an embodiment, a therapeutically effective about 0.01 mg/kg/day to about 50 mg/kg/day, about 0.01 amount ofatherapeutic compound disclosed herein increases mg/kg/day to about 75 mg/kg/day, or about 0.01 mg/kg/day to the weight or height of an individual is determined by an about 100 mg/kg/day. In a further embodiment, an effective increase in the individuals weight or height Velocity as com amount ofatherapeutic compound disclosed herein may be in pared to an individual nor receiving a therapeutic compound the range of, without limitation, about 0.1 mg/kg/day to about for appetite reduction. In an embodiment, weight and/or 10 mg/kg/day, about 0.1 mg/kg/day to about 15 mg/kg/day, height Velocity can be calculated by taking measurements of about 0.1 mg/kg/day to about 20 mg/kg/day, about 0.1 mg/kg/ height and/or weight of an individual over a period of time day to about 25 mg/kg/day, about 0.1 mg/kg/day to about 30 and measuring an increase or decrease in an individuals mg/kg/day, about 0.1 mg/kg/day to about 35 mg/kg/day, height and/or weight over the period of time. In an embodi about 0.1 mg/kg/day to about 40 mg/kg/day, about 0.1 mg/kg/ ment, weight Velocity is calculated by taking three time day to about 45 mg/kg/day, about 0.1 mg/kg/day to about 50 points, time 0 upon initiation of medication to treat ADHD, mg/kg/day, about 0.1 mg/kg/day to about 75 mg/kg/day, or time 1 addition of an appetite stimulant, time 2 the last data about 0.1 mg/kg/day to about 100 mg/kg/day. point after initiation of combination treatment. In an embodi 0.126 In an embodiment, an effective amount of a thera ment, a formula to calculate weight and height Velocity for peutic compound disclosed herein may be in the range of stimulant alone is (weightT1-weight TO)/days from Time 0 without limitation, about 1 mg/kg/day to about 10 mg/kg/day, to time 1. In an embodiment, a formula to calculate weight about 1 mg/kg/day to about 15 mg/kg/day, about 1 mg/kg/day velocity for combination treatment is (weightT2-weight T1)/ to about 20 mg/kg/day, about 1 mg/kg/day to about 25 mg/kg/ days from time 1 to time 2. In an embodiment, to evaluate day, about 1 mg/kg/day to about 30 mg/kg/day, about 1 whether weight velocity increased after addition of an appe mg/kg/day to about 35 mg/kg/day, about 1 mg/kg/day to tite stimulant, the weight velocity of time 0 to time 1 is about 40 mg/kg/day, about 1 mg/kg/day to about 45 mg/kg/ compared to the weight velocity from time 1 to time 2. In an day, about 1 mg/kg/day to about 50 mg/kg/day, about 1 embodiment, height Velocity is calculated by taking three mg/kg/day to about 75 mg/kg/day, or about 1 mg/kg/day to time points, time 0 upon initiation of medication to treat about 100 mg/kg/day. In an additional embodiment, an effec ADHD, time 1 addition of an appetite stimulant, time 2 the tive amount of a therapeutic compound disclosed herein may last data point after initiation of combination treatment. The be in the range of without limitation, about 5 mg/kg/day to formula to calculate height Velocity for stimulant alone is about 10 mg/kg/day, about 5 mg/kg/day to about 15 mg/kg/ (weightT1-weight TO)/days from Time 0 to time 1. The for day, about 5 mg/kg/day to about 20 mg/kg/day, about 5 mula to calculate height Velocity for combination treatment is mg/kg/day to about 25 mg/kg/day, about 5 mg/kg/day to (weightT2-weight T1)/days from time 1 to time 2. In an about 30 mg/kg/day, about 5 mg/kg/day to about 35 mg/kg/ embodiment, to evaluate whether height velocity increased day, about 5 mg/kg/day to about 40 mg/kg/day, about 5 after addition of an appetite stimulant, the height velocity of mg/kg/day to about 45 mg/kg/day, about 5 mg/kg/day to time 0 to time 1 is compared to the height velocity from time about 50 mg/kg/day, about 5 mg/kg/day to about 75 mg/kg/ 1 to time 2. day, or about 5 mg/kg/day to about 100 mg/kg/day. 0.125. In an embodiment, a therapeutically effective I0127. In an embodiment, a therapeutically effective amount ofatherapeutic compound disclosed herein generally amount ofatherapeutic compound disclosed herein generally is in the range of about 0.001 mg/kg/day to about 100 mg/kg/ is in the range of about 1 mg/day to about 3,000 mg/day. In an day. In an additional embodiment, an effective amount of a additional embodiment, an effective amount of a therapeutic therapeutic compound disclosed herein may be, without limi compound disclosed herein may be, without limitation, at tation, at least 0.001 mg/kg/day, at least 0.01 mg/kg/day, at least 50 mg/day, at least 100 mg/day, at least 150 mg/day, at least 0.1 mg/kg/day, at least 1.0 mg/kg/day, at least 5.0 mg/kg/ least 200 mg/day, at least 250 mg/day, at least 300 mg/day, at day, at least 10 mg/kg/day, at least 15 mg/kg/day, at least 20 least 350 mg/day, at least 400 mg/day, at least 450 mg/day, at mg/kg/day, at least 25 mg/kg/day, at least 30 mg/kg/day, at least 500 mg/day, at least 550 mg/day, at least 600 mg/day, at least 35 mg/kg/day, at least 40 mg/kg/day, at least 45 mg/kg/ least 650 mg/day, at least 700 mg/day, at least 750 mg/day, at day, or at least 50 mg/kg/day. In a further embodiment, an least 800 mg/day, at least 850 mg/day, at least 900 mg/day, at effective amount of a therapeutic compound disclosed herein least 950 mg/day, at least 1,000 mg/day, at least 1.50 mg/day, may be in the range of, without limitation, about 0.001 mg/kg/ at least 1,100 mg/day, at least 1,150 mg/day, at least 1,200 day to about 10 mg/kg/day, about 0.001 mg/kg/day to about mg/day, at least 1,250 mg/day, at least 1,300 mg/day, at least 15 mg/kg/day, about 0.001 mg/kg/day to about 20 mg/kg/day, 1,350 mg/day, at least 1,400 mg/day, at least 1,450 mg/day, at about 0.001 mg/kg/day to about 25 mg/kg/day, about 0.001 least 1,500 mg/day, at least 1,600 mg/day, at least 1,700 mg/kg/day to about 30 mg/kg/day, about 0.001 mg/kg/day to mg/day, at least 1,800 mg/day, at least 1,900 mg/day, at least about 35 mg/kg/day, about 0.001 mg/kg/day to about 40 2,000 mg/day, at least 2,100 mg/day, at least 2,200 mg/day, at mg/kg/day, about 0.001 mg/kg/day to about 45 mg/kg/day, least 2,300 mg/day, at least 2,400 mg/day, at least 2,500 about 0.001 mg/kg/day to about 50 mg/kg/day, about 0.001 mg/day, at least 2,600 mg/day, at least 2,700 mg/day, at least mg/kg/day to about 75 mg/kg/day, or about 0.001 mg/kg/day 2,800 mg/day, at least 2,900 mg/day, or at least 3,000 mg/day. to about 100 mg/kg/day. In a further embodiment, an effective In an additional embodiment, an effective amount of a thera amount ofatherapeutic compound disclosed herein may be in peutic compound disclosed herein may be between, without US 2014/010O249 A1 Apr. 10, 2014

limitation, about 50 mg/day to about 1,000 mg/day, about 100 about 0.1 mg/kg/day to about 40 mg/kg/day, about 0.1 mg/kg/ mg/day to about 1,000 mg/day, about 150 mg/day to about day to about 45 mg/kg/day, about 0.1 mg/kg/day to about 50 1,000 mg/day, about 200 mg/day to about 1,000 mg/day, mg/kg/day, about 0.1 mg/kg/day to about 75 mg/kg/day, or about 250 mg/day to about 1,000 mg/day, about 300 mg/day about 0.1 mg/kg/day to about 100 mg/kg/day. to about 1,000 mg/day, about 350 mg/day to about 1,000 0129. In an embodiment, an effective amount of an mg/day, about 400 mg/day to about 1,000 mg/day, about 450 amphetamine, methylphenidate or cyproheptadine disclosed mg/day to about 1,000 mg/day, about 500 mg/day to about herein may be in the range of, without limitation, about 1 1,000 mg/day, about 50 mg/day to about 1,500 mg/day, about mg/kg/day to about 10 mg/kg/day, about 1 mg/kg/day to 100 mg/day to about 1,500 mg/day, about 150 mg/day to about 15 mg/kg/day, about 1 mg/kg/day to about 20 mg/kg/ about 1,500 mg/day, about 200 mg/day to about 1,500 day, about 1 mg/kg/day to about 25 mg/kg/day, about 1 mg/day, about 250 mg/day to about 1,500 mg/day, about 300 mg/kg/day to about 30 mg/kg/day, about 1 mg/kg/day to mg/day to about 1,500 mg/day, about 350 mg/day to about about 35 mg/kg/day, about 1 mg/kg/day to about 40 mg/kg/ 1,500 mg/day, about 400 mg/day to about 1,500 mg/day, day, about 1 mg/kg/day to about 45 mg/kg/day, about 1 about 450 mg/day to about 1,500 mg/day, about 500 mg/day mg/kg/day to about 50 mg/kg/day, about 1 mg/kg/day to to about 1,500 mg/day, about 1,000 mg/day to about 3,000 about 75 mg/kg/day, or about 1 mg/kg/day to about 100 mg/day, about 1,100 mg/day to about 3,000 mg/day, about mg/kg/day. In an additional embodiment, an effective amount 1,200 mg/day to about 3,000 mg/day, about 1,3000 mg/day to of an amphetamine, methylphenidate or cyproheptadine dis about 3,000 mg/day, about 1,400 mg/day to about 3,000 closed herein may be in the range of, without limitation, about mg/day, about 1,500 mg/day to about 3,000 mg/day, about 5 mg/kg/day to about 10 mg/kg/day, about 5 mg/kg/day to 1,600 mg/day to about 3,000 mg/day, about 1,700 mg/day to about 15 mg/kg/day, about 5 mg/kg/day to about 20 mg/kg/ about 3,000 mg/day, about 1,800 mg/day to about 3,000 day, about 5 mg/kg/day to about 25 mg/kg/day, about 5 mg/day, about 1,900 mg/day to about 3,000 mg/day, or about mg/kg/day to about 30 mg/kg/day, about 5 mg/kg/day to 2,000 mg/day to about 3,000 mg/day. about 35 mg/kg/day, about 5 mg/kg/day to about 40 mg/kg/ 0128. In an embodiment, a therapeutically effective day, about 5 mg/kg/day to about 45 mg/kg/day, about 5 amount of an amphetamine, methylphenidate or cyprohepta mg/kg/day to about 50 mg/kg/day, about 5 mg/kg/day to dine disclosed herein generally is in the range of about 0.001 about 75 mg/kg/day, or about 5 mg/kg/day to about 100 mg/kg/day to about 100 mg/kg/day. In an additional embodi mg/kg/day. ment, an effective amount of an amphetamine disclosed 0.130. In an embodiment, dosing can be single dosage or herein may be, without limitation, at least 0.001 mg/kg/day, at cumulative (serial dosing), and can be readily determined by least 0.01 mg/kg/day, at least 0.1 mg/kg/day, at least 1.0 one skilled in the art. In an additional embodiment, treatment mg/kg/day, at least 5.0 mg/kg/day, at least 10 mg/kg/day, at of ADHD and/or a psychological and/or neurological disor least 15 mg/kg/day, at least 20 mg/kg/day, at least 25 mg/kg/ der, including without limitation, migrane, anti-serotonergic day, at least 30 mg/kg/day, at least 35 mg/kg/day, at least 40 side effects, narcolepsy, excessive sleepiness associated with mg/kg/day, at least 45 mg/kg/day, or at least 50 mg/kg/day. In shift work, obstructive sleep apnea as an adjunct to continu a further embodiment, an effective amount of an amphet ous positive airways pressure ("CPAP), exogenous obesity, amine, methylphenidate or cyproheptadine disclosed herein disruptive behaviour disorder including oppositional defiant may be in the range of, without limitation, about 0.001 mg/kg/ disorder (“ODD) and conduct disorder (“CD), obesity, day to about 10 mg/kg/day, about 0.001 mg/kg/day to about depression (including, without limitation, augmentation of 15 mg/kg/day, about 0.001 mg/kg/day to about 20 mg/kg/day, antidepressants in treating refractory depression and cancer about 0.001 mg/kg/day to about 25 mg/kg/day, about 0.001 related depression), neural insult, fatigue (including, without mg/kg/day to about 30 mg/kg/day, about 0.001 mg/kg/day to limitation, disease-related fatigue in patients with HIV. about 35 mg/kg/day, about 0.001 mg/kg/day to about 40 advanced cancer, multiple Sclerosis, myotonic dystrophy, mg/kg/day, about 0.001 mg/kg/day to about 45 mg/kg/day, depression, fibromyalgia and hepatitis C), lethargy, binge about 0.001 mg/kg/day to about 50 mg/kg/day, about 0.001 eating disorder, Schizophrenia, sleep cycle disorder, cocaine mg/kg/day to about 75 mg/kg/day, or about 0.001 mg/kg/day addiction, Parkinson's Disease, combat and non-combat to about 100 mg/kg/day. In a further embodiment, an effective related PTSD and tic, may comprise a one-time administra amount of an amphetamine, methylphenidate or cyprohepta tion of an effective dose of a pharmaceutical composition dine disclosed herein may be in the range of without limita disclosed herein. In a further embodiment, treatment of tion, about 0.01 mg/kg/day to about 10 mg/kg/day, about 0.01 ADHD and/or a psychological and/or neurological disorder, mg/kg/day to about 15 mg/kg/day, about 0.01 mg/kg/day to including without limitation, migrane, anti-serotonergic side about 20 mg/kg/day, about 0.01 mg/kg/day to about 25 effects, narcolepsy, excessive sleepiness associated with shift mg/kg/day, about 0.01 mg/kg/day to about 30 mg/kg/day, work, obstructive sleep apnea as an adjunct to continuous about 0.01 mg/kg/day to about 35 mg/kg/day, about 0.01 positive airways pressure (“CPAP), exogenous obesity, dis mg/kg/day to about 40 mg/kg/day, about 0.01 mg/kg/day to ruptive behaviour disorder including oppositional defiant dis about 45 mg/kg/day, about 0.01 mg/kg/day to about 50 order (“ODD) and conduct disorder (“CD), obesity, depres mg/kg/day, about 0.01 mg/kg/day to about 75 mg/kg/day, or sion (including, without limitation, augmentation of about 0.01 mg/kg/day to about 100 mg/kg/day. In a further antidepressants in treating refractory depression and cancer embodiment, an effective amount of an amphetamine, meth related depression), neural insult, fatigue (including, without ylphenidate or cyproheptadine disclosed herein may be in the limitation, disease-related fatigue in patients with HIV. range of, without limitation, about 0.1 mg/kg/day to about 10 advanced cancer, multiple Sclerosis, myotonic dystrophy, mg/kg/day, about 0.1 mg/kg/day to about 15 mg/kg/day, depression, fibromyalgia and hepatitis C), lethargy, binge about 0.1 mg/kg/day to about 20 mg/kg/day, about 0.1 mg/kg/ eating disorder, Schizophrenia, sleep cycle disorder, cocaine day to about 25 mg/kg/day, about 0.1 mg/kg/day to about 30 addiction, Parkinson's Disease, combat and non-combat mg/kg/day, about 0.1 mg/kg/day to about 35 mg/kg/day, related PTSD and tic, may comprise multiple administrations US 2014/010O249 A1 Apr. 10, 2014 26 of an effective dose of a pharmaceutical composition carried lene oxide), poly(vinyl pyrrolidone), poly(vinyl alcohol), out over a range of time periods, such as, e.g., once daily, polyoxazoline, poly(acryloylmorpholine), and combinations twice daily, trice daily, once every few days, or once weekly. thereof. In an additional embodiment, the water soluble poly In an embodiment, the timing of administration can vary from mer is a poly(alkylene oxide) Such as, without limitation, a individual to individual, depending upon Such factors as the poly(ethylene glycol) derivative. In an embodiment, a water severity of an individuals symptoms. For example, in an soluble polymer has, without limitation, a nominal average embodiment, without limitation, an effective dose of a phar molecular weight in the range from about 2,000 Daltons to maceutical composition disclosed herein can be administered about 150,000 Daltons, from about 2,000 Daltons to about to an individual once daily for an indefinite period of time, or 125,000 Daltons, from about 2,000 Daltons to about 100,000 until the individual no longer requires therapy. A person of Daltons, from about 2,000 Daltons to about 75,000 Daltons, ordinary skill in the art will recognize that the condition of the from about 2,000 Daltons to about 50,000 Daltons, from individual can be monitored throughout the course of treat about 2,000 Daltons to about 25,000 Daltons, from about ment and that the effective amount of a pharmaceutical com 5,000 Daltons to about 150,000 Daltons, from about 5,000 position disclosed herein that is administered can be adjusted Daltons to about 100,000 Daltons, from about 5,000 Daltons accordingly. to about 75,000 Daltons, from about 5,000 Daltons to about 0131. In an embodiment, various routes of administration 50,000 Daltons, from about 5,000 Daltons to about 25,000 can be useful for administering a therapeutic compound dis Daltons, from about 10,000 Daltons to about 100,000 Dal closed herein, according to a method of treating a coughing tons, from about 10,000 Daltons to about 75,000 Daltons, condition disclosed herein. In an embodiment, a pharmaceu from about 10,000 Daltons to about 50,000 Daltons, from tical composition may be administered to an individual by about 10,000 Daltons to about 25,000 Daltons. In an embodi any of a variety of means depending, without limitation, on ment, a water Soluble polymer has, without limitation, a the type of condition to be treated, the location of the condi nominal average molecular weight of at least 150,000 Dal tion to be treated, the specific therapeutic compound or com tons, at least 125,000 Daltons, at least 100,000 Daltons, at position used, or other compound to be included in the com least 75,000 Daltons, at least 50,000 Daltons, at least 25,000 position, and the history, risk factors and symptoms of the Daltons. In an additional embodiment, the extended release, individual. As such, without limitation, topical, Sublingual, Sustained release or long acting form of a therapeutic com rectal, vaginal, trancutaneious, oral, inhaled, intranasal, Sub pound is linked, without limitation, to a polymer, including, cutaneous, intravenous, enteral or parenteral routes of admin without limitation, to a water soluble polymer through, with istration may be suitable for of treating ADHD and/or a psy out limitation, a stable linker or a releasable linker. chological and/or neurological disorder, including without I0133. In an embodiment, the pharmaceutical composi limitation, migrane, anti-serotonergic side effects, narco tions of the invention, including, without limitation a thera lepsy, excessive sleepiness associated with shift work, peutic compound, may further comprise one or more phar obstructive sleep apnea as an adjunct to continuous positive maceutically acceptable excipients to provide a airways pressure (“CPAP), exogenous obesity, disruptive pharmaceutical composition. In an additional embodiment, behaviour disorder including oppositional defiant disorder excipients include, without limitation, carbohydrates, (“ODD) and conduct disorder (“CD), obesity, depression starches (e.g., corn starch), inorganic salts, antimicrobial (including, without limitation, augmentation of antidepres agents, antioxidants, binders/fillers, Surfactants, lubricants sants in treating refractory depression and cancer-related (e.g., calcium or magnesium Stearate), glidants such as talc, depression), neural insult, fatigue (including, without limita disintegrants, diluents, buffers, acids, bases, film coats, com tion, disease-related fatigue in patients with HIV, advanced binations thereof, and the like. cancer, multiple Sclerosis, myotonic dystrophy, depression, fibromyalgia and hepatitis C), lethargy, binge eating disorder, I0134. In an embodiment, a pharmaceutical composition of Schizophrenia, sleep cycle disorder, cocaine addiction, Par the invention, including, without limitation a therapeutic kinson's Disease, combat and non-combat related PTSD and compound, may include one or more carbohydrates Such as a ticdisclosed herein and Such routes include, without limita Sugar, a derivatized Sugar Such as an alditol, aldonic acid, an tion, both local and systemic delivery of a therapeutic com esterified Sugar, and/or a Sugar polymer. Specific carbohy pound or composition disclosed herein. In an embodiment, drate excipients include, for example, without limitation: compositions comprising either a single therapeutic com monosaccharides, such as fructose, maltose, galactose, glu pound disclosed herein, or two or more therapeutic com cose, D-mannose, Sorbose, and the like; disaccharides. Such pounds disclosed herein are intended for inhaled, enteral, as lactose, Sucrose, trehalose, cellobiose, and the like; parenteral, topical, intranasal, Sublingual, Subcutaneous, polysaccharides, such as raffinose, melezitose, maltodex intravenous, rectal, transcutaneous (for example, without trins, dextrans, starches, and the like; and alditols, such as limitation, through a patch placed on the skin of an individual mannitol. Xylitol, maltitol, lactitol. Xylitol, Sorbitol (glucitol), being treated) and/or vaginal use may be prepared according pyranosyl Sorbitol, myoinositol, and the like. to any method known to the art for the manufacture of phar I0135) In an embodiment, pharmaceutical compositions of maceutical compositions. the invention, including, without limitation, a therapeutic 0.132. In an embodiment, the therapeutic compound compound, are potato and corn-based starches such as includes, without limitation, an extended release, Sustained Sodium starch glycolate and directly compressible modified release or long acting form. In an additional embodiment, the starch. extended release, Sustained release or long acting form of a 0.136. In an embodiment, further representative excipients therapeutic compound is linked, without limitation, to a poly include, without limitation, inorganic salt or buffers such as mer, including, without limitation, to a water soluble poly citric acid, sodium chloride, potassium chloride, Sodium Sul mer. In an embodiment, a water-soluble polymer is selected, fate, potassium nitrate, Sodium phosphate monobasic, without limitation, from the group consisting of poly(alky Sodium phosphate dibasic, and combinations thereof. US 2014/010O249 A1 Apr. 10, 2014 27

0.137 In an embodiment, the pharmaceutical composition, 0143. These foregoing pharmaceutical excipients along including, without limitation, a therapeutic compound, may with other excipients are described in “Remington: The Sci also include, without limitation, an antimicrobial agent, with ence & Practice of Pharmacy'. 19.sup.th ed., Williams & out limitation, for preventing or deterring microbial growth. Williams, (1995), the “Physician's Desk Reference', 52.sup. In an embodiment, non-limiting examples of antimicrobial nd ed., Medical Economics, Montvale, N.J. (1998), and agents suitable for the present invention include, without Kibbe, A.H., Handbook of Pharmaceutical Excipients, 3.sup. limitation, benzalkonium chloride, benzethonium chloride, rd Edition, American Pharmaceutical Association, Washing benzyl alcohol, cetylpyridinium chloride, chlorobutanol, ton, D.C., 2000. phenol, phenylethyl alcohol, phenylmercuric nitrate, thimer 0144. In an embodiment, the compositions encompass all Sol, and combinations thereof. types of formulations and in particular those that are Suited for 0.138. In an embodiment, a pharmaceutical composition of oral administration, without limitation, tablets, lozenges, the invention, including, without limitation a therapeutic orally dissolved strips, capsules, syrups, oral Suspensions, compound may also contain one or more antioxidants. In an emulsions, granules, sprinkles and pellets. In an additional additional embodiment, antioxidants are used to prevent oxi embodiment, formulations include, without limitation, aero dation, thereby preventing the deterioration of the drug(s) or Sols, transdermal patches, gels, creams, ointments, supposi other components of the preparation. In a further embodi tories, powders or lyophilates that can be reconstituted, as ment, Suitable antioxidants for use in the present invention well as liquids, such as for use in an oral or parenteral product. include, for example, without limitation, ascorbyl palmitate, In an embodiment, Suitable diluents for reconstituting Solid butylated hydroxyanisole, butylated hydroxytoluene, hypo compositions, without limitation, prior to injection, include phosphorous acid, monothioglycerol, propyl gallate, sodium bacteriostatic water for injection, dextrose 5% in water, phos bisulfite, sodium formaldehyde sulfoxylate, sodium met phate-buffered saline, Ringer's Solution, saline, Sterile water, abisulfite, and combinations thereof. deionized water, and combinations thereof. In an additional 0.139. In an embodiment, additional excipients include, embodiment, liquid pharmaceutical compositions, Solutions without limitation, Surfactants such as polysorbates without and Suspensions are envisioned. limitation, “Tween 20 and “Tween 80, and pluronics such 0145. In an embodiment, for oral, rectal, vaginal, sublin as, without limitation, F68 and F88 (both of which are avail gual and/or intranasal delivery formulations, tablets can be able from BASF, Mount Olive, N.J.), sorbitan esters, lipids made by compression or molding, optionally with one or (e.g., phospholipids such as lecithin and other phosphatidyl more accessory ingredients or additives. In an embodiment, cholines, and phosphatidylethanolamines), fatty acids and compressed tablets are prepared, for example, by compress fatty esters, steroids such as cholesterol, and chelating agents, ing in a Suitable tabletting machine, the active ingredients in such as EDTA, zinc and other such suitable cations. a free-flowing form Such as a powder or granules, optionally 0140. In an embodiment, a pharmaceutical composition of mixed with a binder (for example, without limitation, povi the invention, including, without limitation a therapeutic done, gelatin, hydroxypropylmethyl cellulose), lubricant, compound, may optionally include one or more acids or inert diluent, preservative, disintegrant (for example, without bases. In an embodiment, non-limiting examples of acids that limitation, sodium starch glycolate, cross-linked povidone, can be used include, without limitation, those acids selected cross-linked sodium carboxymethyl cellulose) and/or Sur from the group consisting of hydrochloric acid, acetic acid, face-active or dispersing agent. phosphoric acid, citric acid, malic acid, lactic acid, formic 0146 In an embodiment, molded tablets are made, for acid, trichloroacetic acid, nitric acid, perchloric acid, phos example, without limitation, by molding in a suitable tablet phoric acid, Sulfuric acid, fumaric acid, and combinations ting machine, a mixture of powdered compounds moistened thereof. In an embodiment, suitable bases include, without with an inert liquid diluent. In an embodiment, the tablets may limitation, bases selected from the group consisting of optionally be coated or scored, and may be formulated so as Sodium hydroxide, Sodium acetate, ammonium hydroxide, to provide slow or controlled release of the active ingredients, potassium hydroxide, ammonium acetate, potassium acetate, using, for example, without limitation, hydroxypropylmethyl Sodium phosphate, potassium phosphate, sodium citrate, cellulose in varying proportions to provide the desired release Sodium formate, sodium Sulfate, potassium Sulfate, potas profile. In an embodiment, tablets may optionally be provided sium fumerate, and combinations thereof. with a coating, without limitation, such as a thin film, Sugar 0141. In an embodiment, the amount of any individual coating, or an enteric coating to provide release in parts of the excipient in the composition will vary depending on the role gut other than the stomach. In an embodiment, processes, of the excipient, the dosage requirements of the active agent equipment, and toll manufacturers for tablet and capsule components, and particular needs of the composition. In an making are well-known in the art. embodiment, the optimal amount of any individual excipient 0.147. In an embodiment, capsule formulations may uti is determined through routine experimentation, without limi lize, without limitation, either hard or soft capsules, includ tation, by preparing compositions containing varying ing, without limitation, gelatin capsules or vegetarian cap amounts of the excipient (ranging from low to high), exam Sules Such aS those made Out of ining the stability and other parameters, and then determining hydroxymethylpropylcellulose (HMPC). In an embodiment, the range at which optimal performance is attained with no a type of capsule is a gelatin capsule. In an embodiment, significant adverse effects. capsules may be filled using a capsule filling machine Such as, 0142. In an embodiment, the excipient will be present in without limitation, those available from commercial Suppli the composition in an amount of, without limitation, about erS Such as Miranda International or employing capsule 1% to about 99% by weight, preferably from about 5% to manufacturing techniques well-known in the industry, as about 98% by weight, more preferably from about 15 to about described in detail in Pharmaceutical Capules, 2.sup.nd Ed., 95% by weight of the excipient, with concentrations less than F. Podczeck and B. Jones, 2004. In an embodiment, capsule 30% by weight most preferred. formulations may be prepared, without limitation, using atoll US 2014/010O249 A1 Apr. 10, 2014 28 manufacturing center Such as the Chao Center for Industrial II.(R). (Marquest Medical Products). In an embodiment, a Pharmacy & Contract Manufacturing, located at Purdue composition of the invention may also, without limitation, be Research Park. delivered using a pressurized, metered dose inhaler (MDI), 0148. In an embodiment, formulations for topical admin e.g., the Ventolin.R. metered dose inhaler, containing a solu istration in the mouth include lozenges comprising, without tion or Suspension of a combination of drugs as described limitation, the active ingredients, generally in a flavored base herein in a pharmaceutically inert liquid propellant, for Such as Sucrose and acacia or tragacanth and pastilles com example, without limitation, a chlorofluorocarbon or fluoro prising the active ingredients in an inert base such as gelatin carbon. and glycerin or Sucrose and acacia. 0.155. In an embodiment, formulations suitable for 0149. In an embodiment, a pharmaceutical composition parenteral administration include, without limitation, aque for topical administration may also be formulated, without ous and non-aqueous isotonic sterile Solutions suitable for limitation, as an ointment, cream, Suspension, lotion, powder, injection, as well as aqueous and non-aqueous sterile Suspen Solution, paste, gel, spray, aerosol or oil. In an embodiment, sions. the formulation may be, without limitation, in the form of a 0156. In an embodiment, parenteral formulations of the patch (e.g., a transdermal patch) or a dressing Such as a invention are optionally contained, without limitation, in bandage or adhesive plaster impregnated with active ingredi unit-dose or multi-dose sealed containers, for example, with ents and optionally one or more excipients or diluents. In an out limitation, ampoules and vials, and may be stored in a embodiment, topical formulations may additionally, without freeze-dried (lyophilized) condition requiring only the addi limitation, include a compound that enhances absorption or tion of the sterile liquid carrier, for example, water for injec penetration of the ingredients through the skin or other tions, immediately prior to use. In an embodiment, extempo affected areas, such as dimethylsulfoxidem bisabolol, oleic raneous injection Solutions and Suspensions may be prepared, acid, isopropyl myristate, and D-limonene, to name a few. without limitation, from sterile powders, granules and tablets 0150. In an embodiment, for emulsions, the oily phase is of the types previously described. constituted, without limitation, from known ingredients in a 0157. In an embodiment, a formulation of the invention known manner. In an embodiment, while this phase may may also be, without limitation, a Sustained release formula comprise merely an emulsifier (otherwise known as an emul tion, Such that each of the drug components is released or gent), it desirably comprises, without limitation, a mixture of absorbed slowly over time, when compared to a non-Sus at least one emulsifier with a fat and/or an oil. In an embodi tained release formulation. In an embodiment, Sustained ment, a hydrophilic emulsifier is included, without limitation, release formulations may, without limitation, employ pro together with a lipophilic emulsifier that acts as a stabilizer. In drug forms of the active agent, delayed-release drug delivery an embodiment, the emulsifier(s) with or without stabilizer(s) systems such as, without limitation, liposomes or polymer make up, without limitation, the so-called emulsifying wax, matrices, hydrogels, or covalent attachment of a polymer and the wax together with the oil and/or fat make up, without Such as polyethylene glycol to the active agent. limitation, the so-called emulsifying ointment base which 0158. In an embodiment, in addition to the ingredients forms the oily dispersed phase of cream formulations. In an particularly mentioned above, the formulations of the inven embodiment, illustrative emulgents and emulsion stabilizers tion may optionally include, without limitation, other agents include, without limitation, Tween 60, Span 80, cetostearyl conventional in the pharmaceutical arts and particular type of alcohol, myristyl alcohol, glyceryl monostearate and sodium formulation being employed, for example, without limita lauryl sulfate. tion, for oral administration forms, the composition for oral 0151. In an embodiment, formulations for rectal adminis administration may also include additional agents as Sweet tration are typically, without limitation, in the form of a Sup eners, thickeners or flavoring agents. pository with a suitable base comprising, for example, cocoa 0159. In an embodiment, the compositions of the present butter or a salicylate. invention may also be prepared, without limitation, in a form 0152. In an embodiment, formulations suitable for vaginal Suitable for veterinary applications. administration generally take the form, without limitation, of 0160. In an embodiment, the anti-arthritic compositions a Suppository, tampon, cream, gel, paste, foam or spray. described herein are, without limitation, in unit dosage form, 0153. In an embodiment, formulations suitable for nasal meaning a quantity of a combination of drugs of the inven administration, wherein the carrier is a Solid, include, without tion, appropriate for a single dose, or multiple doses, in one or limitation, a coarse powder having a particle size, for more premeasured or pre-packaged forms. In an additional example, without limitation, in the range of about 20 to about embodiment, a type of solid dosage form, without limitation, 500 microns. In an additional embodiment, such a formula is a capsule containing each of an antiviral compound, a tion is typically administered, without limitation, by rapid broad-spectrum antibiotic, and an antiprotozoal compound, inhalation through the nasal passage, for example, without or any two of the foregoing. In an embodiment, dosage forms limitation, from a container of the powder held in proximity to and modes of administration are discussed in greater detail in the nose. In an embodiment, a formulation for nasal delivery the sections that follow. may be, without limitation, in the form of a liquid, e.g., a nasal 0.161. In an embodiment, provided herein is a kit or pack spray or nasal drops. age containing, without limitation, at least one combination 0154. In an embodiment, aerosolizable formulations for composition of the invention, accompanied by instructions inhalation may be, without limitation, in dry powder form for use. (e.g., Suitable for administration by a dry powder inhaler), or, (0162. In an embodiment, in instances in which each of the alternatively, may be in liquid form, e.g., for use in a nebu drugs themselves are administered, without limitation, as lizer. In an embodiment, nebulizers for delivering an aero individual or separate dosage forms (e.g., capsules or tablets), solized solution include, without limitation, the AERX.TM. the kit comprises, without limitation, each of the drugs mak (Aradigm), the Ultravent.(R). (Mallinkrodt), and the Acorn ing up the composition of the invention, along with instruc US 2014/010O249 A1 Apr. 10, 2014 29 tions for use. In an additional embodiment, the drug compo of treatment she was 47%" and 59 lbs, corresponding to 70' nents, without limitation, may be packaged in any manner and 14" percentiles when compared to girls her age. At five Suitable for administration, so long as the packaging, when years of treatment she was 4'97/8" and 64/2 lbs, corresponding considered along with the instructions for administration, to 59' and 7" percentiles when compared to girls her age. without limitation, clearly indicates the manner in which each 0166 The girl was then prescribed Periactinata dosage of of the drug components is to be administered. In a further 2 mg b.i.d. to attempt to stimulate appetite. The dose was embodiment, each of the drug components of the combina taken in the morning and then in the afternoon. After one year tion may, without limitation, be combined into a single she was 411/2" and 72% lbs, corresponding to 33' and 5' administrable dosage form Such as a capsule. percentiles when compared to girls her age. The girl was then 0163 Various embodiments according to the above may prescribed Periactin at a dose of 4 mg. b.i.d. After two months be readily envisioned, and would of course depend upon the on this dose, she was 5'4" and 76 lbs, corresponding to 37" particular combination of drugs employed for treatment, their and 8" percentiles when compared to girls her age. At 8 corresponding dosage forms, recommended dosages, months on this dose, she was 5"/2" and 80 lbs, corresponding intended patient population, and the like. In an embodiment, to 41 and 8" percentiles when compared to girls her age. At the packaging may be in any form commonly employed for one year on this dose, she was 5'2%" and 89/2 lbs, corre the packaging of pharmaceuticals, such as medication punch sponding to 51 and 17" percentiles when compared to girls cards or blisters, and may utilize any of a number of features her age. At 18 months on this dose, she was 5'35/8" and 99/2 Such as different colors, wrapping, tamper-resistant packag lbs, corresponding to 56" and 30" percentiles when com ing, blister paks, dessicants, and the like. pared to girls her age. Additionally, the attentiveness of the girl increase following the prescription of Periactin as she EXAMPLES increased her food intake during the day. Example 1 Example 3 Treatment of a Patient Suffering from ADHD with Treatment of Patients Suffering from ADHD and and without an Appetite Stimulant Reduction in Appetite 0164. A patient suffering from ADHD is prescribed and 0.167 Eight patients, identified as patients A-H, that came administered an amphetamine to treat ADHD. The patient in suffering from ADHD were treated for ADHD. Each takes the amphetamine once a day in the morning or after patient was prescribed an amphetamine or methylphenidate noon. Following administration, the patient Suffers a loss of to treat ADHD and each patient following such treatment appetite and reduces their caloric intake. As a result, the Suffered a reduction in appetite and failed to gain Sufficient glucose level measured in the blood drops as shown in FIG. 1 weight. Each patient was then prescribed an appetite simulant and the patient Suffers a lack of attentiveness as measured by to be taken along with the amphetamine or methylphenidate. CGI-S and CGI-I. When the patient is administered an The patients weight, height and attentiveness were then fol amphetamine and Cyproheptadine once a day either in the lowed during the course of treatment. morning or afternoon, the patient’s appetite resumes and the 0.168. The age range of the patients was from 6-15 years of patient increases their caloric intake. As a result, the glucose age, with a mean age at the start of treatment for ADHD of 8.4 level measured in the blood increases as shown in FIG. 1 and years of age. The mean age at the start of the combination the patients attentiveness recovers as measured by CGI-S treatment wherein the patient was administered an amphet and CGI-I. By taking the appetite stimulant during the time amine or methylphenidate and an appetite stimulant was 10.3 when the patient was awake, the patient increased their years of age. The mean treatment period for the eight patients caloric intake during times when the patient needed to main was 1,108 days with a mean of 2.55 ADHD medication tain their attentiveness in order to have reasonable cognition changes during the treatment period. Attentiveness in the and/or social behaviour. eight patients was measured using CGI-S and CGI-I. Patients weight and height velocity were measured to identify a dif Example 2 ference in weight and height gain prior to and after addition of an appetite stimulant to the treatment for ADHD. Weight Once a Day Periactin Velocity was calculated by taking three time points, time 0 0.165 Case study: A six-year and ten month old girl was upon initiation of medication to treat ADHD, time 1 addition presented by her parents for symptoms of attention deficit of an appetite stimulant, time 2 the last data point after ini hyperactivity disorder. Her size at evaluation was 413/4" and tiation of combination treatment. The formula to calculate 50 lbs, corresponding to the 81 and 50" percentiles when weight velocity for stimulant alone is (weightT1-weight TO)/ compared to girls her age. She responded well to treatment days from Time 0 to time 1. The formula to calculate weight with various forms of methylphenidate, utilizing at various velocity for combination treatment is (weightT2-weight T1)/ times both short-acting formulations, as well as a trial on a days from time 1 to time 2. transdermal patch. A side-effect suffered by the girl was (0169. Following initiation of treatment for ADHD, but Suppression of appetite and a lack of significant weight gain. prior to the initiation of combination treatment, the mean loss At three months following the initiation of treatment for by a patient was 41 percentile points in the weight curve as ADHD, the girl was 427s and 50/2 lbs, corresponding to the compared to the expected weight gain over the same time 85" and 34" percentiles when compared to girls her age. At period by the patient if not provided the ADHD treatment. one year, she was 44%" and 53 lbs, corresponding to the 84" The mean loss was 34 percentile points in the height curve as and 36" percentiles when compared to girls her age. At two compared to the expected growth in height over the same time years she was 45%" and 54 lbs, corresponding to the 72" and period by the patient if not provided the ADHD treatment. For 17"percentiles when compared to girls her age. At four years the eight patients, the mean weight velocity with the ADHD US 2014/010O249 A1 Apr. 10, 2014 30 treatment only was 3.455 g/day. This compares to a mean at 15 mg and Periactin at 4 mgb.i.d. Following initiation of weight velocity of 13.972 g/day in patients administered the combination therapy, Patient B began to gain weight as shown combination treatment as shown in FIG.2. This corresponded in FIG. 6, but their CGI-S score remained 3 as shown in FIG. to a 304% increase in the weight gain by the patients follow 7. With an increase in Patient B’s appetite seen following the ing administration of the combination treatment comprising initiation of the combination treatment, the Focalin XR dose an amphetamine or methylphenidate and an appetite stimu was raised to 30 mg at day 1279 and shortly thereafter, the lant, Cyproheptadine. Similarly, the eight patients saw an CGI-S score dropped to 2 as seen in FIG.7, while the patients increase in their height velocity following initiation of the weight continued to increase reaching a maximal amount as combination treatment. The mean height Velocity of the eight seen in FIG. 6. Through the use of Periactin, Patient B was patients when administered only a treatment for ADHD was able to increase the dose of Focalin XR without a concomitant 0.091 cm/day. This compared to a mean height velocity of loss of appetite, thus allowing Patient B’s attentiveness to be 0.180 cm/day in patients following administration of the increased. combination treatment. This corresponds to a 98% increase in the rate of height addition for patients following initiation of Example 6 the combination treatment. In addition, the eight patients saw a mean increase of 17.5 percentile points in their weight curve Patient C following the initiation of combination treatment versus the aforementioned loss of 41 percentile points for administra 0173 Patient C was a male who was 9 years and approxi tion of the ADHD treatment without an appetite stimulant. mately 3 months when treatment for ADHD was initiated. Concordantly, the eight patients saw a mean increase of 16.7 Patient C was administered 36 mg of Concerta at the initiation percentile points in their height curve following the initiation of treatment for ADHD. Initially, there was little weight gain of combination treatment versus the aforementioned loss of followed by weight loss as shown in FIG. 8. On day 350 34 percentile points for administration of the ADHD treat following the initiation of treatment with Concerta for ment without an appetite stimulant. ADHD, Patient C began a combination treatment that 0170 The mean number of days to the first follow-up with included both Concerta at 36 mg and Periactin at 4 mg. b.i.d. a patient following initiation of the combination treatment Following initiation of combination therapy, Patient C began was 73 days. At this first follow-up, the mean weight velocity to gain weight as shown in FIG. 8, with a decrease in their of the patient was 27.3 g/day. This resulted in a 790% increase CGI-S score from 5 to 4 as shown in FIG. 9. in weight addition with combination treatment at the first Example 7 follow-up. Further, all eight patients on the combination treat ment were able to maintain their highest weight as of the last follow-up date. Patient D 0.174 Patient D was a male who was 7 years and approxi Example 4 mately 1 month when treatment for ADHD was initiated. Patient D was administered 18 mg of Concerta at the initiation Patient A of treatment for ADHD. On day 23 following the initiation of 0171 Patient A was a male who was 6 years and approxi treatment with Concerta for ADHD, Patient D began a com mately 3 months when treatment for ADHD was initiated. bination treatment that included both Concerta at 18 mg and Patient A was administered 18 mg of Concerta. Initially, Periactin at 2 mg administered in the morning. Following following a short loss in weight, patient A began to gain initiation of combination therapy, Patient D began to gain weight, but at about day 371 after initiation of treatment, weight at an accelerated pace as shown in FIG. 10, with a drop Patient A began to lose weight again as shown in FIG. 4. The in Patient D’s CGI-S Score from 6 to 5 as shown in FIG. 11. loss of weight continued until on day 661 Patient A was With the increase in weight gain resultant from the combina prescribed and began to take 4 mg. b.i.d. of Periactin. Follow tion treatment, Patient D was able to have the dose of Con ing initiation of the combination treatment, Patient Abegan to certa increased to 27 mg, which resulted in Patient D's CGI-S gain weight and the increase in height began to accelerate as score dropping again from 5 to 4 as shown in FIG. 11, with shown in FIG. 4. Additionally, following initiation of the only a slight decrease in the ability of Patient D to continue to combination treatment, Patient A also saw a decrease in his gain weight. In addition, though the change lagged the initia CGI-S score, going from a score of 4 that had been constant tion of administration of Periactin to Patient D, the combina for almost 400 days to a score of 3 as shown in FIG. 5. tion treatment also increased the growth rate in Patient D's height, even after the dose of Concerta was increased as seen Example 5 in FIG.10. Through the use of Periactin, Patient D was able to increase the dose of Concerta without a concomitant loss of Patient B appetite, thus allowing Patient D's attentiveness to be increased. 0172 Patient B was a male who was 7 years and approxi mately 8 months when treatment for ADHD was initiated. Example 8 Patient B was administered 10 mg of Focalin XR at the initiation of treatment for ADHD. The dose of Focalin XR was raised to 15 mg approximately 8 months later. Initially, Patient E weight gain was slow and then became slightly erratic with 0.175 Patient E was a male who was 11 years and approxi gains of weight between follow-up appointments followed by mately two weeks when treatment for ADHD was initiated. loss of weight as shown in FIG. 6. On day 865 following the Patient E was administered 27 mg of Concerta at the initiation initiation of treatment with Focalin XR for ADHD, Patient B of treatment for ADHD and then switched to a dose of 10 mg began a combination treatment that included both Focalin XR of Focalin XRonday 119 after initiation of treatment. Patient US 2014/010O249 A1 Apr. 10, 2014

E was then switched to a dose of 15 mg of Focalin XR on day as shown in FIG. 16, with a drop in Patient G's CGI-S score 162 after initiation of treatment. Increasing the dose of Foca from 4 to 3 as shown in FIG. 17. With the results seen in FIGS. lin XR reduced Patient Es CGI-S score from 6 to 5 as shown 16 and 17, Patient G, the dose of Periactin administered to in FIG. 13, with no additional improvement. Additionally, Patient G was decreased to 2 mgb.i.d. Patient Es weight did not increase substantively during this time as shown in FIG. 12. On day 23 following the initiation Example 11 of treatment with Concerta and then Focalin XR for ADHD, Patient E began a combination treatment that included both Patient H Focalin XR at a higher dose of 20 mg and Periactin at 4 mg administered in the morning. Following initiation of combi 0.178 Patient H was a male who was 11 years and approxi nation therapy, Patient E began to gain weight at an acceler mately 6 months when treatment for ADHD was initiated. ated pace as shown in FIG. 12, which increased when Peri Patient H was administered 40 mg of Vvyanase at the initia actin was administered b.i.d. on day 836 following initiation tion of treatment for ADHD. There was little weight gain by of therapy. In addition, Patient Es CGI-S score dropped from Patient H after initiation of treatment as shown in FIG. 18, 5 to 4 following the addition of Periactin to the combination though there was a drop in Patient H's CGI-S score from 6 to treatment and then from 4 to 3 when the Periactin was dosed 5 as shown in FIG. 19. On day 109 following the initiation of b.i.d. Through the use of Periactin, Patient E was able to treatment with Vvyanase for ADHD, Patient G began a com increase the dose of Focalin XR without a concomitant loss of bination treatment that included both Vvyanase at 40 mg and appetite, thus allowing Patient Es attentiveness to be Periactin at 2 mg b.i.d. Following initiation of combination increased. therapy, Patient G began to gain weight as shown in FIG. 18. Patient H was last seen on day 200 after initiation of treatment Example 9 for ADHD, at which time the CGI-S score had not changed from the prior date of examination as seen in FIG. 19, though Patient F it is understood that an examination so soon after initiation of 0176 Patient F was a male who was 6 years and approxi combination treatment does not necessarily mean that Patient mately 10 months when treatment for ADHD was initiated. H's CGI-S score did not drop further after day 200 as a result Patient F was administered Ritalin LA at a dose of 20 mg and of the increase in caloric intake. Focalin at a dose of 5 mg at the initiation of treatment for ADHD and then switched to Ritalin LA at a dose of 30 mg and Example 12 Focalin at a dose of 5 mg on day 46 after initiation of treat ment. Patient F was then switched to a Daytrana patch at a Impact of Combination Treatment on ADHD dose of 15 mg on day 469 and then increased to a dose of 20 Severity (CGI-S) mg on day 606 after initiation of treatment. Increasing the (0179 CGI-S data for each Patient A-H was plotted dose of Ritalin LA and then Switching to a Daytrana patch together in to allow examination of the effectiveness of an reduced Patient Fs CGI-S score from 7 to 6 and then 6 to 5 as appetite stimulant, in this case, Periactin, to decrease the shown in FIG. 15, with no additional improvement. Addition CGI-S score of the patients. As the data in FIG. 20 shows, in ally, Patient Fs weight did not increase substantively during general, the addition of an appetite simulant to a treatment for this time as shown in FIG. 14. On day 1547 following the ADHD over time lowered the CGI-S of a Patient by at least a initiation of treatment for ADHD, Patient F began a combi score of 1 as compared to the same patient prior to receipt of nation treatment that included both a Daytrana patch, now at the appetite stimulant. This is also shown in FIG. 21. In some a increased dose of 30 mg and Periactin at 2 mg administered cases, this was due in part to the ability of the patient to b.i.d. Following initiation of combination therapy, Patient F increase the dose of the treatment for ADHD following ini began to gain weight at an accelerated pace as shown in FIG. tiation of the combination treatment. Overall, combination 14, which increased when the dose of Periactin was increased treatment decreased severity as measured by CGI-S by 43% to 4 mgb.i.d. on day 1950 following the initiation of therapy. versus the baseline and showed a 22% improvement over Through the use of Periactin, Patient F was able to increase ADHD treatment alone, with a mean CGI-S score of 4.4 with the dose of the Daytrana patch without a concomitant loss of ADHD treatment alone and 3.4 for combination treatment. appetite, thus allowing Patient Fs attentiveness to be increased. Example 13 Example 10 Impact of Treatment on Improvement in ADHD Patient G 0180 Patients A-H had their CGI-I scores noted at each 0177 Patient G was a male who was 8 years and approxi visit with a clinician. Measurements of the CGI-I scores of mately 10 months when treatment for ADHD was initiated. Patients A-H found that the patients CGI-I scores improved Patient G was administered 15 mg of Focalin XR at the following initiation of a combination treatment as shown in initiation of treatment for ADHD. Following initiation of FIG. 22. More particularly, patients on combination treat treatment, Patient G's CGI-S score dropped from 5 to 4 as ment had CGI-I scores that showed the patient was either seen in FIG. 17. On day 546 following the initiation of treat minimally improved or much improved following treatment ment with Focalin XR for ADHD, Patient G began a combi as compared to patients receiving ADHD medication only, nation treatment that included both Focalin XR at 15 mg and several of whom were minimally worse or showed no change, Periactin at 4 mg administered b.i.d. Following initiation of with none showing much improved as shown in FIG. 22. combination therapy, Patient G began to gain height at an Overall, combination treatment decreased severity as mea accelerated pace and continued to gain weight at a good pace sured by CGI-I showed 30% improvement over ADHD treat US 2014/010O249 A1 Apr. 10, 2014 32 ment alone, with a mean CGI-S score of 3.4 with ADHD Geodon, Abilify, Clozaril, Xanax, Xanax XR, Klonopin, Ati treatment alone and 2.4 for combination treatment. van, Buspar, Ambien CR, Ambien, Lunesta, Sonata, RoZ erem, Lithiu, Lithobid, Eskalith, Depakote, Tegretol, Carba Example 14 trol, Trileptal, Lamictal, Topamax, Neurontin and the therapeutic compounds identified in Table 1. 0181. The patient is a 34 year old man suffering from chronic migraines. The man is administered an amphetamine 0187. The method according to any one of claims 1-4, along with a pain killer and the severity of the migraines are wherein the symptoms associated with attention deficit dis reduced over time, but the appetite of the man is similarly order is reduced by at least 10%, at least 15%, at least 20%, at reduced. Over time, while taking the amphetamine and pain least 25%, at least 30%, at least 35%, at least 40%, at least killer, the man loses weight and Suffers fatigue and a reduc 45%, at least 50%, at least 55%, at least 60%, at least 65%, at tion in attentiveness. The man is then administered an appetite least 70%, at least 75%, at least 80%, at least 85%, at least stimulant to take with the amphetamine and pain killer. The 90%, or at least 95%. man’s migraines continue to remain significantly reduced 0188 The method according to any one of claims 1-4, over time, but his appetite is restored and he maintains his wherein the severity associated with attention deficit disorder weight over the same period of time. is reduced by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at Example 15 least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or 0182. The patient is a 42 year old woman suffering from at least 95%. narcolepsy. The woman is administered an amphetamine 0189 The method according to any one of claims 1-4, along with sleep medication and the severity of the narco wherein the symptoms associated with attention deficit dis lepsy is reduced over time, but the appetite of the woman is order is reduced by about 10% to about 100%, about 20% to similarly reduced. Over time, while taking the amphetamine about 100%, about 30% to about 100%, about 40% to about and sleep medication, the woman loses weight and Suffers 100%, about 50% to about 100%, about 60% to about 100%, fatigue and a reduction in attentiveness. The woman is then about 70% to about 100%, about 80% to about 100%, about administered an appetite stimulant to take with the amphet 10% to about 90%, about 20% to about 90%, about 30% to amine and sleep medication. The woman’s migraines con about 90%, about 40% to about 90%, about 50% to about tinue to remain significantly reduced over time, but her appe 90%, about 60% to about 90%, about 70% to about 90%, tite is restored and she maintains his weight over the same about 10% to about 80%, about 20% to about 80%, about 30% period of time. to about 80%, about 40% to about 80%, about 50% to about 0183. A method of treating an individual with a disorder 80%, or about 60% to about 80%, about 10% to about 70%, associated with an attention deficit disorder, the method com about 20% to about 70%, about 30% to about 70%, about 40% prises the step of administering to an individual in need thereof a pharmaceutical composition which comprises to about 70%, or about 50% to about 70%. 0190. The method according to any one of claims 1-4, administration of a therapeutic compound to treat the atten wherein the dose of the therapeutic compound to treat the tion deficit disorder and a therapeutic compound to treat a attention deficit disorder is in the range of at least 0.001 reduction in appetite, wherein administration reduces a mg/kg/day, at least 0.01 mg/kg/day, at least 0.1 mg/kg/day, at symptom of a disorder associated with an attention deficit least 1.0 mg/kg/day, at least 5.0 mg/kg/day, at least 10 mg/kg/ disorder and increases the attentiveness of the individual, day, at least 15 mg/kg/day, at least 20 mg/kg/day, at least 25 thereby treating the individual. mg/kg/day, at least 30 mg/kg/day, at least 35 mg/kg/day, at 0184 The method of claim 1, wherein the attention deficit least 40 mg/kg/day, at least 45 mg/kg/day, or at least 50 disorder is Attention Deficit Hyperactivity Disorder mg/kg/day. (ADHD). 0185. The method of claim 1, wherein the therapeutic 0191 The method according to any one of claims 1-4, compound administered for the treatment of an attention defi wherein the dose of the therapeutic compound to treat the cit disorder is an amphetamine or a methylphenidate. attention deficit disorder is in the range of about 0.001 mg/kg/ 0186 The method of claim3, wherein the amphetamine or day to about 100 mg/kg/day. methylphenidate is selected from the group consisting of 0.192 The method according to any one of claims 1-4, OROS methylphenidate (Concerta), dextroamphetamine wherein the dose of the therapeutic compound to treat the immediate/sustained release (Adderall/Adderall XR), dexm attention deficit disorder is in the range of about 0.001 mg/kg/ ethylphenidate (Focalin), Focalin XR, Metadate CD, Meta day to about 10 mg/kg/day, about 0.001 mg/kg/day to about date ER, NWP09, Dexedrine, dextroamphetamine 15 mg/kg/day, about 0.001 mg/kg/day to about 20 mg/kg/day, (Dexedrine), Dexedrine Spanisules, Methylin ER (Ritalin about 0.001 mg/kg/day to about 25 mg/kg/day, about 0.001 SR), methylphenidate (Ritalin), and methylphenidate CR, mg/kg/day to about 30 mg/kg/day, about 0.001 mg/kg/day to Ritalin, Ritalin LA, SD-483, SPD-503, Ritalin SR, Intuniv about 35 mg/kg/day, about 0.001 mg/kg/day to about 40 ER, Intuniv, Methylin, Daytrana, Equasym, Dixirit, Kapvay, mg/kg/day, about 0.001 mg/kg/day to about 45 mg/kg/day, Daytrana Patch, Methylin chewable, Methylin liquid, Dex about 0.001 mg/kg/day to about 50 mg/kg/day, about 0.001 trostat, Strattera, Tenex, Catapres, Catapres TTS patch, mg/kg/day to about 75 mg/kg/day, or about 0.001 mg/kg/day Prozac, Serefam, Zoloft, Luvox, Paxil, Paxil CR, Pexeva, to about 100 mg/kg/day. Celexa, Lexapro, Tofranil, Norpamin, Elavil, Pamelor, Sine 0193 The method according to any of claims 1-11, quan, Anafranil, Wellbutrin, Wellbutrin SR, Wellbutrin XL, wherein the therapeutic compound to treat the attention defi Effexor, Effexor XR, Remeron, Cymbalta, Nardil, Parnate, cit disorder is administered to an individual topical, Sublin Emsam patch, Haldol, Orap, Prolixin, Mellaril, Thorazine, gual, rectal, vaginal, trancutaneous, oral, inhaled, intranasal, Stelazine, Moban, Loxitane, Risperdal, Zyprexa, Seroquel, Subcutaneous, intravenous, enteral or parenteral. US 2014/010O249 A1 Apr. 10, 2014

0194 The method according to any of claims 1-11, receptor antagonists (e.g., haloperidol, chlorpromazine, olan wherein the therapeutic compound to treat the attention defi Zapine, risperidone, quetiapine, etc.), Marinol, Megace, cit disorder is administered as a liquid, a Solid, a semi-solid or Megace ES, C.-adrenergic receptor antagonists (such as dox an aerosol. aZosin, carvedilol, propanolol, colonidine), Serefam, C2-adr 0.195 The method according to any of claims 1-4, wherein energic receptor agonists (e.g., clonidine, guanfacine, etc.). the therapeutic compound is formulated as a tablet, lozenge, Some beta blockers such as propanolol, natural or synthetic orally dissolved strip, capsule, syrup, oral Suspension, emul CB, receptor agonists (e.g., THC or dronabinol (found in Sion, granule, sprinkle or pellet. Cannabis), tetrahydrocannibinol, diphenydramine, promet 0196. The method of claim 1, wherein the therapeutic hazine, B vitamin supplements, nabilone, JWH-018 etc.), compound is a long acting, Sustained release, extended Corticosteroids (e.g. prednisone or dexamethasone), Sodium release, immediate release, slow release, or controlled release valproate (Depakote), Megestrol, Pregabalin, Sulfonylurea therapeutic compound. antidiabetic drugs such as glibenclamide and chlorpropam 0197) The method of claim 14, wherein the therapeutic ide, steroids (including, without limitation, boldenone, compound is released over a period of about 3 days after oxymetholone, dexamethasone, or methandrostenolone, administration, about 7 days after administration, about 10 prednisone, hydrocortisone, Oxandrolone, nandrolone, test days after administration, about 15 days after administration, osterone). Some kappa opioid receptoragonists such as tiflua about 20 days after administration, about 25 days after admin dom, hormones such as mederoxyprogesteronemirtazapine istration, about 30 days after administration, about 45 days (Remeron), a tetracyclic antidepressant, cyproheptadine (Pe after administration, about 60 days after administration, riactin), an antihistamine; nandrolone, oxymetholone, and about 75 days after administration, or about 90 days after oxandrolone (Anadrol-50, Durabolin, Hybolin, anti-IL6 anti administration. body, selective androgen receptor modulator (“SARM), 0198 The method of claim 14, wherein the therapeutic Oxandrin, and other brand names), VT-122 (a coadministra compound is released over a period of at least 3 days after tion of propranolol and etodolac), type 4 melanocortin recep administration, at least 7 days after administration, at least 10 tor antagonis, IL6 antagonist, synthetic ghrelin, myostatin days after administration, at least 15 days after administra decoy receptor, fast skeletal muscle troponin-activating Sub tion, at least 20 days after administration, at least 25 days after stance, anticatabolic/anabolic transforming agent MT-102, administration, at least 30 days after administration, at least celecoxib, testosterone, vitamin D, OHR/AVR118, soluble 45 days after administration, at least 60 days after adminis version of the ActRIIB receptor, 5-HT antagonists, Cox-2 tration, at least 75 days after administration, or at least 90 days inhibitor, thalidomide, omega-3 fatty acids, anticyclooxyge after administration nase-2 drugs and megestrol acetate (Megace). In addition to (0199 The method of claim 14, wherein the therapeutic these prescription drugs, fish oil (eicosapentaenoic acid or compound is released over a period of about 1 day after EPA), EATMOR, other vitamins and natural or artificial administration, about 2 days after administration, about 3 appetite stimulants. days after administration, about 4 days after administration, 0207. The method of claim 23, wherein the orexigenic about 5 days after administration, about 6 days after admin drug is cyproheptadine hydrochloride. istration or about 7 days or more after administration. 0200. The method according to any of claim 1, wherein the 0208. The method according to any one of claim 1 or pharmaceutical composition includes pharmaceutical accept 23-25, wherein the symptoms associated with appetite reduc able components. tion is reduced by at least 10%, at least 15%, at least 20%, at 0201 The method of claim 18, wherein the pharmaceuti least 25%, at least 30%, at least 35%, at least 40%, at least cal acceptable components is selected from the group con 45%, at least 50%, at least 55%, at least 60%, at least 65%, at sisting of a salt, a Surfactant, an amino acid, a stabilizer or a least 70%, at least 75%, at least 80%, at least 85%, at least buffer. 90%, or at least 95%. 0202 The method of claim 18, wherein the salt is selected 0209. The method according to any one of claim 1 or from the group consisting of citric acid, sodium chloride, 23-25, wherein the symptoms associated with appetite reduc potassium chloride, Sodium sulfate, potassium nitrate, tion is reduced by about 10% to about 100%, about 20% to Sodium phosphate monobasic or sodium phosphate dibasic. about 100%, about 30% to about 100%, about 40% to about 0203 The method of claim 18, wherein the surfactant is a 100%, about 50% to about 100%, about 60% to about 100%, polysorbate. about 70% to about 100%, about 80% to about 100%, about 0204 The method of claim 21, wherein the polysorbate is 10% to about 90%, about 20% to about 90%, about 30% to selected from the group consisting of Tween 20, Tween 80, about 90%, about 40% to about 90%, about 50% to about F68, F88, sorbitain esters, lipids, fatty acids or fatty esters. 90%, about 60% to about 90%, about 70% to about 90%, 0205 The method of claim 1, wherein the therapeutic about 10% to about 80%, about 20% to about 80%, about 30% compound to treat a appetite reduction is an orexigenic drug. to about 80%, about 40% to about 80%, about 50% to about 0206. The method of claim 23, wherein the orexigenic 80%, or about 60% to about 80%, about 10% to about 70%, drug is selected from the group of alcohol, GHB, and other about 20% to about 70%, about 30% to about 70%, about 40% sedatives such as Some benzodiazepine and nonbenzodiaz to about 70%, or about 50% to about 70%. epine tranquilizers and sleeping pills, anti-depressants (some 0210. The method according to any one of claim 1 or SSRIs, Mianserin, etc.), 5-HT, receptor antagonists/inverse 23-25, wherein the symptoms associated with reduction in the agonists (e.g., mirtazapine, mianserin, olanzapine, quetiap severity of appetite reduction is reduced by at least 10%, at ine, risperidone, amitriptyline, imipramine, cyproheptadine, least 15%, at least 20%, at least 25%, at least 30%, at least etc.), H receptor antagonists/inverse agonists (e.g., bucliz 35%, at least 40%, at least 45%, at least 50%, at least 55%, at ine, mirtazapine, mianserin, olanzapine, quetiapine, n-3 fatty least 60%, at least 65%, at least 70%, at least 75%, at least acids, amitriptyline, chlorpheniramine maleate, etc.), D/D 80%, at least 85%, at least 90% or at least 95%. US 2014/010O249 A1 Apr. 10, 2014 34

0211. The method according to any one of claim 1 or pound to 7.5 pounds, form 1 pound to 5 pounds, from 2 23-25, wherein the severity associated with reduction in pounds to ten pounds, from 2 pounds to 7.5 pounds. appetite is reduced by about 10% to about 100%, about 20% 0216. The method according to any of claim 1 or 23-25, to about 100%, about 30% to about 100%, about 40% to about wherein the treatment for appetite reduction increases the 100%, about 50% to about 100%, about 60% to about 100%, attentiveness of a patient by at least 10%, at least 15%, at least about 70% to about 100%, about 80% to about 100%, about 20%, at least 25%, at least 30%, at least 35%, at least 40%, at 10% to about 90%, about 20% to about 90%, about 30% to least 45%, at least 50%, at least 55%, at least 60%, at least about 90%, about 40% to about 90%, about 50% to about 65%, at least 70%, at least 75%, at least 80%, at least 85%, at 90%, about 60% to about 90%, about 70% to about 90%, least 90% or at least 95%. about 10% to about 80%, about 20% to about 80%, about 30% 0217. The method according to any of claim 1 or 23-25, to about 80%, about 40% to about 80%, about 50% to about wherein the treatment for appetite reduction increases the 80%, or about 60% to about 80%, about 10% to about 70%, attentiveness of a patient by about 10% to about 100%, about about 20% to about 70%, about 30% to about 70%, about 40% 20% to about 100%, about 30% to about 100%, about 40% to to about 70%, or about 50% to about 70%. about 100%, about 50% to about 100%, about 60% to about 0212. The method according to any one of claim 1 or 100%, about 70% to about 100%, about 80% to about 100%, 23-25, wherein the treatment for appetite reduction results in about 10% to about 90%, about 20% to about 90%, about 30% an increase in weight by at least 10%, at least 15%, at least to about 90%, about 40% to about 90%, about 50% to about 20%, at least 25%, at least 30%, at least 35%, at least 40%, at 90%, about 60% to about 90%, about 70% to about 90%, least 45%, at least 50%, at least 55%, at least 60%, at least about 10% to about 80%, about 20% to about 80%, about 30% 65%, at least 70%, at least 75%, at least 80%, at least 85%, at to about 80%, about 40% to about 80%, about 50% to about least 90% or at least 95%. 80%, or about 60% to about 80%, about 10% to about 70%, 0213. The method according to any one of claim 1 or about 20% to about 70%, about 30% to about 70%, about 40% 23-25, wherein the treatment for appetite reduction results in to about 70%, or about 50% to about 70%. an increase in weight by about 10% to about 100%, about 0218. The method according to any one of claim 1 or 20% to about 100%, about 30% to about 100%, about 40% to 23-35, wherein the dose of the therapeutic compound to treat about 100%, about 50% to about 100%, about 60% to about the reduction in appetite is in the range of at least 0.001 100%, about 70% to about 100%, about 80% to about 100%, mg/kg/day, at least 0.01 mg/kg/day, at least 0.1 mg/kg/day, at about 10% to about 90%, about 20% to about 90%, about 30% least 1.0 mg/kg/day, at least 5.0 mg/kg/day, at least 10 mg/kg/ to about 90%, about 40% to about 90%, about 50% to about day, at least 15 mg/kg/day, at least 20 mg/kg/day, at least 25 90%, about 60% to about 90%, about 70% to about 90%, mg/kg/day, at least 30 mg/kg/day, at least 35 mg/kg/day, at about 10% to about 80%, about 20% to about 80%, about 30% least 40 mg/kg/day, at least 45 mg/kg/day, or at least 50 to about 80%, about 40% to about 80%, about 50% to about mg/kg/day. 80%, or about 60% to about 80%, about 10% to about 70%, 0219. The method according to any one of claim 1 or about 20% to about 70%, about 30% to about 70%, about 40% 23-35, wherein the dose of the therapeutic compound to treat to about 70%, or about 50% to about 70%. reduction in appetite is in the range of about 0.001 mg/kg/day to about 100 mg/kg/day. 0214. The method according to any one of claim 1 or 0220. The method according to any one of claim 1 or 23-25, wherein the treatment for appetite reduction results in 23-35, wherein the dose of the therapeutic compound to treat an increase in height by at least 10%, at least 15%, at least the reduction in appetite is in the range of about 0.001 mg/kg/ 20%, at least 25%, at least 30%, at least 35%, at least 40%, at day to about 10 mg/kg/day, about 0.001 mg/kg/day to about least 45%, at least 50%, at least 55%, at least 60%, at least 15 mg/kg/day, about 0.001 mg/kg/day to about 20 mg/kg/day, 65%, at least 70%, at least 75%, at least 80%, at least 85%, at about 0.001 mg/kg/day to about 25 mg/kg/day, about 0.001 least 90% or at least 95%. mg/kg/day to about 30 mg/kg/day, about 0.001 mg/kg/day to 0215. The method according to any one of claim 1 or about 35 mg/kg/day, about 0.001 mg/kg/day to about 40 23-25, wherein the treatment for appetite reduction results in mg/kg/day, about 0.001 mg/kg/day to about 45 mg/kg/day, an increase in weight by at least 0.5 pounds, at least 1 pound, about 0.001 mg/kg/day to about 50 mg/kg/day, about 0.001 at least 1.5 pounds, at least 2 pounds, at least 2.5 pounds, at mg/kg/day to about 75 mg/kg/day, or about 0.001 mg/kg/day least 3 pounds, at least 3.5 pounds, at least 4 pounds, at least to about 100 mg/kg/day. 4.5 pounds, at least 5 pounds, at least 5.5 pounds, at least 6 pounds, at least 6.5 pounds, at least 7 pounds, at least 7.5 0221) The method according to any of claim 1 or 23-25, pounds, at least 8 pounds, at least 8.5 pounds, at least 9 wherein the therapeutic compound to treat the reduction in pounds, at least 9.5 pounds, at least 10 pounds, at least 10.5 appetite is administered to an individual topical, Sublingual, pounds, at least 11 pounds, at least 11.5 pounds, at least 12 rectal, vaginal, trancutaneous, oral, inhaled, intranasal, Sub pounds, at least 12.5 pounds, at least 13 pounds, at least 13.5 cutaneous, intravenous, enteral or parenteral. pounds, at least 14 pounds, at least 14.5 pounds, at least 15 0222. The method according to any of claim 1 or 23-35, pounds, at least 20 pounds, at least 25 pounds, at least 30 wherein the therapeutic compound to treat the reduction in pounds, at least 50 pounds. In another embodiment, a thera appetite is administered as a liquid, a solid, a semi-solid oran peutic compound disclosed herein for the treatment of appe aerosol. tite reduction results in an increase in weight by, e.g., from 0.5 0223) The method according to any of claim 1 or 23-35, pounds to 50 pounds, from 0.5 pounds to 30 pounds, from 0.5 wherein the therapeutic compound is formulated as a tablet, pounds to 25 pounds, from 0.5 pounds to 20 pounds, from 0.5 lozenge, orally dissolved strip, capsule, syrup, oral Suspen pounds to 15 pounds, from 0.5 pounds to ten pounds, from 0.5 Sion, emulsion, granule, sprinkle or pellet. pounds to 7.5 pounds, from 0.5 pounds to 5 pounds, from 1 0224. The method according to any of claim 1 or 23-35, pound to 15 pounds, from 1 pound to 10 pounds, from 1 wherein the therapeutic compound is a long acting, Sustained US 2014/010O249 A1 Apr. 10, 2014

release, extended release, immediate release, slow release, or 0238. The method of any of claim 1 or 51-53, wherein the controlled release therapeutic compound. patients CGI-S score is reduced by about 10% to about 0225. The method according to any of claim 1 or 23-35, 100%, about 20% to about 100%, about 30% to about 100%, wherein the therapeutic compound is released over a period of about 40% to about 100%, about 50% to about 100%, about about 3 days after administration, about 7 days after admin 60% to about 100%, about 70% to about 100%, about 80% to istration, about 10 days after administration, about 15 days about 100%, about 10% to about 90%, about 20% to about after administration, about 20 days after administration, 90%, about 30% to about 90%, about 40% to about 90%, about 25 days after administration, about 30 days after admin about 50% to about 90%, about 60% to about 90%, about 70% istration, about 45 days after administration, about 60 days to about 90%, about 10% to about 80%, about 20% to about after administration, about 75 days after administration, or 80%, about 30% to about 80%, about 40% to about 80%, about 90 days after administration. about 50% to about 80%, or about 60% to about 80%, about 0226. The method according to any of claim 1 or 23-35, 10% to about 70%, about 20% to about 70%, about 30% to wherein the therapeutic compound is released over a period of about 70%, about 40% to about 70%, or about 50% to about at least 3 days after administration, at least 7 days after admin 70%. istration, at least 10 days after administration, at least 15 days 0239. The method of claim 1, wherein the increase in after administration, at least 20 days after administration, at attentiveness by an individual is measured by CGI-I. least 25 days after administration, at least 30 days after 0240. The method of claim 57, wherein the CGI-I scale is administration, at least 45 days after administration, at least from 1 to 7. 60 days after administration, at least 75 days after adminis tration, or at least 90 days after administration 0241 The method of claim 58, wherein a measurement of 0227. The method according to any of claim 1 or 23-35, 7 identifies an individual that is very much worse, 6 identifies wherein the therapeutic compound is released over a period of an individual that is much worse, 5 identifies an individual about 1 day after administration, about 2 days after adminis that is minimally worse, 4 identifies an individual that is no tration, about 3 days after administration, about 4 days after change, 3 identifies an individual that is minimally improved, administration, about 5 days after administration, about 6 2 identifies an individual that is much improved and a mea days after administration or about 7 days or more after admin surement of 1 identifies an individual that is very much istration. improved. 0228. The method according to any of claim 1 or 23-35, 0242. The method of any of claim 1 or 57-59, wherein the wherein the pharmaceutical composition includes pharma increase in attentiveness measured CGI-I is by a reduction in ceutical acceptable components. the score by 1 or more as compared to a patient not receiving 0229. The method of claim 46, wherein the pharmaceuti a therapeutic compound to treat a reduction in appetite. cal acceptable components is selected from the group con 0243 The method of any of claim 1 or 57-59, wherein the sisting of a salt, a Surfactant, an amino acid, a stabilizer or a patients CGI-S score is reduced by at least 10%, at least 15%, buffer. at least 20%, at least 25%, at least 30%, at least 35%, at least 0230. The method of claim 47, wherein the salt is selected 40%, at least 45%, at least 50%, at least 55%, at least 60%, at from the group consisting of citric acid, sodium chloride, least 65%, at least 70%, at least 75%, at least 80%, at least potassium chloride, Sodium sulfate, potassium nitrate, 85%, at least 90% or at least 95%. Sodium phosphate monobasic or sodium phosphate dibasic. 0244. The method of any of claim 1 or 57-59, wherein the 0231. The method of claim 46, wherein the surfactant is a patients CGI-S score is reduced by about 10% to about polysorbate. 100%, about 20% to about 100%, about 30% to about 100%, 0232. The method of claim 49, wherein the polysorbate is about 40% to about 100%, about 50% to about 100%, about selected from the group consisting of Tween 20, Tween 80, 60% to about 100%, about 70% to about 100%, about 80% to F68, F88, sorbitain esters, lipids, fatty acids or fatty esters. about 100%, about 10% to about 90%, about 20% to about 0233. The method of claim 1, wherein the increase in 90%, about 30% to about 90%, about 40% to about 90%, attentiveness by an individual is measured by CGI-S. about 50% to about 90%, about 60% to about 90%, about 70% 0234. The method of claim 51, wherein the CGI-S scale is to about 90%, about 10% to about 80%, about 20% to about from 1 to 7. 80%, about 30% to about 80%, about 40% to about 80%, 0235. The method of claim 52, wherein a measurement of about 50% to about 80%, or about 60% to about 80%, about 7 identifies an individual that is extremely ill, 6 identifies an 10% to about 70%, about 20% to about 70%, about 30% to individual that is severely ill, 5 identifies an individual that is about 70%, about 40% to about 70%, or about 50% to about markedly ill, 4 identifies an individual that is moderately ill, 3 70%. identifies an individual that is mildly ill, 2 identifies an indi 0245. The method of claim 1, wherein the increase in vidual that is borderline ill and a measurement of 1 identifies attentiveness by an individual is measured by the pacademic an individual that is normal. performance rating scale, ADD evaluation scale-3rd edition 0236. The method of any of claim 1 or 51-53, wherein the (ADDES-3), ADHD rating scale-IV (ADHD-RS-IV), youth increase in attentiveness measured by CGI-S is by a reduction self report (broadband instrument), Conners parent rating in the score by 1 or more as compared to a patient not receiv scale-revised (CPRS-R), Conners teacher rating scale-re ing a therapeutic compound to treat a appetite reduction. vised (CTRS-R), Conners 3 self-reporting scale (Conner 0237. The method of any of claim 1 or 51-53, wherein the 3-SR, ages 8-18 y), home situations questionnaire-revised, patients CGI-S score is reduced by at least 10%, at least 15%, inattention/overactivity with aggression (IOWA) Conners at least 20%, at least 25%, at least 30%, at least 35%, at least teacher's rating scale, Swanson Nolan and Pelham IV scale 40%, at least 45%, at least 50%, at least 55%, at least 60%, at (SNAP-IV), Swanson Kotkin Agler M-Flynn and Pelham least 65%, at least 70%, at least 75%, at least 80%, at least (SKAMP), Vanderbilt ADHD diagnostic parent rating scale 85%, at least 90% or at least 95%. (VADPRS), Vanderbilt ADHD diagnostic teacher rating scale US 2014/010O249 A1 Apr. 10, 2014 36

(VADTRS), behavior assessment system for children-2nd about 30% to about 80%, about 40% to about 80%, about 50% edition (BASC-2) or the Conners rating scale long version. to about 80%, or about 60% to about 80%, about 10% to about 0246 A pharmaceutical composition comprising a thera 70%, about 20% to about 70%, about 30% to about 70%, peutic compound for a disorder associated with an attention about 40% to about 70%, or about 50% to about 70%. deficit disorder and a therapeutic compound for a disorder 0253 A pharmaceutical composition according to any one associated with a reduction in appetite, wherein the pharma of claims 64-67, wherein the dose of the therapeutic com ceutical composition reduces a symptom of a disorder asso pound to treat the attention deficit disorder is in the range of ciated with an attention deficit disorder and increases the at least 0.001 mg/kg/day, at least 0.01 mg/kg/day, at least 0.1 attentiveness of the individual, thereby treating the indi mg/kg/day, at least 1.0 mg/kg/day, at least 5.0 mg/kg/day, at vidual. least 10 mg/kg/day, at least 15 mg/kg/day, at least 20 mg/kg/ 0247. A pharmaceutical composition of claim 64, wherein day, at least 25 mg/kg/day, at least 30 mg/kg/day, at least 35 the attention deficit disorder is Attention Deficit Hyperactiv mg/kg/day, at least 40 mg/kg/day, at least 45 mg/kg/day, or at ity Disorder (ADHD). least 50 mg/kg/day. 0248. A pharmaceutical composition of claim 64, wherein 0254. A pharmaceutical composition according to any one the therapeutic compound administered for the treatment of of claims 64-67, wherein the dose of the therapeutic com an attention deficit disorder is an amphetamine or a meth pound to treat the attention deficit disorder is in the range of ylphenidate. about 0.001 mg/kg/day to about 100 mg/kg/day. 0249. A pharmaceutical composition of claim 66, wherein 0255. A pharmaceutical composition according to any one the amphetamine or methylphenidate is selected from the of claims 64-67, wherein the dose of the therapeutic com group consisting of OROS methylphenidate (Concerta), dex pound to treat the attention deficit disorder is in the range of troamphetamine immediate? sustained release (Adderall/ about 0.001 mg/kg/day to about 10 mg/kg/day, about 0.001 Adderall XR), dexmethylphenidate (Focalin), Focalin XR, mg/kg/day to about 15 mg/kg/day, about 0.001 mg/kg/day to Metadate CD, Metadate ER, NWP09, Dexedrine, dextroam about 20 mg/kg/day, about 0.001 mg/kg/day to about 25 phetamine (Dexedrine), Dexedrine Spansules, Methylin ER mg/kg/day, about 0.001 mg/kg/day to about 30 mg/kg/day, (Ritalin SR), methylphenidate (Ritalin), and methylpheni about 0.001 mg/kg/day to about 35 mg/kg/day, about 0.001 date CR, Ritalin, Ritalin LA, SD-483, SPD-503, Ritalin SR, mg/kg/day to about 40 mg/kg/day, about 0.001 mg/kg/day to Intuniv ER, Intuniv, Methylin, Daytrana, Equasym, Dixirit, about 45 mg/kg/day, about 0.001 mg/kg/day to about 50 Kapvay, Daytrana Patch, Methylin chewable, Methylin liq mg/kg/day, about 0.001 mg/kg/day to about 75 mg/kg/day, or uid, Dextrostat, Strattera, Tenex, Catapres, Catapres TTS about 0.001 mg/kg/day to about 100 mg/kg/day. patch, Prozac, Serefam, Zoloft, Luvox, Paxil, Paxil CR, Pex 0256 A pharmaceutical composition according to any one eva, Celexa, Lexapro, Tofranil, Norpamin, Elavil, Pamelor, of claims 64-67, wherein the therapeutic compound to treat Sinequan, Anafranil, Wellbutrin, Wellbutrin SR, Wellbutrin the attention deficit disorder is administered to an individual XL, Effexor, Effexor XR, Remeron, Cymbalta, Nardil, Par topical, Sublingual, rectal, vaginal, trancutaneous, oral, nate, Emsam patch, Haldol, Orap, Prolixin, Mellaril. Thora inhaled, intranasal, Subcutaneous, intravenous, enteral or zine, Stelazine, Moban, Loxitane, Risperdal, Zyprexa, Sero parenteral. quel, Geodon, Abilify, Clozaril, Xanax, Xanax XR, Klonopin, Ativan, Buspar, Ambien CR, Ambien, Lunesta, 0257. A pharmaceutical composition according to any one Sonata, Rozerem, Lithiu, Lithobid, Eskalith, Depakote, of claims 64-67, wherein the therapeutic compound to treat Tegretol, Carbatrol, Trileptal, Lamictal, Topamax, Neurontin the attention deficit disorder is administered as a liquid, a and the therapeutic compounds identified in Table 1. Solid, a semi-solid or an aerosol. 0250) A pharmaceutical composition according to any one 0258. A pharmaceutical composition according to any one of claims 64-67, wherein the symptoms associated with atten of claims 64-67, wherein the therapeutic compound is formu tion deficit disorder is reduced by at least 10%, at least 15%, lated as a tablet, lozenge, orally dissolved strip, capsule, at least 20%, at least 25%, at least 30%, at least 35%, at least syrup, oral Suspension, emulsion, granule, sprinkle or pellet. 40%, at least 45%, at least 50%, at least 55%, at least 60%, at 0259. A pharmaceutical composition according to claim least 65%, at least 70%, at least 75%, at least 80%, at least 64, wherein the therapeutic compound is a long acting, Sus 85%, at least 90%, or at least 95%. tained release, extended release, immediate release, slow 0251 A pharmaceutical composition according to any one release, or controlled release therapeutic compound. of claims 64-67, wherein the severity associated with atten 0260 A pharmaceutical composition according to claim tion deficit disorder is reduced by at least 10%, at least 15%, 77, wherein the therapeutic compound is released over a at least 20%, at least 25%, at least 30%, at least 35%, at least period of about 3 days after administration, about 7 days after 40%, at least 45%, at least 50%, at least 55%, at least 60%, at administration, about 10 days after administration, about 15 least 65%, at least 70%, at least 75%, at least 80%, at least days after administration, about 20 days after administration, 85%, at least 90%, or at least 95%. about 25 days after administration, about 30 days after admin 0252 A pharmaceutical composition according to any one istration, about 45 days after administration, about 60 days of claims 64-67, wherein the symptoms associated with atten after administration, about 75 days after administration, or tion deficit disorder is reduced by about 10% to about 100%, about 90 days after administration. about 20% to about 100%, about 30% to about 100%, about 0261 A pharmaceutical composition according to claim 40% to about 100%, about 50% to about 100%, about 60% to 77, wherein the therapeutic compound is released over a about 100%, about 70% to about 100%, about 80% to about period of at least 3 days after administration, at least 7 days 100%, about 10% to about 90%, about 20% to about 90%, after administration, at least 10 days after administration, at about 30% to about 90%, about 40% to about 90%, about 50% least 15 days after administration, at least 20 days after to about 90%, about 60% to about 90%, about 70% to about administration, at least 25 days after administration, at least 90%, about 10% to about 80%, about 20% to about 80%, 30 days after administration, at least 45 days after adminis US 2014/010O249 A1 Apr. 10, 2014 37 tration, at least 60 days after administration, at least 75 days synthetic ghrelin, myostatin decoy receptor, fast skeletal after administration, or at least 90 days after administration muscle troponin-activating Substance, anticatabolic/anabolic 0262 A pharmaceutical composition according to claim transforming agent MT-102, celecoxib, testosterone, Vitamin 77, wherein the therapeutic compound is released over a D, OHR/AVR118, soluble version of the ActRIIB receptor, period of about 1 day after administration, about 2 days after 5-HT antagonists, Cox-2 inhibitor, thalidomide, omega-3 administration, about 3 days after administration, about 4 fatty acids, anticyclooxygenase-2 drugs and megestrol days after administration, about 5 days after administration, acetate (Megace). In addition to these prescription drugs, fish about 6 days after administration or about 7 days or more after oil (eicosapentaenoic acid or EPA), EATMOR, other vita administration. mins and natural or artificial appetite stimulants. 0263. A pharmaceutical composition according to claim 0270. A pharmaceutical composition according to claim 1, wherein the pharmaceutical composition includes pharma 87, wherein the orexigenic drug is cyproheptadine hydrochlo ceutical acceptable components. ride. 0264. A pharmaceutical composition according to claim 0271 A pharmaceutical composition according to any one 81, wherein the pharmaceutical acceptable components is of claims 64 and 86-88, wherein the symptoms associated selected from the group consisting of a salt, a Surfactant, an with appetite reduction is reduced by at least 10%, at least amino acid, a stabilizer or a buffer. 15%, at least 20%, at least 25%, at least 30%, at least 35%, at 0265 A pharmaceutical composition according to claim least 40%, at least 45%, at least 50%, at least 55%, at least 82, wherein the salt is selected from the group consisting of 60%, at least 65%, at least 70%, at least 75%, at least 80%, at citric acid, sodium chloride, potassium chloride, Sodium Sul least 85%, at least 90%, or at least 95%. fate, potassium nitrate, sodium phosphate monobasic or 0272 A pharmaceutical composition according to any one Sodium phosphate dibasic. of claims 64 and 86-88, wherein the symptoms associated 0266. A pharmaceutical composition according to 81, with appetite reduction is reduced by about 10% to about wherein the Surfactant is a polysorbate. 100%, about 20% to about 100%, about 30% to about 100%, 0267 A pharmaceutical composition according to claim about 40% to about 100%, about 50% to about 100%, about 84, wherein the polysorbate is selected from the group con 60% to about 100%, about 70% to about 100%, about 80% to sisting of Tween 20, Tween 80, F68, F88, sorbitain esters, about 100%, about 10% to about 90%, about 20% to about lipids, fatty acids or fatty esters. 90%, about 30% to about 90%, about 40% to about 90%, 0268 A pharmaceutical composition according to claim about 50% to about 90%, about 60% to about 90%, about 70% 64, wherein the therapeutic compound to treat a appetite to about 90%, about 10% to about 80%, about 20% to about reduction is an orexigenic drug. 80%, about 30% to about 80%, about 40% to about 80%, 0269. A pharmaceutical composition according to claim about 50% to about 80%, or about 60% to about 80%, about 86, wherein the orexigenic drug is selected from the group of 10% to about 70%, about 20% to about 70%, about 30% to alcohol, GHB, and other sedatives such as some benzodiaz about 70%, about 40% to about 70%, or about 50% to about epine and nonbenzodiazepine tranquilizers and sleeping pills, 70%. anti-depressants (some SSRIs, Mianserin, etc.), 5-HT, receptor antagonists/inverse agonists (e.g., mirtazapine, 0273 A pharmaceutical composition according to any one mianserin, olanzapine, quetiapine, risperidone, amitriptyline, of claims 64 and 86-88, wherein the symptoms associated imipramine, cyproheptadine, etc.), H receptor antagonists/ with reduction in the severity of appetite reduction is reduced inverse agonists (e.g., buclizine, mirtazapine, mianserin, by at least 10%, at least 15%, at least 20%, at least 25%, at olanzapine, quetiapine, n-3 fatty acids, amitriptyline, chlor least 30%, at least 35%, at least 40%, at least 45%, at least pheniramine maleate, etc.), D/D receptor antagonists (e.g., 50%, at least 55%, at least 60%, at least 65%, at least 70%, at haloperidol, chlorpromazine, olanzapine, risperidone, que least 75%, at least 80%, at least 85%, at least 90% or at least tiapine, etc.), Marinol, Megace, Megace ES, C-adrenergic 95%. receptor antagonists (such as doxazosin, carvedilol, pro 0274. A pharmaceutical composition according to any one panolol, colonidine), Serefam, C-adrenergic receptor ago of claims 64 and 86-88, wherein the severity associated with nists (e.g., clonidine, guanfacine, etc.), some beta blockers reduction in appetite is reduced by about 10% to about 100%, Such as propanolol, natural or synthetic CB, receptoragonists about 20% to about 100%, about 30% to about 100%, about (e.g., THC or dronabinol (found in Cannabis), tetrahydrocan 40% to about 100%, about 50% to about 100%, about 60% to nibinol, diphenydramine, promethazine, B vitamin Supple about 100%, about 70% to about 100%, about 80% to about ments, nabilone, JWH-018 etc.), Corticosteroids (e.g. pred 100%, about 10% to about 90%, about 20% to about 90%, nisone or dexamethasone), Sodium valproate (Depakote), about 30% to about 90%, about 40% to about 90%, about 50% Megestrol, Pregabalin, Sulfonylurea antidiabetic drugs such to about 90%, about 60% to about 90%, about 70% to about as glibenclamide and chlorpropamide, Steroids (including, 90%, about 10% to about 80%, about 20% to about 80%, without limitation, boldenone, oxymetholone, dexametha about 30% to about 80%, about 40% to about 80%, about 50% Sone, or methandrostenolone, prednisone, hydrocortisone, to about 80%, or about 60% to about 80%, about 10% to about Oxandrolone, nandrolone, testosterone), some kappa opioid 70%, about 20% to about 70%, about 30% to about 70%, receptor agonists such as tifluadom, hormones Such as med about 40% to about 70%, or about 50% to about 70%. eroxyprogesteronemirtazapine (Remeron), a tetracyclic anti 0275 A pharmaceutical composition according to any one depressant, cyproheptadine (Periactin), an antihistamine; of claims 64 and 86-88, wherein the treatment for appetite nandrolone, oxymetholone, and Oxandrolone (Anadrol-50, reduction results in an increase in weight by at least 10%, at Durabolin, Hybolin, anti-IL6 antibody, selective androgen least 15%, at least 20%, at least 25%, at least 30%, at least receptor modulator (“SARM), Oxandrin, and other brand 35%, at least 40%, at least 45%, at least 50%, at least 55%, at names), VT-122 (a coadministration of propranolol and etod least 60%, at least 65%, at least 70%, at least 75%, at least olac), type 4 melanocortin receptor antagonis, IL6 antagonist, 80%, at least 85%, at least 90% or at least 95%. US 2014/010O249 A1 Apr. 10, 2014

0276 A pharmaceutical composition according to any one to about 80%, about 50% to about 80%, or about 60% to about of claims 64 and 86-88, wherein the treatment for appetite 80%, about 10% to about 70%, about 20% to about 70%, reduction results in an increase in weight by about 10% to about 30% to about 70%, about 40% to about 70%, or about about 100%, about 20% to about 100%, about 30% to about 50% to about 70%. 100%, about 40% to about 100%, about 50% to about 100%, 0281 A pharmaceutical composition according to any one about 60% to about 100%, about 70% to about 100%, about of claims 64 and 86-88, wherein the dose of the therapeutic 80% to about 100%, about 10% to about 90%, about 20% to compound to treat the reduction in appetite is in the range of about 90%, about 30% to about 90%, about 40% to about at least 0.001 mg/kg/day, at least 0.01 mg/kg/day, at least 0.1 90%, about 50% to about 90%, about 60% to about 90%, mg/kg/day, at least 1.0 mg/kg/day, at least 5.0 mg/kg/day, at about 70% to about 90%, about 10% to about 80%, about 20% least 10 mg/kg/day, at least 15 mg/kg/day, at least 20 mg/kg/ to about 80%, about 30% to about 80%, about 40% to about day, at least 25 mg/kg/day, at least 30 mg/kg/day, at least 35 80%, about 50% to about 80%, or about 60% to about 80%, mg/kg/day, at least 40 mg/kg/day, at least 45 mg/kg/day, or at about 10% to about 70%, about 20% to about 70%, about 30% least 50 mg/kg/day. to about 70%, about 40% to about 70%, or about 50% to about 0282. A pharmaceutical composition according to any one 70%. of claims 64 and 86-88, wherein the dose of the therapeutic 0277. A pharmaceutical composition according to any one compound to treat reduction in appetite is in the range of of claims 64 and 86-88, wherein the treatment for appetite about 0.001 mg/kg/day to about 100 mg/kg/day. reduction results in an increase in height by at least 10%, at 0283 A pharmaceutical composition according to any one least 15%, at least 20%, at least 25%, at least 30%, at least of claims 64 and 86-88, wherein the dose of the therapeutic 35%, at least 40%, at least 45%, at least 50%, at least 55%, at compound to treat the reduction in appetite is in the range of least 60%, at least 65%, at least 70%, at least 75%, at least about 0.001 mg/kg/day to about 10 mg/kg/day, about 0.001 80%, at least 85%, at least 90% or at least 95%. mg/kg/day to about 15 mg/kg/day, about 0.001 mg/kg/day to 0278 A pharmaceutical composition according to any one about 20 mg/kg/day, about 0.001 mg/kg/day to about 25 of claims 64 and 86-88, wherein the treatment for appetite mg/kg/day, about 0.001 mg/kg/day to about 30 mg/kg/day, reduction results in an increase in weight by at least 0.5 about 0.001 mg/kg/day to about 35 mg/kg/day, about 0.001 pounds, at least 1 pound, at least 1.5 pounds, at least 2 pounds, mg/kg/day to about 40 mg/kg/day, about 0.001 mg/kg/day to at least 2.5 pounds, at least 3 pounds, at least 3.5 pounds, at about 45 mg/kg/day, about 0.001 mg/kg/day to about 50 least 4 pounds, at least 4.5 pounds, at least 5 pounds, at least mg/kg/day, about 0.001 mg/kg/day to about 75 mg/kg/day, or 5.5 pounds, at least 6 pounds, at least 6.5 pounds, at least 7 about 0.001 mg/kg/day to about 100 mg/kg/day. pounds, at least 7.5 pounds, at least 8 pounds, at least 8.5 0284. A pharmaceutical composition according to any one pounds, at least 9 pounds, at least 9.5 pounds, at least 10 of claims 64 and 86-88, wherein the therapeutic compound to pounds, at least 10.5 pounds, at least 11 pounds, at least 11.5 treat the reduction in appetite is administered to an individual pounds, at least 12 pounds, at least 12.5 pounds, at least 13 topical, Sublingual, rectal, vaginal, trancutaneous, oral, pounds, at least 13.5 pounds, at least 14 pounds, at least 14.5 inhaled, intranasal, Subcutaneous, intravenous, enteral or pounds, at least 15 pounds, at least 20 pounds, at least 25 parenteral. pounds, at least 30 pounds, at least 50 pounds. In another 0285) A pharmaceutical composition according to any one embodiment, a therapeutic compound disclosed herein for of claims 64 and 86-102, wherein the therapeutic compound the treatment of appetite reduction results in an increase in to treat the reduction in appetite is administered as a liquid, a weight by, e.g., from 0.5 pounds to 50 pounds, from 0.5 Solid, a semi-solid or an aerosol. pounds to 30 pounds, from 0.5 pounds to 25 pounds, from 0.5 0286 A pharmaceutical composition according to any one pounds to 20 pounds, from 0.5 pounds to 15 pounds, from 0.5 of claims 64 and 86-102, wherein the therapeutic compound pounds to ten pounds, from 0.5 pounds to 7.5 pounds, from is formulated as a tablet, lozenge, orally dissolved strip, cap 0.5 pounds to 5 pounds, from 1 pound to 15 pounds, from 1 Sule, syrup, oral Suspension, emulsion, granule, sprinkle or pound to 10 pounds, from 1 pound to 7.5 pounds, form 1 pellet. pound to 5 pounds, from 2 pounds to ten pounds, from 2 0287. A pharmaceutical composition according to any one pounds to 7.5 pounds. of claims 64 and 86-103, wherein the therapeutic compound 0279 A pharmaceutical composition according to any one is a long acting, Sustained release, extended release, immedi of claims 64 and 86-88, wherein the treatment for appetite ate release, slow release, or controlled release therapeutic reduction increases the attentiveness of a patient by at least compound. 10%, at least 15%, at least 20%, at least 25%, at least 30%, at 0288 A pharmaceutical composition according to any one least 35%, at least 40%, at least 45%, at least 50%, at least of claims 64 and 86-103, wherein the therapeutic compound 55%, at least 60%, at least 65%, at least 70%, at least 75%, at is released over a period of about 3 days after administration, least 80%, at least 85%, at least 90% or at least 95%. about 7 days after administration, about 10 days after admin 0280 A pharmaceutical composition according to any one istration, about 15 days after administration, about 20 days of claims 64 and 86-88, wherein the treatment for appetite after administration, about 25 days after administration, reduction increases the attentiveness of a patient by about about 30 days after administration, about 45 days after admin 10% to about 100%, about 20% to about 100%, about 30% to istration, about 60 days after administration, about 75 days about 100%, about 40% to about 100%, about 50% to about after administration, or about 90 days after administration. 100%, about 60% to about 100%, about 70% to about 100%, 0289. A pharmaceutical composition according to any one about 80% to about 100%, about 10% to about 90%, about of claims 64 and 86-103, wherein the therapeutic compound 20% to about 90%, about 30% to about 90%, about 40% to is released over a period of at least 3 days after administration, about 90%, about 50% to about 90%, about 60% to about at least 7 days after administration, at least 10 days after 90%, about 70% to about 90%, about 10% to about 80%, administration, at least 15 days after administration, at least about 20% to about 80%, about 30% to about 80%, about 40% 20 days after administration, at least 25 days after adminis US 2014/010O249 A1 Apr. 10, 2014 39 tration, at least 30 days after administration, at least 45 days about 60% to about 80%, about 10% to about 70%, about 20% after administration, at least 60 days after administration, at to about 70%, about 30% to about 70%, about 40% to about least 75 days after administration, or at least 90 days after 70%, or about 50% to about 70%. administration 0302 A pharmaceutical composition according to claim 0290 A pharmaceutical composition according to any one 64, wherein the increase in attentiveness by an individual is of claims 64 and 86-103, wherein the therapeutic compound measured on by CGI-I. is released over a period of about 1 day after administration, 0303 A pharmaceutical composition according to claim about 2 days after administration, about 3 days after admin 120, wherein the CGI-I scale is from 1 to 7. istration, about 4 days after administration, about 5 days after administration, about 6 days after administration or about 7 0304. A pharmaceutical composition according to claim days or more after administration. 121, wherein a measurement of 7 identifies an individual that 0291. A pharmaceutical composition according to any one is very much worse, 6 identifies an individual that is much of claims 64 and 86-108, wherein the pharmaceutical com worse, 5 identifies an individual that is minimally worse, 4 position includes pharmaceutical acceptable components. identifies an individual that is no change, 3 identifies an 0292 A pharmaceutical composition according to claim individual that is minimally improved, 2 identifies an indi 109, wherein the pharmaceutical acceptable components is vidual that is much improved and a measurement of 1 iden selected from the group consisting of a salt, a Surfactant, an tifies an individual that is very much improved. amino acid, a stabilizer or a buffer. 0305. A pharmaceutical composition according to any of 0293 A pharmaceutical composition according to claim claim 64 or 120-122, wherein the increase in attentiveness 110, wherein the salt is selected from the group consisting of measured CGI-I is by a reduction in the score by 1 or more as citric acid, sodium chloride, potassium chloride, Sodium Sul compared to a patient not receiving a therapeutic compound fate, potassium nitrate, sodium phosphate monobasic or to treat a reduction in appetite. Sodium phosphate dibasic. 0306 A pharmaceutical composition according to any of 0294. A pharmaceutical composition according to claim claim 64 or 120-122, wherein the patient's CGI-S score is 110, wherein the surfactant is a polysorbate. reduced by at least 10%, at least 15%, at least 20%, at least 0295) A pharmaceutical composition according to claim 25%, at least 30%, at least 35%, at least 40%, at least 45%, at 112, wherein the polysorbate is selected from the group con least 50%, at least 55%, at least 60%, at least 65%, at least sisting of Tween 20, Tween 80, F68, F88, sorbitain esters, 70%, at least 75%, at least 80%, at least 85%, at least 90% or lipids, fatty acids or fatty esters. at least 95%. 0296. A pharmaceutical composition according to claim 0307. A pharmaceutical composition according to any of 64, wherein the increase in attentiveness by an individual is claim 64 or 120-122, wherein the patient's CGI-S score is measured by CGI-S. reduced by about 10% to about 100%, about 20% to about 0297. A pharmaceutical composition according to claim 100%, about 30% to about 100%, about 40% to about 100%, 114, wherein the CGI-S scale is from 1 to 7. about 50% to about 100%, about 60% to about 100%, about 0298. A pharmaceutical composition according to claim 70% to about 100%, about 80% to about 100%, about 10% to 115, wherein a measurement of 7 identifies an individual that about 90%, about 20% to about 90%, about 30% to about is extremely ill, 6 identifies an individual that is severely ill, 5 90%, about 40% to about 90%, about 50% to about 90%, identifies an individual that is markedly ill, 4 identifies an about 60% to about 90%, about 70% to about 90%, about 10% individual that is moderately ill, 3 identifies an individual that to about 80%, about 20% to about 80%, about 30% to about is mildly ill, 2 identifies an individual that is borderline ill and 80%, about 40% to about 80%, about 50% to about 80%, or a measurement of 1 identifies an individual that is normal. about 60% to about 80%, about 10% to about 70%, about 20% 0299. A pharmaceutical composition according to any of to about 70%, about 30% to about 70%, about 40% to about claim 64 or 114-116, wherein the increase in attentiveness 70%, or about 50% to about 70%. measured by CGI-S is by a reduction in the score by 1 or more 0308) A pharmaceutical composition according to claim as compared to a patient not receiving a therapeutic com 64, wherein the increase in attentiveness by an individual is pound to treat a appetite reduction. measured by the pacademic performance rating scale, ADD 0300. A pharmaceutical composition according to any of evaluation scale-3rd edition (ADDES-3), ADHD rating claim 64 or 114-116, wherein the patients CGI-S score is scale-IV (ADHD-RS-IV), youth self report (broadband reduced by at least 10%, at least 15%, at least 20%, at least instrument), Conners parent rating scale-revised (CPRS-R), 25%, at least 30%, at least 35%, at least 40%, at least 45%, at Conners teacher rating scale-revised (CTRS-R), Conners 3 least 50%, at least 55%, at least 60%, at least 65%, at least self-reporting scale (Conner 3-SR: ages 8-18 y), home situa 70%, at least 75%, at least 80%, at least 85%, at least 90% or tions questionnaire-revised, inattention/overactivity with at least 95%. aggression (IOWA) Conners teacher's rating scale, Swanson 0301 A pharmaceutical composition according to any of Nolan and Pelham IV scale (SNAP-IV), Swanson Kotkin claim 64 or 114-116, wherein the patients CGI-S score is Agler M-Flynn and Pelham (SKAMP), Vanderbilt ADHD reduced by about 10% to about 100%, about 20% to about diagnostic parent rating scale (VADPRS), Vanderbilt ADHD 100%, about 30% to about 100%, about 40% to about 100%, diagnostic teacher rating scale (VADTRS), behavior assess about 50% to about 100%, about 60% to about 100%, about ment system for children-2nd edition (BASC-2) or the Con 70% to about 100%, about 80% to about 100%, about 10% to ners rating scale long version. about 90%, about 20% to about 90%, about 30% to about 0309. A method of treating an individual with a disorder 90%, about 40% to about 90%, about 50% to about 90%, associated with a psychological and/or neurological disorder, about 60% to about 90%, about 70% to about 90%, about 10% the method comprises the step of administering to an indi to about 80%, about 20% to about 80%, about 30% to about vidual in need thereof a pharmaceutical composition which 80%, about 40% to about 80%, about 50% to about 80%, or comprises a therapeutic compound consisting of an amphet US 2014/010O249 A1 Apr. 10, 2014 40 amine and/or a methylphenidate and a therapeutic compound 10% to about 90%, about 20% to about 90%, about 30% to to treat a reduction in appetite, thereby treating the individual. about 90%, about 40% to about 90%, about 50% to about 0310. The method of claim 127, wherein, the psychologi 90%, about 60% to about 90%, about 70% to about 90%, cal and/or neurological disorder is selected from the group of about 10% to about 80%, about 20% to about 80%, about 30% migrane, anti-serotonergic side effects, narcolepsy, excessive to about 80%, about 40% to about 80%, about 50% to about sleepiness associated with shift work, obstructive sleep apnea 80%, or about 60% to about 80%, about 10% to about 70%, as an adjunct to continuous positive airways pressure about 20% to about 70%, about 30% to about 70%, about 40% (“CPAP), exogenous obesity, disruptive behaviour disorder to about 70%, or about 50% to about 70%. including oppositional defiant disorder (“ODD) and conduct 0316 The method according to any one of claims 127 disorder (“CD), obesity, depression (including, without 130, wherein the dose of the therapeutic compound to treat limitation, augmentation of antidepressants in treating refrac the attention deficit disorder is in the range of at least 0.001 tory depression and cancer-related depression), neural insult, mg/kg/day, at least 0.01 mg/kg/day, at least 0.1 mg/kg/day, at fatigue (including, without limitation, disease-related fatigue least 1.0 mg/kg/day, at least 5.0 mg/kg/day, at least 10 mg/kg/ in patients with HIV, advanced cancer, multiple Sclerosis, day, at least 15 mg/kg/day, at least 20 mg/kg/day, at least 25 myotonic dystrophy, depression, fibromyalgia and hepatitis mg/kg/day, at least 30 mg/kg/day, at least 35 mg/kg/day, at C), lethargy, binge eating disorder, Schizophrenia, sleep cycle least 40 mg/kg/day, at least 45 mg/kg/day, or at least 50 disorder, cocaine addiction, Parkinson's Disease, combat and mg/kg/day. non-combat related PTSD and/or tic. 0317. The method according to any one of claims 127 0311. The method of claim 127, wherein the therapeutic 130, wherein the dose of the therapeutic compound to treat compound to treat phychological or neurological disorder is the attention deficit disorder is in the range of about 0.001 an amphetamine or methylphenidate. mg/kg/day to about 100 mg/kg/day. 0312 The method of claim 129, wherein the amphetamine 0318. The method according to any one of claims 127 or methylphenidate is selected from the group consisting of 130, wherein the dose of the therapeutic compound to treat OROS methylphenidate (Concerta), dextroamphetamine the attention deficit disorder is in the range of about 0.001 immediate/sustained release (Adderall/Adderall XR), dexm mg/kg/day to about 10 mg/kg/day, about 0.001 mg/kg/day to ethylphenidate (Focalin), Focalin XR, Metadate CD, Meta about 15 mg/kg/day, about 0.001 mg/kg/day to about 20 date ER, NWP09, Dexedrine, dextroamphetamine mg/kg/day, about 0.001 mg/kg/day to about 25 mg/kg/day, (Dexedrine), Dexedrine Spanisules, Methylin ER (Ritalin about 0.001 mg/kg/day to about 30 mg/kg/day, about 0.001 SR), methylphenidate (Ritalin), and methylphenidate CR, mg/kg/day to about 35 mg/kg/day, about 0.001 mg/kg/day to Ritalin, Ritalin LA, SD-483, SPD-503, Ritalin SR, Intuniv about 40 mg/kg/day, about 0.001 mg/kg/day to about 45 ER, Intuniv, Methylin, Daytrana, Equasym, Dixirit, Kapvay, mg/kg/day, about 0.001 mg/kg/day to about 50 mg/kg/day, Daytrana Patch, Methylin chewable, Methylin liquid, Dex about 0.001 mg/kg/day to about 75 mg/kg/day, or about 0.001 trostat, Strattera, Tenex, Catapres, Catapres TTS patch, mg/kg/day to about 100 mg/kg/day. Prozac, Serefam, Zoloft, Luvox, Paxil, Paxil CR, Pexeva, 0319. The method according to any of claims 127-136, Celexa, Lexapro, Tofranil, Norpamin, Elavil, Pamelor, Sine wherein the therapeutic compound to treat the attention defi quan, Anafranil, Wellbutrin, Wellbutrin SR, Wellbutrin XL, cit disorder is administered to an individual topical, Sublin Effexor, Effexor XR, Remeron, Cymbalta, Nardil, Parnate, gual, rectal, vaginal, trancutaneous, oral, inhaled, intranasal, Emsam patch, Haldol, Orap, Prolixin, Mellaril, Thorazine, Subcutaneous, intravenous, enteral or parenteral. Stelazine, Moban, Loxitane, Risperdal, Zyprexa, Seroquel, 0320. The method according to any of claims 127-136, Geodon, Abilify, Clozaril, Xanax, Xanax XR, Klonopin, Ati wherein the therapeutic compound to treat the attention defi van, Buspar, Ambien CR, Ambien, Lunesta, Sonata, RoZ cit disorder is administered as a liquid, a solid, a semi-solid or erem, Lithiu, Lithobid, Eskalith, Depakote, Tegretol, Carba an aerosol. trol, Trileptal, Lamictal, Topamax, Neurontin and the 0321. The method according to any of claims 127-130, therapeutic compounds identified in Table 1. wherein the therapeutic compound is formulated as a tablet, 0313 The method according to any one of claims 127 lozenge, orally dissolved strip, capsule, syrup, oral Suspen 130, wherein the symptoms associated with attention deficit Sion, emulsion, granule, sprinkle or pellet. disorder is reduced by at least 10%, at least 15%, at least 20%, 0322 The method of claim 127, wherein the therapeutic at least 25%, at least 30%, at least 35%, at least 40%, at least compound is a long acting, Sustained release, extended 45%, at least 50%, at least 55%, at least 60%, at least 65%, at release, immediate release, slow release, or controlled release least 70%, at least 75%, at least 80%, at least 85%, at least therapeutic compound. 90%, or at least 95%. 0323. The method of claim 140, wherein the therapeutic 0314. The method according to any one of claims 127 compound is released over a period of about 3 days after 130, wherein the severity associated with attention deficit administration, about 7 days after administration, about 10 disorder is reduced by at least 10%, at least 15%, at least 20%, days after administration, about 15 days after administration, at least 25%, at least 30%, at least 35%, at least 40%, at least about 20 days after administration, about 25 days after admin 45%, at least 50%, at least 55%, at least 60%, at least 65%, at istration, about 30 days after administration, about 45 days least 70%, at least 75%, at least 80%, at least 85%, at least after administration, about 60 days after administration, 90%, or at least 95%. about 75 days after administration, or about 90 days after 0315. The method according to any one of claims 127 administration. 130, wherein the symptoms associated with attention deficit 0324. The method of claim 140, wherein the therapeutic disorder is reduced by about 10% to about 100%, about 20% compound is released over a period of at least 3 days after to about 100%, about 30% to about 100%, about 40% to about administration, at least 7 days after administration, at least 10 100%, about 50% to about 100%, about 60% to about 100%, days after administration, at least 15 days after administra about 70% to about 100%, about 80% to about 100%, about tion, at least 20 days after administration, at least 25 days after US 2014/010O249 A1 Apr. 10, 2014

administration, at least 30 days after administration, at least stance, anticatabolic/anabolic transforming agent MT-102, 45 days after administration, at least 60 days after adminis celecoxib, testosterone, vitamin D, OHR/AVR118, soluble tration, at least 75 days after administration, or at least 90 days version of the ActRIIB receptor, 5-HT antagonists, Cox-2 after administration inhibitor, thalidomide, omega-3 fatty acids, anticyclooxyge 0325 The method of claim 140, wherein the therapeutic nase-2 drugs and megestrol acetate (Megace). In addition to compound is released over a period of about 1 day after these prescription drugs, fish oil (eicosapentaenoic acid or administration, about 2 days after administration, about 3 EPA), EATMOR, other vitamins and natural or artificial days after administration, about 4 days after administration, appetite stimulants. about 5 days after administration, about 6 days after admin 0333. The method of claim 149, wherein the orexigenic istration or about 7 days or more after administration. drug is cyproheptadine hydrochloride. 0326. The method according to any of claim 127, wherein 0334. The method according to any one of claim 127 or the pharmaceutical composition includes pharmaceutical 149-151, wherein the symptoms associated with appetite acceptable components. reduction is reduced by at least 10%, at least 15%, at least 0327. The method of claim 144, wherein the pharmaceu 20%, at least 25%, at least 30%, at least 35%, at least 40%, at tical acceptable components is selected from the group con least 45%, at least 50%, at least 55%, at least 60%, at least sisting of a salt, a Surfactant, an amino acid, a stabilizer or a 65%, at least 70%, at least 75%, at least 80%, at least 85%, at buffer. least 90%, or at least 95%. 0328. The method of claim 145, wherein the salt is 0335 The method according to any one of claim 127 or selected from the group consisting of citric acid, sodium 149-151, wherein the symptoms associated with appetite chloride, potassium chloride, Sodium sulfate, potassium reduction is reduced by about 10% to about 100%, about 20% nitrate, Sodium phosphate monobasic or Sodium phosphate to about 100%, about 30% to about 100%, about 40% to about dibasic. 100%, about 50% to about 100%, about 60% to about 100%, 0329. The method of claim 144, wherein the surfactant is about 70% to about 100%, about 80% to about 100%, about a polysorbate. 10% to about 90%, about 20% to about 90%, about 30% to 0330. The method of claim 147, wherein the polysorbateis about 90%, about 40% to about 90%, about 50% to about selected from the group consisting of Tween 20, Tween 80, 90%, about 60% to about 90%, about 70% to about 90%, F68, F88, sorbitain esters, lipids, fatty acids or fatty esters. about 10% to about 80%, about 20% to about 80%, about 30% 0331. The method of claim 127, wherein the therapeutic to about 80%, about 40% to about 80%, about 50% to about compound to treat an appetite reduction is an orexigenic drug. 80%, or about 60% to about 80%, about 10% to about 70%, 0332 The method of claim 149, wherein the orexigenic about 20% to about 70%, about 30% to about 70%, about 40% drug is selected from the group of alcohol, GHB, and other to about 70%, or about 50% to about 70%. sedatives such as Some benzodiazepine and nonbenzodiaz 0336. The method according to any one of claim 127 or epine tranquilizers and sleeping pills, anti-depressants (some 149-151, wherein the symptoms associated with reduction in SSRIs, Mianserin, etc.), 5-HT, receptor antagonists/inverse the severity of appetite reduction is reduced by at least 10%, agonists (e.g., mirtazapine, mianserin, olanzapine, quetiap at least 15%, at least 20%, at least 25%, at least 30%, at least ine, risperidone, amitriptyline, imipramine, cyproheptadine, 35%, at least 40%, at least 45%, at least 50%, at least 55%, at etc.), H receptor antagonists/inverse agonists (e.g., bucliz least 60%, at least 65%, at least 70%, at least 75%, at least ine, mirtazapine, mianserin, olanzapine, quetiapine, n-3 fatty 80%, at least 85%, at least 90% or at least 95%. acids, amitriptyline, chlorpheniramine maleate, etc.), D/D 0337 The method according to any one of claim 127 or receptor antagonists (e.g., haloperidol, chlorpromazine, olan 149-151, wherein the severity associated with reduction in Zapine, risperidone, quetiapine, etc.), Marinol, Megace, appetite is reduced by about 10% to about 100%, about 20% Megace ES, C-adrenergic receptor antagonists (such as dox to about 100%, about 30% to about 100%, about 40% to about aZosin, carvedilol, propanolol, colonidine), Serefam, C2-adr 100%, about 50% to about 100%, about 60% to about 100%, energic receptor agonists (e.g., clonidine, guanfacine, etc.). about 70% to about 100%, about 80% to about 100%, about Some beta blockers such as propanolol, natural or synthetic 10% to about 90%, about 20% to about 90%, about 30% to CB, receptor agonists (e.g., THC or dronabinol (found in about 90%, about 40% to about 90%, about 50% to about Cannabis), tetrahydrocannibinol, diphenydramine, promet 90%, about 60% to about 90%, about 70% to about 90%, hazine, B vitamin supplements, nabilone, JWH-018 etc.), about 10% to about 80%, about 20% to about 80%, about 30% Corticosteroids (e.g. prednisone or dexamethasone), Sodium to about 80%, about 40% to about 80%, about 50% to about valproate (Depakote), Megestrol, Pregabalin, Sulfonylurea 80%, or about 60% to about 80%, about 10% to about 70%, antidiabetic drugs such as glibenclamide and chlorpropam about 20% to about 70%, about 30% to about 70%, about 40% ide, Steroids (including, without limitation, boldenone, to about 70%, or about 50% to about 70%. oxymetholone, dexamethasone, or methandrostenolone, 0338. The method according to any one of claim 127 or prednisone, hydrocortisone, Oxandrolone, nandrolone, test 149-151, wherein the treatment for appetite reduction results osterone), some kappa opioid receptoragonists such as tiflua in an increase in weight by at least 10%, at least 15%, at least dom, hormones such as mederoxyprogesteronemirtazapine 20%, at least 25%, at least 30%, at least 35%, at least 40%, at (Remeron), a tetracyclic antidepressant, cyproheptadine (Pe least 45%, at least 50%, at least 55%, at least 60%, at least riactin), an antihistamine; nandrolone, oxymetholone, and 65%, at least 70%, at least 75%, at least 80%, at least 85%, at oxandrolone (Anadrol-50. Durabolin, Hybolin, anti-IL6 anti least 90% or at least 95%. body, selective androgen receptor modulator (“SARM), 0339. The method according to any one of claim 127 or Oxandrin, and other brand names), VT-122 (a coadministra 149-151, wherein the treatment for appetite reduction results tion of propranolol and etodolac), type 4 melanocortin recep in an increase in weight by about 10% to about 100%, about tor antagonis, IL6 antagonist, synthetic ghrelin, myostatin 20% to about 100%, about 30% to about 100%, about 40% to decoy receptor, fast skeletal muscle troponin-activating Sub about 100%, about 50% to about 100%, about 60% to about US 2014/010O249 A1 Apr. 10, 2014 42

100%, about 70% to about 100%, about 80% to about 100%, mg/kg/day, at least 0.01 mg/kg/day, at least 0.1 mg/kg/day, at about 10% to about 90%, about 20% to about 90%, about 30% least 1.0 mg/kg/day, at least 5.0 mg/kg/day, at least 10 mg/kg/ to about 90%, about 40% to about 90%, about 50% to about day, at least 15 mg/kg/day, at least 20 mg/kg/day, at least 25 90%, about 60% to about 90%, about 70% to about 90%, mg/kg/day, at least 30 mg/kg/day, at least 35 mg/kg/day, at about 10% to about 80%, about 20% to about 80%, about 30% least 40 mg/kg/day, at least 45 mg/kg/day, or at least 50 to about 80%, about 40% to about 80%, about 50% to about mg/kg/day. 80%, or about 60% to about 80%, about 10% to about 70%, 0345 The method according to any one of claim 127 or about 20% to about 70%, about 30% to about 70%, about 40% 149-161, wherein the dose of the therapeutic compound to to about 70%, or about 50% to about 70%. treat reduction in appetite is in the range of about 0.001 0340. The method according to any one of claim 127 or mg/kg/day to about 100 mg/kg/day. 149-151, wherein the treatment for appetite reduction results 0346. The method according to any one of claim 127 or in an increase in height by at least 10%, at least 15%, at least 149-161, wherein the dose of the therapeutic compound to 20%, at least 25%, at least 30%, at least 35%, at least 40%, at treat the reduction in appetite is in the range of about 0.001 least 45%, at least 50%, at least 55%, at least 60%, at least mg/kg/day to about 10 mg/kg/day, about 0.001 mg/kg/day to 65%, at least 70%, at least 75%, at least 80%, at least 85%, at about 15 mg/kg/day, about 0.001 mg/kg/day to about 20 least 90% or at least 95%. mg/kg/day, about 0.001 mg/kg/day to about 25 mg/kg/day, 0341 The method according to any one of claim 127 or about 0.001 mg/kg/day to about 30 mg/kg/day, about 0.001 149-151, wherein the treatment for appetite reduction results mg/kg/day to about 35 mg/kg/day, about 0.001 mg/kg/day to in an increase in weight by at least 0.5 pounds, at least 1 about 40 mg/kg/day, about 0.001 mg/kg/day to about 45 pound, at least 1.5 pounds, at least 2 pounds, at least 2.5 mg/kg/day, about 0.001 mg/kg/day to about 50 mg/kg/day, pounds, at least 3 pounds, at least 3.5 pounds, at least 4 about 0.001 mg/kg/day to about 75 mg/kg/day, or about 0.001 pounds, at least 4.5 pounds, at least 5 pounds, at least 5.5 mg/kg/day to about 100 mg/kg/day. pounds, at least 6 pounds, at least 6.5 pounds, at least 7 0347 The method according to any of claim 127 or 149 pounds, at least 7.5 pounds, at least 8 pounds, at least 8.5 161, wherein the therapeutic compound to treat the reduction pounds, at least 9 pounds, at least 9.5 pounds, at least 10 in appetite is administered to an individual topical. Sublin pounds, at least 10.5 pounds, at least 11 pounds, at least 11.5 gual, rectal, vaginal, trancutaneous, oral, inhaled, intranasal, pounds, at least 12 pounds, at least 12.5 pounds, at least 13 Subcutaneous, intravenous, enteral or parenteral. pounds, at least 13.5 pounds, at least 14 pounds, at least 14.5 0348. The method according to any of claim 127 or 149 pounds, at least 15 pounds, at least 20 pounds, at least 25 161, wherein the therapeutic compound to treat the reduction pounds, at least 30 pounds, at least 50 pounds. In another in appetite is administered as a liquid, a solid, a semi-solid or embodiment, a therapeutic compound disclosed herein for an aerosol. the treatment of appetite reduction results in an increase in 0349 The method according to any of claim 127 or 149 weight by, e.g., from 0.5 pounds to 50 pounds, from 0.5 161, wherein the therapeutic compound is formulated as a pounds to 30 pounds, from 0.5 pounds to 25 pounds, from 0.5 tablet, lozenge, orally dissolved strip, capsule, syrup, oral pounds to 20 pounds, from 0.5 pounds to 15 pounds, from 0.5 Suspension, emulsion, granule, sprinkle or pellet. pounds to ten pounds, from 0.5 pounds to 7.5 pounds, from 0350. The method according to any of claim 127 or 149 0.5 pounds to 5 pounds, from 1 pound to 15 pounds, from 1 161, wherein the therapeutic compound is a long acting, pound to 10 pounds, from 1 pound to 7.5 pounds, form 1 Sustained release, extended release, immediate release, slow pound to 5 pounds, from 2 pounds to ten pounds, from 2 release, or controlled release therapeutic compound. pounds to 7.5 pounds. 0351. The method according to any of claim 1 or 23-35, 0342. The method according to any of claim 127 or 149 wherein the therapeutic compound is released over a period of 151, wherein the treatment for appetite reduction increases about 3 days after administration, about 7 days after admin the attentiveness of a patient by at least 10%, at least 15%, at istration, about 10 days after administration, about 15 days least 20%, at least 25%, at least 30%, at least 35%, at least after administration, about 20 days after administration, 40%, at least 45%, at least 50%, at least 55%, at least 60%, at about 25 days after administration, about 30 days after admin least 65%, at least 70%, at least 75%, at least 80%, at least istration, about 45 days after administration, about 60 days 85%, at least 90% or at least 95%. after administration, about 75 days after administration, or 0343. The method according to any of claim 127 or 149 about 90 days after administration. 151, wherein the treatment for appetite reduction increases 0352. The method according to any of claim 127 or 149 the attentiveness of a patient by about 10% to about 100%, 161, wherein the therapeutic compound is released over a about 20% to about 100%, about 30% to about 100%, about period of at least 3 days after administration, at least 7 days 40% to about 100%, about 50% to about 100%, about 60% to after administration, at least 10 days after administration, at about 100%, about 70% to about 100%, about 80% to about least 15 days after administration, at least 20 days after 100%, about 10% to about 90%, about 20% to about 90%, administration, at least 25 days after administration, at least about 30% to about 90%, about 40% to about 90%, about 50% 30 days after administration, at least 45 days after adminis to about 90%, about 60% to about 90%, about 70% to about tration, at least 60 days after administration, at least 75 days 90%, about 10% to about 80%, about 20% to about 80%, after administration, or at least 90 days after administration about 30% to about 80%, about 40% to about 80%, about 50% 0353. The method according to any of claim 127 or 149 to about 80%, or about 60% to about 80%, about 10% to about 161, wherein the therapeutic compound is released over a 70%, about 20% to about 70%, about 30% to about 70%, period of about 1 day after administration, about 2 days after about 40% to about 70%, or about 50% to about 70%. administration, about 3 days after administration, about 4 0344) The method according to any one of claim 127 or days after administration, about 5 days after administration, 149-161, wherein the dose of the therapeutic compound to about 6 days after administration or about 7 days or more after treat the reduction in appetite is in the range of at least 0.001 administration. US 2014/010O249 A1 Apr. 10, 2014

0354. The method according to any of claim 127 or 149 CR, Ambien, Lunesta, Sonata, Rozerem, Lithiu, Lithobid, 161, wherein the pharmaceutical composition includes phar Eskalith, Depakote, Tegretol, Carbatrol, Trileptal, Lamictal, maceutical acceptable components. Topamax, Neurontin and the therapeutic compounds identi 0355 The method of claim 172, wherein the pharmaceu fied in Table 1. tical acceptable components is selected from the group con 0363 A pharmaceutical composition according to any one sisting of a salt, a Surfactant, an amino acid, a stabilizer or a of claims 177-180, wherein the symptoms associated with buffer. attention deficit disorder is reduced by at least 10%, at least 0356. The method of claim 173, wherein the salt is 15%, at least 20%, at least 25%, at least 30%, at least 35%, at selected from the group consisting of citric acid, sodium least 40%, at least 45%, at least 50%, at least 55%, at least chloride, potassium chloride, Sodium sulfate, potassium 60%, at least 65%, at least 70%, at least 75%, at least 80%, at nitrate, Sodium phosphate monobasic or Sodium phosphate least 85%, at least 90%, or at least 95%. dibasic. 0364. A pharmaceutical composition according to any one 0357 The method of claim 172, wherein the surfactant is of claims 177-180, wherein the severity associated with atten a polysorbate. tion deficit disorder is reduced by at least 10%, at least 15%, 0358. The method of claim 175, wherein the polysorbateis at least 20%, at least 25%, at least 30%, at least 35%, at least selected from the group consisting of Tween 20, Tween 80, 40%, at least 45%, at least 50%, at least 55%, at least 60%, at F68, F88, sorbitain esters, lipids, fatty acids or fatty esters. least 65%, at least 70%, at least 75%, at least 80%, at least 0359 A pharmaceutical composition for the treatment of 85%, at least 90%, or at least 95%. an individual with a disorder associated with a psychological 0365. A pharmaceutical composition according to any one and/or neurological disorder, which comprises a therapeutic of claims 177-180, wherein the symptoms associated with compound consisting of an amphetamine and/or a meth attention deficit disorder is reduced by about 10% to about ylphenidate and a therapeutic compound to treat a reduction 100%, about 20% to about 100%, about 30% to about 100%, in appetite, thereby treating the individual. about 40% to about 100%, about 50% to about 100%, about 0360. The pharmaceutical composition of claim 177, 60% to about 100%, about 70% to about 100%, about 80% to wherein, the psychological and/or neurological disorder is about 100%, about 10% to about 90%, about 20% to about selected from the group of migrane, anti-serotonergic side 90%, about 30% to about 90%, about 40% to about 90%, effects, narcolepsy, excessive sleepiness associated with shift about 50% to about 90%, about 60% to about 90%, about 70% work, obstructive sleep apnea as an adjunct to continuous to about 90%, about 10% to about 80%, about 20% to about positive airways pressure ("CPAP), exogenous obesity, dis 80%, about 30% to about 80%, about 40% to about 80%, ruptive behaviour disorder including oppositional defiant dis about 50% to about 80%, or about 60% to about 80%, about order (“ODD) and conduct disorder (“CD), obesity, depres 10% to about 70%, about 20% to about 70%, about 30% to sion (including, without limitation, augmentation of about 70%, about 40% to about 70%, or about 50% to about antidepressants in treating refractory depression and cancer 70%. related depression), neural insult, fatigue (including, without 0366 A pharmaceutical composition according to any one limitation, disease-related fatigue in patients with HIV. of claims 177-180, wherein the dose of the therapeutic com advanced cancer, multiple Sclerosis, myotonic dystrophy, pound to treat the attention deficit disorder is in the range of depression, fibromyalgia and hepatitis C), lethargy, binge at least 0.001 mg/kg/day, at least 0.01 mg/kg/day, at least 0.1 eating disorder, Schizophrenia, sleep cycle disorder, cocaine mg/kg/day, at least 1.0 mg/kg/day, at least 5.0 mg/kg/day, at addiction, Parkinson's Disease, combat and non-combat least 10 mg/kg/day, at least 15 mg/kg/day, at least 20 mg/kg/ related PTSD and/or tic. day, at least 25 mg/kg/day, at least 30 mg/kg/day, at least 35 0361. A pharmaceutical composition of claim 177, mg/kg/day, at least 40 mg/kg/day, at least 45 mg/kg/day, or at wherein the therapeutic compound administered for the treat least 50 mg/kg/day. ment of a psychological or neurological disorder is an 0367 A pharmaceutical composition according to any one amphetamine or a methylphenidate. of claims 177-180, wherein the dose of the therapeutic com 0362. A pharmaceutical composition of claim 179, pound to treat the attention deficit disorder is in the range of wherein the amphetamine or methylphenidate is selected about 0.001 mg/kg/day to about 100 mg/kg/day. from the group consisting of OROS methylphenidate (Con 0368. A pharmaceutical composition according to any one certa), dextroamphetamine immediate/sustained release of claims 177-180, wherein the dose of the therapeutic com (Adderall/Adderall XR), dexmethylphenidate (Focalin), pound to treat the attention deficit disorder is in the range of Focalin XR, Metadate CD, Metadate ER, NWP09, about 0.001 mg/kg/day to about 10 mg/kg/day, about 0.001 Dexedrine, dextroamphetamine (Dexedrine), Dexedrine mg/kg/day to about 15 mg/kg/day, about 0.001 mg/kg/day to SpanSules, Methylin ER (Ritalin SR), methylphenidate (Ri about 20 mg/kg/day, about 0.001 mg/kg/day to about 25 talin), and methylphenidate CR, Ritalin, Ritalin LA, SD-483, mg/kg/day, about 0.001 mg/kg/day to about 30 mg/kg/day, SPD-503, Ritalin SR, Intuniv ER, Intuniv, Methylin, Day about 0.001 mg/kg/day to about 35 mg/kg/day, about 0.001 trana, Equasym, Dixirit, KapVay, Daytrana Patch, Methylin mg/kg/day to about 40 mg/kg/day, about 0.001 mg/kg/day to chewable, Methylin liquid, Dextrostat, Strattera, Tenex, Cat about 45 mg/kg/day, about 0.001 mg/kg/day to about 50 apres, Catapres TTS patch, Prozac, Serefam, Zoloft, Luvox, mg/kg/day, about 0.001 mg/kg/day to about 75 mg/kg/day, or Paxil, Paxil CR, Pexeva, Celexa, Lexapro, Tofranil, Nor about 0.001 mg/kg/day to about 100 mg/kg/day. pamin, Elavil, Pamelor, Sinequan, Anafranil, Wellbutrin, 0369 A pharmaceutical composition according to any one Wellbutrin SR, Wellbutrin XL, Effexor, Effexor XR, of claims 177-180, wherein the therapeutic compound to treat Remeron, Cymbalta, Nardil, Parnate, Emsam patch, Haldol, the attention deficit disorder is administered to an individual Orap, Prolixin, Mellaril, Thorazine, Stelazine, Moban, Loxi topical, Sublingual, rectal, vaginal, trancutaneous, oral, tane, Risperdal, Zyprexa, Seroguel, Geodon, Abilify, Cloz inhaled, intranasal, Subcutaneous, intravenous, enteral or aril, Xanax, Xanax XR, Klonopin, Ativan, Buspar, Ambien parenteral. US 2014/010O249 A1 Apr. 10, 2014 44

0370 A pharmaceutical composition according to any one mianserin, olanzapine, quetiapine, risperidone, amitriptyline, of claims 177-180, wherein the therapeutic compound to treat imipramine, cyproheptadine, etc.), H receptor antagonists/ the attention deficit disorder is administered as a liquid, a inverse agonists (e.g., buclizine, mirtazapine, mianserin, Solid, a semi-solid or an aerosol. olanzapine, quetiapine, n-3 fatty acids, amitriptyline, chlor 0371. A pharmaceutical composition according to any one pheniramine maleate, etc.), D/D receptor antagonists (e.g., of claims 177-180, wherein the therapeutic compound is for haloperidol, chlorpromazine, olanzapine, risperidone, que mulated as a tablet, lozenge, orally dissolved strip, capsule, tiapine, etc.), Marinol, Megace, Megace ES, C.-adrenergic syrup, oral Suspension, emulsion, granule, sprinkle or pellet. receptor antagonists (such as doxazosin, carvedilol, pro 0372 A pharmaceutical composition according to claim panolol, colonidine), Serefam, C-adrenergic receptor ago 177, wherein the therapeutic compound is a long acting, nists (e.g., clonidine, guanfacine, etc.). Some beta blockers Sustained release, extended release, immediate release, slow Such as propanolol, natural or synthetic CB, receptoragonists release, or controlled release therapeutic compound. (e.g., THC or dronabinol (found in Cannabis), tetrahydrocan 0373) A pharmaceutical composition according to claim nibinol, diphenydramine, promethazine, B vitamin Supple 190, wherein the therapeutic compound is released over a ments, nabilone, JWH-018 etc.), Corticosteroids (e.g. pred period of about 3 days after administration, about 7 days after nisone or dexamethasone), Sodium valproate (Depakote), administration, about 10 days after administration, about 15 Megestrol, Pregabalin, Sulfonylurea antidiabetic drugs such days after administration, about 20 days after administration, as glibenclamide and chlorpropamide, Steroids (including, about 25 days after administration, about 30 days after admin without limitation, boldenone, oxymetholone, dexametha istration, about 45 days after administration, about 60 days Sone, or methandrostenolone, prednisone, hydrocortisone, after administration, about 75 days after administration, or Oxandrolone, nandrolone, testosterone), some kappa opioid about 90 days after administration. receptor agonists such as tifluadom, hormones such as med 0374. A pharmaceutical composition according to claim eroxyprogesteronemirtazapine (Remeron), a tetracyclic anti 190, wherein the therapeutic compound is released over a depressant; cyproheptadine (Periactin), an antihistamine; period of at least 3 days after administration, at least 7 days nandrolone, oxymetholone, and Oxandrolone (Anadrol-50, after administration, at least 10 days after administration, at Durabolin, Hybolin, anti-IL6 antibody, selective androgen least 15 days after administration, at least 20 days after receptor modulator (“SARM), Oxandrin, and other brand administration, at least 25 days after administration, at least names), VT-122 (a coadministration of propranolol and etod 30 days after administration, at least 45 days after adminis olac), type 4 melanocortin receptor antagonis, IL6 antagonist, tration, at least 60 days after administration, at least 75 days synthetic ghrelin, myostatin decoy receptor, fast skeletal after administration, or at least 90 days after administration muscle troponin-activating Substance, anticatabolic/anabolic 0375. A pharmaceutical composition according to claim transforming agent MT-102, celecoxib, testosterone, Vitamin 190, wherein the therapeutic compound is released over a D, OHR/AVR118, soluble version of the ActRIIB receptor, period of about 1 day after administration, about 2 days after 5-HT antagonists, Cox-2 inhibitor, thalidomide, omega-3 administration, about 3 days after administration, about 4 fatty acids, anticyclooxygenase-2 drugs and megestrol days after administration, about 5 days after administration, acetate (Megace). In addition to these prescription drugs, fish about 6 days after administration or about 7 days or more after oil (eicosapentaenoic acid or EPA), EATMOR, other vita administration. mins and natural or artificial appetite stimulants. 0376. A pharmaceutical composition according to claim 0383. A pharmaceutical composition according to claim 177, wherein the pharmaceutical composition includes phar 199, wherein the orexigenic drug is cyproheptadine hydro maceutical acceptable components. chloride. 0377. A pharmaceutical composition according to claim 0384. A pharmaceutical composition according to any one 194, wherein the pharmaceutical acceptable components is of claims 177 and 199-201, wherein the symptoms associated selected from the group consisting of a salt, a Surfactant, an with appetite reduction is reduced by at least 10%, at least amino acid, a stabilizer or a buffer. 15%, at least 20%, at least 25%, at least 30%, at least 35%, at 0378. A pharmaceutical composition according to claim least 40%, at least 45%, at least 50%, at least 55%, at least 195, wherein the salt is selected from the group consisting of 60%, at least 65%, at least 70%, at least 75%, at least 80%, at citric acid, sodium chloride, potassium chloride, Sodium Sul least 85%, at least 90%, or at least 95%. fate, potassium nitrate, sodium phosphate monobasic or 0385) A pharmaceutical composition according to any one Sodium phosphate dibasic. of claims 177 and 199-201, wherein the symptoms associated 0379 A pharmaceutical composition according to 194, with appetite reduction is reduced by about 10% to about wherein the Surfactant is a polysorbate. 100%, about 20% to about 100%, about 30% to about 100%, 0380 A pharmaceutical composition according to claim about 40% to about 100%, about 50% to about 100%, about 197, wherein the polysorbate is selected from the group con 60% to about 100%, about 70% to about 100%, about 80% to sisting of Tween 20, Tween 80, F68, F88, sorbitain esters, about 100%, about 10% to about 90%, about 20% to about lipids, fatty acids or fatty esters. 90%, about 30% to about 90%, about 40% to about 90%, 0381 A pharmaceutical composition according to claim about 50% to about 90%, about 60% to about 90%, about 70% 177, wherein the therapeutic compound to treat a appetite to about 90%, about 10% to about 80%, about 20% to about reduction is an orexigenic drug. 80%, about 30% to about 80%, about 40% to about 80%, 0382 A pharmaceutical composition according to claim about 50% to about 80%, or about 60% to about 80%, about 199, wherein the orexigenic drug is selected from the group 10% to about 70%, about 20% to about 70%, about 30% to of alcohol, GHB, and other sedatives such as some benzodi about 70%, about 40% to about 70%, or about 50% to about azepine and nonbenzodiazepine tranquilizers and sleeping 70%. pills, anti-depressants (some SSRIs, Mianserin, etc.). 5-HT, 0386 A pharmaceutical composition according to any one receptor antagonists/inverse agonists (e.g., mirtazapine, of claims 177 and 199-201, wherein the symptoms associated US 2014/010O249 A1 Apr. 10, 2014

with reduction in the severity of appetite reduction is reduced embodiment, a therapeutic compound disclosed herein for by at least 10%, at least 15%, at least 20%, at least 25%, at the treatment of appetite reduction results in an increase in least 30%, at least 35%, at least 40%, at least 45%, at least weight by, e.g., from 0.5 pounds to 50 pounds, from 0.5 50%, at least 55%, at least 60%, at least 65%, at least 70%, at pounds to 30 pounds, from 0.5 pounds to 25 pounds, from 0.5 least 75%, at least 80%, at least 85%, at least 90% or at least pounds to 20 pounds, from 0.5 pounds to 15 pounds, from 0.5 95%. pounds to ten pounds, from 0.5 pounds to 7.5 pounds, from 0387. A pharmaceutical composition according to any one 0.5 pounds to 5 pounds, from 1 pound to 15 pounds, from 1 of claims 177 and 199-201, wherein the severity associated pound to 10 pounds, from 1 pound to 7.5 pounds, form 1 with reduction in appetite is reduced by about 10% to about pound to 5 pounds, from 2 pounds to ten pounds, from 2 100%, about 20% to about 100%, about 30% to about 100%, pounds to 7.5 pounds. about 40% to about 100%, about 50% to about 100%, about 0392 A pharmaceutical composition according to any one 60% to about 100%, about 70% to about 100%, about 80% to of claims 177 and 199-201, wherein the treatment for appetite about 100%, about 10% to about 90%, about 20% to about reduction increases the attentiveness of a patient by at least 90%, about 30% to about 90%, about 40% to about 90%, 10%, at least 15%, at least 20%, at least 25%, at least 30%, at about 50% to about 90%, about 60% to about 90%, about 70% least 35%, at least 40%, at least 45%, at least 50%, at least to about 90%, about 10% to about 80%, about 20% to about 55%, at least 60%, at least 65%, at least 70%, at least 75%, at 80%, about 30% to about 80%, about 40% to about 80%, least 80%, at least 85%, at least 90% or at least 95%. about 50% to about 80%, or about 60% to about 80%, about 0393 A pharmaceutical composition according to any one 10% to about 70%, about 20% to about 70%, about 30% to of claims 177 and 199-201, wherein the treatment for appetite about 70%, about 40% to about 70%, or about 50% to about reduction increases the attentiveness of a patient by about 70%. 10% to about 100%, about 20% to about 100%, about 30% to 0388 A pharmaceutical composition according to any one about 100%, about 40% to about 100%, about 50% to about of claims 177 and 199-201, wherein the treatment for appetite 100%, about 60% to about 100%, about 70% to about 100%, reduction results in an increase in weight by at least 10%, at about 80% to about 100%, about 10% to about 90%, about least 15%, at least 20%, at least 25%, at least 30%, at least 20% to about 90%, about 30% to about 90%, about 40% to 35%, at least 40%, at least 45%, at least 50%, at least 55%, at about 90%, about 50% to about 90%, about 60% to about least 60%, at least 65%, at least 70%, at least 75%, at least 90%, about 70% to about 90%, about 10% to about 80%, 80%, at least 85%, at least 90% or at least 95%. about 20% to about 80%, about 30% to about 80%, about 40% 0389. A pharmaceutical composition according to any one to about 80%, about 50% to about 80%, or about 60% to about of claims 177 and 199-201, wherein the treatment for appetite 80%, about 10% to about 70%, about 20% to about 70%, reduction results in an increase in weight by about 10% to about 30% to about 70%, about 40% to about 70%, or about about 100%, about 20% to about 100%, about 30% to about 50% to about 70%. 100%, about 40% to about 100%, about 50% to about 100%, 0394. A pharmaceutical composition according to any one about 60% to about 100%, about 70% to about 100%, about of claims 177 and 199-201, wherein the dose of the therapeu 80% to about 100%, about 10% to about 90%, about 20% to tic compound to treat the reduction in appetite is in the range about 90%, about 30% to about 90%, about 40% to about of at least 0.001 mg/kg/day, at least 0.01 mg/kg/day, at least 90%, about 50% to about 90%, about 60% to about 90%, 0.1 mg/kg/day, at least 1.0 mg/kg/day, at least 5.0 mg/kg/day, about 70% to about 90%, about 10% to about 80%, about 20% at least 10 mg/kg/day, at least 15 mg/kg/day, at least 20 to about 80%, about 30% to about 80%, about 40% to about mg/kg/day, at least 25 mg/kg/day, at least 30 mg/kg/day, at 80%, about 50% to about 80%, or about 60% to about 80%, least 35 mg/kg/day, at least 40 mg/kg/day, at least 45 mg/kg/ about 10% to about 70%, about 20% to about 70%, about 30% day, or at least 50 mg/kg/day. to about 70%, about 40% to about 70%, or about 50% to about 70%. 0395. A pharmaceutical composition according to any one 0390 A pharmaceutical composition according to any one of claims 177 and 199-201, wherein the dose of the therapeu of claims 177 and 199-201, wherein the treatment for appetite tic compound to treat reduction in appetite is in the range of reduction results in an increase in height by at least 10%, at about 0.001 mg/kg/day to about 100 mg/kg/day. least 15%, at least 20%, at least 25%, at least 30%, at least 0396 A pharmaceutical composition according to any one 35%, at least 40%, at least 45%, at least 50%, at least 55%, at of claims 177 and 199-201, wherein the dose of the therapeu least 60%, at least 65%, at least 70%, at least 75%, at least tic compound to treat the reduction in appetite is in the range 80%, at least 85%, at least 90% or at least 95%. of about 0.001 mg/kg/day to about 10 mg/kg/day, about 0.001 0391 A pharmaceutical composition according to any one mg/kg/day to about 15 mg/kg/day, about 0.001 mg/kg/day to of claims 177 and 199-201, wherein the treatment for appetite about 20 mg/kg/day, about 0.001 mg/kg/day to about 25 reduction results in an increase in weight by at least 0.5 mg/kg/day, about 0.001 mg/kg/day to about 30 mg/kg/day, pounds, at least 1 pound, at least 1.5 pounds, at least 2 pounds, about 0.001 mg/kg/day to about 35 mg/kg/day, about 0.001 at least 2.5 pounds, at least 3 pounds, at least 3.5 pounds, at mg/kg/day to about 40 mg/kg/day, about 0.001 mg/kg/day to least 4 pounds, at least 4.5 pounds, at least 5 pounds, at least about 45 mg/kg/day, about 0.001 mg/kg/day to about 50 5.5 pounds, at least 6 pounds, at least 6.5 pounds, at least 7 mg/kg/day, about 0.001 mg/kg/day to about 75 mg/kg/day, or pounds, at least 7.5 pounds, at least 8 pounds, at least 8.5 about 0.001 mg/kg/day to about 100 mg/kg/day. pounds, at least 9 pounds, at least 9.5 pounds, at least 10 0397. A pharmaceutical composition according to any one pounds, at least 10.5 pounds, at least 11 pounds, at least 11.5 of claims 177 and 199-201, wherein the therapeutic com pounds, at least 12 pounds, at least 12.5 pounds, at least 13 pound to treat the reduction in appetite is administered to an pounds, at least 13.5 pounds, at least 14 pounds, at least 14.5 individual topical, Sublingual, rectal, vaginal, trancutaneous, pounds, at least 15 pounds, at least 20 pounds, at least 25 oral, inhaled, intranasal, Subcutaneous, intravenous, enteral pounds, at least 30 pounds, at least 50 pounds. In another or parenteral. US 2014/010O249 A1 Apr. 10, 2014 46

0398. A pharmaceutical composition according to any one these described embodiments will become apparent to those of claims 177 and 199-215, wherein the therapeutic com ofordinary skill in the art upon reading the foregoing descrip pound to treat the reduction in appetite is administered as a tion. The inventor expects skilled artisans to employ Such liquid, a solid, a semi-solid or an aerosol. variations as appropriate, and the inventors intend for the 0399. A pharmaceutical composition according to any one present invention to be practiced otherwise than specifically of claims 177 and 199-215, wherein the therapeutic com described herein. Accordingly, this invention includes all pound is formulated as a tablet, lozenge, orally dissolved modifications and equivalents of the Subject matter recited in strip, capsule, syrup, oral Suspension, emulsion, granule, the claims appended hereto as permitted by applicable law. sprinkle or pellet. Moreover, any combination of the above-described embodi 0400. A pharmaceutical composition according to any one ments in all possible variations thereof is encompassed by the of claims 177 and 199-215, wherein the therapeutic com invention unless otherwise indicated herein or otherwise pound is a long acting, Sustained release, extended release, clearly contradicted by context. immediate release, slow release, or controlled release thera peutic compound. 0411 Groupings of alternative embodiments, elements, or 04.01. A pharmaceutical composition according to any one steps of the present invention are not to be construed as of claims 177 and 199-215, wherein the therapeutic com limitations. Each group member may be referred to and pound is released over a period of about 3 days after admin claimed individually or in any combination with other group istration, about 7 days after administration, about 10 days members disclosed herein. It is anticipated that one or more after administration, about 15 days after administration, members of a group may be included in, or deleted from, a about 20 days after administration, about 25 days after admin group for reasons of convenience and/or patentability. When istration, about 30 days after administration, about 45 days any such inclusion or deletion occurs, the specification is after administration, about 60 days after administration, deemed to contain the group as modified thus fulfilling the about 75 days after administration, or about 90 days after written description of all Markush groups used in the administration. appended claims. 0402. A pharmaceutical composition according to any one 0412 Unless otherwise indicated, all numbers expressing of claims 177 and 199-218, wherein the therapeutic com a characteristic, item, quantity, parameter, property, term, and pound is released over a period of at least 3 days after admin So forth used in the present specification and claims are to be istration, at least 7 days after administration, at least 10 days understood as being modified in all instances by the term after administration, at least 15 days after administration, at “about.” As used herein, the term “about” means that the least 20 days after administration, at least 25 days after characteristic, item, quantity, parameter, property, or term so administration, at least 30 days after administration, at least qualified encompasses a range of plus or minus ten percent 45 days after administration, at least 60 days after adminis above and below the value of the stated characteristic, item, tration, at least 75 days after administration, or at least 90 days quantity, parameter, property, or term. Accordingly, unless after administration indicated to the contrary, the numerical parameters set forthin 0403. A pharmaceutical composition according to any one the specification and attached claims are approximations that of claims 199-218, wherein the therapeutic compound is may vary. At the very least, and not as an attempt to limit the released over a period of about 1 day after administration, application of the doctrine of equivalents to the scope of the about 2 days after administration, about 3 days after admin claims, each numerical indication should at least be construed istration, about 4 days after administration, about 5 days after in light of the number of reported significant digits and by administration, about 6 days after administration or about 7 applying ordinary rounding techniques. Notwithstanding that days or more after administration. the numerical ranges and values setting forth the broad scope 0404 A pharmaceutical composition according to any one of the invention are approximations, the numerical ranges and of claims 199-218, wherein the pharmaceutical composition values set forth in the specific examples are reported as pre includes pharmaceutical acceptable components. cisely as possible. Any numerical range or value, however, 0405. A pharmaceutical composition according to claim inherently contains certain errors necessarily resulting from 222, wherein the pharmaceutical acceptable components is the standard deviation found in their respective testing mea selected from the group consisting of a salt, a Surfactant, an Surements. Recitation of numerical ranges of values herein is amino acid, a stabilizer or a buffer. merely intended to serve as a shorthand method of referring 0406 A pharmaceutical composition according to claim individually to each separate numerical value falling within 223, wherein the salt is selected from the group consisting of the range. Unless otherwise indicated herein, each individual citric acid, sodium chloride, potassium chloride, Sodium Sul value of a numerical range is incorporated into the present fate, potassium nitrate, sodium phosphate monobasic or specification as if it were individually recited herein. Sodium phosphate dibasic. 0413. The terms “a” “an,” “the and similar referents used 0407. A pharmaceutical composition according to claim in the context of describing the present invention (especially 222, wherein the surfactant is a polysorbate. in the context of the following claims) are to be construed to 0408. A pharmaceutical composition according to claim cover both the singular and the plural, unless otherwise indi 225, wherein the polysorbate is selected from the group con cated herein or clearly contradicted by context. All methods sisting of Tween 20, Tween 80, F68, F88, sorbitain esters, described herein can be performed in any suitable order lipids, fatty acids or fatty esters. unless otherwise indicated herein or otherwise clearly con 04.09. A kit comprising a pharmaceutical composition of tradicted by context. The use of any and all examples, or any preceding claim. exemplary language (e.g., “such as') provided herein is 0410 Certain embodiments of the present invention are intended merely to better illuminate the present invention and described herein, including the best mode knownto the inven does not pose a limitation on the Scope of the invention tors for carrying out the invention. Of course, variations on otherwise claimed. No language in the present specification US 2014/010O249 A1 Apr. 10, 2014 47 should be construed as indicating any non-claimed element erem, Lithiu, Lithobid, Eskalith, Depakote, Tegretol, Carba essential to the practice of the invention. trol, Trileptal, Lamictal, Topamax, Neurontin and the 0414 Specific embodiments disclosed herein may be fur therapeutic compounds identified in Table 1. ther limited in the claims using consisting of or consisting 5. The method according to claim 1, wherein the severity essentially of language. When used in the claims, whether as associated with attention deficit disorder is reduced by at least filed or added per amendment, the transition term “consisting 10%, at least 15%, at least 20%, at least 25%, at least 30%, at of excludes any element, step, or ingredient not specified in least 35%, at least 40%, at least 45%, at least 50%, at least the claims. The transition term “consisting essentially of 55%, at least 60%, at least 65%, at least 70%, at least 75%, at limits the scope of a claim to the specified materials or steps least 80%, at least 85%, at least 90%, or at least 95%. and those that do not materially affect the basic and novel 6. The method according to claim 4, wherein the dose of the characteristic(s). Embodiments of the present invention so therapeutic compound to treat the attention deficit disorder is claimed are inherently or expressly described and enabled in the range of at least 0.001 mg/kg/day, at least 0.01 mg/kg/ herein. day, at least 0.1 mg/kg/day, at least 1.0 mg/kg/day, at least 5.0 0415 All patents, patent publications, and other publica mg/kg/day, at least 10 mg/kg/day, at least 15 mg/kg/day, at tions referenced and identified in the present specification are least 20 mg/kg/day, at least 25 mg/kg/day, at least 30 mg/kg/ individually and expressly incorporated herein by reference day, at least 35 mg/kg/day, at least 40 mg/kg/day, at least 45 in their entirety for the purpose of describing and disclosing, mg/kg/day, or at least 50 mg/kg/day. for example, the compositions and methodologies described 7. The method according to claim 1, wherein the therapeu in Such publications that might be used in connection with the tic compound to treat the attention deficit disorder is admin present invention. These publications are provided solely for istered to an individual topical, Sublingual, rectal, vaginal, their disclosure prior to the filing date of the present applica trancutaneous, oral, inhaled, intranasal, Subcutaneous, intra tion. Nothing in this regard should be construed as an admis venous, enteral or parenteral. sion that the inventors are not entitled to antedate such dis 8. The method of claim 1, wherein the therapeutic com closure by virtue of prior invention or for any other reason. All pound to treat a appetite reduction is an orexigenic drug. statements as to the date or representation as to the contents of 9. The method of claim 8, wherein the orexigenic drug is these documents is based on the information available to the selected from the group of alcohol, GHB, and other sedatives applicants and does not constitute any admission as to the Such as some benzodiazepine and nonbenzodiazepine tran correctness of the dates or contents of these documents. quilizers and sleeping pills, anti-depressants (some SSRIs, 1. A method of treating an individual with a disorder asso Mianserin, etc.). 5-HT, receptor antagonists/inverse ago ciated with an attention deficit disorder, the method com nists (e.g., mirtazapine, mianserin, olanzapine, quetiapine, prises the step of administering to an individual in need risperidone, amitriptyline, imipramine, cyproheptadine, thereof a pharmaceutical composition which comprises etc.), H receptor antagonists/inverse agonists (e.g., bucliz administration of a therapeutic compound to treat the atten ine, mirtazapine, mianserin, olanzapine, quetiapine, n-3 fatty tion deficit disorder and a therapeutic compound to treat a acids, amitriptyline, chlorpheniramine maleate, etc.), D/D reduction in appetite, wherein administration reduces a receptor antagonists (e.g., haloperidol, chlorpromazine, olan symptom of a disorder associated with an attention deficit Zapine, risperidone, quetiapine, etc.), Marinol, Megace, disorder and increases the attentiveness of the individual, Megace ES, C.-adrenergic receptor antagonists (such as dox thereby treating the individual. aZosin, carvedilol, propanolol, colonidine), Serefam, C2-adr 2. The method of claim 1, wherein the attention deficit energic receptor agonists (e.g., clonidine, guanfacine, etc.). disorder is Attention Deficit Hyperactivity Disorder Some beta blockers such as propanolol, natural or synthetic (ADHD). CB, receptor agonists (e.g., THC or dronabinol (found in 3. The method of claim 1, wherein the therapeutic com Cannabis), tetrahydrocannibinol, diphenydramine, promet pound administered for the treatment of an attention deficit hazine, B vitamin supplements, nabilone, JWH-018 etc.), disorder is an amphetamine or a methylphenidate. Corticosteroids (e.g. prednisone or dexamethasone), Sodium 4. The method of claim 3, wherein the amphetamine or valproate (Depakote), Megestrol, Pregabalin, Sulfonylurea methylphenidate is selected from the group consisting of antidiabetic drugs such as glibenclamide and chlorpropam OROS methylphenidate (Concerta), dextroamphetamine ide, steroids (including, without limitation, boldenone, immediate/sustained release (Adderall/Adderall XR), dexm oxymetholone, dexamethasone, or methandrostenolone, ethylphenidate (Focalin), Focalin XR, Metadate CD, Meta prednisone, hydrocortisone, Oxandrolone, nandrolone, test date ER, NWP09, Dexedrine, dextroamphetamine osterone). Some kappa opioid receptoragonists such as tiflua (Dexedrine), Dexedrine Spanisules, Methylin ER (Ritalin dom, hormones such as mederoxyprogesteronemirtazapine SR), methylphenidate (Ritalin), and methylphenidate CR, (Remeron), a tetracyclic antidepressant, cyproheptadine (Pe Ritalin, Ritalin LA, SD-483, SPD-503, Ritalin SR, Intuniv riactin), an antihistamine; nandrolone, oxymetholone, and ER, Intuniv, Methylin, Daytrana, Equasym, Dixirit, Kapvay, oxandrolone (Anadrol-50, Durabolin, Hybolin, anti-IL6 anti Daytrana Patch, Methylin chewable, Methylin liquid, Dex body, selective androgen receptor modulator (“SARM), trostat, Strattera, Tenex, Catapres, Catapres TTS patch, Oxandrin, and other brand names), VT-122 (a coadministra Prozac, Serefam, Zoloft, Luvox, Paxil, Paxil CR, Pexeva, tion of propranolol and etodolac), type 4 melanocortin recep Celexa, Lexapro, Tofranil, Norpamin, Elavil, Pamelor, Sine tor antagonis, IL6 antagonist, synthetic ghrelin, myostatin quan, Anafranil, Wellbutrin, Wellbutrin SR, Wellbutrin XL, decoy receptor, fast skeletal muscle troponin-activating Sub Effexor, Effexor XR, Remeron, Cymbalta, Nardil, Parnate, stance, anticatabolic/anabolic transforming agent MT-102, Emsam patch, Haldol, Orap, Prolixin, Mellaril, Thorazine, celecoxib, testosterone, vitamin D, OHR/AVR118, soluble Stelazine, Moban, Loxitane, Risperdal, Zyprexa, Seroquel, version of the ActRIIB receptor, 5-HT antagonists, Cox-2 Geodon, Abilify, Clozaril, Xanax, Xanax XR, Klonopin, Ati inhibitor, thalidomide, omega-3 fatty acids, anticyclooxyge van, Buspar, Ambien CR, Ambien, Lunesta, Sonata, RoZ nase-2 drugs and megestrol acetate (Megace). In addition to US 2014/010O249 A1 Apr. 10, 2014 48 these prescription drugs, fish oil (eicosapentaenoic acid or phetamine immediate/sustained release (Adderall/Adderall EPA), EATMOR, other vitamins and natural or artificial XR), dexmethylphenidate (Focalin), Focalin XR, Metadate appetite stimulants. CD, Metadate ER, NWP09, Dexedrine, dextroamphetamine 10. The method of claim 8, wherein the orexigenic drug is (Dexedrine), Dexedrine Spanisules, Methylin ER (Ritalin cyproheptadine hydrochloride. SR), methylphenidate (Ritalin), and methylphenidate CR, 11. The method according to claim 1, wherein the Symp Ritalin, Ritalin LA, SD-483, SPD-503, Ritalin SR, Intuniv toms associated with appetite reduction is reduced by at least ER, Intuniv, Methylin, Daytrana, Equasym, Dixirit, Kapvay, 10%, at least 15%, at least 20%, at least 25%, at least 30%, at Daytrana Patch, Methylin chewable, Methylin liquid, Dex least 35%, at least 40%, at least 45%, at least 50%, at least trostat, Strattera, Tenex, Catapres, Catapres TTS patch, 55%, at least 60%, at least 65%, at least 70%, at least 75%, at Prozac, Serefam, Zoloft, Luvox, Paxil, Paxil CR, Pexeva, least 80%, at least 85%, at least 90%, or at least 95%. Celexa, Lexapro, Tofranil, Norpamin, Elavil, Pamelor, Sine 12. The method according claim 1, wherein the treatment quan, Anafranil, Wellbutrin, Wellbutrin SR, Wellbutrin XL, for appetite reduction results in an increase in weight by at Effexor, Effexor XR, Remeron, Cymbalta, Nardil, Parnate, least 0.5 pounds, at least 1 pound, at least 1.5 pounds, at least Emsam patch, Haldol, Orap, Prolixin, Mellaril, Thorazine, 2 pounds, at least 2.5 pounds, at least 3 pounds, at least 3.5 Stelazine, Moban, Loxitane, Risperdal, Zyprexa, Seroquel, pounds, at least 4 pounds, at least 4.5 pounds, at least 5 Geodon, Abilify, Clozaril, Xanax, Xanax XR, Klonopin, Ati pounds, at least 5.5 pounds, at least 6 pounds, at least 6.5 van, Buspar, Ambien CR, Ambien, Lunesta, Sonata, RoZ pounds, at least 7 pounds, at least 7.5 pounds, at least 8 erem, Lithiu, Lithobid, Eskalith, Depakote, Tegretol, Carba pounds, at least 8.5 pounds, at least 9 pounds, at least 9.5 trol, Trileptal, Lamictal, Topamax, Neurontin and the pounds, at least 10 pounds, at least 10.5 pounds, at least 11 therapeutic compounds identified in Table 1. pounds, at least 11.5 pounds, at least 12 pounds, at least 12.5 19. A pharmaceutical composition according to claim 15, pounds, at least 13 pounds, at least 13.5 pounds, at least 14 wherein the severity associated with attention deficit disorder pounds, at least 14.5 pounds, at least 15 pounds, at least 20 is reduced by at least 10%, at least 15%, at least 20%, at least pounds, at least 25 pounds, at least 30 pounds, at least 50 25%, at least 30%, at least 35%, at least 40%, at least 45%, at pounds. In another embodiment, a therapeutic compound least 50%, at least 55%, at least 60%, at least 65%, at least disclosed herein for the treatment of appetite reduction results 70%, at least 75%, at least 80%, at least 85%, at least 90%, or in an increase in weight by, e.g., from 0.5 pounds to 50 at least 95%. pounds, from 0.5 pounds to 30 pounds, from 0.5 pounds to 25 20. A pharmaceutical composition according to claim 15, pounds, from 0.5 pounds to 20 pounds, from 0.5 pounds to 15 wherein the symptoms associated with attention deficit dis pounds, from 0.5 pounds to ten pounds, from 0.5 pounds to order is reduced by about 10% to about 100%, about 20% to 7.5 pounds, from 0.5 pounds to 5 pounds, from 1 pound to 15 about 100%, about 30% to about 100%, about 40% to about pounds, from 1 pound to 10 pounds, from 1 pound to 7.5 100%, about 50% to about 100%, about 60% to about 100%, pounds, form 1 pound to 5 pounds, from 2 pounds to ten about 70% to about 100%, about 80% to about 100%, about pounds, from 2 pounds to 7.5 pounds. 10% to about 90%, about 20% to about 90%, about 30% to 13. The method according to claim 1, wherein the thera about 90%, about 40% to about 90%, about 50% to about peutic compound to treat the reduction in appetite is admin 90%, about 60% to about 90%, about 70% to about 90%, istered to an individual topical, Sublingual, rectal, vaginal, about 10% to about 80%, about 20% to about 80%, about 30% trancutaneous, oral, inhaled, intranasal, Subcutaneous, intra to about 80%, about 40% to about 80%, about 50% to about venous, enteral or parenteral. 80%, or about 60% to about 80%, about 10% to about 70%, 14. The method of claim 1, wherein an increase in atten about 20% to about 70%, about 30% to about 70%, about 40% tiveness is measured by CGI-I and the method results in a to about 70%, or about 50% to about 70%. reduction in the CGI-I score by at least 10%, at least 15%, at 21. A pharmaceutical composition according to claim 15, least 20%, at least 25%, at least 30%, at least 35%, at least wherein the dose of the therapeutic compound to treat the 40%, at least 45%, at least 50%, at least 55%, at least 60%, at attention deficit disorder is in the range of about 0.001 mg/kg/ least 65%, at least 70%, at least 75%, at least 80%, at least day to about 10 mg/kg/day, about 0.001 mg/kg/day to about 85%, at least 90% or at least 95%. 15 mg/kg/day, about 0.001 mg/kg/day to about 20 mg/kg/day, 15. A pharmaceutical composition comprising a therapeu about 0.001 mg/kg/day to about 25 mg/kg/day, about 0.001 tic compound for a disorder associated with an attention mg/kg/day to about 30 mg/kg/day, about 0.001 mg/kg/day to deficit disorder and a therapeutic compound for a disorder about 35 mg/kg/day, about 0.001 mg/kg/day to about 40 associated with a reduction in appetite, wherein the pharma mg/kg/day, about 0.001 mg/kg/day to about 45 mg/kg/day, ceutical composition reduces a symptom of a disorder asso about 0.001 mg/kg/day to about 50 mg/kg/day, about 0.001 ciated with an attention deficit disorder and increases the mg/kg/day to about 75 mg/kg/day, or about 0.001 mg/kg/day attentiveness of the individual, thereby treating the indi to about 100 mg/kg/day. vidual. 22. A pharmaceutical composition according to any one of 16. A pharmaceutical composition of claim 15, wherein the claim 15, wherein the therapeutic compound to treat the atten attention deficit disorder is Attention Deficit Hyperactivity tion deficit disorder is administered to an individual topical, Disorder (ADHD). Sublingual, rectal, vaginal, trancutaneous, oral, inhaled, intra 17. A pharmaceutical composition of claim 15, wherein the nasal, Subcutaneous, intravenous, enteral or parenteral. therapeutic compound administered for the treatment of an 23. A pharmaceutical composition according to claim 15, attention deficit disorder is an amphetamine or a meth wherein the orexigenic drug is selected from the group of ylphenidate. alcohol, GHB, and other sedatives such as some benzodiaz 18. A pharmaceutical composition of claim 17, wherein the epine and nonbenzodiazepine tranquilizers and sleeping pills, amphetamine or methylphenidate is selected from the group anti-depressants (some SSRIs, Mianserin, etc.), 5-HT, consisting of OROS methylphenidate (Concerta), dextroam receptor antagonists/inverse agonists (e.g., mirtazapine, US 2014/01 00249 A1 Apr. 10, 2014 49 mianserin, olanzapine, quetiapine, risperidone, amitriptyline, 5-HT, antagonists, Cox-2 inhibitor, thalidomide, omega-3 imipramine, cyproheptadine, etc.), H receptor antagonists/ fatty acids, anticyclooxygenase-2 drugs and megestrol inverse agonists (e.g., buclizine, mirtazapine, mianserin, acetate (Megace). In addition to these prescription drugs, fish olanzapine, quetiapine, n-3 fatty acids, amitriptyline, chlor oil (eicosapentaenoic acid or EPA), EATMOR, other vita pheniramine maleate, etc.), D/D, receptor antagonists (e.g., mins and natural or artificial appetite stimulants. haloperidol, chlorpromazine, olanzapine, risperidone, que 24. A pharmaceutical composition according to claim 15, tiapine, etc.), Marinol, Megace, Megace ES, C-adrenergic wherein the orexigenic drug is cyproheptadine hydrochlo receptor antagonists (such as doxazosin, carvedilol, pro ride. panolol, colonidine), Serefam, C2-adrenergic receptor ago 25. A pharmaceutical composition according to claim 15, nists (e.g., clonidine, guanfacine, etc.), some beta blockers wherein the treatment for appetite reduction results in an Such as propanolol, natural or synthetic CB, receptoragonists increase in weight by at least 0.5 pounds, at least 1 pound, at (e.g., THC or dronabinol (found in Cannabis), tetrahydrocan least 1.5 pounds, at least 2 pounds, at least 2.5 pounds, at least nibinol, diphenydramine, promethazine, B vitamin supple 3 pounds, at least 3.5 pounds, at least 4 pounds, at least 4.5 ments, nabilone, JWH-018 etc.), Corticosteroids (e.g. pred pounds, at least 5 pounds, at least 5.5 pounds, at least 6 nisone or dexamethasone), Sodium valproate (Depakote), pounds, at least 6.5 pounds, at least 7 pounds, at least 7.5 Megestrol, Pregabalin, Sulfonylurea antidiabetic drugs such pounds, at least 8 pounds, at least 8.5 pounds, at least 9 as glibenclamide and chlorpropamide, steroids (including, pounds, at least 9.5 pounds, at least 10 pounds, at least 10.5 without limitation, boldenone, oxymetholone, dexametha pounds, at least 11 pounds, at least 11.5 pounds, at least 12 Sone, or methandrostenolone, prednisone, hydrocortisone, pounds, at least 12.5 pounds, at least 13 pounds, at least 13.5 Oxandrolone, nandrolone, testosterone), some kappa opioid pounds, at least 14 pounds, at least 14.5 pounds, at least 15 receptor agonists such as tifluadom, hormones such as med pounds, at least 20 pounds, at least 25 pounds, at least 30 eroxyprogesteronemirtazapine (Remeron), a tetracyclic anti pounds, at least 50 pounds. In another embodiment, a thera depressant; cyproheptadine (Periactin), an antihistamine; peutic compound disclosed herein for the treatment of appe nandrolone, oxymetholone, and oxandrolone (Anadrol-50, tite reduction results in an increase in weight by, e.g., from 0.5 Durabolin, Hybolin, anti-IL6 antibody, selective androgen pounds to 50 pounds, from 0.5 pounds to 30 pounds, from 0.5 receptor modulator (“SARM), Oxandrin, and other brand pounds to 25 pounds, from 0.5 pounds to 20 pounds, from 0.5 names), VT-122 (a coadministration of propranolol and etod pounds to 15 pounds, from 0.5 pounds to ten pounds, from 0.5 olac), type 4 melanocortin receptor antagonis, IL6 antagonist, pounds to 7.5 pounds, from 0.5 pounds to 5 pounds, from 1 Synthetic ghrelin, myostatin decoy receptor, fast skeletal pound to 15 pounds, from 1 pound to 10 pounds, from 1 muscle troponin-activating substance, anticatabolic/anabolic pound to 7.5 pounds, form 1 pound to 5 pounds, from 2 transforming agent MT-102, celecoxib, testosterone, vitamin pounds to ten pounds, from 2 pounds to 7.5 pounds. D, OHR/AVR118, soluble version of the ActRIIB receptor,