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(12) Patent Application Publication (10) Pub. No.: US 2013/0045979 A1 Sanfilippo (43) Pub

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(12) Patent Application Publication (10) Pub. No.: US 2013/0045979 A1 Sanfilippo (43) Pub US 20130.045979A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0045979 A1 Sanfilippo (43) Pub. Date: Feb. 21, 2013 (54) METHOD OF TREATING MAJOR Publication Classification DEPRESSIVE DSORDER (51) Int. Cl. (75) Inventor: Louis Sanfilippo, New Haven, CT (US) A613 L/65 (2006.01) A613 L/496 (2006.01) A613 L/53 (2006.01) (73) Assignee: LCS GROUP, LLC, New Haven, CT A6IP 25/24 (2006.01) (US) (52) U.S. Cl. .................... 514/242: 514/626; 514/253.04 (57) ABSTRACT The invention provides methods of treating depressive disor (21) Appl. No.: 13/585.426 ders, in particular major depression but other depressive orders also, with prodrug stimulants or analogs including amphetamine prodrugs, methylphenidate prodrugs, and (22) Filed: Aug. 14, 2012 methylphenidate analogs. Such methods of treatment may utilize the prodrug stimulant or analog as monotherapy or, more commonly, as an adjunct to antidepressant medication Related U.S. Application Data treatment to augment their effect. The invention includes combination methods of treatment in which an amphetamine (63) Continuation of application No. 12/646,441, filed on prodrug, methylphenidate prodrug, or methylphenidate ana Dec. 23, 2009, now abandoned, which is a continua- log is administered to an individual in need with one or more tion of application No. 12/666.460, filed on Oct. 6, other active agents, either in separate forms or as a single 2010, now Pat. No. 8,318,813, filed as application No. pharmaceutical formulation. Packaged pharmaceutical com PCT/US2008/001002 on Jan. 24, 2008. positions containing an amphetamine or methylphenidate s prodrug, instructions for using the prodrug to treat certain (60) Provisional application No. 60/972,046, filed on Sep. disorders, and optionally one or more other active agents are 13, 2007. provided by the invention. US 2013/0045979 A1 Feb. 21, 2013 METHOD OF TREATING MAJOR behaviors and weight gain may be a direct effect of Such DEPRESSIVE DSORDER medication(s). Psychotropic medications may also exacer bate an underlying binge eating disorder in Some patients. FIELD OF INVENTION 0006 Medical complications associated with binge eating disorder include high blood pressure, high cholesterol and 0001. The inventor has discovered that amphetamine pro triglycerides, kidney disease (and failure), gallbladder dis drugs and methylphenidate prodrugs are useful for treating a ease, arthritis, bone deterioration, stroke, upper respiratory number of central nervous system disorders. Methods of infections, skin disorders, menstrual irregularities, ovarian treating binge eating disorders, obesity resulting from binge abnormalities, and pregnancy complications. Psychiatric eating behavior, and depression are included herein. The problems associated with, or exacerbated by, binge eating invention includes methods of treating certain co-morbidities disorder include depressive disorders, mood disorders, anxi in ADHD (Attention-Deficit Hyperactivity Disorder) and ety disorders, ADHD and ADD, personality disorders, other ADD patients; for example the invention includes methods of eating disorders, Suicidal thoughts, and Substance abuse dis treating generalized anxiety disorder, obsessional and rumi orders. native thought disorders, and obsessive/compulsive behavior 0007 Individuals with binge eating disorder may respond in ADHD and ADD patients. Methods of treatment include to treatment with antidepressants, though Such medications methods in which the amphetamine prodrug, methylpheni may contribute to a worsening of binge eating symptoms, date prodrug, or methylphenidate analog is the only active along with weight gain, either at the outset of treatment or agent. The invention also includes combination methods of over time. treatment in which an amphetamine prodrug, methylpheni 0008 2. Depression date prodrug, or methylphenidate analog is administered with 0009. Depression is often difficult to treat, as some one or more other active agents. Methods of use described patients fail to respond to an initial pharmacologic interven herein include informing a user that an amphetamine prodrug, tion and a decision must be made to Switch agents, augment methylphenidate prodrug, or methylphenidate analog may be with another medication(s), or combine multiple pharmaco used to treat any of the disorders listed above. The invention logic agents. Combining medications, while often helpful, includes pharmaceutical compositions comprising an can sometimes be problematic with added side effect bur amphetamine prodrug, methylphenidate prodrug, or meth dens. Side effects of certain psychotropic medication some ylphenidate analog together with one or more other active times used to offer adjunct treatment to patients already tak agents in a single dosage form. Packaged pharmaceutical ing antidepressants may include weight gain and obesity. compositions containing an amphetamine prodrug, meth 0010 Individuals treated for major depressive disorders ylphenidate prodrug, or methylphenidate analog with instruc may show a positive response or full remission of symptoms tions for using the composition to treat one of the disorders to medication treatment, though recent clinical evidence Sug listed above are also provided. gests remission rates following an adequate course of mono therapy treatment may as low as 30-40%. Further, clinical BACKGROUND studies suggest an unusually large percentage of depressed 0002 1. Binge Eating Disorder and Obesity Resulting individuals treated with antidepressant medication, greater from Binge Eating Disorder than 30-40% in various clinical studies, show only a partial 0003 Binge Eating Disorder is a form of Eating Disorder response (for example, full remission is not achieved but there Not Otherwise Specified according the Diagnostic and Sta is some measure of improvement in depressive symptoms). tistical Manual of Mental Disorders (DSM-IV-TR). As Some patients may be refractory or resistant to treatment defined by the DSM-IV-TR, it is characterized by recurrent and fail to respond to one, or in Some cases, multiple mono binge eating episodes. therapy and combination antidepressant medication treat 0004 Commonly described symptoms of binge eating mentS. disorder include frequent dieting and weight loss, hoarding of 0011 Major depressive disorders similarly may lead to food, hiding empty food containers, eating late at night, attri deteriorating physical health and may increase the risk of bution of one's successes and failures to weight, avoiding morbidity and mortality in patients with concurrent medical Social situations where food may be present, and feeling conditions. depressed or anxious. Binge eating also may cause rapid and 0012 Similarly, depressive disorders are often associated unhealthy weight gain (or loss), weight fluctuations, and with, or may exacerbate, other mood disorders, anxiety dis chronic erratic eating behavior. Binge eating disorder and orders, attention deficit hyperactivity disorder (ADHD or symptoms associated with binge eating disorder may result in ADD), psychotic disorders, personality disorders, eating dis obesity though obesity is not necessarily a result of binge orders, cognition and cognitive disorders, Substance abuse eating disorder. Further, patients with binge eating disorder disorders, and Suicidal ideation. are often not obese and may even have a below normal 0013 There exists an unmet and important clinical need weight. for treatments for binge eating disorders, obesity resulting 0005. The biological basis of binge eating disorder is from binge eating behavior, and depression that is only par poorly understood. Binge eating disorder is difficult to treat tially responsive to medication and intractable (e.g. treat and carries significant medical and psychiatric risks. Pharma ment-resistant) depression. The present invention fulfills this cologic interventions have been of limited Success and some need and provides additional advantages described herein. times cause a worsening of binge eating symptoms. A number of psychotropic medications, including but not limited to SUMMARY OF THE INVENTION antidepressants, antipsychotics, antimanic agents, and mood 0014. The inventor has discovered that amphetamine pro modulating medications are known to cause binge eating, drugs, including lisdexamfetamine dimesylate, methylpheni dysregulation of appetite, and weight gain. Binge eating date prodrugs, and certain methylphenidate analogs, are use US 2013/0045979 A1 Feb. 21, 2013 ful for treating binge eating disorders, obesity resulting from 0020. The invention includes articles of manufacture com binge eating behavior, and depression. Furthermore amphet prising an amphetamine prodrug, methylphenidate prodrug, amine prodrugs, methylphenidate prodrugs, and certain or methylphenidate analog in a container and printed label methylphenidate analogs have been found useful for treating ing. The printed labeling states that the amphetamine pro certain co-morbidities in ADHD and ADD patients. The drug, methylphenidate prodrug, or methylphenidate analog is invention includes methods of treating generalized anxiety useful for treating a binge eating disorder, obesity resulting disorder, obsessional and ruminative thought disorders, and from binge eating behavior, or depression. In other embodi obsessive/compulsive behavior in patients, particularly in ments the printed labeling states that the amphetamine pro ADHD/ADD patients. Methods of using amphetamine pro drug, methylphenidate prodrug, methylphenidate
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