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US 2005O118286A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0118286 A1 Suffin et al. (43) Pub. Date: Jun. 2, 2005 (54) COMPOSITIONS AND METHODS FOR Publication Classification TREATMENT OF NERVOUS SYSTEM DSORDERS (51) Int. Cl." ..................... A61K 38/05; A61K 31/5377; A61K 31/522; A61K 31/445; (75) Inventors: Stephen C. Suffin, Sherman Oaks, CA A61K 31/137; A61K 31/138; (US); W. Hamlin Emory, Malibu, CA A61K 31/403; A61K 35/78 (US); Leonard Brandt, San Juan (52) U.S. Cl. ...................... 424/752; 514/18; 514/263.31; Capistrano, CA (US) 514/411; 514/317; 514/649; 514/651; 514/618; 514/235.5 (57) ABSTRACT Correspondence Address: The present invention contemplates compositions and meth MEDLEN & CARROLL, LLP ods to treat patients having a nervous System disorder with Suite 350 a formulation comprising an anticonvulsant and a neuroac 101 Howard Street tive modulator. Also described is a method to predict the San Francisco, CA 94105 (US) probability of a significant recovery when a treating an individual patient having a nervous System disorder with a Assignee: CNS Response formulation comprising an anticonvulsant and a neuroactive (73) modulator. Specifically, methods for predicting patient prog nosis include, but are not limited to, quantitative electroen Appl. No.: 10/972,188 cephalography, psychometric test batteries, biological indi (21) cators, brain metabolic indicators, genotype profiles, neuroimaging, objective test measurements and multi-mo (22) Filed: Oct. 22, 2004 dalities. The present invention also discloses a device pro Viding an organized dispensation of the above formulations Related U.S. Application Data Such that the patient or medical perSonnel may easily and accurately decrease the daily dosage of a third drug and (63) Continuation of application No. 10/697,497, filed on increase the daily dosage of a formulation comprising an Oct. 30, 2003. anticonvulsant and a neuroactive modulator. Patent Application Publication Jun. 2, 2005 Sheet 1 of 7 US 2005/0118286 A1 Figure 1 Patent Application Publication Jun. 2, 2005 Sheet 2 of 7 US 2005/0118286 A1 Patent Application Publication Jun. 2, 2005 Sheet 3 of 7 US 2005/0118286 A1 Panel A : Panel B Z WWWW, Figure 3 Patent Application Publication Jun. 2 Patent Application Publication Jun. 2, 2005 Sheet 5 of 7 US 2005/0118286 A1 i Patent Application Publication Jun. 2, 2005 Sheet 6 of 7 US 2005/0118286 A1 Figure 6 Patent Application Publication Jun. 2, 2005 Sheet 7 of 7 US 2005/0118286 A1 Figure 7 US 2005/0118286 A1 Jun. 2, 2005 COMPOSITIONS AND METHODS FOR commonly used drugs for depressive disorders include the TREATMENT OF NERVOUS SYSTEM DSORDERS tricyclic antidepressants, Selective Serotonin reuptake inhibi tors, Selective norepinephrine reuptake inhibitors, lithium FIELD OF INVENTION carbonate, and the monoamine oxidase inhibitors. These drugs are Suggested to increase the Synaptic level of neu 0001. In one embodiment, this invention relates to pre rotransmitters, most notably, norepinephrine, Serotonin and dicting the probability of a significant recovery following dopamine. Though Some Success has been achieved in the pharmaceutical treatment of nervous System disorders. In treatment of depression using a monotherapy approach, one embodiment, this invention relates to predicting the however, a significant number of patients are either non probability of a significant recovery from a nervous System responsive (i.e., refractory) or whose Symptomology actu disorder by a combination of at least two pharmaceutical ally worSens following the Standard course of monotherapy. formulations. In another embodiment, this invention relates to predicting the probability of a significant recovery fol 0005. It is well acknowledged in the art that the treatment lowing the treatment of nervous System disorders by at least of nervous System disorders is complicated by diagnostic one pharmaceutical formulation combined with a medical uncertainties. Successful efforts to maximize the association device. In another embodiment, this invention relates to between Specific clinical Syndromes and predictable predicting the probability of a Significant recovery following responses indicate that treatment of nervous System disor derS may one day transition from a State of art, to one of the treatment of nervous System disorders by a combination Science. Efforts to Solve the problem of patient response and of an anticonvulsant and a neuroactive modulator. improved efficacy of drug therapy has become a primary focus of nervous System treatment and a reliable method to BACKGROUND predict patient response prior to treatment is clearly need. 0002 Nervous system disorders are known to encompass Also, often what is clearly needed is a Safe and effective a wide variety of clinically significant conditions. In general, pharmaceutical combination designed for long-term treat primary psychiatric disorders are categorized according to ment in patients exhibiting nervous System disorders. the Diagnostic and Statistical Manual of Mental Disorders, SUMMARY 4th Edition (i.e., referred to hereinafter as DSM-IV) and may be represented as: i) Disorders Usually First Diagnosed in 0006. In one embodiment, this invention relates to pre Infancy, Childhood, or Adolescence; ii) Cognitive Disor dicting the probability of a significant recovery following ders; Mental Disorders. Due to a General Medical Condition; pharmaceutical treatment of nervous system disorders. In iii) Substance-Related Disorders; iv) Schizophrenia and one embodiment, this invention relates to predicting the Other Psychotic Disorders; v) Mood Disorders; vi) Anxiety probability of a significant recovery from a nervous System Disorders; vii) Somatoform Disorders; Factitious Disorder; disorder by a pharmaceutical formulation. In another Dissociative Disorders; viii) Sexual and Gender Identity embodiment, this invention relates to predicting the prob Disorders; ix). Eating Disorders; Sleep Disorders; x) ability of a Significant recovery following the treatment of Impulse-Control Disorders Not Elsewhere Classified; nervous System disorders by at least one pharmaceutical Adjustment Disorder; and xi) Personality Disorders. Neu formulation combined with a medical device. In another rologically based diseases, however, are also properly embodiment, this invention relates to predicting the prob defined in terms of a nervous System disorder. Current ability of a Significant recovery following the treatment of clinical treatment for both psychiatric disorders and neuro nervous System disorders by a formulation comprising an logical diseases is generally pharmaceutically-oriented. anticonvulsant and a neuroactive modulator. However, in psychiatric disorders an emphasis is also placed 0007 One advantage of the present invention contem upon a critical patient psychotherapy. plates a composition comprising a formulation comprising an anticonvulsant and a neuroactive modulator. In one 0003. The use of prescription drugs for psychiatric dis embodiment, the formulation comprises oXcarbazepine and orders is generally recognized, for example: i) neuroleptic or the neuroactive modulator. In one embodiment, the neuro antipsychotic drugs for Severe psychotic illness, ii) mood active modulator includes, but is not limited to, a neurotrans Stabilizing or antidepressant drugs to generally treat affec mitter reuptake inhibitor, a neurotransmitter receptor agent tive disorders, and iii) antianxiety or sedative drugs to treat or a neurotransmitter metabolic inhibitor. In one embodi anxiety States or other related conditions and vi) Stimulants ment, the neurotransmitter reuptake inhibitor comprises a to treat hyperactive or attention deficit disorders. Successful monoaminergic reuptake inhibitor. In one embodiment, the long-term treatment, however, is problematic due to physi monoaminergic reuptake inhibitor comprises bupropion. In ological adaptations involving tolerance, addiction and one embodiment, the monoaminergic reuptake inhibitor refractoriness. In addition to these shortcomings, problems comprises a noradrenergic/dopaminergic reuptake inhibitor. involving less-than-dramatic efficacy is not unusual. Baldes In one embodiment, the noradrenergic/dopaminergic Sarini R. J., “Drugs and Treatment Of Psychiatric Disorders' reuptake inhibitor comprises hydroxybupropion. In another In: Goodman and Gilman's The Pharmacological Basis Of embodiment, the monoaminergic reuptake inhibitor is a Therapeutics, Eighth Edition, Goodman et al., Eds, Perma Selective noradrenergic reuptake inhibitor. In one embodi gon Press, New York (1990). ment, the Selective noradrenergic reuptake inhibitor com 0004 Traditionally, nervous system disorders have been prises an optically pure (S,S)-hydroxybupropion. In another treated by Sequentially administering a single drug (i.e., embodiment, the form of said formulation includes, but is monotherapy) where partially effective monotherapeutic not limited to, tablets, oral liquids, intrapulmonary liquids, drugs are combined until a fully effective combination is capsules, transdermal patches, polymer-coated tablets, lipo found (i.e., a trial and error method, inherently incorporating Somes, microSpheres, aerosols, fast-dissolve compounds or a large degree of random chance). For example, the most Sterile injectable Solutions. US 2005/0118286 A1 Jun. 2, 2005 0008 One advantage of the present invention contem one embodiment, the form of the formulation is selected plates a pharmaceutical formulation comprising oXcarba
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