US 2011 0207718A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0207718A1 Bird (43) Pub. Date: Aug. 25, 2011 (54) COMPOSITIONS AND METHODS FOR A63L/466 (2006.01) TREATING PSYCHATRIC DISORDERS A6II 3/4458 (2006.01) A63/492 (2006.01) (75) Inventor: Philip Bird, Maroochydore (AU) A6IP 25/18 (2006.01) A6IP 25/28 (2006.01) (73) Assignee: GOSFORTH CENTRE A6IP 25/00 (2006.01) (HOLDINGS) PTY LTD., A6IP3/00 (2006.01) Maroochydore (AU) A6IP 25/22 (2006.01) A6IP 25/14 (2006.01) 1-1. A6IP27/02 (2006.01) (22) PCT Filed: Aug. 6, 2009 A6IP 25/08 (2006.01) (86). PCT No.: PCT/AU2O09/OO1OOO (52) U.S. Cl. ......... 514/217: 514/557; 514/454: 514/391; 514/317; 514/359 S371 (c)(1), (2), (4) Date: May 6, 2011 (57) ABSTRACT (30) Foreign Application Priority Data Methods of treating psychiatric disorders are provided which include administration of one or more anti-epileptic agents Aug. 6, 2008 (AU) ................................ 20O8904O16 and, optionally, one or more a psychostimulants. Also pro Aug. 6, 2008 (AU) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 20O8904O21 vided are pharmaceutical compositions comprising, in com bination, one or more anti-epileptic agents and one or more Publication Classification psychostimulants. Psychiatric disorders include those asso (51) Int. Cl. ciated with impaired cognitive processing, degenerative dis A6 IK3I/55 (2006.01) orders such as Mild Cognitive Impairment, Parkinson's dis A6 IK3I/I9 (2006.01) ease, dementia, non-compliance with therapeutic regimes A6 IK3I/36 (2006.01) and eating disorders, although without limitation thereto. US 2011/0207718A1 Aug. 25, 2011 COMPOSITIONS AND METHODS FOR the gains in motivation provided by the stimulant will inevi TREATING PSYCHATRC DSORDERS tably wane resulting in the associated return of symptoms. FIELD OF THE INVENTION SUMMARY OF THE INVENTION 0004. The present inventor has extended initial observa 0001 THIS INVENTION relates to therapy of psychiatric tions in treating ADHD and certain other DSM-IV-TR disor disorders using anti-epileptic agents, alone or in combination ders with anti-epileptic agents, alone or in combination with with a psychoStimulant. In particular, the invention relates to a psychoStimulant, to treatment of other psychiatric disor methods and compositions for treating psychiatric disorders ders. Particularly, although not exclusively, the present inven associated with impaired, abnormal or reduced cognitive pro tion addresses a significant need for effective treatment cessing, particularly that which enables higher executive options for therapy of psychiatric disorders with an underly functioning. ing defect or abnormality in cognitive processes associated with higher order executive functioning. 0005. In a first aspect the invention provides a method of BACKGROUND OF THE INVENTION treating a psychiatric disorder other than epilepsy, bipolar disorder or attention deficit hyperactivity disorder (ADHD), 0002 Cognitive processing enables humans to selectively in a subject in need thereof, including the step of administer attend, filter, reflect and prioritise incoming information and ing to the Subject one or more anti-epileptic agents, or phar integrate this with thoughts and ideas. These processes are maceutically acceptable salt thereof, to thereby treat the psy particularly important for higher executive function. Execu chiatric disorder, wherein the amount of anti-epileptic agent tive functions are necessary for goal-directed behavior. They is sub-therapeutic for mood stabilization treatment of epi include the ability to initiate and stop actions, to monitor and lepsy or epileptic symptoms. change behavior as needed, and to plan future behavior when faced with novel tasks and situations. Executive functions 0006. In a second aspect, the invention provides one or include a set of cognitive abilities that control and regulate more anti-epileptic agents, or pharmaceutically acceptable other abilities and behaviours, to allow humans to anticipate salt thereof, for use in treating a psychiatric disorder other outcomes and adapt to changing situations. Further, the abil than epilepsy, bipolar disorder or attention deficit hyperactiv ity to form new concepts and think abstractly is often consid ity disorder (ADHD), wherein the amount of anti-epileptic ered a component of executive function. In particular, this agent is sub-therapeutic for mood Stabilization treatment of includes the cognitive functions of sequencing, organising epilepsy or epileptic symptoms. and integrating Social information and appears to be used 0007 Preferably, the psychiatric disorder of the first and during the complex interpersonal interaction which forms the second aspects is not a DSM-IV-TR Communication Disor basis of human social communication and interaction. Defec der, Pervasive Development Disorder or Anxiety Disorder. tive or abnormal cognitive processing can therefore become 0008. In a third aspect, the invention provides a method of apparent in behaviours that are controlled by higher executive treating a psychiatric disorder other than epilepsy, bipolar functioning. Defects in cognitive processing may result in disorder or attention deficit hyperactivity disorder (ADHD), hyper-focusing on a specific topic during conversation and/or in a subject in need thereof, including the step of administer an inability to process simultaneously the multiple lines of ing to the Subject one or more anti-epileptic agents, or phar thought that usually and automatically take place in normal maceutically acceptable salt thereof, and one or more psy Social interaction. Instead the individual may select a pre chostimulants, orpharmaceutically acceptable salt thereof, to ferred, more comfortable, and probably more familiar topic. thereby treat the psychiatric disorder, wherein the amount of As a consequence, resistance to or difficulty in following the anti-epileptic agent is Sub-therapeutic for mood stabilization natural flow of conversation is apparent. treatment of epilepsy or epileptic symptoms. 0003. Furthermore, compliance with pharmacotherapy is 0009. In a fourth aspect, the invention provides one or a long standing and difficult problem with individuals both more anti-epileptic agents, or pharmaceutically acceptable with and without attention and concentration impairment. salt thereof, and one or more psychoStimulants, or pharma Reduced compliance affects and potentially limits the effi ceutically acceptable salt thereof, in combination for use in cacy of all interventions, frequently being the most limiting treating a psychiatric disorder other than epilepsy, bipolar factor in providing Sustained psychotherapeutic benefit. For disorder or attention deficit hyperactivity disorder (ADHD), example, the 12 month compliance rate for use of psycho wherein the amount of anti-epileptic agent is Sub-therapeutic stimulants in adults is approximately 33%. The core areas of for mood stabilization treatment of epilepsy or epileptic impairment appear to be in the sequence and organisation of symptoms. thoughts. This is seen clinically with adults with a diagnosis 0010. In one embodiment of the aforementioned aspects, of attention deficit hyperactivity disorder (ADHD); a DSM the psychiatric disorder is associated with an impairment or IV-TR disorder as described in the Fourth Edition of the deficiency in higher order executive functioning. Diagnostic and Statistical Manual of Mental Disorders 0011. In another embodiment of the aforementioned (American Psychiatric Association, 2000), and Snyder, Nuss aspects, the psychiatric disorder is not a developmental dis baum, & Robins (Eds.), 2006, ibid (especially Box 2) and order or a disorder usually diagnosed in infancy, childhood or Weiss & Murray, 2003 and most commonly treated with adolescence. psychostimulants. The initial and at times dramatic improve 0012. In yet another embodiment of the aforementioned ment frequently gives way to a returning disorganisation, and aspects, the psychiatric disorder is a degenerative disorder. non-adherence with medication and an eventual cessation of 0013. In still yet another embodiment of the aforemen treatment. Unless there is a concurrent improvement in the tioned aspects, the psychiatric disorder is a psychotic disor automatic and effortless ability to process Social information, der. US 2011/0207718A1 Aug. 25, 2011 0014. In still yet another embodiment of the aforemen 1:10 to 10:1, about 1:5 to 5:1, about 1:4 to 4:1, about 1:3 to tioned aspects, the psychiatric disorder is associated with 3:1, about 1:2 to 2:1, or about 1:1 reduced adherence, or non-compliance, with a medication 0025. In other preferred embodiments, the respective regime that includes the administration of a therapeutic agent amounts of anti-epileptic agent and psychoStimulant may be other than, or in addition to, a psychoStimulant. (a) from about 0.1 mg to 50 mg sodium valproate, or a deriva 0.015. In a further embodiment of the aforementioned tive thereof, and from 0.1 to 20 mg dextroamphetamine sul aspects, the psychiatric disorder is an eating disorder. phate; (b) from about 1 mg to 400 mg sodium valproate, or a 0016. In certain particular embodiments, the psychiatric derivative thereof, and from 1 to 200 mg dextroamphetamine disorder is selected from the group consisting of degenerative Sulphate; (c) from about 0.5 mg to 80 mg topiramate and from disorders and/or movement disorders such as Parkinson's 1 to 400 mg methylphenidate; (d) from about 0.5 mg to 80 mg disease, dementia