Compositions and methods for treating psychiatric disorders

Abstract

Methods of treating psychiatric disorders are provided which include administration of one or more anti-epileptic agents and, optionally, one or more a psychostimulants. Also provided are pharmaceutical compositions comprising, in combination, one or more anti-epileptic agents and one or more psychostimulants. Psychiatric disorders include those associated with impaired cognitive processing, degenerative disorders such as Mild Cognitive Impairment, Parkinson's disease, dementia, non-compliance with therapeutic regimes and eating disorders, although without limitation thereto.

1 . A method of treating a psychiatric disorder other than epilepsy, bipolar disorder or attention deficit hyperactivity disorder (ADHD), in a subject in need thereof, including the step of administering to the subject one or more anti-epileptic agents, or a pharmaceutically acceptable salt thereof, to thereby treat the psychiatric disorder, wherein the amount of anti-epileptic agent is subtherapeutic for mood stabilization, treatment of epilepsy or epileptic symptoms. 
     
     
         2 . A method of treating a psychiatric disorder other than epilepsy, bipolar disorder or attention deficit hyperactivity disorder (ADHD), in a subject in need thereof, including the step of administering to the subject one or more anti-epileptic agents, or a pharmaceutically acceptable salt thereof, and one or more psychostimulants, or pharmaceutically acceptable salt thereof, to thereby treat the psychiatric disorder, wherein the amount of anti-epileptic agent is subtherapeutic for mood stabilization, treatment of epilepsy or epileptic symptoms. 
     
     
         3 . The method of  claim 1 , wherein the psychiatric disorder is selected from: a psychiatric disorder associated with an impairment or deficiency in higher order executive functioning; a psychiatric disorder other than a developmental disorder; a degenerative disorder; a psychotic disorder; an eating disorder; and a psychiatric disorder associated with reduced compliance or non-compliance with a medication regime including administration of a therapeutic agent other than, or in addition to, the psychostimulant. 
     
     
         4 . The method of  claim 1 , which is not a Communication Disorder; a Pervasive Development Disorder; or an Anxiety Disorder. 
     
     
         5 . The method of  claim 1 , wherein the psychiatric disorder is selected from the group consisting of: degenerative disorders and/or movement disorders, dementia and Mild Cognitive Impairment addiction; reduced adherence, or non-compliance, with a medication regime; eye gaze-associated disorders; dysthymia; psychotic disorders; eating disorders; sleep disorders; and personality disorders. 
     
     
         6 . The method of  claim 1 , wherein a single anti-epileptic agent is administered. 
     
     
         7 . The method of  claim 1 , wherein two or more anti-epileptic agents are administered. 
     
     
         8 . The method of  claim 1 , wherein the amount of anti-epileptic agent(s) is less than 50% of the daily dose of anti-epileptic agent typically effective in mood stabilization or treating epilepsy or epileptic symptoms. 
     
     
         9 . The method of  claim 8 , wherein the amount of anti-epileptic agent is less than 40%, 30%, 20% or 10% of the daily dose of anti-epileptic agent typically effective in mood stabilization or treating epilepsy or epileptic symptoms. 
     
     
         10 . The method of  claim 1 , wherein the anti-epileptic agent is selected from the group consisting of: AMPA antagonists, Benzodiazepines, Barbiturates, Valproates, GABA analogs, Iminostilbenes, Hydantoins, NMDA antagonists, Sodium channel blockers, Carboxylic acids, oxazolidinediones, succinimides, pyrrolidines, sulphonamides, aminobutyric acids, sulfamate-substituted monosaccharides, carboxamides, aromatic allylic alcohols, ureas, phenyltriazines, carbamates, pyrrolidines, losigamone, retigabine, rufinamide (1[(2,6 difluorophenyl)methyl]triazole-4-carboxamide), SPD 421 (DP-VPA), T-2000, XP-13512, acetazolamide, clomthiazole edisilate, zonisamide, felbamate, topiramate, tiagabine, levetiracetam, briveracetam, GSK-362115, GSK-406725, ICA-69673, CBD cannabis derivative, isovaleramide (NPS-1776), RWJ-333369 (carisbamate), safmamide, seletracetam, soretolide, stiripentol, and valrocemide. 
     
     
         11 . The method of  claim 10 , wherein the anti-epileptic agent is selected from the group consisting of: carbamazepine, clobazam, clonazepam, ethosuximide, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenyloin, pregabalin, primidone, retigabine, rufinamide, talampanel, tiagabine, topiramate, valproate or derivatives thereof, vigabatrin and zonisamide. 
     
     
         12 . The method of  claim 11 , wherein the anti-epileptic agent is selected from the group consisting of: valproate or derivatives thereof, rufinamide, topiramate, and phenyloin. 
     
     
         13 . The method of  claim 2 , wherein the psychostimulant is selected from the group consisting of: Adrafmil, Amantadine, Armodafinil, Carphedon, Modafinil, 4-Fluoroamphetamine, 4-Fluoromethamphetamine, 4-Methylmethcathinone, 4-MTA, α-PPP, Amphechloral, Amphetamine, Dextroamphetamine, Adderall, Amphetaminil, Benzphetamine, Bupropion, Cathinone, Chlorphentermine, Clobenzorex, Clortermine, Cypenamine, Diethylpropion, Dimethoxyamphetamine, Dimethylamphetamine, Dimethylcathinone, Diphenyl prolinol, Ephedrine, Epinephrine, Ethcathinone, Ethylamphetamine, Fencamfamine, Fenethylline, Fenfluramine, Fenproporex, Feprosidnine, Furfenorex, Levomethamphetamine, Lisdexamfetamine, L-lysine-d-amphetamine, MDMA, Mefenorex, Methamphetamine, Methcathinone, Methoxyphedrine, Methylone, Octopamine, Parahydroxyamphetamine, PMA, PMEA, PMMA, PPAP, Phendimetrazine, Phenmetrazine, Phentermine, Phenylephrine, Phenylpropanolamine, Prolintane, Propylamphetamine, Pseudoephedrine, Selegiline, Synephrine, Tenamphetamine, Xylopropamine; piperazines, BZP, MeOPP, MBZP, mCPP, 2C-B-BZP, Tropanes, Brasofensine, CFT, Cocaethylene, Cocaine, Dimethocaine, Lometopane, PIT, PTT, RTI-121, Tesofensine, Troparil, WF-23, WF-33, Cholinergics, Arecoline, Cotinine, Convulsants, Bicuculline, Gabazine, Pentetrazol, Picrotoxin, Strychnine, Thujone; Phenylaminooxazoles, 4-Methyl-aminorex, Aminorex, Clominorex, Fenozolone, Fluminorex, Pemoline, Thozalinone, Amineptine, Bemegride, BPAP, Clenbuterol, Clofenciclan, Cyclopentamine, Cyprodenate, Desoxypipradrol, Ethylphenidate, Ethamivan, Gilutensin, GYKI-52895, Hexacyclonate, Indanorex, Indatraline, Isometheptene, Mazindol, MDPV, Mesocarb, methylphenidate, Dexmethylphenidate, Naphthylisopropylamine, Nikethamide, Nocaine, Nomifensine, Phacetoperane, Phthalimidopropiophenone, Pipradrol, Prolintane, Propylhexedrine, Pyrovalerone, Tuamine, Vanoxerine, Yohimbine, Zylofuramine, Deanol, Diethylaminoethanol, Dimefline Hydrochloride, Etilamfetamine Hydrochloride, Fencamfamin Hydrochloride, Fenetylline Hydrochloride, Fenfluramine Hydrochloride, Fenproporex Hydrochloride, Lobeline Hydrochloride, Pentetrazol, and Propylhexedrine. 
     
     
         14 . A pharmaceutical composition comprising, in combination, one or more anti-epileptic agents, or a pharmaceutically acceptable salt thereof, and one or more psychostimulants, or pharmaceutically acceptable salt thereof; together with a pharmaceutically acceptable carrier, diluent and/or excipient; wherein the amount of anti-epileptic agent is sub-therapeutic for mood stabilization, treatment of epilepsy or epileptic symptoms. 
     
     
         15 . A pharmaceutical kit comprising a first pharmaceutical composition comprising (i) one or more anti-epileptic agents or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier, diluent and/or excipient and (ii) a second pharmaceutical composition comprising one or more psychostimulants together with a pharmaceutically acceptable carrier, diluent and/or excipient; wherein the amount of anti-epileptic agent is sub-therapeutic for mood stabilization treatment of epilepsy or epileptic symptoms. 
     
     
         16 . The pharmaceutical kit of  claim 15 , wherein the first pharmaceutical composition is provided as a dosage unit containing a dose of anti-epileptic agent which is sub-therapeutic for mood stabilization or epilepsy. 
     
     
         17 . The pharmaceutical composition of  claim 14 , wherein the anti-epileptic agent is selected from the group consisting of: AMPA antagonists, Benzodiazepines, Barbiturates, Valproates, GABA analogs, Iminostilbenes, Hydantoins, NMDA antagonists, Sodium channel blockers, Carboxylic acids, oxazolidinediones, succinimides, pyrrolidines, sulphonamides, aminobutyric acids, sulfamate-substituted monosaccharides, carboxamides, aromatic allylic alcohols, ureas, phenyltriazines, carbamates, pyrrolidines, losigamone, retigabine, rufmamide (1[(2,6 difluorophenyl)methyl]triazole-4-carboxamide), SPD 421 (DP-VPA), T-2000, XP-13512, acetazolamide, clomthiazole edisilate, zonisamide, felbamate, topiramate, tiagabine, levetiracetam, briveracetam, GSK-362115, GSK-406725, ICA-69673, CBD cannabis derivative, isovaleramide (NPS-1776), RWJ-333369 (carisbamate), saxinamide, seletracetam, soretolide, stiripentol, and valrocemide. 
     
     
         18 . The pharmaceutical composition of  claim 17 , wherein the anti-epileptic agent is selected from the group consisting of: carbamazepine, clobazam, clonazepam, ethosuximide, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenyloin, pregabalin, primidone, retigabine, rufmamide, talampanel, tiagabine, topiramate, valproate or derivatives thereof, vigabatrin and zonisamide. 
     
     
         19 . The pharmaceutical composition of  claim 18 , wherein the anti-epileptic agent is selected from the group consisting of: valproate or derivatives thereof, rufmamide, topiramate, and phenyloin. 
     
     
         20 . The pharmaceutical composition of  claim 14 , wherein the amount of anti-epileptic agent is less than 50% of the daily dose of anti-epileptic agent typically effective in mood stabilization or in treating epilepsy or epileptic symptoms when used alone. 
     
     
         21 . The pharmaceutical composition of  claim 20 , wherein the amount of anti-epileptic agent is less than 40%, 30%, 20% or 10% of the daily dose of anti-epileptic agent typically effective in mood stabilization or in treating epilepsy or epileptic symptoms when used alone. 
     
     
         22 . The pharmaceutical composition of  claim 14 , wherein the psychostimulant is selected from the group consisting of: Adrafinil, Amantadine, Armodafinil, Carphedon, Modafinil, 4-Fluoroamphetamine, 4-Fluoromethamphetamine, 4-Methylmethcathinone, 4-MTA, α-PPP, Amphechloral, Amphetamine, Dextroamphetamine, Adderall, Amphetaminil, Benzphetamine, Bupropion, Cathinone, Chlorphentermine, Clobenzorex, Clortermine, Cypenamine, Diethylpropion, Dimethoxyamphetamine, Dimethylamphetamine, Dimethylcathinone, Diphenyl prolinol, Ephedrine, Epinephrine, Ethcathinone, Ethylamphetamine, Fencamfamine, Fenethylline, Fenfluramine, Fenproporex, Feprosidnine, Furfenorex, Levomethamphetamine, Lisdexamfetamine, L-lysine-d-amphetamine, MDMA, Mefenorex, Methamphetamine, Methcathinone, Methoxyphedrine, Methylone, Octopamine, Parahydroxyamphetamine, PMA, PMEA, PMMA, PPAP, Phendimetrazine, Phenmetrazine, Phentermine, Phenylephrine, Phenylpropanolamine, Prolintane, Propylamphetamine, Pseudoephedrine, Selegiline, Synephrine, Tenamphetamine, Xylopropamine; piperazines, BZP, MeOPP, MBZP, mCPP, 2C-B-BZP, Tropanes, Brasofensine, CFT 3  Cocaethylene, Cocaine, Dimethocaine, Lometopane, PIT, PTT, RTI-121, Tesofensine, Troparil, WF-23, WF-33, Cholinergics, Arecoline, Cotinine, Convulsants, Bicuculline, Gabazine, Pentetrazol, Picrotoxin, Strychnine, Thujone; Phenylaminooxazoles, 4-Methyl-aminorex, A minorex, Clominorex, Fenozolone, Fluminorex, Pemoline, Thozalinone, Amineptine, Bemegride, BPAP, Clenbuterol, Clofenciclan, Cyclopentamine, Cyprodenate, Desoxypipradrol, Ethylphenidate, Ethamivan, Gilutensin, GYKI-52895, Hexacyclonate, Indanorex, Indatraline, Isonietheptene, Mazindol, MDPV, Mesocarb, methylphenidate, Dexmethylphenidate, Naphthylisopropylamine, Nikethamide, Nocaine, Nomifensine, Phacetoperane, Phthalimidopropiophenone, Pipradrol, Prolintane, Propylhexedrine, Pyrovalerone, Tuamine, Vanoxerine, Yohimbine, Zylofuramine, Deanol, Diethylaminoethanol, Dimefline Hydrochloride, Etilamfetamine Hydrochloride, Fencamfamin Hydrochloride, Fenetylline Hydrochloride, Fenfluramine Hydrochloride, Fenproporex Hydrochloride, Lobeline Hydrochloride, Pentetrazol, and Propylhexedrine. 
     
     
         23 . The pharmaceutical composition of  claim 14 , wherein the ratio of administered anti-epileptic agent to psychostimulant agent is selected from the group consisting of: (i) from about 1:800 to 800:1; from about 1:400 to 400:1; from about 1:100 to 100:1; from about 1:10 to 10:1; from about 1:5 to 5:1; from about 1:2 to 2:1; and about 1:1. 
     
     
         24 . The pharmaceutical composition of  claim 14  comprising: (a) from about 0.1 mg to 50 mg sodium valproate, or a derivative thereof, and from 0.1 to 20 mg dextroamphetamine sulphate; (b) from about 1 mg to 400 mg sodium valproate, or a derivative thereof, and from 1 to 200 mg dextroamphetamine sulphate; (c) from about 0.5 mg to 80 mg topiramate and from 1 to 400 mg methylphenidate; (d) from about 0.5 mg to 80 mg topiramate and from 1 to 200 mg dextroamphetamine sulphate; (e) from about 0.25 mg to 80 mg phenyloin and from 1 to 400 mg methylphenidate; (f) from about 0.25 mg to 80 mg phenyloin and dextroamphetamine sulphate from about 1 to 200 mg; (g) from about 0.5 mg to 200 mg rufinamide and from 1 to 400 mg methylphenidate; or (h) from about 0.5 mg to 200 mg rufinamide and from 1 to 200 mg dextroamphetamine sulphate. 
     
     
         25 . The pharmaceutical composition of  claim 14  comprising: (A) from about 1 mg to 400 mg sodium valproate, or a derivative thereof, and from about 1 to 80 mg Phenyloin and from about 1 to 200 mg dextroamphetamine sulphate; (B) from about 1 mg to 2000 mg sodium valproate, or a derivative thereof, and from about 1 to 80 mg Phenyloin and from about 1 to 200 mg dextroamphetamine sulphate; (C) from about 1 mg to 2000 mg sodium valproate, or a derivative thereof, and from about 1 to 80 mg Topiramate and from about 1 to 200 mg dextroamphetamine sulphate; or (D) from about 1 mg to 2000 mg sodium valproate, or a derivative thereof, and from about 1 to 80 mg Phenyloin and from about 1 to 400 mg methylphenidate. 
     
     
         26 . The pharmaceutical composition of  claim 14 , which is in an administrable dosage form selected from the group consisting of a tablet, a multiparticulate formulation for oral administration; a solution, a sustained release formulation, a suspension or elixir for oral administration, an injectable formulation, an implantable device, a topical preparation, a solid state and or depot type transdermal delivery device(s), a suppository, a buccal tablet, and an inhalation formulation such as a controlled release particle formulation or spray, mist or other topical vehicle, intended to be inhaled or instilled into the sinuses. 
     
     
         27 . The pharmaceutical composition of  claim 26 , further defined as a solid oral dosage form formulated as a tablet or capsule. 
     
     
         28 . The method of  claim 2 , wherein the anti-epileptic agent, or a pharmaceutically acceptable salt thereof, and the psychostimulant, or pharmaceutically acceptable salt thereof, are administered in the form of a pharmaceutical composition comprising, in combination, one or more anti-epileptic agents, or a pharmaceutically acceptable salt thereof, and one or more psychostimulants, or pharmaceutically acceptable salt thereof; together with a pharmaceutically acceptable carrier, diluent and/or excipient; wherein the amount of anti-epileptic agent is sub-therapeutic for mood stabilization, treatment of epilepsy or epileptic symptoms.