COMPOSITIONS AND METHODS FOR TREATING PSYCHIATRIC DISORDERS

• US 20110207718A1
• Filed: 08/06/2009
• Published: 08/25/2011
• Est. Priority Date: 08/06/2008
• Status: Abandoned Application

• Current Assignee: Gosforth Centre Holdings Pty., Ltd.
• Original Assignee: Gosforth Centre Holdings Pty., Ltd.
• Inventors: Bird, Philip
• Application Number:
  US13/057,628
• Publication Number:
  US 20110207718A1
• Time in Patent Office: Days
• US Class Current: 514/217
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/166 having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/35 having six-membered rings with one oxygen as the only ring hetero atom
• CPC Class Codes: A61K 31/4166 having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
• CPC Class Codes: A61K 31/4458 only substituted in position 2, e.g. methylphenidate
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/26 Psychostimulants, e.g. nicotine, cocaine
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 : Anorexiants; Antiobesity agents

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.

Claims

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.

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.

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.

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.

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.

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.

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, CFT₃ 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.

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.