Composition and method for treatment of depression and psychosis in humans

• US 10,660,887 B2
• Filed: 07/16/2017
• Issued: 05/26/2020
• Est. Priority Date: 07/12/2012
• Status: Active Grant

• Current Assignee: Glytech, LLC
• Original Assignee: Glytech, LLC
• Inventors: Javitt, Daniel C.
• Primary Examiner(s): Barsky, Jared
• Application Number:
  US15/650,912
• Publication Number:
  US 20170312275A1
• Time in Patent Office: 1,045 Days
• Field of Search: None
• 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 31/06 the aromatic ring being substituted by nitro groups
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 31/42 Oxazoles
• CPC Class Codes: A61K 31/431 containing further heterocyclic rings, e.g. ticarcillin, azlocillin, oxacillin
• CPC Class Codes: A61K 31/4525 containing a five-membered ring with oxygen as a ring hetero atom
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 31/553 having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
• CPC Class Codes: A61K 31/554 having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Compositions and methods for the treatment of depression and psychoses in humans are disclosed. More particularly, the invention is directed to formulations containing antipsychotic and/or antidepressant medications and also containing an NMDAR antagonist. The present Invention Is also directed to methods tor the treatment of humans suffering from depression and other psychoses, including, schizophrenia, by administration of the inventive compositions in antidepressant and/or antipsychotic effective amounts.

Claims

1. A method for reducing at least one anxiogenic side effect of a selective 5-HT2A antagonist, the method comprising:

administering to the subject an anxiogenic side effect-inducing amount of

a selective 5-HT2A antagonist selected from the group consisting of volinanserin (MDL-100907), eplivanserin (SR-46,349), pimavanserin, and pruvanserin (EMD-281,014);

once akathisia is induced, continuing to administer the selective 5-HT2A antagonist at a same dosage and frequency that caused the anxiogenic side effect; and

administering a therapeutically effective amount of a second composition comprising D-cycloserine (DCS) at a dosage in excess of 500 mg/day, wherein the DCS produces a NMDA receptor antagonistic blood plasma concentration measured at greater than 25 micrograms/mL, thereby reducing the anxiogenic side effect.

2. The method of claim 1, wherein the subject has a neuropsychiatric disorder.

3. The method of claim 2, wherein the neuropsychiatric disorder is a depressive disorder.

4. The method of claim 3, wherein the depressive disorder is bipolar disorder.

5. The method of claim 3, wherein the depressive disorder is major depressive disorder.

6. The method of claim 1, wherein the selective 5-HT2A antagonist and the second composition are administered intramuscularly, intravenously, intraperitoneally, parentally, or orally.

7. The method of claim 1, wherein the selective 5-HT2A antagonist and the second composition are formulated as a single composition for administration to the subject.

8. The method of claim 1, wherein the anxiogenic side effect s akathisia.

9. A method for administering a selective 5-HT2A receptor antagonist to a subject, but with reduced anxiogenic side effects, the method comprising:

administering to a subject in need thereof

an effective, side-effect-inducing amount of a selective 5-HT2A receptor antagonist selected from the group consisting of volinanserin (MDL-100907), eplivanserin (SR-46,349), pimavanserin, and pruvanserin (EMD-281,014); and

a therapeutically effective amount of D-cycloserine (DCS) at a dosage in excess of 500 mg/day, wherein the administration of DCS produces a NMDA receptor antagonistic blood plasma concentration measured at greater than 25 micrograms/mL.

10. The method claim 9, wherein the subject has a neuropsychiatric disorder.

11. The method of claim 10, wherein the neuropsychiatric disorder is a depressive disorder.

12. The method of claim 11, wherein the depressive disorder is bipolar disorder.

13. The method of claim 11, wherein the depressive disorder is major depressive disorder.

14. The method of claim 9, wherein the selective 5-HT2A antagonist and the DCS are administered intramuscularly, intravenously, intraperitoneally, parentally, or orally.

15. The method of claim 9, wherein the wherein the 5-HT2A antagonist and the DCS are formulated as a single composition for administration to the subject.

16. The method of claim 9, wherein the anxiogenic side effect is akathisia.