Composition and method for treatment of depression and psychosis in humans

• US 10,583,138 B2
• Filed: 05/24/2018
• Issued: 03/10/2020
• Est. Priority Date: 07/12/2012
• Status: Active Grant

• Current Assignee: NeuroRx, Inc. (NRX Pharmaceuticals, Inc.)
• Original Assignee: Glytech, LLC
• Inventors: Javitt, Daniel C.
• Primary Examiner(s): Barsky, Jared
• Application Number:
  US15/987,932
• Publication Number:
  US 20180263976A1
• Time in Patent Office: 656 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

Abstract

This application relates to combination compositions for use in treatment of depression, and which can alleviate the anxiogenic side effects of certain antidepressant and antipsychotic medications. Methods for treatment of depression and medicament side effects, particular anxiety, akathisia, and associated suicidality are also described herein.

Claims

1. A pharmaceutical composition for treatment of depression and associated suicidality comprising:

an NMDAR-antagonist effective amount of D-cycloserine; and

an effective amount of an atypical antipsychotic that is a combined dopamine D2/5-HT2A receptor antagonist,

wherein the NMDAR-antagonist effective amount of D-cycloserine is sufficient to produce a sustained blood plasma concentration in excess of 25 microgram/mL but lower than 125 microgram/mL, and

wherein the atypical antipsychotic is lurasidone, and wherein the effective amount of the lurasidone is between 20 mg-200 mg per day.

2. The pharmaceutical composition of claim 1, wherein the NMDAR-antagonist effective amount of D-cycloserine is in excess of 500 mg/day and less than 1000 mg.

3. The pharmaceutical composition of claim 1 wherein the NMDAR antagonist effective amount of D-cycloserine is in excess of 10 mg/kg/day, and is less than 25 mg/kg/d.

4. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is formulated for sustained release.

5. The pharmaceutical composition of claim 1, further comprising an enteric coating.

6. The pharmaceutical composition of claim 1, wherein the NMDAR-antagonist effective amount of D-cycloserine is provided as a prodrug.