COMPOSITION AND METHOD FOR TREATMENT OF DEPRESSION AND PSYCHOSIS IN HUMANS
This application relates to combination compositions for use in treatment of depression, comprising an effective amount of an N-methyl-D-aspartate receptor (NMDAR) antagonist combined with an anti-depressant agent or an atypical antipsychotic approved for treatment of depression. In a preferred embodiment, D-cycloserine is administered at a dose of about 10 mg/kg/d and is formulated to produce sustained blood levels in excess of about 25 microgram/mL.
1 . A method for treatment of depression or suicidal ideation comprising:
administering to a subject in need thereof
a first agent comprising D-cycloserine at an antagonist dose; and
a second agent comprising an anti-depressant or atypical antipsychotic, wherein the D-cycloserine is administered at a dose of ≥500 to ≤1000 mg/kg, and is formulated to produce an average plasma level in the subject of greater than 25 μg/mL, thereby treating the depression or suicide ideation.
2 . The method of claim 1 , wherein the depression is major depressive disorder or bipolar disorder.
3 . The method of claim 1 , wherein administering the first and second agents reduces symptoms of depression, the incidence of suicide, suicide ideation, or a combination thereof.
4 . The method of claim 1 wherein the second agent is selected from the group consisting of paroxetine, dapoxetine and indalpine.
5 . The method of claim 1 , wherein the first and second agents are provided in a single pharmaceutical composition.
6 . The method of claim 1 , wherein the depression is major depression.
7 . The method of claim 1 , wherein the second agent is selected from the group consisting of monoamine oxidase inhibitors (MAOI), tricyclic antidepressants (TCAs), tetracyclic antidepressants (TeCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), selective serotonin reuptake inhibitors (SSRIs), 5-HT2A antagonists, serotonin/norephinephrine (SNRI) reuptake inhibitors and atypical antidepressants.
8 . The method of claim 7 , wherein the MAOI is selected from the group consisting of isocarboxazid, phenlzine, and selegeline.
9 . The method of claim 7 , wherein the TCA is selected from the group consisting of imipramine and clomipramine.
10 . The method of claim 7 , wherein the TeCA is selected from the group consisting of amoxapine, setiptiline, maprotiline, mianserin and mirtazapine.
11 . The method of claim 7 , wherein the NDRI is selected from the group consisting of bupropion and methylphenidate.
12 . The method of claim 7 , wherein the SSRI is selected from the group consisting of sertraline, fluoxetine, citalopram, escitalopram, proxetine, fluvoxamine and trazadone.
13 . The method of claim 7 , wherein the SNRI is selected from the group consisting of venlafaxine, desvenlafaxine and duloxetine.
14 . The method of claim 7 , wherein the wherein the atypical antidepressant is selected from the group consisting of vilazodone, vortioxetine, milnacipran, and levomilnacipran.
15 . The method of claim 1 , wherein the atypical antipsychotic is selected from the group consisting of olanzapine, risperidone, and brexpiprazole.
16 . The method of claim 1 , wherein the subject has depressive or mixed episodes associated with bipolar depression.
17 . The method of claim 2 , wherein the bipolar disorder is either bipolar type I or bipolar type II depressive disorder.
18 . The method of claim 1 , wherein the depression is atypical, agitated, or melancholic depression.
19 . The method of claim 1 wherein, the depression is dysthymic disorder or is associated with mania.
20 . The method of claim 1 , wherein first agent further comprises an enteric coating.