Dosage Regimen, Medication Dispensing Package and Uses Thereof for the Treatment of Major Depressive Disorder

Abstract

This invention provides an oral dosage regimen for the treatment of depression, a pharmaceutically acceptable medication dispensing package containing multiple dosage units of medicaments comprising an oral dosage regimen of D-cycloserine for the treatment of depression, a pharmaceutical composition comprising D-cycloserine formulated for oral administration providing a dosage of 1000 mg/day alone or in combination with antidepressant agents and uses thereof.

1 . An oral dosage regimen consisting essentially of two active ingredients, wherein a first of said two active ingredients is D-cycloserine at a dosage of from about 500 mg/day-1200 mg/day and wherein a second of said two active ingredients is a therapeutic agent for the treatment of depression, for reduction of the incidence of suicide or for the treatment of suicide ideation in a subject or population, or a combination thereof. 
     
     
         2 . The oral dosage regimen of  claim 1 , wherein said second therapeutic agent comprises a tetracyclic antidepressant (TeCA), selective serotonin reuptake inhibitor (SSRI), a serotonin/norephinephrine reuptake inhibitor (SNRI) or a combination thereof. 
     
     
         3 . The oral dosage regimen of  claim 1 , wherein said second therapeutic agent is venlafaxine. 
     
     
         4 . The oral dosage regimen of  claim 1 , wherein said second therapeutic agent is an antipsychotic agent, which antipsychotic agent is also approved for the treatment of depression 
     
     
         5 . The oral dosage regimen of  claim 4 , wherein said antipsychotic agent is selected from the group consisting of quetiapine, risperidone, olanzapine and aripiprazole 
     
     
         6 . The oral dosage regimen of  claim 1 , wherein said two active ingredients are provided in a single pharmaceutical composition. 
     
     
         7 . The oral dosage regimen of  claim 1 , wherein said second therapeutic agent is provided at a subtherapeutic dose, if said second therapeutic agent were provided alone. 
     
     
         8 . A method for treating depression in a subject in need thereof, said method comprising providing said subject with the oral dosage regimen of  claim 1 . 
     
     
         9 . The method of  claim 8 , wherein said subject suffers from mania. 
     
     
         10 . The method of  claim 8 , wherein said subject suffers from bipolar disorder. 
     
     
         11 . The method of  claim 8 , wherein said subject has previously received treatment with an anti-depressant agent. 
     
     
         12 . The method of  claim 11 , wherein said anti-depressant agent is ketamine. 
     
     
         13 . The method of  claim 11 , wherein said anti-depressant agent is an anti-NMDA agent. 
     
     
         14 . The method of  claim 8 , wherein patients have pretreatment plasma levels ≧300 μM glycine. 
     
     
         15 . The method of  claim 8 , wherein said subject possesses a polymorphism for a GLDC allele. 
     
     
         16 . The method of  claim 8 , wherein said subject possesses a polymorphism at locus rs10975641, rs11789777, rs10975734, rs1658957, rs11612037, rs7485577, rs2988418, rs1755615 or rs12004478 of the GLDC gene. 
     
     
         17 . A method for reducing the incidence or treating suicide or suicide ideation in a subject or population in need thereof, said method comprising providing said subject with the oral dosage regimen of  claim 1 . 
     
     
         18 . The method of  claim 17 , wherein patients have pretreatment plasma levels ≧300 μM glycine. 
     
     
         19 . The method of  claim 17 , wherein said subject possesses a polymorphism for a GLDC allele. 
     
     
         20 . The method of  claim 17 , wherein said subject possesses a polymorphism at locus rs10975641, rs11789777, rs10975734, rs1658957, rs11612037, rs7485577, rs2988418, rs1755615 or rs12004478 of the GLDC gene.