Esketamine for the treatment of depression

Abstract

The present invention provides methods of maintaining stable remission or stable response achieved by a patient with depression following administration of a therapeutically effective amount of esketamine during an initial administration phase, comprising continuing administration of a therapeutically effective amount of esketamine for at least five months during a subsequent administration phase. The present invention also provides methods for the long term treatment of depression in a patient, comprising administering to the patient in need of the treatment a clinically proven safe and clinically proven effective therapeutically effective amount of esketamine for at least six months. In some embodiments, the depression is major depressive disorder or treatment resistant depression.

What is claimed is: 
     
         1 . A method of delaying time to relapse in a patient having treatment resistant depression, the method having an induction phase of 4 weeks, and a subsequent maintenance phase, comprising
 intranasally administering an aqueous formulation comprising esketamine and/or a pharmaceutically acceptable salt thereof in the induction phase to provide a therapeutically effective amount of about 56 mg or about 84 mg of esketamine per induction phase treatment session to the patient, wherein the induction phase treatment session occurs at a frequency of twice weekly during the induction phase; and   intranasally administering an aqueous formulation comprising esketamine and/or a pharmaceutically acceptable salt thereof in the maintenance phase to provide a therapeutically effective amount of about 56 mg or about 84 mg of esketamine per maintenance phase treatment session to the patient, wherein the maintenance phase treatment session occurs at a frequency of once weekly or once every other week during the maintenance phase; and   co-administering a therapeutically effective amount of one or more oral antidepressants during the induction phase and the maintenance phase;   wherein the patient achieves stable remission or stable response and thereafter continues the maintenance phase treatment sessions and co-administering of the one or more oral antidepressants during the maintenance phase.   
     
     
         2 . The method of  claim 1 , wherein the patient continues the maintenance phase treatment sessions and co-administering of the one or more oral antidepressants for at least 9 weeks. 
     
     
         3 . The method of  claim 1 , wherein the patient continues the maintenance phase treatment sessions and co-administering of the one or more oral antidepressants for at least 17 weeks. 
     
     
         4 . The method of  claim 1 , wherein the patient continues the maintenance phase treatment sessions and co-administering of the one or more oral antidepressants for at least 25 weeks. 
     
     
         5 . The method of  claim 1 , wherein the patient continues the maintenance phase treatment sessions and co-administering of the one or more oral antidepressants for at least 33 weeks. 
     
     
         6 . The method of  claim 1 , wherein the patient continues the maintenance phase treatment sessions and co-administering of the one or more oral antidepressants for at least 61 weeks. 
     
     
         7 . The method of  claim 1 , wherein the patient continues the maintenance phase treatment sessions and co-administering of the one or more oral antidepressants for at least 81 weeks. 
     
     
         8 . The method of  claim 1 , wherein the aqueous formulation comprises esketamine hydrochloride during the induction phase and maintenance phase. 
     
     
         9 . The method of  claim 1 , wherein the esketamine hydrochloride is present in a concentration in the range of from about 160 mg/mL to about 163 mg/mL, based on the total volume of the aqueous formulation. 
     
     
         10 . The method of  claim 1 , wherein the patient achieves stable response. 
     
     
         11 . The method of  claim 1 , wherein the patient achieves stable remission. 
     
     
         12 . The method of  claim 1 , wherein the one or more oral antidepressants is a serotonin and norepinephrine reuptake inhibitor (SNRI), a selective serotonin reuptake inhibitor (SSRI), or combination thereof. 
     
     
         13 . The method of  claim 1 , wherein the time to relapse is delayed relative to a patient that achieves stable remission or stable response being treated with one or more oral antidepressants without co-administration of esketamine and thereafter continues administration of the one or more oral antidepressants without co-administration of esketamine. 
     
     
         14 . The method of  claim 13  wherein the one or more antidepressants is a serotonin and norepinephrine reuptake inhibitor (SNRI), a selective serotonin reuptake inhibitor (SSRI), or combination thereof. 
     
     
         15 . The method of  claim 14 , wherein the aqueous formulation comprises esketamine hydrochloride during the induction phase and maintenance phase. 
     
     
         16 . The method of  claim 8 , wherein the esketamine hydrochloride is present in a concentration in the range of from about 160 mg/mL to about 163 mg/mL, based on the total volume of the aqueous formulation. 
     
     
         17 . The method of  claim 8 , wherein the patient achieves stable response. 
     
     
         18 . The method of  claim 8 , wherein the patient achieves stable remission. 
     
     
         19 . The method of  claim 8 , wherein the one or more oral antidepressants is a serotonin and norepinephrine reuptake inhibitor (SNRI), a selective serotonin reuptake inhibitor (SSRI), or combination thereof. 
     
     
         20 . The method of  claim 8 , wherein the time to relapse is delayed relative to a patient that achieves stable remission or stable response being treated with one or more oral antidepressants without co-administration of esketamine and thereafter continues administration of the one or more oral antidepressants without co-administration of esketamine. 
     
     
         21 . The method of  claim 20  wherein the one or more antidepressants is a serotonin and norepinephrine reuptake inhibitor (SNRI), a selective serotonin reuptake inhibitor (SSRI), or combination thereof. 
     
     
         22 . The method of  claim 1 , wherein the patient achieves the stable remission or stable response after 16 weeks of the initial maintenance phase treatment sessions. 
     
     
         23 . The method of  claim 22 , wherein the aqueous formulation comprises esketamine hydrochloride during the induction phase and maintenance phase. 
     
     
         24 . The method of  claim 23 , wherein the esketamine hydrochloride is present in a concentration in the range of from about 160 mg/mL to about 163 mg/mL, based on the total volume of the aqueous formulation. 
     
     
         25 . The method of  claim 23 , wherein the patient achieves stable response. 
     
     
         26 . The method of  claim 23 , wherein the patient achieves stable remission. 
     
     
         27 . The method of  claim 23 , wherein the one or more oral antidepressants is a serotonin and norepinephrine reuptake inhibitor (SNRI), a selective serotonin reuptake inhibitor (SSRI), or combination thereof. 
     
     
         28 . The method of  claim 23 , wherein the patient continues the maintenance phase treatment sessions and co-administering of the one or more oral antidepressants for at least 81 weeks. 
     
     
         29 . The method of  claim 22 , wherein the time to relapse is delayed relative to a patient that achieves stable remission or stable response after 16 weeks of the initial maintenance phase treatment sessions and thereafter continues with the administration of the one or more oral antidepressants without co-administration of esketamine.