Delivery Of Esketamine For The Treatment Of Depression

Abstract

The present invention provides devices and methods for treating depression in a patient, comprising administering to the patient in need of the treatment a therapeutically effective amount of esketamine. In some embodiments, the depression is major depressive disorder or treatment resistant depression. In other embodiments, the therapeutically effective amount is clinically proven safe and/or effective. Also provided are methods to mitigate the risk or misuse or abuse of esketamine, instructions for use of the esketamine product, and methods for selling a drug product containing esketamine.

1 . A method for administering esketamine to a human patient in need thereof, wherein said method comprises dispensing said esketamine from a device that comprises:
 a proximal end, and a distal end that is offset from the proximal end along a distal direction;   a housing configured to house a drug product therein;   a plunger that extends from the proximal end towards the distal end along the distal direction, and that is translatable relative to the housing along the distal direction, and a proximal direction that is opposite the distal direction;   a tip that extends from the distal end towards the proximal end and is configured to be received in a nasal passage; and   a nose rest that extends outwardly away from the housing and that is configured to rest against a nostril when the tip is received in a nasal passage,   wherein said dispensing achieves a maximum plasma concentration (C max ) of esketamine of 45 to about 165 ng/mL and an area under the plasma concentration-time curve from time 0 to time of last quantifiable concentration (AUC last ) of about 125 to about 490 ng*h/mL, or a combination thereof.   
     
     
         2 . The method of  claim 1 , wherein said device contains about 28 mg of esketamine and said dispensing achieves a maximum plasma concentration (C max ) of esketamine of about 45 to about 75 ng/mL, an area 456 under the plasma concentration-time curve from time 0 to time of last quantifiable concentration (AUC last ) of about 125 to about 185 ng*h/mL, or a combination thereof. 
     
     
         3 . The method of  claim 1 , wherein said device contains about 56 mg of esketamine and dispensing achieves a maximum plasma concentration (C max ) of esketamine of about 65 to about 120 ng/mL, an area under the plasma concentration-time curve from time 0 to time of last quantifiable concentration (AUC last ) of about 210 to about 320 ng*h/mL, or a combination thereof. 
     
     
         4 . The method of  claim 1 , wherein said device comprises about 84 mg of esketamine and said dispensing achieves a maximum plasma concentration (C max ) of about 90 to about 165 ng/mL, an area under the plasma concentration-time curve from time 0 to time of last quantifiable concentration (AUC last ) of about 305 to about 490 ng*h/mL, or a combination thereof. 
     
     
         5 . The method of  claim 1 , wherein the esketamine is administered to a patient that is supervised by a healthcare professional. 
     
     
         6 . The method of  claim 1 , wherein the esketamine is administered in two sprays from said device. 
     
     
         7 . The method of  claim 6 , wherein one spray is administered to each nostril of said patient. 
     
     
         8 . The method of  claim 6 , wherein the single device is discarded following the second spray. 
     
     
         9 . The method of  claim 1 , wherein the esketamine is administered in conjunction with an oral antidepressant. 
     
     
         10 . The method of  claim 9 , wherein the human patient is being treated for depression and said esketamine is being administer in an induction phase, wherein the induction phase has a duration of about 4 weeks comprising:
 intranasally administering about 28 mg to about 84 mg of esketamine per induction phase treatment session to said patient, wherein the induction phase treatment session occurs at a frequency of twice weekly during the induction phase.   
     
     
         11 . The method of  claim 10 , wherein the depression the human patient is being treated for is treatment-resistant depression. 
     
     
         12 . The method of  claim 11 , wherein subsequent to the induction phase there is a maintenance phase comprising:
 intranasally administering about 56 mg to about 84 mg of esketamine per maintenance phase treatment session to said patient, wherein the maintenance phase treatment session occurs at a frequency of at most once weekly during the maintenance phase.   
     
     
         13 . The method of  claim 12 , wherein the human patient is treated with the induction phase and maintenance phase to avoid cognitive impairment.