Compositions and methods for treating middle-of-the-night insomnia

Abstract

The present invention provides compositions and methods for treating middle-of-the-night insomnia without residual sedative effects upon awakening by dosing an amount of zolpidem or a salt thereof to a subject who awakens from sleep and desires to resume sleep for less than 5 hours. The step of dosing is performed after the subject awakens from sleep and the amount permits the subject to awaken at a time about four hours after dosing without residual sedative effects.

1 . A method of treating MOTN insomnia in a subject, comprising the steps of:
 dosing a solid pharmaceutical composition comprising an effective sleep-inducing amount of zolpidem or a salt thereof to a subject who awakens from sleep and desires to resume sleep for less than 5 hours,   wherein the solid pharmaceutical composition comprises about 1.5 mg to about 2.0 mg or 3.0 mg to about 3.75 mg of zolpidem hemitartrate or a molar equivalent amount of a pharmaceutically acceptable form of zolpidem,   wherein the step of dosing the solid pharmaceutical composition is performed after the subject awakens from sleep,   wherein the subject has a plasma level of greater than 20 ng/ml within 20 minutes of dosing,   wherein the solid pharmaceutical composition dissolves or disintegrates in about 10 minutes or less in the subject's mouth, and   wherein said amount permits the subject to awaken at a time about four hours after dosing without residual sedative effects.   
     
     
         2 . The method of  claim 1 , wherein the solid pharmaceutical composition further comprises a binder and a disintegrating agent. 
     
     
         3 . The method of  claim 1 , wherein the solid pharmaceutical composition is administered sublingually. 
     
     
         4 . The method of  claim 3 , wherein the solid pharmaceutical composition further comprises a carbonate buffer and bicarbonate buffer that raise the pH of a subject's saliva to a pH greater than 7.8. 
     
     
         5 . The method of  claim 1 , wherein a mean peak plasma concentration of zolpidem between about 20 to about 100 ng/ml is produced within about 30 minutes. 
     
     
         6 . The method of  claim 1 , wherein a therapeutically effective amount of zolpidem enters the bloodstream within about 30 minutes. 
     
     
         7 . The method of  claim 1 , wherein the solid pharmaceutical composition is a lozenge. 
     
     
         8 . The method of  claim 1 , wherein the solid pharmaceutical composition is a tablet. 
     
     
         9 . The method of  claim 1 , wherein the solid pharmaceutical composition further comprises sodium stearyl fumarate. 
     
     
         10 . A method of treating MOTN insomnia in a subject without administering zolpidem before initial sleep onset, comprising the steps of:
 dosing a solid pharmaceutical composition comprising an effective sleep-inducing amount of zolpidem or a salt thereof to a subject who awakens from sleep and desires to resume sleep for less than 5 hours,   wherein the solid pharmaceutical composition comprises about 1.5 mg to about 2.0 mg or 3.0 mg to about 3.75 mg of zolpidem hemitartrate or a molar equivalent amount of a pharmaceutically acceptable form of zolpidem,   wherein the step of dosing the solid pharmaceutical composition is performed after the subject awakens from sleep,   wherein the subject has a plasma level of greater than 20 ng/ml within 20 minutes of dosing, and   wherein said amount permits the subject to awaken at a time about four hours after dosing without residual sedative effects.   
     
     
         11 . The method of  claim 10 , wherein the solid pharmaceutical composition further comprises a binder and a disintegrating agent. 
     
     
         12 . The method of  claim 10 , wherein the solid pharmaceutical composition is administered sublingually. 
     
     
         13 . The method of  claim 12 , wherein the solid pharmaceutical composition further comprises a carbonate buffer and bicarbonate buffer that raise the pH of a subject's saliva to a pH greater than 7.8. 
     
     
         14 . The method of  claim 10 , wherein a mean peak plasma concentration of zolpidem between about 20 to about 100 ng/ml is produced within about 30 minutes. 
     
     
         15 . The method of  claim 10 , wherein a therapeutically effective amount of zolpidem enters the bloodstream within about 30 minutes. 
     
     
         16 . The method of  claim 10 , wherein the solid pharmaceutical composition is a lozenge. 
     
     
         17 . The method of  claim 10 , wherein the solid pharmaceutical composition is a tablet. 
     
     
         18 . The method of  claim 10 , wherein the solid pharmaceutical composition further comprises sodium stearyl fumarate. 
     
     
         19 . The method of  claim 10 , wherein the solid pharmaceutical composition dissolves or disintegrates in about 10 minutes or less in the subject's mouth.