Combination of sedative and a neurotransmitter modulator, and methods for improving sleep quality and treating depression

Abstract

One aspect of the present invention relates to pharmaceutical compositions containing two or more active agents that when taken together can be used to treat, e.g., insomnia. The first component of the pharmaceutical composition is a GABA receptor modulating compound. The second component of the pharmaceutical composition is a serotonin reuptake inhibitor, a norepinephrine reuptake inhibitor, a 5-HT 2A modulator, or dopamine reuptake inhibitor. In certain embodiments, the pharmaceutical composition comprises eszopiclone. In a preferred embodiment, the pharmaceutical composition comprises eszopiclone and fluoxetine. The present invention also relates to a method of treating a sleep abnormality, treating insomnia, treating depression, augmenting antidepressant therapy, eliciting a dose-sparing effect, reducing depression relapse, improving the efficacy of antidepressant therapy or improving the tolerability of antidepressant therapy, comprising co-administering to a patient in need thereof a GABA-receptor-modulating compound; and a SRI, NRI, 5-HT 2A modulator or DRI.

We claim: 
     
         1 . A pharmaceutical composition comprising eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a norepinephrine reuptake inhibitor. 
     
     
         2 . A pharmaceutical composition according to  claim 1  comprising eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a norepinephrine reuptake inhibitor, wherein said norepinephrine reuptake inhibitor is desipramine, maprotiline, lofepramine, reboxetine, oxaprotiline, fezolamine, tomoxetine, or (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them. 
     
     
         3 . A method of treating a patient suffering from a sleep abnormality, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of norepinephrine reuptake inhibitor. 
     
     
         4 . A method according to  claim 3  of treating a patient suffering from a sleep abnormality wherein said sleep abnormality is transient, short-term or chronic insomnia, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of a norepinephrine reuptake inhibitor. 
     
     
         5 . A pharmaceutical composition comprising eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a dopamine reuptake inhibitor. 
     
     
         6 . A pharmaceutical composition according to  claim 5  comprising eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a dopamine reuptake inhibitor, said dopamine reuptake inhibitor is amineptine, bupropion, GBR-12935, venlafaxine, desmethylvenlafaxine, or 2β-propanoyl-3β-(4-tolyl)-tropane, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them. 
     
     
         7 . A method of treating a patient suffering from a sleep abnormality, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of a dopamine reuptake inhibitor. 
     
     
         8 . A method according to  claim 7  of treating a patient suffering from a sleep abnormality wherein said sleep abnormality is transient, short-term or chronic insomnia, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of a dopamine reuptake inhibitor.