Eszopiclone co-administered with fluoxetine in patients with insomnia coexisting with major depressive disorder.
BACKGROUND
Insomnia and major depressive disorder (MDD) can coexist. This study evaluated the effect of adding eszopiclone to fluoxetine.


METHODS
Patients who met DSM-IV criteria for both MDD and insomnia (n = 545) received morning fluoxetine and were randomized to nightly eszopiclone 3 mg (ESZ+FLX) or placebo (PBO+FLX) for 8 weeks. Subjective sleep and daytime function were assessed weekly. Depression was assessed with the 17-item Hamilton Rating Scale for Depression (HAM-D-17) and the Clinical Global Impression Improvement (CGI-I) and Severity items (CGI-S).


RESULTS
Patients in the ESZ+FLX group had significantly decreased sleep latency, wake time after sleep onset (WASO), increased total sleep time (TST), sleep quality, and depth of sleep at all double-blind time points (all p < .05). Eszopiclone co-therapy also resulted in: significantly greater changes in HAM-D-17 scores at Week 4 (p = .01) with progressive improvement at Week 8 (p = .002); significantly improved CGI-I and CGI-S scores at all time points beyond Week 1 (p < .05); and significantly more responders (59% vs. 48%; p = .009) and remitters (42% vs. 33%; p = .03) at Week 8. Treatment was well tolerated, with similar adverse event and dropout rates.


CONCLUSIONS
In this study, eszopiclone/fluoxetine co-therapy was relatively well tolerated and associated with rapid, substantial, and sustained sleep improvement, a faster onset of antidepressant response on the basis of CGI, and a greater magnitude of the antidepressant effect.
Fava
Maurizio
M
Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA 02114, USA. mfava@partners.org
McCall
W Vaughn
WV
Krystal
Andrew
A
Wessel
Thomas
T
Rubens
Robert
R
Caron
Judy
J
Amato
David
D
Roth
Thomas
T
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000627:therapeutic use; D053961:Azabicyclo Compounds; D003866:Depressive Disorder / Q000150:complications* / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D012650:Self Disclosure; D012720:Severity of Illness Index; D012890:Sleep / Q000187:drug effects; D007319:Sleep Initiation and Maintenance Disorders / Q000150:complications* / Q000188:drug therapy* / Q000523:psychology; D013997:Time Factors; D016896:Treatment Outcome
D018687:Antidepressive Agents, Second-Generation; D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; D005473:Fluoxetine; C515050:zopiclone