Elsevier

Biological Psychiatry

Volume 59, Issue 11, 1 June 2006, Pages 1052-1060
Biological Psychiatry

Original article
Eszopiclone Co-Administered With Fluoxetine in Patients With Insomnia Coexisting With Major Depressive Disorder

https://doi.org/10.1016/j.biopsych.2006.01.016Get rights and content

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.

Section snippets

Methods and Materials

This randomized, double-blind, placebo-controlled, parallel-group study was conducted at 67 sites in the United States. The study consisted of subjects with MDD and comorbid insomnia treated daily for 10 weeks with fluoxetine hydrochloride (starting dose 20 mg; dose range: 20–40 mg/day) and randomized to also receive either eszopiclone 3 mg or placebo nightly for 8 weeks, followed by a 2-week single-blind placebo run-out period. All patients gave written informed consent, the institutional

Patient Disposition

A total of 985 patients were screened for study inclusion; 545 of screened patients were randomized and received treatment, and 373 (68.4%) of the randomized patients completed the trial. The three main reasons for screen failures were: 1) patients did not complete three daily diary calls during the baseline period required for randomization, 2) patients had a positive urine drug screen, and 3) patients did not meet the minimum score for the HAM-D-17. The overall discontinuation rates and

Discussion

The present trial is the first large-scale, double-blind, randomized clinical trial of adjunctive use of an FDA-approved insomnia treatment with an SSRI for treatment of insomnia coexisting with a new episode of MDD. In this study, eszopiclone/fluoxetine co-therapy was associated with rapid, substantial, and sustained improvement on the self-reported sleep end points beginning the first night of treatment and continuing throughout the 8-week treatment period. Self-report measures of daytime

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