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Eszopiclone Co-Administered With Fluoxetine in Patients With Insomnia Coexisting With Major Depressive Disorder
Abstract
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.
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“Both BzRAs and low-dose se -dating ADs have been evaluated as adjunctive agents to other full-dose antidepressants for treatment of comorbid insomnia in patients with depression. 63,64”
From Clinical Guideline for the Evaluation and Management of Chronic Insomnia in Adults (2008) · cites this paper as [63]
In the citing paper
“There is clinical evidence for the antidepressant effects of subtype selective GABAAR compounds as eszopiclone, a positive GABAAR modulator with postulated selectivity for α2/α3GABAARs [138], has a synergistic effect when given in combination with fluoxetine in patients with depression and insomnia [139].”
From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [139]
In the citing paper
“Moreover, co-therapy for depression and insomnia leads to better outcomes than monotherapy for depression [20].”
From The effects of exercise on sleep in unipolar depression: a systematic review and network meta-analysis (2021) · cites this paper as [20]
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Metadata
- Authors
- Fava, M., McCall, W. V., Krystal, A., Wessel, T., Rubens, R., Caron, J., Amato, D., & Roth, T.
- Affiliations
- Wake Forest University Health Sciences (US)
- Duke Medical Center (US)
- Sunovion (United States) (US)
- Henry Ford Hospital (US)
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2006-06
- Volume
- 59
- Issue
- 11
- Pages
- 1052-1060
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2000979605
- Cited by
- 480
- References
- 35
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 10 · 2023: 11 · 2022: 8 · 2021: 21 · 2020: 6 · 2019: 16 · 2018: 23 · 2017: 16 · 2016: 26 · 2015: 29 · 2014: 29 · 2013: 37 · 2012: 37
- FWCI
- 46.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Health Sciences › Medicine › Physiology (medical) › Obstructive Sleep Apnea Research
- Keywords
- eszopiclone, fluoxetine, insomnia, major depressive disorder, sleep quality, sleep latency, antidepressant response, co-therapy, daytime functioning
- MeSH terms
- Adult, Depressive Disorder, Double-Blind Method, Drug Therapy, Combination, Female, Fluoxetine, Humans, Hypnotics and Sedatives, Sleep Initiation and Maintenance Disorders, Male, Middle Aged, Piperazines, Psychiatric Status Rating Scales, Self Disclosure, Severity of Illness Index, Sleep, Time Factors, Treatment Outcome, Antidepressive Agents, Second-Generation, Azabicyclo Compounds
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