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Cited by 215Sleep and related disordersTreatment of Major DepressionSleep and Wakefulness Research

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Comparative effects of nefazodone and fluoxetine on sleep in outpatients with major depressive disorder

Open access
Rush, A.John, Armitage, Roseanne, Gillin, J.Christian, Yonkers, Kimberly A, Winokur, Andrew, Moldofsky, Harvey, Vogel, Gerald W, Kaplita, Stephen B, Fleming, Jonathan B, Montplaisir, Jacques, Erman, Milton K, Albala, Bruce J, McQuade, Robert D·1998·Biological Psychiatry
DOI 10.1016/s0006-3223(98)00092-4
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Abstract

BACKGROUND: Sleep disturbances are common in major depressive disorder. In previous open-label trials, nefazodone improved sleep continuity and increased rapid eye movement (REM) sleep, while not affecting stage 3/4 sleep or REM latency: in contrast, fluoxetine suppressed REM sleep. This study compared the objective and subjective effects of nefazodone and fluoxetine on sleep. METHODS: This paper reports combined results of three identical, multisite, randomized, double-blind, 8-week, acute-phase trials comparing nefazodone (n = 64) with fluoxetine (n = 61) in outpatients with nonpsychotic major depressive disorder and insomnia. Sleep electroencephalographic (EEG) recordings were gathered at baseline and weeks 2, 4, and 8. Clinical ratings were obtained at weeks 1-4, 6, and 8. RESULTS: Nefazodone and fluoxetine were equally effective in reducing depressive symptoms; however, nefazodone differentially and progressively increased (while fluoxetine reduced) sleep efficiency and reduced (while fluoxetine increased) the number of awakenings in a linear fashion over the 8-week trial. Fluoxetine, but not nefazodone, prolonged REM latency and suppressed REM sleep. Nefazodone significantly increased total REM sleep time. Clinical evaluations of sleep quality were significantly improved with nefazodone compared with fluoxetine. CONCLUSIONS: Nefazodone and fluoxetine were equally effective antidepressants. Nefazodone was associated with normal objective, and clinician- and patient-rated assessments of sleep when compared with fluoxetine. These differential sleep EEG effects are consistent with the notion that nefazodone and fluoxetine may have somewhat different modes and spectra of action.

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  • Sleep was significantly less efficient, and nocturnal awakenings were significantly greater, with fluoxetine (20-40mg) when compared to nefazodone (100-500mg).

    “(Rush et al., 1998) found that sleep was significantly less efficient, and nocturnal awakenings were significantly greater, with fluoxetine (20-40mg) when compared to nefazodone (100-500mg).”

    From Antidepressants and their effect on sleep (2005) · cites this paper as Rush et al., 1998

    The Effects on Sleep section reports significantly lower sleep efficiency and more awakenings with fluoxetine than with nefazodone, and the Results section confirms the fluoxetine range of 20–40 mg/day. The nefazodone range is imprecise: the Treatment section says it began at 100 mg twice daily, while Results gives a daily dose range of 200–500 mg, not 100–500 mg/day. Page numbers are unavailable in our copy. (LLM, conf=0.85)

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  • Fluoxetine significantly suppressed REM sleep, while nefazodone significantly increased the time spent in REM sleep.

    “Fluoxetine significantly suppressed REM sleep, while nefazodone significantly increased the time spent in REM sleep.”

    From Antidepressants and their effect on sleep (2005) · cites this paper as Rush et al., 1998

  • Nefazodone was associated with less nocturnal disturbance than fluoxetine.

    “Previous analyses indicated that nefazodone was associated with less nocturnal disturbance than fluoxetine (Rush et al., 1998) or paroxetine (Hicks et al., 2002).”

    From Antidepressants and their effect on sleep (2005) · cites this paper as Rush et al., 1998

  • In patients receiving nefazodone, total REM sleep time increased, in contrast to the expected REM suppression associated with fluoxetine treatment.

    “study demonstrated an increase in total REM sleep time in patients receiving nefazodone in contrast to the expected REM suppression associated with fluoxetine treatment [Rush et al., 1998].”

    From Depression, sleep physiology, and antidepressant drugs (2001) · cites this paper as Rush et al., 1998

  • In recent studies comparing nefazodone and fluoxetine in 125 patients with major depression, clinical efficacy was comparable for both groups.

    “Recent studies compared the effects of nefazodone and fluoxetine on sleep parameters in 125 patients with major depression [Gillin et al., 1997;Armitage et al., 1997;Rush et al., 1998].Standard dosing regimen were employed for both drugs in these studies.Clinical efficacy was comparable for both groups.”

    From Depression, sleep physiology, and antidepressant drugs (2001) · cites this paper as Rush et al., 1998

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Citations

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Research works printed but not linked: 30

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Metadata

Authors
Rush, A. J., Armitage, R., Gillin, J. C., Yonkers, K. A., Winokur, A., Moldofsky, H., Vogel, G. W., Kaplita, S. B., Fleming, J. B., Montplaisir, J., Erman, M. K., Albala, B. J., & McQuade, R. D.
Affiliations
  • The University of Texas Southwestern Medical Center (US)
  • University of California San Diego (US)
  • Hospital of the University of Pennsylvania (US)
  • University of Toronto (CA)
  • Emory University (US)
  • Bristol-Myers Squibb (United States) (US)
  • University of British Columbia (CA)
  • Hôpital du Sacré-Cœur de Montréal (CA)
  • Scripps Clinic Medical Group (US)
Corresponding author
Rush, A.John
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
1998-07
Volume
44
Issue
1
Pages
3-14
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/s0006-3223(98)00092-4
OpenAlex
W2084065055
Cited by
215
References
3
Citations by year
2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 6 · 2017: 2 · 2016: 5 · 2015: 4 · 2014: 6 · 2013: 6 · 2012: 5
FWCI
13.22
Type
journal article
Language
en
Open access
Licence
Locations
  • Biological Psychiatry (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Bristol-Myers Squibb
  • University of Texas Southwestern Medical Center
  • National Institute of Mental Health (P50MH041115)
Topics
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Keywords
nefazodone, fluoxetine, major depressive disorder, insomnia, sleep disorders, REM sleep, REM latency, sleep efficiency, sleep EEG, antidepressant effects on sleep, outpatients
MeSH terms
Adult, Ambulatory Care, Circadian Rhythm, Depressive Disorder, Double-Blind Method, Electroencephalography, Female, Fluoxetine, Humans, Sleep Initiation and Maintenance Disorders, Male, Middle Aged, Piperazines, Receptors, Serotonin, Sleep, Sleep, REM, Triazoles, Wakefulness, Comorbidity, Selective Serotonin Reuptake Inhibitors, Antidepressive Agents, Second-Generation

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