Comparative effects of nefazodone and fluoxetine on sleep in outpatients with major depressive disorder.
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.
Rush
A J
AJ
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas 75235-9086, USA.
Armitage
R
R
Gillin
J C
JC
Yonkers
K A
KA
Winokur
A
A
Moldofsky
H
H
Vogel
G W
GW
Kaplita
S B
SB
Fleming
J B
JB
Montplaisir
J
J
Erman
M K
MK
Albala
B J
BJ
McQuade
R D
RD
D000328:Adult; D000553:Ambulatory Care; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology / Q000627:therapeutic use*; D002940:Circadian Rhythm / Q000187:drug effects; D015897:Comorbidity; D003866:Depressive Disorder / Q000188:drug therapy* / Q000453:epidemiology; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines; D011985:Receptors, Serotonin / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy* / Q000453:epidemiology; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use*; D014851:Wakefulness / Q000187:drug effects
D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D010879:Piperazines; D011985:Receptors, Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014230:Triazoles; C051752:nefazodone