Abstract
This study investigated the effects of open-label fluoxetine (20 mg/d) on the polysomnogram (PSG) in depressed outpatients (n = 58) who were treated for 5 weeks, after which dose escalation was available (≤40 mg/d), based on clinical judgment. Thirty-six patients completed all 10 weeks of acute phase treatment and responded (HRS-D≤ 10). PSG assessments were conducted and subjective sleep evaluations were gathered at baseline and at weeks 1, 5, and 10. Of the 36 subjects who completed the acute phase, 17 were reevaluated after 30 weeks on continuation phase treatment and 13 after approximately 7 weeks (range 6–8 weeks) following medication discontinuation. Acute phase treatment in responders was associated with significant increases in REM latency, Stage 1 sleep, and REM density, as well as significant decreases in sleep efficiency, total REM sleep, and Stage 2 sleep. Conversely, subjective measures of sleep indicated a steady improvement during acute phase treatment. After fluoxetine was discontinued, total REM sleep and sleep efficiency were found to be increased as compared to baseline.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
American Psychiatric Association. (1987): Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised. Washington, DC, American Psychiatric Press
Armitage R, Hoffmann R, Loewy D, Moffitt A . (1989): Variations in period-analyzed EEG asymmetry in REM and NREM sleep. Psychophysiology 26: 329–336
Armitage R, Rush AJ, Trivedi M, Cain J, Roffwarg HP . (1994): The effects of nefazodone on sleep architecture in depression. Neuropsychopharmacology 10: 123–127
Armitage R, Trivedi M, Rush AJ . (1995): Fluoxetine and oculomotor activity during sleep in depressed patients. Neuropsychopharmacology 12: 159–165
Ciapparelli A, Dani A, Figura A, Gemignani A, Guazzelli M . (1992): The effects of fluoxetine (FL) on sleep pattern: A clinical and all-night EEG study in patients with major depression. J Sleep Res 1: 41
Depression Guideline Panel. (1993): Clinical Practice Guideline. Depression in Primary Care: Volume 2: Treatment of Major Depression. (AHCPR Publication No. 93-0551.) Rockville, MD, U.S. Dept. of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research.
Dorsey CM, Lukas SE, Cunningham SL . (1996): Fluoxetine-induced sleep disturbance in depressed patients. Neuropsychopharmacology 14: 437–442
Hamilton M . (1960): A rating scale for depression. J Neurol Neurosurg Psychiatry 23: 56–62
Hamilton M . (1967): Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 6: 278–296
Heiligenstein JH, Faries DE, Rush AJ, Andersen JS, Pande AC, Roffwarg HP, Dunner D, Gillin JC, James SP, Lahmeyer H, Zajecka J, Tollefson GD, Gardner DM . (1994): Latency to rapid eye movement sleep as a predictor of treatment response to fluoxetine and placebo in nonpsychotic depressed outpatients. Psychiatry Res 52: 327–339
Hendrickse WA, Roffwarg HP, Granneman BD, Orsulak PJ, Armitage R, Cain JW, Battaglia J, Debus J, Rush AJ . (1994): The effects of fluoxetine on the polysomnogram of depressed outpatients: A pilot study. Neuropsychopharmacology 10: 85–91
López-Ibor JJ Jr . (1988): The involvement of serotonin in psychiatric disorders and behavior. Br J Psychiatry 153(suppl 3):26–39
Luebke JI, Greene RW, Semba K, Kamondi A, McCarley RW, Reinder PB . (1992): Serotonin hyperpolarizes cholinergic low-threshold burst neurons in the rat laterodorsal tegmental nucleus in vitro. Proc Natl Acad Sci USA 89: 743–747
Keck PE Jr, Hudson JI, Dorsey CM, Campbell PI . (1991): Effect of fluoxetine on sleep. Biol Psychiatry 29: 618–619
Kupfer DJ, Spiker DG, Coble PA, Neil JF, Ulrich R, Shaw DH . (1981): Sleep and treatment prediction in endogenous depression. Am J Psychiatry 138: 429–434
McCarley RW . (1982): REM sleep and depression: Common neurobiological control mechanisms. Am J Psychiatry 139: 565–570
Meltzer HY, Lowy MT . (1987): The serotonin hypothesis of depression. In Meltzer HY (ed), Psychopharmacology: The Third Generation of Progress. New York, Raven Press, pp 513–526
Mitani A, Ito K, Hallanger AE, Wainer BH, Kataoka K, McCarley RW . (1988): Cholinergic projections from the laterodorsal and pedunculopontine tegmental nuclei to the pontine giganticellular tegmental field in the cat. Brain Res 451: 397–402
Nicholson AN, Pascoe PA . (1988): Studies on the modulation of the sleep-wakefulness continuum in man by fluoxetine, a 5-HT uptake inhibitor. Neuropharmacology 27: 597–602
Nofzinger EA, Reynolds III CF, Thase ME, Frank E, Jennings JR, Fasiczka AL, Sullivan LR, Kupfer DJ . (1995): REM sleep enhancement by bupropion in depressed men. Am J Psychiatry 152: 274–276
Nunez P . (1981): Electrical Fields of the Brain. New York, Oxford Universities Press
Orsulak PJ, Kenney JT, Debus JR, Crowley G, Wittman PD . (1988): Determination of the antidepressant fluoxetine and its metabolite in serum by reverse-phase HPLC, with ultraviolet detection. Clin Chem 34: 1875–1878
Rechtschaffen A, Kales A . (eds) (1968): A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. Washington, DC, National Institute of Health, (NIH Publ No. 204). US Government Printing Office.
Reynolds CF III, Kupfer DJ . (1987): Sleep research in affective illness. State-of-the-art circa 1987. Sleep 10: 199–215
Rush AJ, Cain JW, Raese J, Stewart RS, Waller DA, Debus JR . (1991): Neurobiological bases for psychiatric disorders. In Rosenberg RN (ed), Comprehensive Neurology. New York, Raven Press, pp 555–608
Rush AJ, Giles DE, Jarrett RJ, Fedlman-Koffler F, Debus JR, Weissenberger JE, Orsulak PJ, Roffwarg HP . (1989): Reduced REM latency predicts response to tricyclic medication in depressed outpatients. Biol Psychiatry 26: 61–72
Rush AJ, Giles DE, Schlesser MA, Fulton CL, Weissenburger JE, Burns CT . (1986): The Inventory for Depressive Symptomatology (IDS). Psychiatry Res 18: 65–87
Rush AJ, Gullion CM, Basco MR, Jarrett RB, Trivedi MH . (1996): The inventory of depressive symptomatology (IDS): Psychometric properties. Psychol Med 26: 477–486
Saletu B, Frey R, Krupka M, Anderer P, Grunberger J, See WR . (1991): Sleep laboratory studies on the single-dose effects of serotonin reuptake inhibitors paroxetine and fluoxetine on human sleep and awakening qualities. Sleep 14: 439–447
Schenck CS, Mahowald MW, Kim SW, O'Connor KA, Hurwitz TD . (1992): Prominent eye movements during NREM sleep and REM sleep behavior disorder associated with fluoxetine treatment of depression and obsessive-compulsive disorder. Sleep 15: 226–235
Shiromani PJ, Armstrong DM, Berkowitz A, Jeste DV, Gillin JC . (1988): Distribution of choline acetyltransferase immunoreacive somata in the feline brainstem: Implications for REM sleep generation. Sleep 11: 1–16
Siegel JM . (1990): Mechanisms of sleep control. J Clin Neurophysiol 7: 49–65
Spitzer RL, Williams JBW, Gibbon M, First MB . (1992): The Structured Clinical Interview for DSM-III-R (SCID) I: History, rationale, and description. Arch Gen Psychiatry 49: 624–629
van Bemmel AL, van den Hoofdakker RH, Beersma DGM, Bouhuys AL . (1993): Changes in sleep polygraphic variables and clinical state in depressed patients during treatment with citalopram. Psychopharmacology 113: 225–230
von Bardeleben U, Steiger A, Gerken A, Holsboer F . (1989): Effects of fluoxetine upon pharmacoendocrine and sleep-EEG parameters in normal controls. Int Clin Psychopharmacol 4(Suppl 1):1–5
Vogel GW, Buffenstein A, Minter K, Hennessey A . (1990): Drug effects on REM sleep and on endogenous depression. Neurosci Biobehav Rev 14: 49–63
Acknowledgements
The authors wish to express their appreciation to John R. Debus, M.D., Jeff Bostic, M.D., Terry Cook, L.V.N., and David Dunnam, B.S., for assistance with data collection; Darwynn Cole, and the technical staff of the Sleep Study Unit; to Fastword Inc., of Dallas, David Savage and Theresa Ranne, for their secretarial assistance; and to Kenneth Z. Altshuler, M.D., Stanton Sharp Distinguished Chair, Professor and Chairman, for his administrative support. This study was supported in part by a contract from Eli Lilly and Company and a grant from the National Alliance for Research in Schizophrenia and Depression (Dr. Trivedi).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Trivedi, M., Rush, A., Armitage, R. et al. Effects of Fluoxetine on the Polysomnogram in Outpatients with Major Depression. Neuropsychopharmacol 20, 447–459 (1999). https://doi.org/10.1016/S0893-133X(98)00131-6
Received:
Revised:
Accepted:
Issue date:
DOI: https://doi.org/10.1016/S0893-133X(98)00131-6
Keywords
This article is cited by
-
Continuous home cage monitoring of activity and sleep in mice during repeated paroxetine treatment and discontinuation
Psychopharmacology (2023)
-
Agomelatine treatment corrects impaired sleep-wake cycle and sleep architecture and increases MT1 receptor as well as BDNF expression in the hippocampus during the subjective light phase of rats exposed to chronic constant light
Psychopharmacology (2020)
-
Preliminary Evidence for a Relationship Between Sleep Disturbance and Global Attributional Style in Depression
Cognitive Therapy and Research (2012)
-
Sleep disturbances and suicidality: a common association to look for in clinical practise and preventive care
EPMA Journal (2011)
-
Altered sleep architecture and higher incidence of subsyndromal depression in low endogenous melatonin secretors
European Archives of Psychiatry and Clinical Neuroscience (2010)
