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Table of Contents
Vol. 42, No. 2, 2000
Issue release date: July 2000
Neuropsychobiology 2000;42:69–81
(DOI:10.1159/000026676)

Effects of Selective Serotonin Reuptake Inhibitors on Objective and Subjective Sleep Quality

Oberndorfer S. · Saletu-Zyhlarz G. · Saletu B.
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Abstract

The purpose of this paper is to review the effects of selective serotonin (5-HT) reuptake inhibitors on objective and subjective sleep and awakening quality measures. Polysomnography (PSG) demonstrated in both healthy volunteers and depressed patients a decrease in sleep efficiency and total sleep time, a lengthening of sleep latency and a deterioration in sleep continuity, including an increase in the number of awakenings and wake time during the total sleep period. Sleep architecture mostly showed an increase in S1 and S2 and a decrease in S3, S4 and REM sleep as well as a lengthening of REM latency. Objective awakening quality, if measured at all by psychometry, generally showed no decrements. Concerning subjective sleep and awakening quality, normals demonstrated either no changes or a tendency towards a deterioration, while in patients some improvement was observed. Reasons for this discrepancy will be discussed. Novel 5-HT reuptake inhibitors with additional modes of action such as 5-HT2 antagonism (e.g. trazodone, nefazodone) are more likely to improve objective and subjective sleep quality, although some shortcomings may be inherent in regard to comorbidity (e.g. sleep-related breathing disorders). Thus, PSG seems to be a necessity for diagnosis and treatment of complex sleep disorders.

Copyright © 2000 S. Karger AG, Basel



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References

  1. Thase M: Depression, sleep, and antidepressants. J Clin Psychiatry 1998;59(suppl 4):55–65.
  2. Reynolds C: Sleep in affective disorders; in Dryger MH, Roth T, Dement WC (eds): Principles and Practice of Sleep Medicine. Philadelphia, Saunders, 1989; pp 413–415.
  3. Armitage R, Hoffmann R: Sleep electrophysiology of major depressive disorders. Curr Rev Mood Anxiety Disord 1997;1:139–668.
  4. Lauer C, Riemann D, Wiegand M, Berger M: From early to late adulthood: Changes in EEG sleep for depressed patients and healthy volunteers. Biol Psychiatry 1991;29:979.
  5. Benca R, Obermeyer W, Thisted R, Gillin J: Sleep and psychiatric disorders. A meta-analysis. Arch Gen Psychiatry 1992;49:651–668.
  6. Sharpley A, Cowen P: Effect of pharmacologic treatments on the sleep of depressed patients. Biol Psychiatry 1995;15:85–98.

    External Resources

  7. Berger M, Riemann D, Hochli D, Spiegel R: The cholinergic rapid eye movement sleep induction test with RS 86: State or trait marker of depression? Arch Gen Psychiatry 1989;46:421–428.
  8. da Roza Davis J, Sharpley A, Solomon R, Cowen P: Sleep and 5HT2 receptor sensitivity in recovered depressed patients. J Affective Disord 1992;24:177–181.
  9. Saletu B: Psychopharmaka, Gehirntätigkeit und Schlaf. Neurophysiologische Aspekte der Psychopharmakologie und Pharmakopsychiatrie. Bibl Psychiatr. Basel, Karger, 1976, vol 155.
  10. Hindmarch I, Harrison C, Shilingford C: An investigation of the effects of lofepramine, nomefensine, amitriptyline and placebo on aspects of memory and psychomotor performance related to car driving. Int Clin Psychopharmacol 1988;3:157–165.

    External Resources

  11. Fairweather D, Kerr J, Hilton S, Hindmarch I: A placebo-controlled double-blind evaluation of the pharmacodynamics of fengabine vs amitriptyline following single and multiple doses in elderly volunteers. Br J Pharmacol 1993;35:278–283.
  12. Grimsley S, Jahn M: Paroxetine, sertraline, and fluvoxamine: New selective serotonin reuptake inhibitors. Clin Pharmacy 1992;11:930–957.
  13. Frazer A: Pharmacology of antidepressants. J Clin Psychopharmacol 1997;17(suppl 1):2–18.
  14. Tulloch I, Johnson A: Pharmacologic profile of paroxetine, a new selective serotonin reuptake inhibitor. J Clin Psychiatry 1992;53(2 suppl):7–12.
  15. Oswald I, Adam K: Effects of paroxetine on human sleep. Br J Clin Pharmacol 1986;22:97–99.

    External Resources

  16. Sharpley A, Williamson D, Attenburrow M, Pearson G, Sargent P, Cowen P: The effects of paroxetine and nefazodone on sleep: A placebo controlled trial. Psychopharmacology 1996;126:50–54.
  17. Röschke J, Kögel P, Schlösser R, Wagner P, Mann K, Rossbach W, Benkert O: Analysis of sleep EEG microstructure in subchronic paroxetine treatment of healthy subjects. Psychopharmacology 1997;132:44–49.
  18. Saletu B, Frey R, Krupka M, Anderer P, Grünberger J, See W: Sleep laboratory studies on the single-dose effects of serotonin reuptake inhibitors paroxetine and fluoxetine on human sleep and wakening qualities. Sleep 1991;14:439–447.
  19. Dilger M, Goldberg R, DiPhillip M, Fry J: REM sleep suppression and paroxetine. Sleep Res 1995;24:42.
  20. Staner L, Kerkhofs M, Detroux D, Leyman S, Linkowski P, Mendlewicz J: Acute, subchronic and withdrawal sleep EEG changes during treatment with paroxetine and amitriptyline: A double blind randomized trial in major depression. Sleep 1995;18:470–477.

    External Resources

  21. Hutchinson D, Tong S: A double blind study in general practice to compare the efficiency and tolerability of paroxetine and amitriptyline in depressed elderly patients. Br J Clin Med 1991;2:43–57.
  22. Ontiveros A, Garcia-Barriga C: A double blind comparative study of paroxetine and fluoxetine in out patients with depression. Br J Clin Res 1997;8:23–32.
  23. Dorman T: Sleep and paroxetine: A comparison with mianserin in elderly depressed patients. Int Clin Psychopharmacol 1992;6(suppl 4):53–58.
  24. Baldwin D: A multicenter double blind comparison of nefazodone and paroxetine in the treatment of outpatients with moderate to severe depression. J Clin Psychiatry 1996;57(suppl 2):46–52.
  25. Armitage R, Rush A, Trivedi M, Cain J, Roffwarg H: The effect of nefazodone on sleep architecture in depression. Neuropsychopharmacology 1994;10:123–127.
  26. Vasar V, Appelberg B, Rimon R, Selvaratnam J: The effects of fluoxetine on sleep: A longitudinal, double-blind polysomnographic study of healthy volunteers. Int Clin Psychopharmacol 1994;9:203–206.
  27. Saletu B, Grünberger J: Classification and determination of cerebral bioavailability of fluoxetine. J Clin Psychiatry 1985;46:45–52.

    External Resources

  28. Nicholson A, Pascoe P: Studies of the modulation of the sleep-wakefulness continuum in man by fluoxetine, a 5-HT uptake inhibitor. Neuropharmacology 1988;27:597–602.
  29. Keck P, Hudson J, Dorsey C, Campbell P: Effect of fluoxetine on Sleep. Biol Psychiatry 1991;29:618–619.
  30. Hendrickse W: The effects of fluoxetine on the polysomnograph of depressed outpatients: A pilot study. Neuropsychopharmacology 1994;10:85–91.
  31. Schenk C, Mahowald M, Suck Won Kim, O’Conner K, Hurwitz T: Prominent eye movement during NREM sleep and REM sleep behavior disorder associated with fluoxetine treatment of depression and obsessive-compulsive disorder. Sleep 1992;15:226–235.
  32. Gillin J, Rapaport M, Erman M, Winokur A, Albala B: A comparison of nefazodone and fluoxetine on mood and objective, subjective, and clinician rated measures of sleep in depressed patients. A double-blind, 8-week clinical trial. J Clin Psychiatry 1997;58:185–192.

    External Resources

  33. Armitage R, Yonkers K, Cole D, Rush A: A multicenter double blind comparison of the effects of nefazodone and fluoxetine on sleep architecture and quality of sleep in depressed outpatients. J Clin Psychopharmacol 1997;17:161–168.
  34. Dorsey C, Lukas S, Cunningham S: Fluoxetine-induced sleep disturbances in depressed patients. Neuropsychopharmacology 1996;14:437–442.
  35. Dossenbach M, Martenyi F, De Verga E: Sleep quality during fluoxetine therapy in depression. Biol Psychiatry 1997;42:1.
  36. Fairweather D, Kerr J, Harrison D, Moon C, Hindmarch I: A double blind comparison of the effects of fluoxetine and amitriptyline on cognitive function in elderly depressed patients. Hum Psychopharmacol 1993;8:41–47.
  37. Kerkhofs M, Rielaert C, Maertelaer V, Linkowski P, Czarka M, Mendlewicz J: Fluoxetine in major depression: Efficiency, safety and effects on sleep polysomnographic variables. Int Clin Psychopharmacol 1990;5:252–260.
  38. Rush A, Armitage R, Gillin J, Yonkers K, Winokur A, Moldofsky H, Vogel G, Kapilta S, Fleming J, Montplaisir J, Erman M, Albala B, McQuade R: Comparative effects of nefazodone and fluoxetine on sleep in outpatients with major depressive disorder. Biol Psychiatry 1998;44:3–14.
  39. Saletu B: Pharmacodynamics and EEG; in Krijzer F, Herrmann W (eds): Advances in Pharmaco-EEG. Practical and Theoretical Considerations in Preclinical and Clinical Studies. Berlin, IPEG, 1996, pp 187–204.
  40. Neckelmann D, Bjorvatn B, Bjorkum A, Ursin R: Citalopram: Differential sleep/wake and EEG-power spectrum effects after single dose and chronic administration. Behav Brain Res 1996;79:183–192.

    External Resources

  41. Van Bemmel A, Van den Hoofdakker R, Beersma D, Bouhuys A: Changes in sleep polygraphic variables and clinical state during treatment with citalopram. Psychopharmacology 1993;113:225–230.
  42. Rosenberg C, Damsbo N, Fuglum E, Jacobsen L, Horsgard S: Citalopram and imipramine in the treatment of depressive patients in general practice. A nordic multicenter clinical study. Int Clin Psychopharmacol 1994;9(suppl 1):41–48.
  43. Bech P, Cialdella P: Citalopram in depression-meta-analysis of intended and unintended effect. Int Clin Psychopharmacol 1992;6(suppl 5):45–54.
  44. Saletu B, Grünberger J, Linzmayer L, Anderer P: On central effects of serotonin reuptake inhibitors: Quantitative EEG and psychometric studies with sertraline and zimelidine. J Neural Transm 1986;67:241–266.
  45. Reimherr F, Byerley W, Ward M: Psychopharmacol Bull 1988;24:200–205.
  46. Doogan D, Caillard V: Sertraline: A new antidepressant. J Clin Psychiatry 1988;49(suppl 8):46–51.
  47. Sewitch D, Biniaur I: Sleep architecture and mood effects of sertraline in outpatients with major depression: A preliminary report. Sleep Res 1991;20:189.
  48. Winokur A, Sewitch D, Biniaur I, Phillips J: Effects of sertraline on sleep architecture in patients with major depression. Clin Neuropharmacol 1992;15(suppl 1):84B.
  49. Aguglia E, Casacchia M, Cassano G, Faravelli C, Ferrari G, Giordano P: Double blind study of the efficiency and safety of sertraline versus fluoxetine in major depression. Int Clin Psychopharmacol 1993;8:197–202.
  50. Bennie E, Mullin J, Martindale J: A double blind multicenter trial comparing sertraline and fluoxetine in outpatients with major depression. J Clin Psychiatry 1995;56:229–237.

    External Resources

  51. Saletu B, Grünberger J, Rajna P, Karobath M: Clovoxamine and fluvoxamine-2 biogenic amine reuptake inhibiting antidepressants: Quantitative EEG, psychometric and pharmacokinetic studies in man. J Neural Transm 1980;49:63–86.

    External Resources

  52. Kupfer D, Perel J: Fluvoxamine versus desipramine: Comparative polysomnographic effects. Biol Psychiatry 1991;29:23–40.
  53. Berger M, Emerich H, Lund R, Riemann D, Lauer D, Zerssen D: Schlaf EEG Variablen als Verlaufskriterien und Prädiktoren einer Antidepressivatherapie mit Fluvoxamin/Oxaprotilin; in Hippius H, Matussek N (eds): Differentialtherapie der Depression: Möglichkeiten und Grenzen. Basel, Karger, 1985, pp 120–132.
  54. Kiev A, Feiger A: A double blind comparison of fluvoxamine and paroxetine in the treatment of depressed outpatients. J Clin Psychiatry 1997;58:146–152.

    External Resources

  55. Saletu B, Schjerve M, Grünberger J, Schanda H, Arnold O: Fluoxamine – A new serotonin reuptake inhibitor: First clinical and psychometric experiences in depressed patients. J Neural Transm 1977;41:17–36.

    External Resources

  56. Vogel G, Cohen J, Mulls D, Kensler T, Kaplita S: Nefazodone and REM sleep: How do antidepressant drugs decrease REM sleep? Sleep 1998;21:70–77.

    External Resources

  57. Ware J, Rose V, McBrayer R: The effects of nefazodone, trazodone, buspirone, and placebo on sleep and sleep-related penile erections (NPT) in normal subjects. Sleep Res 1991;20:91.
  58. Sharpley A, Walsh A, Cowen P: Nefazodone – a novel antidepressant – may increase REM sleep. Biol Psychiatry 1992;31:1070–1073.
  59. Montgomery I, Oswald I, Morgan K, Adam K: Trazodone enhances sleep in subjective quality but not in objective duration. Br J Clin Pharmacol 1983;16:139–144.

    External Resources

  60. Yamadera H, Nakamura S, Suzuki H, Endo S: Effects of trazodone hydrochloride and imipramine on polysomnography in healthy subjects. Psychiatry Clin Neurosci 1998;52:439–443.
  61. Ware J, Pittard J: Increased deep sleep after trazodone use: A double-blind placebo-controlled study in healthy young adults. J Clin Psychiatry 1990;51(suppl 9):18–22.
  62. Nierenberg A, Adler L, Peselow E, Zornberg G, Rosenthal M: Trazodone for antidepressant-associated insomnia. Am J Psychiatry 1994;151:1069–1072.
  63. Mouret J, Lemoine P, Minuit M, Benkelfat C, Renardet M: Effects of trazodone on sleep of depressed patients – A polygraphic study. Psychopharmacology 1988;95:37–43.
  64. Van Bemmel A, Havermans R, van Diest R: Effects of trazodone on sleep and clinical state in major depression. Psychopharmacology 1992;107:596–574.
  65. Scharf M, Sachais B: Sleep laboratory evaluation of the effects and efficacy of trazodone in depressed insomniac patients. J Clin Psychiatry 1990;51(suppl 9):13–17.
  66. Blacker R, Shanks N, Chapman N, Davey A: The drug treatment of depression in general practice: A comparison of nocte administration of trazodone with mianserin, dothiepin and amitriptyline. Psychopharmacology 1988;95:18–24.
  67. Moon C, Davey A: The efficacy and residual effects of trazodone (150  mg nocte) and mianserin in the treatment of depressed general practice patients. Psychopharmacology 1988;95:7–13.
  68. Saletu B: Visualizing the living human brain: The techniques and promise of EEG and event-related potentials mapping; in Judd L, Saletu B, Filip V (eds): Basic and Clinical Science of Mental and Addictive Disorders. Bibl Psychiatr. Basel, Karger 1997, vol 167, pp 54–62.
  69. Giles E, Jarret B, Roffwary P, Rush J: Reduced REM latency: A predictor of recurrence in depression. Neuropsychopharmacology 1987;1:33–39.

    External Resources

  70. Kupfer D, Spiker D, Coble P, Neil J, Ulrich R, Shaw D: Sleep and treatment prediction in endogenous depression. Am J Psychiatry 1981;138:429–433.

    External Resources

  71. Rascati K: Drug utilization review of concomitant use of specific serotonin reuptake inhibitors or clomipramine with anxiety/sleep medication. Clin Ther 1995;17:786–790.

    External Resources

  72. De Montigny C, Blier P: Electrophysiological aspects of serotonin neuropharmacology: implication for antidepressant treatments; In Green AR (ed): Neuropharmacology of Serotonin. Oxford, Oxford University Press, 1985, pp 181–195.
  73. Aghajanian G, Graham A, Sheard M: Serotonin containing neurons in brain: Depression of firing by monoamine oxidase inhibitors. Science 1970;169:1100–1102.

    External Resources

  74. da Roza Davis J, Sharpley A, Cowen P: Slow-wave sleep and HT2 receptor sensitivity in generalized anxiety disorder: A pilot study with ritanserin. Psychopharmacology 1992;108:387–389.
  75. Fontaine R, Ontiveros A, Elie R: Double blind comparison of nefazodone, imipramine, and placebo in major depression. J Clin Psychiatry 1994;55:234–241.
  76. Rickels K, Schweitzer E, Clary C: Nefazodone and imipramine in major depression: A placebo controlled trial. Br J Psychiatry 1994;164:802–805.
  77. Davids R, Whittington R, Bryson H: Nefazodone: A review of its pharmacology and clinical efficiency in the management of major depression. Drugs 1997;53:608–636.
  78. Schmidt H: L-tryptophan in the treatment of impaired respiration in sleep. Bull Eur Physiopathol Respir 1983;19:625–629.
  79. Hanzel D, Proia N, Hudgel D: Response of obstructive sleep apnea to fluoxetine and protriptyline. Chest 1991;100:416–421.
  80. Kraiczi H, Hedner J, Dahlöf P, Ejnell H, Carlson J: Effect of serotonin uptake inhibition on breathing during sleep apnea and daytime symptoms in obstructive sleep apnea. Sleep 1999;22:61–67.
  81. Horner R, Innes J, Morrel M, Shea S, Guz A: The effect of sleep on reflex genioglossus muscle activation by stimuli of negative airway pressure in humans. J Physiol (Lond) 1994;645:291–302.
  82. Tangel D, Mezzanotte W, Sandberg E, White D: Influences of NREM sleep on the activity of tonic vs inspiratory phasic muscles in normal men. J Appl Physiol 1992;73:1058–1066.
  83. Remmers J, DeGroot W, Sauerland E, Anch A: Pathogenesis of upper airway occlusion during sleep. J Appl Physiol 1978;44:931–938.

    External Resources

  84. Deegan P, McNicholas W: Pathophysiology of obstructive sleep apnea. Eur Respir J 1995;8:1161–1178.
  85. Kubin L, Reignier C, Tojima H, Taguchi O, Pack A, Davies R: Changes in serotonin level in the hypoglossal nucleus region during carbachol-induced atonia. Brain Res 1994;645:291–302.
  86. Kubin L, Tojima H, Davies R, Pack A: Serotonergic excitatory drive to hypoglossal motoneurons in the decerebrate cat. Neurosci Lett 1992;139:243–248.
  87. Rose D, Khater-Boidin J, Toussaint P, Duron B: Central effects of 5-HT on respiratory and hypoglossal activities in the adult cat. Respir Physiol 1995;101:59–69.
  88. Veasey S, Panckeri K, Hoffman E, Pack A, Hendricks J: The effects of serotonin antagonists in an animal model of sleep-disordered breathing. Am J Respir Crit Care Med 1996;153:776–786.


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