Drugs

, Volume 68, Issue 17, pp 2411–2417 | Cite as

Antidepressants for the Treatment of Insomnia

A Suitable Approach?
Current Opinion

Abstract

The popularity of antidepressants in the treatment of insomnia is not supported by a large amount of convincing data, but rather by opinions and beliefs of the prescribing physicians on the advantages of these agents compared with drugs acting on the benzodiazepine receptor or other drugs used for the treatment of insomnia. The existing data do not allow for clear-cut, evidence-based recommendations concerning the use of antidepressants in insomnia. Our conclusions result from a few short-term studies on single agents, clinical experience and inferences from knowledge on the effect of antidepressants in other indications.

At present prescribing antidepressants for short-term treatment of insomnia can be useful if there is some amount of concomitant depressive symptomology or a history of depression, raising the impression that the present insomnia may be a prodromal sign for a new depressive episode. In all other cases, benzodiazepine receptor agonists, especially the nonbenzodiazepines among them (the so-called ‘z drugs’) should be the drugs of choice.

For long-term treatment, antidepressants are among the pharmacological options, in addition to other groups of psychotropics. Off-label use of antidepressants may be considered for chronic insomnia if there is a concomitant depressive symptomalogy (which is not so pronounced that an antidepressant treatment with adequate higher doses would be required) and if there is no specific indication for one of the other groups of psychotropics (e.g. dementia-related nocturnal agitation, in which case an antipsychotic would be preferred, or circadian problems, in which case melatonin or a melatonin agonist would be favoured).

If antidepressants are used to treat insomnia, sedating ones should be preferred over activating agents such as serotonin reuptake inhibitors. In general, drugs lacking strong cholinergic activity should be preferred. Drugs blocking serotonin 5-HT2A or 5-HT2C receptors should be preferred over those whose sedative property is caused by histamine receptor blockade only. The dose should be as low as possible (e.g. as an initial dose: doxepin 25 mg, mirtazapine 15 mg, trazodone 50 mg, trimipramine 25 mg).

Regarding the lack of substantial data allowing for evidence-based recommendations, we are facing a clear need for well designed, long-term, comparative studies to further define the role of antidepressants versus other agents in the management of insomnia.

Keywords

Melatonin Paroxetine Zolpidem Mirtazapine Trazodone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

No sources of funding were used to assist in the preparation of this article. The author has received speaker honoraria from AstraZeneca, Cephalon and Servier.

References

  1. 1.
    Buscemi N, Vandermeer B, Friesen C, et al. The efficacy and safety of drug treatments for chronic insomnia in adults: a meta-analysis of RCTs. J Gen Int Med 2006; 22: 1335–50CrossRefGoogle Scholar
  2. 2.
    Nowell PD, Mazumdar S, Buysse DJ, et al. Benzodiazepines and zolpidem for chronic insomnia. J Amer Med Assoc 1997; 278: 2170–7CrossRefGoogle Scholar
  3. 3.
    Holbrook AM, Crowther R, Lotter A, et al. Meta-analysis of benzodiazepine use in the treatment of insomnia. CMAJ 2000; 162: 225–33PubMedGoogle Scholar
  4. 4.
    Smith MT, Perlis ML, Park A, et al. Comparative meta-analysis of pharmacotherapy and behavior therapy for persistent insomnia. Am J Psychiatry 2002; 159: 5–11PubMedCrossRefGoogle Scholar
  5. 5.
    Glass J, Lanctot K, Hermann N, et al. Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. Br Med J 2005; 331: 1169CrossRefGoogle Scholar
  6. 6.
    Krystal AD, Walsh JK, Laska E, et al. Sustained efficacy of eszopiclone over 6 months of nightly treatment: results of a randomized, double-blind, placebo-controlled study in adults with chronic insomnia. Sleep 2003; 26: 793–9PubMedGoogle Scholar
  7. 7.
    Walsh JK, Krystal AD, Amato DA, et al. Nightly treatment of primary insomnia with eszopiclone for six months: effect on sleep, quality of life, and work limitations. Sleep 2007; 30: 959–68PubMedGoogle Scholar
  8. 8.
    Krystal AD, Erman M, Zammit GK, et al. Long-term efficacy and safety of zolpidem extended-release 12,5 mg, administered 3 to 7 nights per week for 24 weeks, in patients with chronic primary insomnia: a 6-month, randomized, double-blind, placebo-controlled, parallel-group, multicenter study. Sleep 2008; 31: 79–90PubMedGoogle Scholar
  9. 9.
    Mendelson WB, Roth T, Cassella J, et al. The treatment of chronic insomnia: drug indications, chronic use and abuse liability. Summary of a 2001 New Clinical Drug Evaluation Unit Meeting Symposium. Sleep Med Rev 2004; 8: 7–17Google Scholar
  10. 10.
    Walsh JK, Schweitzer PK. Ten-year trends in the pharmacological treatment of insomnia. Sleep 1999; 22: 371–5PubMedGoogle Scholar
  11. 11.
    Anonymous. What's wrong with prescribing hypnotics? Drugs Ther Bull 2004; 42 (12): 89–93Google Scholar
  12. 12.
    Walsh JK. Pharmacologic management of insomnia. J Clin Psychiatry 2004; 65 Suppl. 16: 41–5CrossRefGoogle Scholar
  13. 13.
    Reite M, Ruddy J, Nagel K. Concise guide to evaluation and management of sleep disorders. 3rd ed. Washington, DC: American Psychiatric Publishing, Inc., 2002Google Scholar
  14. 14.
    Wilson S, Argyropoulos S. Antidepressants and sleep: a qualitative review of the literature. Drugs 2005; 65(7): 927–47PubMedCrossRefGoogle Scholar
  15. 15.
    Mayers AG, Baldwin DS. Antidepressants and their effect on sleep. Hum Psychopharmacol Clin Exp 2005; 20: 533–59CrossRefGoogle Scholar
  16. 16.
    Hajak G, Rodenbeck A, Voderholzer U, et al. Doxepin in the treatment of primary insomnia: a placebo-controlled, double-blind, polysomnographic study. J Clin Psychiatry 2001 Jun; 62: 453–63PubMedCrossRefGoogle Scholar
  17. 17.
    Walsh JK, Erman M, Erwin CW, et al. Subjective hypnotic efficacy of trazodone and zolpidem in DSM III-R primary insomnia. Hum Psychopharmacol Clin Exp 1998; 13: 191–8CrossRefGoogle Scholar
  18. 18.
    Riemann D, Voderholzer U, Cohrs S, et al. Trimipramine in primary insomnia: results of a polysomnographic double-blind controlled study. Pharmacopsychiatry 2002; 35: 165–74PubMedCrossRefGoogle Scholar
  19. 19.
    Buysse DJ, ReynoldsIII CF, Monk TH, et al. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989; 28: 193–213PubMedCrossRefGoogle Scholar
  20. 20.
    Görtelmeyer R. On the development of a standardized sleep inventory for assessment of sleep. In: Kubicki S, Hermann VW, editors. Methods of sleep research. Stuttgart: Fischer, 1985: 93–8Google Scholar
  21. 21.
    Hajak G, Rodenbeck A, Adler L, et al. Nocturnal melatonion secretion and sleep after doxepin administration in chronic primary insomnia. Pharmacopsychiatry 1996; 29(5): 187–92PubMedCrossRefGoogle Scholar
  22. 22.
    Wiegand MH, Galanakis P, Schreiner R. Nefazodone in primary insomnia: an open pilot study. Prog Neuropsychopharmacol Biol Psychiatry 2004; 28: 1071–8PubMedCrossRefGoogle Scholar
  23. 23.
    Nowell PD, Reynolds CF, Buysse DJ, et al. Paroxetine in the treatment of primary insomnia: preliminary clinical and electroencephalogram sleep data. J Clin Psychiatry 1999; 60: 89–95PubMedCrossRefGoogle Scholar
  24. 24.
    Hohagen F, Fritsch Montero R, Weiss E, et al. Treatment of primary insomnia with trimipramine: an alternative to benzodiazepine hypnotics? Eur Arch Psychiatry Clin Neurosci1994; 242: 329–36CrossRefGoogle Scholar
  25. 25.
    Krystal AD. The changing perspective on chronic insomnia management. J Clin Psychiatry 2004; 65 Suppl. 8: 20–5Google Scholar
  26. 26.
    Ermann MK. Therapeutic options in the treatment of insomnia. J Clin Psychiatry 2005; 66 Suppl. 9: 18–23Google Scholar
  27. 27.
    Hajak G. Therapeutics in insomnia: new paradigms in pharmacological treatment of insomnia. Sleep Med 2005; 7 Suppl. 1: S20–36Google Scholar
  28. 28.
    Wiegand MH, Landry F, Brückner T, et al. Quetiapine in primary insomnia: a pilot study. Psychopharmacology (Berl) 2008; 196: 337–8CrossRefGoogle Scholar
  29. 29.
    Hajak G, Rodenbeck A, Bandelow B, et al. Nocturnal plasma melatonin levels after flunitrazepam administration in healthy subjects. Eur Neuropsychopharmacol 1996; 6: 149–53PubMedCrossRefGoogle Scholar
  30. 30.
    Ghosh A, Hellewell JS. A review of the efficacy of agomelatine in the treatment of major depression. Expert Opin Investig Drugs 2007; 16: 1999–2004PubMedCrossRefGoogle Scholar
  31. 31.
    Adis R&D Profile. Agomelatine: AGO 178, AGO178, S 20098. Drugs R D 2008; 9: 177–83Google Scholar
  32. 32.
    Benkert O, Hippius H. Kompendium der psychiatrischen Pharmakotherapie. Heidelberg: Springer, 2007Google Scholar
  33. 33.
    Asnis GM, Chakraburtty A, DuBoff EA, et al. Zolpidem for persistent insomnia in SSRI-treated depressed patients. J Clin Psychiatry 1999; 60: 668–76PubMedCrossRefGoogle Scholar
  34. 34.
    Becker PM. Treatment of sleep dysfunction and psychiatric disorders. Curr Treat Options Neurol 2006; 8: 367–75PubMedCrossRefGoogle Scholar
  35. 35.
    Pollack M, Kinrys G, Krystal A, et al. Eszopiclone coadministered with escitalopram in patients with insomnia and comorbid generalized anxiety disorder. Arch Gen Psychiatry 2008; 65: 551–62PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  1. 1.Department of Psychiatry and Psychotherapy, Sleep Disorders CenterTechnical University of MunichMunichGermany

Personalised recommendations