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Antidepressants for the Treatment of Insomnia

A Suitable Approach?

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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.

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References

  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: 1335–50

    Article  Google Scholar 

  2. Nowell PD, Mazumdar S, Buysse DJ, et al. Benzodiazepines and zolpidem for chronic insomnia. J Amer Med Assoc 1997; 278: 2170–7

    Article  CAS  Google Scholar 

  3. Holbrook AM, Crowther R, Lotter A, et al. Meta-analysis of benzodiazepine use in the treatment of insomnia. CMAJ 2000; 162: 225–33

    PubMed  CAS  Google Scholar 

  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: 5–11

    Article  PubMed  Google Scholar 

  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: 1169

    Article  Google Scholar 

  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: 793–9

    PubMed  Google Scholar 

  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: 959–68

    PubMed  Google Scholar 

  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: 79–90

    PubMed  Google Scholar 

  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: 7–17

    Google Scholar 

  10. Walsh JK, Schweitzer PK. Ten-year trends in the pharmacological treatment of insomnia. Sleep 1999; 22: 371–5

    PubMed  CAS  Google Scholar 

  11. Anonymous. What's wrong with prescribing hypnotics? Drugs Ther Bull 2004; 42 (12): 89–93

  12. Walsh JK. Pharmacologic management of insomnia. J Clin Psychiatry 2004; 65 Suppl. 16: 41–5

    Article  Google Scholar 

  13. Reite M, Ruddy J, Nagel K. Concise guide to evaluation and management of sleep disorders. 3rd ed. Washington, DC: American Psychiatric Publishing, Inc., 2002

    Google Scholar 

  14. Wilson S, Argyropoulos S. Antidepressants and sleep: a qualitative review of the literature. Drugs 2005; 65(7): 927–47

    Article  PubMed  CAS  Google Scholar 

  15. Mayers AG, Baldwin DS. Antidepressants and their effect on sleep. Hum Psychopharmacol Clin Exp 2005; 20: 533–59

    Article  CAS  Google Scholar 

  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: 453–63

    Article  PubMed  CAS  Google Scholar 

  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: 191–8

    Article  CAS  Google Scholar 

  18. Riemann D, Voderholzer U, Cohrs S, et al. Trimipramine in primary insomnia: results of a polysomnographic double-blind controlled study. Pharmacopsychiatry 2002; 35: 165–74

    Article  PubMed  CAS  Google Scholar 

  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: 193–213

    Article  PubMed  CAS  Google Scholar 

  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: 93–8

    Google Scholar 

  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): 187–92

    Article  PubMed  CAS  Google Scholar 

  22. Wiegand MH, Galanakis P, Schreiner R. Nefazodone in primary insomnia: an open pilot study. Prog Neuropsychopharmacol Biol Psychiatry 2004; 28: 1071–8

    Article  PubMed  CAS  Google Scholar 

  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: 89–95

    Article  PubMed  CAS  Google Scholar 

  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: 329–36

    Article  Google Scholar 

  25. Krystal AD. The changing perspective on chronic insomnia management. J Clin Psychiatry 2004; 65 Suppl. 8: 20–5

    Google Scholar 

  26. Ermann MK. Therapeutic options in the treatment of insomnia. J Clin Psychiatry 2005; 66 Suppl. 9: 18–23

    Google Scholar 

  27. Hajak G. Therapeutics in insomnia: new paradigms in pharmacological treatment of insomnia. Sleep Med 2005; 7 Suppl. 1: S20–36

    Google Scholar 

  28. Wiegand MH, Landry F, Brückner T, et al. Quetiapine in primary insomnia: a pilot study. Psychopharmacology (Berl) 2008; 196: 337–8

    Article  CAS  Google Scholar 

  29. Hajak G, Rodenbeck A, Bandelow B, et al. Nocturnal plasma melatonin levels after flunitrazepam administration in healthy subjects. Eur Neuropsychopharmacol 1996; 6: 149–53

    Article  PubMed  CAS  Google Scholar 

  30. Ghosh A, Hellewell JS. A review of the efficacy of agomelatine in the treatment of major depression. Expert Opin Investig Drugs 2007; 16: 1999–2004

    Article  PubMed  CAS  Google Scholar 

  31. Adis R&D Profile. Agomelatine: AGO 178, AGO178, S 20098. Drugs R D 2008; 9: 177–83

  32. Benkert O, Hippius H. Kompendium der psychiatrischen Pharmakotherapie. Heidelberg: Springer, 2007

    Google Scholar 

  33. Asnis GM, Chakraburtty A, DuBoff EA, et al. Zolpidem for persistent insomnia in SSRI-treated depressed patients. J Clin Psychiatry 1999; 60: 668–76

    Article  PubMed  CAS  Google Scholar 

  34. Becker PM. Treatment of sleep dysfunction and psychiatric disorders. Curr Treat Options Neurol 2006; 8: 367–75

    Article  PubMed  Google Scholar 

  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: 551–62

    Article  PubMed  CAS  Google Scholar 

Download references

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.

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Correspondence to Michael H. Wiegand.

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Wiegand, M.H. Antidepressants for the Treatment of Insomnia. Drugs 68, 2411–2417 (2008). https://doi.org/10.2165/0003495-200868170-00001

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