The Efficacy and Safety of Drug Treatments for Chronic Insomnia in Adults: A Meta-analysis of RCTs

  • Nina Buscemi
  • Ben Vandermeer
  • Carol Friesen
  • Liza BialyEmail author
  • Michelle Tubman
  • Maria Ospina
  • Terry P. Klassen
  • Manisha Witmans
Clinical Review



Hypnotics have a role in the management of acute insomnia; however, the efficacy and safety of pharmacological interventions in the management of chronic insomnia is unclear.


The objective of this paper is to conduct a systematic review of the efficacy and safety of drug treatments for chronic insomnia in adults.

Data Sources

Twenty-one electronic databases were searched, up to July 2006.

Study Selection

Randomized double-blind, placebo-controlled trials were eligible. Quality was assessed using the Jadad scale. Data were pooled using the random effects model.

Data Synthesis

One hundred and five studies were included in the review. Sleep onset latency, as measured by polysomnography, was significantly decreased for benzodiazepines (BDZ), (weighted mean difference: −10.0 minutes; 95% CI: −16.6, −3.4), non-benzodiazepines (non-BDZ) (−12.8 minutes; 95% CI: −16.9, −8.8) and antidepressants (ADP) (−7.0 minutes; 95% CI: −10.7, −3.3). Sleep onset latency assessed by sleep diaries was also improved (BDZ: −19.6 minutes; 95% CI: −23.9, −15.3; non-BDZ: −17.0 minutes; 95% CI: −20.0, −14.0; ADP: −12.2 minutes; 95% CI: −22.3, −2.2). Indirect comparisons between drug categories suggest BDZ and non-BDZ have a similar effect. All drug groups had a statistically significant higher risk of harm compared to placebo (BDZ: risk difference [RD]: 0.15; non-BDZ RD: 0.07; and ADP RD: 0.09), although the most commonly reported adverse events were minor. Indirect comparisons suggest that non-BDZ are safer than BDZ.


Benzodiazepines and non-benzodiazepines are effective treatments in the management of chronic insomnia, although they pose a risk of harm. There is also some evidence that antidepressants are effective and that they pose a risk of harm.


drug treatment chronic insomnia 



We are grateful to members of the technical expert panel for providing input on the direction of the review.

Financial Support

This study was conducted under contract to the Agency for Healthcare Research and Quality (Contract No.C400_000_021), Rockville, MD., funded by the Office of Medical Applications of Research, National Institutes of Health, Bethesda, MD. The study was presented at the NIH State_of_the_Science Conference on Manifestations and Management of Chronic Insomnia in Adults in June 2005.


The authors of this article are responsible for its contents, including any clinical or treatment recommendations. No statement in this article should be construed as an official position of the Agency for Healthcare Research and Quality, the Office of Medical Applications of Research or the U.S. Department of Health and Human Services.

Conflict of Interest

The corresponding author declares, on behalf of all authors, that there are no conflicts of interest to disclose.None disclosed


  1. 1.
    Sateia MJ, Doghramji K, Hauri P, Morin CM. Evaluation of chronic insomnia. An American Academy of Sleep Medicine Review. Sleep 2000;23:1–66.Google Scholar
  2. 2.
    Ford D, Kamerow D. Epidemiological study of sleep disturbances and psychiatric disorders: an opportunity for prevention. JAMA 1989;262:1479–84.PubMedCrossRefGoogle Scholar
  3. 3.
    Simon GE, VonKorff M. Prevalence, burden, and treatment of insomnia in primary care. Am J Psychiatry. 1997;54:1417–23.Google Scholar
  4. 4.
    Leger D, Guilleminault C, Bader G, Levy E, Paillard M. Medical and socio-professional impact of insomnia. Sleep 2002;25:625–9.PubMedGoogle Scholar
  5. 5.
    Ohayon M. Epidemiological study on insomnia in the general population. Sleep 1996;19(3 suppl):S7–15.PubMedGoogle Scholar
  6. 6.
    Roberts RE, Shema SJ, Kaplan GA. Prospective data on sleep complaints and associated risk factors in an older cohort. Psychosom Med. 1999;61:188–96.PubMedGoogle Scholar
  7. 7.
    Foley DJ, Monjan A, Simonsick EM, Wallace RB, Blazer DG. Incidence and remission of insomnia among elderly adults: an epidemiologic study of 6,800 persons over three years. Sleep 1999;22(suppl 2):S366–72.PubMedGoogle Scholar
  8. 8.
    Breslau N, Roth T, Rosenthal L, Andreski P. Sleep disturbances and psychiatric disorders: a longitudinal epidemiological study of young adults. Biol Psychiatry. 1996;39:411–18.PubMedCrossRefGoogle Scholar
  9. 9.
    Wiessman MM, Greenwald A, NinoMurcia G, Dement WC. The morbidity of insomnia uncomplicated by psychiatric disorders. Gen Hosp Psychiatry. 1997;19:245–50.CrossRefGoogle Scholar
  10. 10.
    NIH 1983. Drugs and Insomnia: The Use of Medications To Promote Sleep. NIH Consens Statement Online 1983 Nov 5–17 [cited 2005 08 29];4(10):1–19.Google Scholar
  11. 11.
    NIH 1990. The Treatment of Sleep Disorders of Older People. NIH Consens Statement Online 1990 Mar 26–28 [cited 2005 08 29];8(3):1–22.Google Scholar
  12. 12.
    Nowell PD, Mazumdar S, Buysse DJ, Dew MA, Kupfer DJ. Benzodiazepines and zolpidem for chronic insomnia: meta-analysis of treatment efficacy. J Am Med Assoc. 1997;278:2170–7.CrossRefGoogle Scholar
  13. 13.
    Holbrook AM, Crowther R, Lotter A, Cheng C, King D. Meta-analysis of benzodiazepine use in the treatment of insomnia. Can Med Assoc J. 2000;162:225–33.Google Scholar
  14. 14.
    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.PubMedCrossRefGoogle Scholar
  15. 15.
    Glass J, Lanctot K, Hermmnn N, Sproule BA, Busto U. Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. BMJ 2005;331:1169.PubMedCrossRefGoogle Scholar
  16. 16.
    Dunbar Y, Dodd S, Strobl J, Boland A, Dickson R, Wally T. Comparative efficacy of newer hypnotic agents for the short-term management of insomnia: a systematic review and meta-analysis. Human Psychopharmacol Clin Exp. 2004;19:305–322.CrossRefGoogle Scholar
  17. 17.
    Buscemi N, Vandermeer B, Friesen C, et al. Manifestations and management of chronic insomnia in adults. Evid Rep Technol Assess (Summ). 2005 Jun;(125):1–10.Google Scholar
  18. 18.
    Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12.PubMedCrossRefGoogle Scholar
  19. 19.
    Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. Am Med Assoc. 1995;273:408–12.CrossRefGoogle Scholar
  20. 20.
    Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.PubMedCrossRefGoogle Scholar
  21. 21.
    Deeks JJ, Altman DG, Bradburn MJ. Statistical methods for examining heterogeneity and combining results from several studies in meta-analysis. In: Eggar M, Smith GD, Altman DG, eds. Systematic Reviews in Health Care: Meta-analysis in context. 3rd ed. London: BMJ Publishing Group; 2001:285–312.Google Scholar
  22. 22.
    Bucher HC, Guyatt GH, Griffith LE, et al. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol. 1997;50:683–691.PubMedCrossRefGoogle Scholar
  23. 23.
    Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994;50:1088–101.PubMedCrossRefGoogle Scholar
  24. 24.
    Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. Br Med J. 1997;315:629–34.Google Scholar
  25. 25.
    Duval S, Tweedie R. A nonparametric “tim and fill” method of accounting for publication bias in meta-analysis. J Am Med Assoc. 2000;95:89–98.Google Scholar
  26. 26.
    Light RJ, Pillemer DB. Summing up. The science of reviewing research. Cambridge, MA: Harvard University Press; 1984.Google Scholar
  27. 27.
    Walsh JK, Schweitzer PK. Ten-year trends in the pharmacological treatment of insomnia. Sleep 1999;22(3):371–5.PubMedGoogle Scholar
  28. 28.
    Panneman MJ, Goettsch WG, Kramarz P, Herings RM. The costs of benzodiazepine-associated hospital-treated fall Injuries in the EU: a Pharmo study. Drugs Aging. 2003;20:833–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Soldatos CR, Dikeos DG, Whiehead A. Tolerance and rebound insomnia with rapidly eliminated hypnotics: a meta-analysis of sleep laboratory studies. Int Clin Psychopharmacol. 1999;14(5):287–303.PubMedGoogle Scholar

Copyright information

© Society of General Internal Medicine 2007

Authors and Affiliations

  • Nina Buscemi
    • 1
  • Ben Vandermeer
    • 1
  • Carol Friesen
    • 1
  • Liza Bialy
    • 1
    • 3
    Email author
  • Michelle Tubman
    • 1
  • Maria Ospina
    • 1
  • Terry P. Klassen
    • 1
  • Manisha Witmans
    • 2
  1. 1.University of Alberta/Capital Health Evidence-Based Practice Centre, Department of PediatricsUniversity of AlbertaAlbertaCanada
  2. 2.Department of PediatricsUniversity of AlbertaAlbertaCanada
  3. 3.Aberhart Centre OneEdmontonCanada

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