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Published in: Journal of General Internal Medicine 9/2007

01-09-2007 | Clinical Review

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

Authors: Nina Buscemi, PhD, Ben Vandermeer, MSc, Carol Friesen, MA, MLIS, Liza Bialy, BSc, Michelle Tubman, MSc, Maria Ospina, MSc, Terry P. Klassen, MD, MSc, FRCPC, Manisha Witmans, MD, FRCPC, Dip. ABSM

Published in: Journal of General Internal Medicine | Issue 9/2007

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Abstract

Background

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.

Objective

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.

Conclusions

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.
Literature
1.
go back to reference Sateia MJ, Doghramji K, Hauri P, Morin CM. Evaluation of chronic insomnia. An American Academy of Sleep Medicine Review. Sleep 2000;23:1–66. Sateia MJ, Doghramji K, Hauri P, Morin CM. Evaluation of chronic insomnia. An American Academy of Sleep Medicine Review. Sleep 2000;23:1–66.
2.
go back to reference Ford D, Kamerow D. Epidemiological study of sleep disturbances and psychiatric disorders: an opportunity for prevention. JAMA 1989;262:1479–84.PubMedCrossRef Ford D, Kamerow D. Epidemiological study of sleep disturbances and psychiatric disorders: an opportunity for prevention. JAMA 1989;262:1479–84.PubMedCrossRef
3.
go back to reference Simon GE, VonKorff M. Prevalence, burden, and treatment of insomnia in primary care. Am J Psychiatry. 1997;54:1417–23. Simon GE, VonKorff M. Prevalence, burden, and treatment of insomnia in primary care. Am J Psychiatry. 1997;54:1417–23.
4.
go back to reference Leger D, Guilleminault C, Bader G, Levy E, Paillard M. Medical and socio-professional impact of insomnia. Sleep 2002;25:625–9.PubMed Leger D, Guilleminault C, Bader G, Levy E, Paillard M. Medical and socio-professional impact of insomnia. Sleep 2002;25:625–9.PubMed
5.
go back to reference Ohayon M. Epidemiological study on insomnia in the general population. Sleep 1996;19(3 suppl):S7–15.PubMed Ohayon M. Epidemiological study on insomnia in the general population. Sleep 1996;19(3 suppl):S7–15.PubMed
6.
go back to reference 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.PubMed 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.PubMed
7.
go back to reference 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.PubMed 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.PubMed
8.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
9.
go back to reference Wiessman MM, Greenwald A, NinoMurcia G, Dement WC. The morbidity of insomnia uncomplicated by psychiatric disorders. Gen Hosp Psychiatry. 1997;19:245–50.CrossRef Wiessman MM, Greenwald A, NinoMurcia G, Dement WC. The morbidity of insomnia uncomplicated by psychiatric disorders. Gen Hosp Psychiatry. 1997;19:245–50.CrossRef
10.
go back to reference 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. 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.
11.
go back to reference 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. 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.
12.
go back to reference 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.CrossRef 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.CrossRef
13.
go back to reference 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. 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.
14.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
15.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
16.
go back to reference 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.CrossRef 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.CrossRef
17.
go back to reference 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. 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.
18.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
19.
go back to reference 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.CrossRef 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.CrossRef
20.
go back to reference Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.PubMedCrossRef Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.PubMedCrossRef
21.
go back to reference 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. 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.
22.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
23.
go back to reference Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994;50:1088–101.PubMedCrossRef Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994;50:1088–101.PubMedCrossRef
24.
go back to reference 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. 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.
25.
go back to reference 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. 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.
26.
go back to reference Light RJ, Pillemer DB. Summing up. The science of reviewing research. Cambridge, MA: Harvard University Press; 1984. Light RJ, Pillemer DB. Summing up. The science of reviewing research. Cambridge, MA: Harvard University Press; 1984.
27.
go back to reference Walsh JK, Schweitzer PK. Ten-year trends in the pharmacological treatment of insomnia. Sleep 1999;22(3):371–5.PubMed Walsh JK, Schweitzer PK. Ten-year trends in the pharmacological treatment of insomnia. Sleep 1999;22(3):371–5.PubMed
28.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
29.
go back to reference 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.PubMed 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.PubMed
Metadata
Title
The Efficacy and Safety of Drug Treatments for Chronic Insomnia in Adults: A Meta-analysis of RCTs
Authors
Nina Buscemi, PhD
Ben Vandermeer, MSc
Carol Friesen, MA, MLIS
Liza Bialy, BSc
Michelle Tubman, MSc
Maria Ospina, MSc
Terry P. Klassen, MD, MSc, FRCPC
Manisha Witmans, MD, FRCPC, Dip. ABSM
Publication date
01-09-2007
Publisher
Springer-Verlag
Published in
Journal of General Internal Medicine / Issue 9/2007
Print ISSN: 0884-8734
Electronic ISSN: 1525-1497
DOI
https://doi.org/10.1007/s11606-007-0251-z

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