Timothy J. Wilt, MD, MPH; Roderick MacDonald, MS; Michelle Brasure, PhD, MSPH, MLIS; Carin M. Olson, MD, MS; Maureen Carlyle, MPH; Erika Fuchs, PhD, MPH; Imran S. Khawaja, MD; Susan Diem, MD, MPH; Erin Koffel, PhD; Jeannine Ouellette; Mary Butler, PhD; Robert L. Kane, MD
Grant Support: By Agency for Healthcare Research and Quality (AHRQ) contract HHSA 290-2012-00016-I.
Disclosures: Dr. Wilt reports grants (funding for the evidence report) from AHRQ during the conduct of the study. Mr. MacDonald reports grants from AHRQ and personal fees from the American College of Physicians during the conduct of the study. Dr. Brasure reports a contract with AHRQ during the conduct of the study. Dr. Diem reports grants from AHRQ during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOf InterestForms.do?msNum=M15-1781.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol: Protocol registered at www.crd.york.ac.uk/PROSPERO/ (registration number: CRD42014009908) in May 2014 and published at http://effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productid=%201888. Statistical code: Available at http://srdr.ahrq.gov. Data set: Available in electronic data supplement and in full report at www.effectivehealthcare.ahrq.gov/reports/final.cfm.
Requests for Single Reprints: Timothy J. Wilt, MD, MPH, Minneapolis Veterans Affairs Health Care System, One Veterans Drive, Minneapolis, MN 55417; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Wilt, MacDonald, Olson, and Koffel: Minneapolis Veterans Affairs Health Care System, One Veterans Drive, Minneapolis, MN 55417.
Drs. Brasure, Butler, and Kane and Ms. Ouellette: Division of Health Policy and Management, School of Public Health, MMC 197, Mayo Memorial Building, 420 Delaware Street SE, Minneapolis, MN 55455.
Dr. Fuchs: Center for Interdisciplinary Research in Women's Health, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0128.
Dr. Khawaja: Minnesota Regional Sleep Disorders Center, 701 Park Avenue, G8.220, Minneapolis, MN 55415.
Dr. Diem: Department of Medicine, University of Minnesota School of Medicine, 1100 Washington Avenue S, Minneapolis, MN 55415.
Ms. Carlyle: Optum, Health Economics and Outcomes Research, 11000 Optum Circle, Eden Prairie, MN 55344.
Author Contributions: Conception and design: M. Brasure, M. Butler, M. Carlyle, I.S. Khawaja, E. Koffel, J. Ouellette, T.J. Wilt.
Analysis and interpretation of the data: M. Brasure, M. Butler, M. Carlyle, S. Diem, E. Fuchs, R.L. Kane, E. Koffel, R. MacDonald, T.J. Wilt.
Drafting of the article: M. Brasure, E. Fuchs, E. Koffel, R. MacDonald, J. Ouellette, T.J. Wilt.
Critical revision for important intellectual content: M. Brasure, M. Carlyle, S. Diem, E. Fuchs, R.L. Kane, I.S. Khawaja, E. Koffel, T.J. Wilt.
Final approval of the article: M. Brasure, M. Butler, M. Carlyle, S. Diem, E. Fuchs, R.L. Kane, I.S. Khawaja, E. Koffel, R. MacDonald, C.M. Olson, J. Ouellette, T.J. Wilt.
Provision of study materials or patients: M. Brasure, R. MacDonald.
Statistical expertise: M. Brasure, R. MacDonald, T.J. Wilt.
Obtaining of funding: M. Brasure, R.L. Kane, T.J. Wilt.
Administrative, technical, or logistic support : M. Brasure, M. Carlyle, R.L. Kane, E. Koffel, T.J. Wilt.
Collection and assembly of data: M. Brasure, M. Carlyle, S. Diem, E. Fuchs, R. MacDonald, C.M. Olson, T.J. Wilt.
Pharmacologic interventions are often prescribed for insomnia disorder.
To assess the benefits, harms, and comparative effectiveness of pharmacologic treatments for adults with insomnia disorder.
Several electronic databases (2004–September 2015), reference lists, and U.S. Food and Drug Administration (FDA) documents.
35 randomized, controlled trials of at least 4 weeks' duration that evaluated pharmacotherapies available in the United States and that reported global or sleep outcomes; 11 long-term observational studies that reported harm information; FDA review data for nonbenzodiazepine hypnotics and orexin receptor antagonists; and product labels for all agents.
Data extraction by single investigator confirmed by a second reviewer; dual-investigator assessment of risk of bias; consensus determination of strength of evidence.
Eszopiclone, zolpidem, and suvorexant improved short-term global and sleep outcomes compared with placebo, although absolute effect sizes were small (low- to moderate-strength evidence). Evidence for benzodiazepine hypnotics, melatonin agonists, and antidepressants, and for most pharmacologic interventions in older adults, was insufficient or low strength. Evidence was also insufficient to compare efficacy within or across pharmacotherapy classes or versus behavioral therapy. Harms evidence reported in trials was judged insufficient or low strength; observational studies suggested that use of hypnotics for insomnia was associated with increased risk for dementia, fractures, and major injury. The FDA documents reported that most pharmacotherapies had risks for cognitive and behavioral changes, including driving impairment, and other adverse effects, and they advised dose reduction in women and in older adults.
Most trials were small and short term and enrolled individuals meeting stringent criteria. Minimum important differences in outcomes were often not established or reported. Data were scant for many treatments.
Eszopiclone, zolpidem, and suvorexant may improve short-term global and sleep outcomes for adults with insomnia disorder, but the comparative effectiveness and long-term efficacy of pharmacotherapies for insomnia are not known. Pharmacotherapies for insomnia may cause cognitive and behavioral changes and may be associated with infrequent but serious harms.
Agency for Healthcare Research and Quality. (PROSPERO: CRD42014009908)
Wilt TJ, MacDonald R, Brasure M, Olson CM, Carlyle M, Fuchs E, et al. Pharmacologic Treatment of Insomnia Disorder: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians. Ann Intern Med. 2016;165:103–112. doi: 10.7326/M15-1781
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Published: Ann Intern Med. 2016;165(2):103-112.
Published at www.annals.org on 3 May 2016
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