title: Doxepin for insomnia: a systematic review of randomized placebo-controlled trials.
abstract: Doxepin, a sedating tricyclic drug, at 3 mg and 6 mg doses was recently approved by the U.S. food and drug administration (FDA) for the treatment of insomnia. The objective of this systematic review was to obtain a precise summary of the efficacy and safety of doxepin as a hypnotic. We searched key databases and trial registers up to March 2014 and contacted pharmaceutical companies and the FDA for unpublished data. A total of nine randomized placebo-controlled trials were analyzed. Six studies were on doxepin 1-6 mg/d, two on doxepin 25-300 mg/d, and one on ramelteon 8 mg and doxepin 3 mg combined. All low-dose studies were industry-sponsored. We found that low-dose doxepin had a small to medium effect size against placebo for sleep maintenance and sleep duration but not for sleep initiation at both immediate and short-term posttreatment. There was no significant next-day residual effect with low-dose doxepin. Headache and somnolence were the most common side effects. We concluded that low-dose doxepin for 1-2 nights appeared to be safe and effective in improving sleep. However, a clear conclusion on its short-term benefits and risks as well as withdrawal effects was not possible due to the small number of studies.
authors.affiliation: Department of Psychiatry, University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region.
authors.forename: Wing-Fai
authors.initials: WF
authors.lastname: Yeung
authors.affiliation: Department of Psychiatry, University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region. Electronic address: kfchung@hkucc.hku.hk.
authors.forename: Ka-Fai
authors.initials: KF
authors.lastname: Chung
authors.affiliation: Department of Psychiatry, University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region.
authors.forename: Kam-Ping
authors.initials: KP
authors.lastname: Yung
authors.affiliation: Department of Psychiatry, University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region.
authors.forename: Tommy Ho-Yee
authors.initials: TH
authors.lastname: Ng
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D004316:Doxepin / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007192:Indenes / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D007319:Sleep Initiation and Maintenance Disorders / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration; D055815:Young Adult
chemical_list: D007192:Indenes; D004316:Doxepin; C495910:ramelteon
keywords: Antidepressants; Doxepin; Insomnia; Randomized controlled trials; Systematic review