Treatment of insomnia with tricyclic antidepressants: a meta-analysis of polysomnographic randomized controlled trials

Sleep Med. 2017 Jun;34:126-133. doi: 10.1016/j.sleep.2017.03.007. Epub 2017 Mar 27.

Abstract

Background: Insomnia represents a significant public health burden worldwide. Antidepressants have often been the insomnia treatment of choice in recent decades. Some tricyclic antidepressants (TCAs) have been shown to improve sleep efficiency.

Objective: Assess the efficacy and safety of TCAs for the treatment of insomnia using a meta-analysis of randomized control trials (RCTs).

Methods: Relevant studies were identified in electronic databases such as PubMed, Cochrane, Embase, and Web of Science, up until July 2016. We included all polysomnographic (PSG) RCTs using TCAs to treat insomnia. The primary outcome measure was the total sleep time (TST), although other polysomnographic measures were also investigated. Next-day somnolence and dropout rates were also assessed.

Results: The meta-analysis included nine RCTs. TCAs significantly improved TST compared with placebo (SMD = 0.61, 95% CI = 0.50-0.71, P < 0.00001). Participants receiving TCAs were not more likely to drop out than those receiving a placebo because of adverse side effects (1.71% vs 1.19%, RR = 1.37, 95% CI = 0.67-2.80, P = 0.39) or any other reason (7.08% vs 8.20%; RR = 0.86, 95% CI = 0.60-1.23, P = 0.42). However, the incidence of somnolence was higher in participants receiving TCAs (6.06% vs. 3.21%; RR = 1.82, 95% CI = 1.10-3.00, P = 0.02).

Conclusions: Based on our limited data analysis with two medications at particular doses (most studies included extremely low doxepin), we assert that TCAs can be an effective pharmacological treatment for insomnia. TCAs were found to improve sleep outcome measures, with the notable exception of an 82% increase in somnolence. Overall TCAs have very problematic and dangerous side effects, while TCAs were not found to increase the dropout rate compared with the placebo.

Keywords: Insomnia; Meta-analysis; Tricycle antidepressants.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Humans
  • Polysomnography
  • Randomized Controlled Trials as Topic
  • Sleep Initiation and Maintenance Disorders / diagnosis
  • Sleep Initiation and Maintenance Disorders / drug therapy*
  • Sleep Initiation and Maintenance Disorders / physiopathology

Substances

  • Antidepressive Agents, Tricyclic