Melatonin and melatonin agonists as treatments for benzodiazepines and hypnotics withdrawal in patients with primary insomnia. A systematic review

Drug Alcohol Depend. 2020 Jul 1:212:107994. doi: 10.1016/j.drugalcdep.2020.107994. Epub 2020 Apr 25.

Abstract

Background: Hypnotics (HYP) and benzodiazepines (BZD) are medicines prescribed for the insomnia treatment. Many patients present difficulties in discontinuing the treatment once established. Melatonin (MLT) has been prescribed as a treatment for BZD/HYP detoxification.

Aims: The primary objective of this systematic review is to assess the efficacy of MLT and MLT agonists (melatoninergics) in improving the rate of BZD and/or HYP discontinuation among adults with primary insomnia attempting to discontinue BZD and/or HYP. The secondary objective is to evaluate the partial efficacy of melatoninergic drugs in the discontinuation of BZD and/or HYP consumption in subjects that could not stop their consumption.

Method: A search on Web of Science and Scopus was carried out from database inception to July 1st, 2019.

Results: Three hundred and forty-nine articles were identified but only four were included in the final review. Two were cohort prospective, one placebo-control double blind and one double blind placebo-control cross-over designed study. Total withdrawal (TW) ranged from 0% to 25% in the placebo arm and from 64.3% to 77.8% in the MLT arm. In cohort studies TW figures ranged from 30.8% to 65%. Partial withdrawal ranged between 20% and 30.8% of patients that did not achieve TW with reduction figures of diazepam equivalent dose ranging from 25% to 75%.

Conclusion: MLT has a place in the physician armamentarium to treat the suspension/reduction of BZD/HYP consumption in patients with primary insomnia.

Keywords: Benzodiazepines; Detoxification; Hypnotics; Melatonin; Withdrawal; Z-drugs.

Publication types

  • Systematic Review

MeSH terms

  • Adult
  • Benzodiazepines / adverse effects*
  • Clinical Trials as Topic / methods
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Humans
  • Hypnotics and Sedatives / adverse effects*
  • Male
  • Melatonin / therapeutic use*
  • Middle Aged
  • Observational Studies as Topic / methods
  • Prospective Studies
  • Sleep Initiation and Maintenance Disorders / drug therapy*
  • Sleep Initiation and Maintenance Disorders / epidemiology
  • Substance Withdrawal Syndrome / drug therapy*
  • Substance Withdrawal Syndrome / epidemiology

Substances

  • Hypnotics and Sedatives
  • Benzodiazepines
  • Melatonin