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Research Summary

Melatonin, Benzodiazepines, and Sleep Quality Among Patients Receiving Methadone

Both benzodiazepine abuse and sleep disorders are common worldwide among patients receiving methadone maintenance. This double-blind trial evaluated the effectiveness of melatonin in reducing sleep problems among 80 patients who were receiving methadone maintenance and abusing benzodiazepines. These patients were recruited into a benzodiazepine withdrawal program where they each received melatonin (5 mg per day) for 6 weeks, nothing for 1 week (washout week), and placebo for 6 weeks.

  • Overall, subjects reported higher subjective sleep quality, regardless of treatment arm, at 6 weeks. 
  • About one-third of subjects had stopped using benzodiazepines (as identified by urine toxicology) by 6 weeks. Sleep quality among these subjects was not affected by melatonin but was significantly better than sleep quality among subjects who continued benzodiazepines.
  • Of subjects who continued using benzodiazepines at 6 weeks, sleep quality significantly improved with melatonin versus placebo.
  • Over approximately 21 months, 63 patients stopped using benzodiazepines, although all but 4 relapsed. Time to benzodiazepine relapse was significantly longer among subjects who received melatonin (125 days) versus placebo (42 days) in the first 6 weeks.


This small trial has several findings relevant to the vexing problems of sleep disturbance and benzodiazepine abuse among patients receiving methadone. Most of the improvement in sleep quality was attributable to stopping benzodiazepines, a finding clinicians may choose to highlight when discussing benzodiazepine use with their sleep-disturbed patients who receive methadone. Although melatonin did not improve benzodiazepine discontinuation overall, it improved sleep quality among patients who could not stop benzodiazepines and lengthened the time to relapse among those who did stop. If replicated, these findings will support melatonin's possible use for sleep problems among patients who receive methadone maintenance and use anxiolytics, and as an adjunct to decrease relapse to benzodiazepines. 

Peter D. Friedmann, MD, MPH


Peles E, Hetzroni T, Bar-Hamburger R, et al. Melatonin for perceived sleep disturbances associated with benzodiazepine withdrawal among patients in methadone maintenance treatment: a double-blind randomized clinical trial. Addiction. 2007;102(12):1947–1953.