Meta-Analysis: Melatonin for the Treatment of Primary Sleep Disorders
Melatonin reduced sleep onset latency by about 7 minutes, increased total sleep time by about 8 minutes and improved sleep quality against placebo.
Summary
The authors pooled 19 randomized placebo-controlled trials covering 1,683 people with primary sleep disorders. People taking melatonin fell asleep about 7 minutes faster, slept about 8 minutes longer, and rated their sleep quality higher than those on placebo. The authors note these changes are smaller than those reported for prescription sleep medicines, and that higher doses and longer trials produced larger effects.
Context Note
The effect sizes are small in absolute terms, around 7 to 8 minutes.
Study breakdown
Why this study was done
Primary sleep disorders are sleep problems not caused by another medical condition, a substance or a psychiatric disorder, and that cause real distress or impairment. Melatonin is a hormone the pineal gland releases in step with the daily light cycle, and it is sold over the counter. An earlier meta-analysis had found a benefit, but 7 new trials with 1258 additional subjects had since nearly tripled the available sample. The authors pooled everything to get a more precise estimate and to test whether dose and duration changed the result.
How it was run
The authors searched PubMed using the terms "Melatonin" and "Sleep Disorder", limited to randomized controlled trials and meta-analyses. Trials qualified if they examined primary sleep disorders as defined by DSM-IV, were randomized and placebo-controlled, and had at least 10 participants for parallel designs or 5 for crossover designs. From 268 studies identified, 249 were excluded, leaving 19 studies with 1683 subjects: 14 on insomnia, 4 on delayed sleep phase syndrome and 1 on REM sleep behavior disorder. Doses ranged from 0.05 mg/kg to 5 mg, and durations from 7 days to 182 days.
What they found
All three primary outcomes favored melatonin, and all three effects were small.
- Sleep latency, the time taken to fall asleep, fell by 7.06 minutes (95% CI 4.37 to 9.75, Z = 5.15, p below 0.001).
- Total sleep time rose by 8.25 minutes (95% CI 1.74 to 14.75, Z = 2.48, p = 0.013). Split by measurement type, the gain held on subjective measures (11.93 minutes, 95% CI 4.06 to 19.81, p = 0.002) but not on objective ones (0.33 minutes, 95% CI minus 11.19 to 11.87, p = 0.95).
- Sleep quality improved, with a standardized mean difference of 0.22 (95% CI 0.12 to 0.32, Z = 4.52, p below 0.001) and no significant heterogeneity.
Meta-regression showed longer trials reported greater effects on sleep latency (p = 0.001) and total sleep time (p = 0.004), and higher doses gave greater effects on total sleep time (p = 0.007). Dose and duration had no effect on sleep quality. They set these numbers in context: a previous meta-analysis found benzodiazepines cut sleep latency by 10.0 to 19.6 minutes and non-benzodiazepine sleep medicines by 12.8 to 17 minutes, so prescription drugs are quite likely more effective.
Limitations
The authors list their own. The small number of qualifying trials left the meta-regression underpowered, made worse because one trial of 746 subjects carried a large share of the weight in the overall findings. Too few trials studied children, so the planned comparison between children and adults could not be run. Funding came mainly from National Institutes of Health grants and Brazilian research bodies. The competing interests statement discloses partial funding from an APIRE/Eli Lilly Psychiatric Research Fellowship and an AACAP/Eli Lilly Pilot Research Award, both to the same author. The paper states the funders had no role in the study.
What it means in practice
The direction is consistent and the size is modest. Averaged across trials, people taking melatonin fell asleep about 7 minutes sooner and slept about 8 minutes longer than those on placebo, with a small improvement in rated sleep quality. This is a clinical population, adults and children diagnosed with a primary sleep disorder, so the results do not automatically extend to people without such a diagnosis, or to sleep problems caused by another illness, medication or psychiatric condition. The gain in total sleep time appeared on subjective measures but not on objective ones such as polysomnography or actigraphy. The authors' own framing is that melatonin is less effective than prescription sleep medication.
Study Type
Meta-Analysis
Published
2013
PLOS ONE
Participants
19 studies, 1,683 adults and children with primary sleep disorders
Dose Studied
0.05 mg/kg to 5 mg per night across included trials, for 7 to 182 days
Health Focus
Sleep
Ingredients
Melatonin
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