A 28 day randomized controlled trial published today in Clocks & Sleep reports that a sustained-release formulation of melatonin (2 mg) significantly improved sleep efficiency, total sleep time, and subjective sleep quality in healthy adults who described their sleep as poor. The multicenter study, which enrolled 59 participants aged 30 to 60, found effects large enough to shift average sleep quality from the “poor” to the “good” range on the Pittsburgh Sleep Quality Index (PSQI).
What They Found
The trial randomly assigned 28 participants to receive sustained-release melatonin (melatonin-SR) and 31 to an identical placebo, taken one hour before bedtime for 28 days. All participants were healthy adults who scored 5 or higher on the PSQI at baseline, a threshold commonly used to identify poor sleep quality. None had a diagnosed insomnia disorder.
Objective sleep measures were collected using wrist actigraphy. The melatonin group showed a 3.49 percentage point increase in sleep efficiency over the study period, while the placebo group declined by 6.30 percentage points. The difference between groups was statistically significant (p = 0.001) and carried a large effect size (Cohen’s d = 0.9), meaning the improvement was both reliable and clinically meaningful.
Total sleep time told a similar story. Participants taking melatonin-SR gained an average of 23.8 minutes of sleep per night by day 28. Those on placebo lost 39.3 minutes per night relative to their baseline. The net difference of roughly 63 minutes was significant at p = 0.001.
Sleep onset latency, the time it takes to fall asleep, decreased by 10.3 minutes in the melatonin group. In the placebo group, it increased by 16.7 minutes (p = 0.031). Wake after sleep onset, a measure of how much time is spent awake during the night after first falling asleep, dropped by 14.9 minutes with melatonin and rose by 24.7 minutes with placebo (p = 0.001).
Subjective sleep quality followed the same trajectory. The PSQI global score fell by 5.61 points in the melatonin group by day 28, moving from a mean baseline of 9.43 to 3.82. A PSQI score above 5 indicates poor sleep; a score below 5 indicates good sleep. The placebo group’s PSQI dropped by only 0.65 points, from 9.74 to 9.09. The between-group difference was significant (p = 0.001).
Daytime well-being also improved. On the WHO-5 Well-Being Index, where higher scores reflect better well-being, the melatonin group gained 13.29 points over 28 days. The placebo group gained 0.77 points. That difference also reached significance (p = 0.001).
Adverse events were mild and transient in both groups, with no serious adverse events reported.
Why It Matters
Melatonin is one of the most widely used over-the-counter sleep aids in the world, but the evidence base supporting it has been uneven. Many commercially available melatonin products are immediate-release formulations that produce a sharp spike in circulating melatonin levels followed by a rapid decline. This pharmacokinetic profile does not resemble the body’s own sustained melatonin release through the night, and some sleep researchers have questioned whether immediate-release melatonin is well suited for sleep maintenance problems.
Sustained-release formulations are designed to release melatonin gradually over several hours, more closely mirroring the endogenous overnight melatonin profile. The current study adds to a growing body of evidence that this distinction matters. The improvements in wake after sleep onset and total sleep time are particularly noteworthy, because those are the measures most relevant to people who wake frequently during the night or wake too early and cannot get back to sleep.
The trial is also notable for its choice of participants. By enrolling healthy adults with poor sleep quality rather than patients with insomnia disorder, the researchers targeted a large and often overlooked population. Many people who sleep poorly do not meet diagnostic criteria for insomnia yet still experience significant daytime consequences. A well-tolerated intervention that moves them into the good sleep range on the PSQI, as this study’s melatonin group did, could have broad public health relevance.
The large effect sizes, particularly the Cohen’s d of 0.9 for sleep efficiency, suggest the benefit is not subtle. In sleep research, effect sizes above 0.8 are considered large. A d of 0.9 means the average person in the melatonin group had better sleep efficiency than roughly 82 percent of the placebo group.
Limits
The sample was small (59 participants total), which limits the generalizability of the findings and increases the chance that unmeasured confounders influenced the results. Larger trials are needed to confirm the magnitude and durability of the effect.
The study ran for only 28 days. Whether the benefits of sustained-release melatonin persist over months or years of use remains unknown. Most sleep interventions, including cognitive behavioral therapy for insomnia, are evaluated over longer time frames, and the absence of long-term follow-up data is a meaningful gap.
All participants were healthy adults aged 30 to 60. The results may not apply to younger adults, older adults, or people with medical or psychiatric conditions that affect sleep.
The use of actigraphy rather than polysomnography is another limitation. Actigraphy is a validated tool for estimating sleep patterns in naturalistic settings, but it is less precise than in-laboratory sleep recording for measuring sleep architecture and specific sleep stages.
Finally, the study was funded by a company that manufactures melatonin supplements. While the trial was double-blind and placebo-controlled, industry funding is a consideration when interpreting results. Independent replication by investigators without commercial ties to melatonin products would strengthen confidence in the findings.
Bottom Line
A 2 mg sustained-release melatonin formulation taken one hour before bed for 28 days improved sleep efficiency, total sleep time, sleep onset latency, wake after sleep onset, and daytime well-being in healthy adults with poor sleep quality. The improvements were large enough to move participants from poor to good sleep quality on the PSQI, and side effects were mild. These results support sustained-release melatonin as a reasonable option for adults whose sleep quality is suboptimal but does not meet the threshold for insomnia disorder. Longer and larger trials are needed to establish durability and generalizability.
Source
Thanawala S, Shah R, Lopes A, Kulkarni M, Jain B, Andhalkar N. “Efficacy and Safety of Sustained-Release Melatonin Capsules (2 mg) in Healthy Adults with Poor Sleep Quality: A Randomized, Double-Blind, Placebo-Controlled Trial.” Clocks & Sleep. 2026 May 27;8(2):31. DOI: 10.3390/clockssleep8020031. PMID: 42345841.