The effects of low-dose 0.5-mg melatonin on the free-running circadian rhythms of blind subjects.
Level 3 - non-randomized controlled study
Single-blind controlled trial with small sample size and non-randomized phase initiation
PubMed 14582858 · doi:10.1177/0748730403256796
What was done
Ten totally blind individuals (9 males, aged 32–65) with free-running 6-sulphatoxymelatonin (aMT6s) rhythms (tau 24.23–24.95 h) were studied in a single-blind, placebo-controlled design. Subjects received 0.5 mg oral melatonin or placebo daily at 21:00 h for 26 to 81 days. Urinary cortisol and aMT6s were measured weekly via radioimmunoassay from 24- to 48-h collections. Subjective sleep and daytime naps were recorded via daily diaries.
What was found
Melatonin entrained or shortened the cortisol rhythm period in 7 of 10 subjects (4 entrained with a period indistinguishable from 24 h, 2 entrained after free-running for up to 25 days, and 1 showed a shortened period). Rapid entrainment within 7 days occurred when administration began during the phase-advance portion of the phase response curve (CT6–18). Three subjects started in the phase-delay portion and failed to entrain. Following treatment cessation, rhythms resumed free-running at pre-treatment periods. Subjective nighttime sleep duration increased significantly and daytime nap frequency/duration decreased (exact numerical values not reported in abstract).
Why it matters
This study shows that a low physiologic dose of melatonin (0.5 mg) can entrain the endogenous circadian clock in non-24-hour sleep-wake disorder in blind individuals, highlighting the critical role of circadian timing for treatment initiation.
Limits
Small sample size (n=10) with near-exclusive male representation (90%). The trial used a single-blind design and relied entirely on subjective sleep diaries without objective sleep measures (e.g., polysomnography or actigraphy). Exact numerical sleep metrics and statistical values are omitted from the abstract.
Cited by
- supports Administering a 0.3 to 0.5 mg dose of melatonin in the evening entrains the circadian clock in blind individuals with non-24-hour circadian rhythm disorder.