REM sleep is implicated in neurodevelopment, memory consolidation, and emotional regulation in children.A study shows an association between outpatient melatonin use and a small reduction in rapid eye movement (REM) sleep percentage.
REM sleep percentage was lower among melatonin users vs nonusers (median, 16.7 percent vs 19 percent; raw p<0.001; FDR*-corrected p=0.003). [JAMA Netw Open 2026;9:e2626983]
“By Cohen’s conventions, this finding represents a small effect, and its clinical meaning is genuinely uncertain,” the researchers said. “A difference of this size sits within the night-to-night variability that characterizes REM sleep even in healthy children, and no established threshold defines how large the REM change must be before it carries functional consequences for neurodevelopment, memory, or emotional regulation.”
Wake after sleep onset (WASO) was also lower among melatonin users vs nonusers (median time, 30.8 vs 37.2 mins; raw p=0.04). However, the significance was lost after FDR correction (p=0.13) which, according to the researchers, may reflect three factors: the prescription does not guarantee that melatonin was taken on the night of the polysomnography (PSG); the dose, formulation, and timing were not captured; and the laboratory environment and parental presence may have dominated any small pharmacologic contribution to sleep onset.
There were no associations between melatonin use and differences in total sleep time, non-REM sleep stages, respiratory parameters, arousal architecture, or periodic limb movements, as shown by the lack of significant between-group differences in the 14** exploratory PSG outcomes (FDR-corrected p>0.05 for all).
Study characteristics
“Despite widespread use, little is known about how melatonin is associated with objective sleep architecture in children,” the researchers noted. Available studies have small populations that used actigraphy or parent-reported outcomes rather than PSG, which is the gold standard for assessing sleep stages. [BMJ 2012;345:e6664; J Autism Dev Disord 2012;42:1729-1737]
“This evidence gap is clinically relevant. REM sleep is implicated in neurodevelopment, memory consolidation, and emotional regulation in children,” they added.
The analytic cohort comprised 3,392 children (mean age 8 years, 56.7 percent male) from the NCHSDB***. Of these, 346 were melatonin users and 3,046 were not. The matched cohort comprised 684 children (342 users and 342 nonusers).
Limitations
Of note, the NCHSDB is a single-centre dataset, which requires replication. PSG does not reflect habitual sleep patterns, as it only captures a single laboratory night. Furthermore, REM latency was only scoreable in 316 of the 342 pairs because some studies lacked REM epochs.
“Whether the residual REM association reflects a pharmacologic effect of melatonin, residual confounding, reverse causation, or some combination cannot be determined from these cross-sectional data,” the researchers added. Generalizability may also be limited because the population was overrepresented by children with sleep-disordered breathing, obesity, epilepsy, and neurodevelopmental disorders.
Prospective trials with documented dose, timing, and adherence are thus warranted to shed light on the directionality and significance of the observed REM association.
Implications
“[Nonetheless,] this analysis offers two messages for clinicians who prescribe melatonin to children,” the researchers noted.
First, the small reduction in REM sleep percentage among melatonin users may warrant awareness among clinicians treating kids with neurodevelopmental disorders who may already have reduced baseline REM sleep. Second, the exploratory analysis results are informative, but these do not prove that melatonin has no effect on these parameters.