Effects of Long-Term Melatonin Use in Pediatric Patients
Long-term melatonin use in pediatric patients appears generally safe with few serious adverse events reported, but caution is warranted due to limited high-quality long-term safety data, particularly regarding potential effects on pubertal development and increasing reports of pediatric melatonin ingestions. 1, 2
Safety Profile and Short-Term Effects
General Safety
- Melatonin is generally well-tolerated in pediatric populations with few serious adverse events reported in clinical studies 1
- Non-serious adverse events are more common with melatonin use compared to placebo (Relative risk 1.56,95% CI 1.01-2.43) 2
- Most common short-term side effects include:
- Morning sleepiness
- Headaches
- Somnolence
- Gastrointestinal upset (including loose stools)
- Increased bedwetting in some children 1
Dosing Considerations
- Pediatric dosing varies by age and indication:
Long-Term Effects and Concerns
Pubertal Development
- Limited long-term follow-up studies (2-4 years) suggest little to no influence on pubertal development in most cases 2
- One study with longer follow-up (>7 years) indicated potential delays in pubertal development, though methodological limitations exist 2
- Studies assessing Tanner stages in children using melatonin (mean dose ~3 mg) for approximately 3 years showed no significant differences compared to controls 1
Hormonal Effects
- Concerns exist about potential effects on:
Increasing Use and Safety Concerns
- Pediatric melatonin ingestions reported to poison control centers increased 530% over a 10-year period (2012-2021) 3
- By 2021, melatonin ingestions accounted for 4.9% of all pediatric ingestions reported to poison control centers (compared to 0.6% in 2012) 3
- Hospitalizations due to melatonin ingestions have increased, primarily related to unintentional ingestions in children ≤5 years 3
Special Populations
Children with Neurodevelopmental Disorders
- Long-term follow-up studies in children with DSWPD (Delayed Sleep-Wake Phase Disorder) and ADHD using melatonin doses up to 10 mg for approximately 4 years detected no serious adverse events 1
- Children with autism spectrum disorders showed improvements in sleep latency, duration, and sleep anxiety with melatonin use 1
- 65% of children with neurodevelopmental disorders continued daily melatonin use during long-term follow-up, suggesting sustained benefit 1
Children with Atopic Dermatitis
- Melatonin may benefit some children with atopic dermatitis and sleep disturbances 1
- Dosing considerations for these children:
- 0.5 mg 3-4 hours before bedtime to advance bedtime
- Higher doses for sedating effect: 1 mg in infants, 2.5-3 mg in older children, 5 mg in adolescents 1
Quality Control and Regulatory Concerns
- Melatonin is regulated as a dietary supplement in the US, not subject to FDA approval processes 3, 4
- Concerns exist about purity of available preparations and reliability of stated doses 1
- United States Pharmacopeial Convention Verified formulations are considered most reliable 1
- Evidence supporting US formulations of melatonin in otherwise healthy pediatric populations is lacking 4
Clinical Implications and Recommendations
- Melatonin should be used cautiously in pediatric patients given the limited long-term safety data 2
- Regular reassessment of continued need for melatonin is recommended
- For children with neurodevelopmental disorders, benefits may outweigh potential risks given the documented improvements in sleep parameters 1
- Clinicians should counsel families about proper storage to prevent accidental ingestions, particularly in households with young children 3
- Adverse events related to melatonin use should be reported to regulatory authorities 3
The major gap in knowledge regarding long-term safety calls for judicious use of melatonin in pediatric populations, particularly in otherwise healthy children without significant sleep disorders or neurodevelopmental conditions.