Long-term Side Effects of Melatonin
The long-term safety profile of melatonin remains inadequately studied, with insufficient robust data from extended-duration randomized controlled trials to conclusively establish its safety beyond short-term use, particularly as melatonin supplements are not subject to FDA oversight in the United States. 1
Safety Profile Based on Current Evidence
Short-term Side Effects (Well-Documented)
Most common adverse events reported in clinical trials:
- Daytime sleepiness (1.66%)
- Headache (0.74%)
- Dizziness (0.74%)
- Other sleep-related adverse events (0.74%)
- Hypothermia (0.62%) 2
Less common but reported adverse events:
- Agitation
- Fatigue
- Mood swings
- Nightmares
- Skin irritation
- Palpitations 2
Potential Long-term Concerns
Endocrine System Effects
- Melatonin has profound effects on reproductive systems in animal studies (rodents, sheep, primates) 3
- Potential effects on growth hormone regulation in children
- Possible impacts on reproductive function and development in adolescents 4
Regulatory and Quality Concerns
- Melatonin supplements are not FDA-regulated in the US, leading to:
- Inconsistent dosing between products
- Variable melatonin concentration between product labels and manufacturers
- Lack of standardized quality control 5
Special Populations at Risk
- Children and adolescents: Insufficient long-term safety data
- Patients with epilepsy: Potential interactions with medications
- Patients on warfarin or with hepatic impairment: Possible drug interactions 4
Recommendations for Monitoring and Use
Dosing Considerations
- For adults: 1-5 mg approximately 1-2 hours before bedtime
- For children (when indicated): Weight-based dosing (0.15 mg/kg for DSWPD without comorbidities)
- For elderly patients: Start with lower doses (1-2 mg) and titrate as needed 4
Monitoring Recommendations
- Regular assessment of continued need for treatment
- Periodic attempts to discontinue melatonin to evaluate ongoing necessity
- Monitoring for adverse effects, particularly in long-term use 4
Risk Mitigation
- Use lowest effective dose
- Consider intermittent rather than continuous use
- For children with circadian rhythm disorders, consider stopping treatment at least once a year (preferably during summer holidays) to reassess need 6
Clinical Perspective
While melatonin appears generally safe in short-term studies with few mild-to-moderate adverse events reported, the American Academy of Sleep Medicine acknowledges that "long-term physiologic studies are needed to accurately ascertain any serious chronic risks" 1. The balance of current evidence suggests that melatonin at low to moderate doses (≤5-6 mg daily) appears safe for most individuals 5, but clinicians should remain cautious about extended use, particularly in children and adolescents where developmental effects remain inadequately studied.
When prescribing melatonin, select products with quality verification (such as those with U.S. Pharmacopeia Verification Mark) to ensure consistent dosing 1, and regularly reassess the need for continued therapy.