Long-term Melatonin Use: Safety and Efficacy
Melatonin can be safely taken for years with minimal risk of serious adverse effects, though long-term studies are limited and periodic reassessment of continued need is recommended. 1, 2
Safety Profile of Long-term Melatonin Use
Evidence on Safety
Melatonin is generally well-tolerated with few adverse effects reported in both short-term and longer-term studies 3
Most common side effects are mild and include:
- Daytime sleepiness (1.66%)
- Headache (0.74%)
- Dizziness (0.74%)
- Other sleep-related issues (0.74%)
- Hypothermia (0.62%) 3
Rare but reported effects include agitation, fatigue, mood swings, nightmares, skin irritation, and palpitations 3
Most adverse effects resolve spontaneously within days without dosage adjustment or immediately upon discontinuation 3
Long-term Safety Considerations
- A long-term follow-up study of pediatric patients with DSWPD and ADHD who used melatonin doses up to 10 mg for approximately 4 years detected no serious adverse events 1
- Another open-label prospective study of subjects with neurodevelopmental disabilities who received controlled-release melatonin (up to 15 mg) for up to 3.8 years similarly reported no adverse events 1
- Low to moderate dosages (approximately 5-6 mg daily or less) appear safe for long-term use 2
Special Populations and Concerns
Children and Adolescents
- Caregivers often express concern about potential effects on growth hormone regulation and reproductive function/development 1
- A study assessing Tanner stages in children/adolescents using melatonin (mean dose ~3 mg) for approximately 3 years found no significant differences in pubertal development compared to non-users 1
- For children with DSWPD, it's recommended to stop melatonin treatment at least once a year (preferably during summer holidays) to reassess circadian rhythmicity 4
Drug Interactions and Medical Conditions
- Caution is advised when prescribing to patients taking warfarin due to potential interactions 1
- Patients with epilepsy should use melatonin with caution based on case reports submitted to the WHO 1
- One study reported impaired glucose tolerance in healthy women after acute melatonin administration 1
Dosage and Administration Guidelines
Optimal Dosing
- For adults: 1-5 mg approximately 1-2 hours before bedtime 5
- For adults with DSWPD: 5 mg taken between 7:00-9:00 PM 5
- For children with DSWPD and no comorbidities: 0.15 mg/kg taken 1.5-2 hours before habitual bedtime 5
- For children with DSWPD and psychiatric comorbidities: 3-5 mg (weight-based) taken at 18:00 or 19:00 5
Administration Best Practices
- Consistency in timing is crucial for reinforcing circadian rhythm 5
- Immediate-release formulations are preferred for sleep onset issues, while sustained/prolonged-release formulations are better for sleep maintenance issues 5
- Look for products with USP (United States Pharmacopeia) verification to ensure stated dose accuracy 5
Quality Control Considerations
- In the U.S., melatonin is classified as a dietary supplement without FDA oversight of manufacturing or sale 2
- Melatonin concentration in marketed preparations varies widely between product labels and manufacturers 2
- Choose formulations that are United States Pharmacopeial Convention Verified for most reliable dosing 1
Periodic Reassessment
- Despite evidence supporting safety, it's prudent to periodically reassess the need for continued melatonin use
- For children with DSWPD, consider a trial off melatonin at least once yearly to evaluate if continued treatment is necessary 4
- Monitor for any emerging side effects during long-term use, even though serious adverse events are rare
In conclusion, while melatonin appears safe for long-term use based on available evidence, the scarcity of robust long-term randomized controlled trials limits definitive conclusions about continuous therapy over extended periods 3. However, the existing evidence suggests that melatonin can be safely taken for years with appropriate monitoring and periodic reassessment.