Safety of Lifelong Melatonin Use
Melatonin is generally considered safe for long-term use, with few serious adverse effects reported in clinical studies, though comprehensive data on lifelong use remains limited. 1
Safety Profile of Melatonin
Short-term Safety
- Melatonin is associated with minimal adverse effects in short-term use 1, 2
- Most common reported adverse events include:
- Daytime sleepiness (1.66%)
- Headache (0.74%)
- Dizziness (0.74%)
- Other sleep-related issues (0.74%)
- Hypothermia (0.62%) 2
- These adverse effects typically resolve spontaneously within days or immediately upon discontinuation 2
Long-term Safety
- Studies that address long-term effects are scarce 1
- A meta-analysis of controlled trials with melatonin (10 studies, over 200 subjects) used for ≤3 months reported few adverse events 1
- A randomized, placebo-controlled trial investigating 28-day treatment with 10 mg melatonin revealed no group differences in adverse effects on sleep, subjective sleepiness, or clinical laboratory examinations 1
- Low to moderate dosages (approximately 5-6 mg daily or less) appear safe for long-term use 3
Special Populations and Considerations
Children and Adolescents
- Caution is recommended in children/adolescents 1
- A long-term follow-up study of pediatric patients with DSWPD + ADHD who used melatonin doses up to 10 mg (mean follow-up ~4 years) detected no serious adverse events 1
- Concerns about potential effects on growth hormone regulation (10 mg dose) and reproductive function/development (3 mg dose) have been raised but not confirmed in studies 1
- A questionnaire-based study comparing pubertal development among children using melatonin (mean dose ~3 mg) during pre-puberty to non-users found no significant differences 1
Women of Reproductive Age
- Caution is advised for women of reproductive age 1
- Theoretical concerns exist about potential effects on reproductive function, but clinical evidence of harm is limited 4
Patients with Specific Conditions
- Caution is advised when prescribing to patients taking warfarin due to case reports submitted to WHO 1
- Caution is recommended for patients with epilepsy 1, 5
- Melatonin has been associated with an increase in depressive symptoms in some individuals 1
- A recent publication described impairment in glucose tolerance among healthy women after acute melatonin administration 1
Product Quality Considerations
- Melatonin is considered a dietary supplement in the US and not subject to FDA scrutiny 1, 6
- Concerns exist about purity of available preparations and reliability of stated doses 1
- Formulations that are United States Pharmacopeial Convention Verified can be considered most reliable 1
- Melatonin concentration of marketed preparations varies widely between product labels and manufacturers 3
Practical Recommendations
For adults with sleep disorders:
For special populations:
- Exercise caution in children, adolescents, women of reproductive age, and patients with epilepsy or taking warfarin 1
- Monitor for potential side effects, particularly when initiating therapy
Monitoring during long-term use:
- Be alert for potential adverse effects such as daytime sleepiness, headache, or mood changes
- Consider periodic clinical laboratory examinations during very long-term use, though evidence of necessity is limited
Common Pitfalls to Avoid
- Using unverified melatonin products with uncertain dosing
- Taking melatonin at incorrect times, which can disrupt circadian rhythms rather than help them 5
- Assuming that because melatonin is "natural" it cannot have adverse effects 4
- Using high doses (>5 mg) which appear to offer no additional benefits but may increase risk of side effects 1, 5
While current evidence suggests melatonin is generally safe for long-term use, the scarcity of truly lifelong studies (decades of use) means some uncertainty remains about very extended use. The benefit-risk ratio appears favorable for those with chronic sleep disorders requiring ongoing treatment.