What is the standard dose of melatonin (N-acetyl-5-methoxytryptamine) for a generally healthy adult?

Standard Melatonin Dose for Adults

For generally healthy adults, melatonin is NOT recommended for primary insomnia, but when used for circadian rhythm disorders, the standard dose is 3-5 mg of immediate-release melatonin taken between 19:00-21:00. 1, 2

Primary Insomnia: Not Recommended

• The American Academy of Sleep Medicine explicitly recommends AGAINST using melatonin for chronic insomnia in adults due to minimal efficacy, with only a 9-minute reduction in sleep latency compared to placebo (95% CI: 2-15 minutes). 3, 1
• Meta-analyses show melatonin performs poorly for sleep onset, maintenance, or quality improvement in primary insomnia, with very low quality of evidence. 3
• For primary insomnia, FDA-approved hypnotics (zolpidem 10 mg, eszopiclone 2-3 mg) are more effective alternatives. 1

Circadian Rhythm Disorders: Recommended Dosing

When melatonin IS appropriate (circadian rhythm disorders), the evidence-based dosing is:

• Start with 3-5 mg immediate-release melatonin taken between 19:00-21:00 (7-9 PM). 1, 2
• Continue for at least 28 days to evaluate effectiveness. 1, 2
• The optimal therapeutic range is 3-5 mg; doses above 10 mg risk receptor desensitization with no additional benefit. 1, 4

Formulation Matters

• Immediate-release is superior to sustained-release for most indications. 3, 2
• Sustained-release formulations appear less effective for sleep onset. 2
• The 2 mg prolonged-release formulation showed minimal benefit (8.9 minute reduction in sleep latency) that falls below clinical significance. 3

Dose-Response Relationship

Lower doses may actually be MORE effective than higher doses:

• Higher doses (≥10 mg) can cause receptor desensitization or saturation, disrupting normal circadian signaling. 4
• The American Academy of Sleep Medicine recommends starting at 3 mg with titration in 3 mg increments only if needed, up to a maximum of 12-15 mg. 2, 4
• Doses between 0.5-5 mg are similarly effective, though 5 mg produces faster sleep onset than 0.5 mg. 5

Special Populations

Elderly Adults (>55 years)

• Prolonged-release melatonin 2 mg may provide modest benefit in elderly patients (65-80 years), though evidence quality is low. 3, 2
• One high-quality study found 5 mg melatonin significantly increased sleep efficiency during both biological day and night in older adults by increasing Stage 2 NREM sleep duration. 6
• Doses between 1-6 mg appear effective in elderly populations, though no clear dose-response relationship has been established. 7, 8

Safety Profile

• Common mild side effects include morning headache, morning sleepiness, and gastrointestinal upset, more frequent with higher doses. 1, 2, 4
• No serious adverse reactions have been documented across age groups. 1, 2
• Specific contraindications/cautions: patients taking warfarin, those with epilepsy, and timing errors (morning/afternoon dosing worsens circadian misalignment). 1, 2, 4

Critical Timing Considerations

Timing is as important as dose:

• Take 1.5-2 hours before desired bedtime for circadian rhythm disorders. 2, 4
• NEVER take in the morning or afternoon—this worsens circadian misalignment. 4
• For jet lag crossing 5+ time zones eastward, take close to target bedtime (10 PM-midnight) at destination. 5

Duration of Use

• Long-term use (>3-4 months) is NOT recommended for chronic insomnia due to insufficient safety data. 4
• For circadian rhythm disorders requiring ongoing treatment, periodic reassessment every 3-6 months is indicated. 4
• Consider tapering frequency (every other night) rather than daily use for long-term management. 4

Product Quality Concerns

• Melatonin is regulated as a dietary supplement in the U.S., raising concerns about purity and reliability of stated doses. 2, 4
• Choose United States Pharmacopeial Convention Verified formulations for more reliable dosing. 1, 2

Clinical Algorithm

1. Determine indication: Primary insomnia → Do NOT use melatonin; consider FDA-approved hypnotics. 1
2. For circadian rhythm disorders: Start 3-5 mg immediate-release at 19:00-21:00. 1, 2
3. Assess response after 1-2 weeks using sleep diaries. 4
4. If ineffective: Increase by 3 mg increments up to maximum 12-15 mg. 1, 4
5. Reassess need every 3-6 months and attempt dose reduction. 4