What is the most effective dose of melatonin (N-acetyl-5-methoxytryptamine) for an adult?

Melatonin Dosing for Adults

For adults with delayed sleep-wake phase disorder (DSWPD) or circadian rhythm disorders, use 5 mg of melatonin timed between 19:00-21:00 (7-9 PM), but melatonin should NOT be used for chronic insomnia as it provides no clinically significant benefit. 1

Clinical Decision Algorithm

Step 1: Identify the Sleep Problem

If the patient has chronic insomnia (difficulty falling or staying asleep without circadian misalignment):

• Do NOT prescribe melatonin 1
• The American Academy of Sleep Medicine explicitly advises against melatonin for chronic insomnia based on trials showing no clinically significant improvements in sleep latency, total sleep time, wake after sleep onset, or sleep quality at 2 mg doses 1
• The benefits are approximately equal to harms, making it ineffective for this indication 1
• Consider FDA-approved hypnotics or cognitive behavioral therapy for insomnia (CBT-I) instead 1

If the patient has DSWPD or circadian rhythm disorder (delayed sleep phase, difficulty falling asleep at desired time but normal sleep once initiated):

• Proceed with melatonin 5 mg 2, 1

Step 2: Dosing and Timing for DSWPD

Dose: 5 mg of immediate-release melatonin 2, 1

• Doses between 0.5-5 mg are similarly effective for jet lag, but 5 mg causes faster sleep onset and better sleep quality compared to 0.5 mg 3, 4
• Doses above 5 mg appear no more effective 3, 4
• Slow-release 2 mg formulations are relatively ineffective, suggesting that a short-lived higher peak concentration works better 3, 4

Timing: Administer between 19:00-21:00 (7-9 PM) OR 1.5-2 hours before desired sleep onset 2, 1

• This timing is critical—taking melatonin at the wrong time (early in the day) can cause daytime sleepiness and delay adaptation to the desired sleep schedule 3, 4
• The timing should NOT be at habitual bedtime but rather 1.5-2 hours before the desired sleep time 2, 1

Duration: Continue for minimum 28 days to assess efficacy 2, 1

• Positive results in DSWPD showed sleep latency reductions of 38-44 minutes and total sleep time increases of 41-56 minutes 1

Step 3: Special Populations and Contexts

Adults with DSWPD and comorbid depression:

• The same 5 mg dose between 19:00-21:00 applies 2, 1
• This recommendation is supported for adults both with and without depression 2, 1

Jet lag prevention:

• Use 0.5-5 mg close to target bedtime at destination (10 PM to midnight) 3, 4
• Most effective when crossing 5 or more time zones, particularly eastward travel 3, 4
• The number needed to treat is 2, indicating high effectiveness 3, 4

Older adults (>55 years):

• Recent research suggests 5 mg melatonin significantly increases sleep efficiency during both biological day and night in older adults, primarily by increasing Stage 2 non-REM sleep duration 5
• However, for chronic insomnia specifically, even in elderly patients, the American Academy of Sleep Medicine advises against melatonin use based on very low quality evidence 1

Evidence Quality and Strength

The recommendation for DSWPD represents a weak recommendation based on low-quality evidence from the American Academy of Sleep Medicine 2, 1. However, the data consistently showed positive results with the 5 mg dose regimen 2.

The recommendation against melatonin for chronic insomnia is based on very low quality evidence but represents a clear consensus from sleep medicine guidelines 1.

Important Caveats and Safety Concerns

Contraindications and interactions:

• Patients with epilepsy may come to harm from melatonin 3, 4
• Possible interaction with warfarin requires investigation and caution 3, 4

Side effects:

• Generally mild at usual doses (1-6 mg range) 6
• No evidence of dependence even at high doses 6
• Low incidence of side effects overall 3, 4

Common pitfall:

• The most critical error is using melatonin for chronic insomnia when it has no proven benefit—this delays appropriate treatment with effective therapies 1