Melatonin Supplementation for Adult Sleep Disorders
Primary Recommendation
The American Academy of Sleep Medicine suggests clinicians NOT use melatonin as a treatment for sleep onset or sleep maintenance insomnia in adults with primary insomnia, based on weak evidence demonstrating minimal clinically significant benefit. 1
However, melatonin may have specific utility in circadian rhythm disorders and certain populations, as detailed below.
Evidence-Based Clinical Algorithm
For Primary Insomnia (Most Common Presentation)
- Do not routinely prescribe melatonin for adults with primary insomnia (sleep onset or maintenance difficulties without circadian misalignment). 1
- The evidence base shows that 2 mg doses of melatonin failed to produce clinically significant improvements in:
For Delayed Sleep-Wake Phase Disorder (DSWPD)
- Melatonin IS recommended for DSWPD, where the circadian rhythm is delayed relative to desired sleep schedule. 2
- Dosing protocol: 5 mg taken between 19:00-21:00 (7-9 PM) for at least 28 days. 2
- Mechanism: Works by producing corrective circadian phase shifts, improving alignment of endogenous sleep propensity with desired sleep schedule. 3
- Expected outcomes: In adults without depression, treatment increased total sleep time by 56 minutes and decreased sleep latency by 37.7 minutes. 2
For Elderly Patients (>55 Years)
- Consider prolonged-release melatonin 2 mg in older adults, though evidence quality is low. 1, 2
- Some studies showed statistically significant improvements in sleep efficiency in this age group (placebo: 77.4% vs. sustained release 2 mg: 84.3%). 1
- The elderly may have reduced endogenous melatonin production, providing theoretical rationale for supplementation. 4
Dosing Specifications by Indication
Starting Doses
- DSWPD in adults: 3-5 mg immediate-release, taken between 19:00-21:00. 2
- General sleep support: Start with 3 mg immediate-release if attempting trial despite weak evidence. 2
- Maximum dose: Generally 12-15 mg; doses above 10 mg may cause receptor desensitization. 2
Titration Strategy
- Assess response after 1-2 weeks of consistent use. 5
- If ineffective and no adverse effects occur, increase by 3 mg increments. 5, 6
- Important caveat: Lower doses (3 mg) are often more effective than higher doses (10 mg) due to receptor desensitization at higher doses. 5, 2
Timing of Administration
- For circadian phase shifting: Administer 1.5-2 hours before desired bedtime. 5, 2
- For DSWPD: Administer between 19:00-21:00 regardless of current sleep time. 2
- For parasomnias (if applicable): 30-60 minutes before bedtime. 6
Safety Profile and Adverse Effects
Common Mild Side Effects
- Morning drowsiness or "hangover" effect (indicates dose may be too high). 5, 2
- Headache. 2, 7
- Gastrointestinal upset. 2
- Dizziness. 7
Serious Adverse Events
- No serious adverse reactions documented across multiple studies and age groups. 1, 5, 6, 2
- No rebound or withdrawal effects reported (with one marginal exception in a single study). 1
- High-dose studies (≥10 mg) showed no detectable increase in serious adverse events (Rate Ratio = 0.88). 7
Specific Cautions
- Use caution in patients taking warfarin due to potential interactions. 2
- Use caution in patients with epilepsy based on case reports. 2
- Monitor for mood changes, as melatonin has been associated with increased depressive symptoms in some patients. 5
Quality Control Considerations
Product Selection
- Choose United States Pharmacopeial Convention (USP) Verified formulations when possible for more reliable dosing. 6, 2
- Melatonin is regulated as a dietary supplement in the US, raising concerns about purity and reliability of stated doses. 6
- Actual melatonin content can vary significantly between products. 6
Formulation Considerations
- Immediate-release formulations are preferred over slow-release for sleep onset issues. 2
- Prolonged-release formulations showed some benefit specifically in elderly patients but are less effective for sleep onset. 2
Critical Pitfalls to Avoid
Common Prescribing Errors
- Do not prescribe melatonin as first-line for primary insomnia when cognitive behavioral therapy for insomnia (CBT-I) or other evidence-based treatments are appropriate. 1
- Do not use excessively high doses (>10 mg) assuming "more is better"—receptor desensitization occurs. 5, 2
- Do not prescribe without addressing underlying circadian rhythm issues—melatonin works primarily through circadian phase shifting, not as a direct sedative. 3
Monitoring Parameters
- Assess sleep latency, total sleep time, and night wakings after 1-2 weeks. 5
- Watch for morning grogginess (indicates dose too high). 5
- Monitor for mood changes. 5
Alternative Considerations
When Melatonin Fails or Is Not Tolerated
- Ramelteon 8 mg at bedtime (melatonin receptor agonist) may be considered, though safety in patients <18 years is not established. 5
- Do not use diphenhydramine (Benadryl) for insomnia—efficacy is not well established. 5
- Do not use trazodone for insomnia in the general population. 5
Non-Pharmacologic Interventions
- Melatonin should be used as part of a comprehensive sleep hygiene approach, not as sole intervention. 5
- Address environmental factors, screen time before bed, caffeine intake, and sleep schedule consistency. 5
Divergent Evidence and Nuances
The Paradox of Weak Recommendations Despite Widespread Use
- The American Academy of Sleep Medicine's weak recommendation against melatonin use is based on very low quality evidence with significant heterogeneity, imprecision, and potential publication bias. 1
- Despite this, the task force acknowledged that "a majority of informed patients would be likely to use melatonin compared to no treatment" based on its availability and widespread perception as benign. 1
- Clinical interpretation: The recommendation reflects lack of strong evidence for efficacy rather than evidence of harm. In real-world practice, a time-limited trial (4 weeks) may be reasonable for motivated patients after discussing limited evidence. 6