What is the recommended dosing for melatonin in adults, particularly those with a history of sleep disorders or other medical conditions, such as insomnia, dementia, or epilepsy, and potential interactions with medications like blood thinners, diabetes medications, or sedatives?

Melatonin Dosing for Adults

Direct Recommendation

Do not use melatonin for chronic insomnia in adults—the American Academy of Sleep Medicine explicitly recommends against it based on evidence showing no clinically significant benefit at 2 mg doses. 1, 2, 3 For circadian rhythm disorders like delayed sleep-wake phase disorder (DSWPD), use 5 mg administered 1.5-2 hours before desired sleep onset (between 19:00-21:00). 2, 3

Evidence-Based Dosing Algorithm

Step 1: Identify the Clinical Indication

For Chronic Insomnia (Primary or Comorbid):

• Melatonin is NOT recommended as the 2017 American Academy of Sleep Medicine guideline found only a 9-minute reduction in sleep latency with 2 mg doses—below the threshold for clinical significance. 1, 3
• The quality of evidence was very low, with benefits approximately equal to harms. 1, 2
• Consider FDA-approved hypnotics (eszopiclone 2-3 mg, zolpidem 10 mg, suvorexant 10-20 mg) or cognitive behavioral therapy for insomnia (CBT-I) instead. 1, 2

For Delayed Sleep-Wake Phase Disorder (DSWPD):

• Use 5 mg melatonin administered between 19:00-21:00 (7-9 PM), which is 1.5-2 hours before desired sleep onset, NOT at bedtime. 2, 3, 4
• Continue for a minimum of 28 days to assess efficacy. 2, 3
• This showed reduction in sleep latency by 38-44 minutes and increased total sleep time by 41-56 minutes. 2, 3
• This recommendation applies to adults both with and without comorbid depression. 2

Step 2: Special Population Considerations

Elderly Patients (≥55 Years) with Documented Low Melatonin Production:

• If insomnia is present with documented low endogenous melatonin levels, consider 2 mg prolonged-release formulation 1-2 hours before bedtime for 3-12 weeks. 3, 5
• The 2 mg dose showed approximately 19 minutes reduction in sleep latency in elderly patients compared to placebo. 3
• Prolonged-release formulations are preferred over immediate-release for maintaining sleep throughout the night and mimicking normal physiological circadian rhythm. 3, 5

Neurological Conditions:

• Mild Cognitive Impairment (MCI) and Alzheimer's Disease with Sleep Disorders: Use 2-5 mg (up to 10 mg) as add-on treatment to improve sleep quality and regulate sleep/wake rhythm; prescribe as early as possible for long-term use. 5
• REM Sleep Behavior Disorder: Use immediate-release melatonin shortly before bedtime as first-line treatment due to better side effect profile than clonazepam; effective on clinical symptoms and REM sleep without atonia. 5
• Parkinson's Disease with Sleep Disorders (without RBD): May improve subjective sleep quality, though evidence is insufficient for definitive recommendation. 5
• Epilepsy: Melatonin can be safely used to regulate sleep/wake rhythm and improve insomnia without increasing seizure risk. 5

Step 3: Dosing Pitfalls to Avoid

Critical Timing Errors:

• Do NOT administer melatonin at bedtime—this is the most common error that reduces efficacy. 2, 3, 4
• Administer 1-2 hours before desired sleep onset for circadian phase-shifting effects. 2, 3, 4
• For DSWPD specifically, the window is 19:00-21:00 (7-9 PM). 2, 3

Dose Escalation Mistakes:

• Do not increase dose beyond 5 mg for sleep disorders—escalation provides no definitive additional benefits. 3
• Most over-the-counter preparations contain 3 mg, which falls between the ineffective 2 mg dose for insomnia and the effective 5 mg dose for DSWPD. 6
• Higher doses (≥10 mg) increase risk of adverse events like drowsiness, headache, and dizziness without improving efficacy for sleep. 7

Step 4: Drug Interactions and Safety Monitoring

Drug Interactions:

• No significant drug-drug interactions exist between melatonin and common medications including blood thinners, diabetes medications, doxepin, propranolol, or SSRIs. 3
• Monitor for additive sedation if patients are on multiple CNS-active medications or sedatives. 3
• Melatonin is not listed on the American Geriatrics Society Beers Criteria, representing a safer option than many alternatives in elderly patients. 3

Renal or Hepatic Impairment:

• No specific dose adjustments are required for renal or hepatic impairment, as melatonin has a favorable safety profile with minimal adverse effects. 3
• Elimination half-life in older adults is approximately 1.8-2.1 hours regardless of dose. 8

Safety Profile:

• Melatonin has few serious side effects; common adverse events include drowsiness, headache, and dizziness. 7
• No withdrawal symptoms occur upon discontinuation. 5
• High doses (4 mg) can maintain melatonin levels >50 pg/mL for an average of 10 hours, potentially resulting in elevated levels beyond the typical sleep period and morning grogginess. 8

Step 5: Duration and Monitoring

Trial Duration:

• Minimum 3-4 weeks (preferably 28 days) to assess efficacy before considering dose adjustment or discontinuation. 2, 3
• For elderly patients with insomnia, treatment duration of 3-12 weeks is appropriate. 3, 5
• For neurological conditions like MCI/Alzheimer's, prescribe for long-term use. 5

Formulation Selection:

• For sleep maintenance issues, use prolonged-release (sustained-release) formulations. 3, 5
• For circadian rhythm disorders and REM sleep behavior disorder, use immediate-release formulations. 2, 5