What is the recommended dosing of melatonin (a hormone) for a patient with insomnia, considering factors such as age, medical history, and other health conditions like impaired renal (kidney) or hepatic (liver) function?

Melatonin Dosing for Insomnia

Direct Recommendation

The American Academy of Sleep Medicine explicitly recommends against using melatonin for chronic insomnia in adults, as the evidence shows no clinically significant benefit for sleep onset or maintenance at the studied 2 mg dose. 1, 2 However, melatonin may be considered in specific populations: elderly patients (≥55 years) with documented low melatonin levels or those chronically using benzodiazepines, and for circadian rhythm disorders rather than primary insomnia. 3, 4

Evidence-Based Dosing by Clinical Context

For Chronic Insomnia (NOT Recommended)

• Melatonin is not recommended for treating chronic insomnia based on the 2017 American Academy of Sleep Medicine guideline, which found only a 9-minute reduction in sleep latency compared to placebo (95% CI: 2-15 minutes) with 2 mg doses—below the threshold for clinical significance. 1
• The quality of evidence was very low due to publication bias, heterogeneity, and imprecision, with benefits approximately equal to harms. 3, 2
• Consider FDA-approved hypnotics (suvorexant, eszopiclone, zolpidem) or cognitive behavioral therapy for insomnia (CBT-I) instead. 1, 2

For Elderly Patients (≥55 Years) with Specific Indications

If proceeding despite weak evidence, use the following approach:

• Starting dose: 0.3-2 mg of prolonged-release melatonin taken 1-2 hours before bedtime 3, 5
• Maximum dose: 5 mg nightly, though most evidence supports 2 mg as optimal 3
• The 0.3 mg physiologic dose restored sleep efficiency principally in the mid-third of the night and elevated plasma melatonin to normal nocturnal levels without causing daytime carryover or hypothermia. 5
• The 2 mg dose showed approximately 19 minutes reduction in sleep latency in elderly patients (>55 years) compared to placebo. 3

Best responders include:

• Elderly patients with documented low nocturnal melatonin excretion (6-sulphatoxymelatonin ≤8 μg/night) 4, 6
• Those chronically using benzodiazepines 4
• Patients aged ≥55 years regardless of melatonin levels (age is a better predictor than low melatonin levels) 6

For Circadian Rhythm Disorders (Delayed Sleep-Wake Phase Disorder)

Use 5 mg melatonin administered between 19:00-21:00 (7-9 PM), which is 1.5-2 hours before desired sleep onset, for a minimum of 28 days. 1, 2

• This timing is critical—do not administer at bedtime. 2, 7
• This represents a weak recommendation based on low-quality evidence but showed reduction in sleep latency by 38-44 minutes and increased total sleep time by 41-56 minutes. 2
• For children/adolescents with DSWPD and psychiatric comorbidities (particularly ADHD), use 3 mg if <40 kg or 5 mg if >40 kg, administered at 19:00. 1

Formulation Considerations

• Prolonged-release (sustained-release) formulations are preferred over immediate-release for maintaining sleep throughout the night and mimicking normal physiological circadian rhythm. 3, 5
• Fast-release formulations were used in pediatric DSWPD studies with psychiatric comorbidities. 1

Dosing Pitfalls to Avoid

• Avoid supraphysiological doses (3 mg and above) in elderly patients as they induce hypothermia and cause plasma melatonin to remain elevated into daylight hours, potentially disrupting circadian rhythm. 8, 5
• The commonly available 3 mg over-the-counter dose 9 exceeds the physiologic dose that demonstrated efficacy (0.3 mg) and may cause unnecessary side effects. 5
• Do not increase dose beyond 5 mg—escalation provides no definitive additional benefits. 1
• Timing matters more than dose: administration at bedtime rather than 1-2 hours before is a common error that reduces efficacy. 2, 7

Special Populations

Renal or Hepatic Impairment

• No specific dose adjustments are provided in guidelines for renal or hepatic impairment, as melatonin has a favorable safety profile with minimal adverse effects. 3
• Monitor for additive sedation if patients are on multiple CNS-active medications. 3

Drug Interactions

• No significant drug-drug interactions exist between melatonin and common medications including doxepin, propranolol, or SSRIs, but monitor for additive sedation. 3
• Melatonin is not listed on the American Geriatrics Society Beers Criteria, representing a safer option than many alternatives in elderly patients. 3

Duration and Monitoring

• Trial duration: Minimum 3-4 weeks to assess efficacy before considering dose adjustment. 3
• Long-term use (6 months) showed maintained or enhanced effects on sleep parameters with no signs of tolerance and a favorable safety profile. 6
• Most adverse events are mild with no clinically relevant differences between melatonin and placebo. 6