What are the indications for melatonin (Melatonin)?

Indications for Melatonin

Melatonin is indicated for circadian rhythm sleep-wake disorders—specifically delayed sleep-wake phase disorder (DSWPD) in adults and children, non-24-hour sleep-wake rhythm disorder in blind individuals, and REM sleep behavior disorder—but should be avoided for primary insomnia in adults and irregular sleep-wake rhythm disorder in elderly patients with dementia. 1

Primary Evidence-Based Indications

Delayed Sleep-Wake Phase Disorder (DSWPD)

Adults:

• Melatonin 3-5 mg taken between 19:00-21:00 for at least 28 days is recommended for DSWPD with or without depression 1
• This represents a weak recommendation from the American Academy of Sleep Medicine, but is supported by moderate to high-quality evidence 2
• Start with 3 mg immediate-release formulation and titrate in 3 mg increments only if needed, up to a maximum of 15 mg 3, 1

Children and Adolescents without Comorbidities:

• Weight-based dosing of 0.15 mg/kg administered 1.5-2.0 hours before habitual bedtime is recommended 1
• High-quality evidence demonstrates reduction in initial sleep latency by 38-44 minutes 2, 1
• This dose (approximately 1.6-4.4 mg for typical pediatric weights) shows optimal results 3

Children and Adolescents with Psychiatric Comorbidities:

• Fast-release melatonin at 3 mg if <40 kg or 5 mg if >40 kg, administered at 18:00-19:00 for 4 weeks 1
• High-quality evidence shows mean sleep onset time improvement of 36.57 minutes and reduction in initial sleep latency of 18.70 minutes 2

Non-24-Hour Sleep-Wake Rhythm Disorder in Blind Individuals

• Melatonin is suggested for regulating sleep-wake patterns in blind patients 1, 4
• Meta-analysis confirms efficacy in this population compared to placebo 4

REM Sleep Behavior Disorder

• Dosing ranges from 3-12 mg at bedtime 3, 1
• This represents an off-label but evidence-supported use 3

Irregular Sleep-Wake Rhythm Disorder (ISWRD) in Children with Neurologic Disorders

• Melatonin 2-10 mg during the hour before planned bedtime may improve sleep outcomes in children/adolescents with neurologic disorders and ISWRD 2
• This is a weak recommendation based on moderate-quality evidence from a small sample 2

Conditions Where Melatonin is NOT Indicated

Primary Insomnia in Adults

The American Academy of Sleep Medicine suggests against using melatonin for primary insomnia in adults. 1

• Meta-analyses show only minimal effects on sleep onset (reduction of approximately 7-12 minutes), maintenance, or quality 1, 4
• The effect size is clinically insignificant compared to circadian rhythm disorders 4
• Long-term use beyond 3-4 months is not recommended due to insufficient safety and efficacy data 3, 1

Irregular Sleep-Wake Rhythm Disorder in Elderly with Dementia

Melatonin should be avoided in older people with dementia and ISWRD. 2, 1

• Low-quality evidence shows no improvement in total sleep time with 6 mg slow-release melatonin 2
• Detrimental effects on mood and daytime functioning have been observed in this population 2, 3
• The risk of harm outweighs potential benefits 2

Critical Dosing Principles

Lower Doses May Be More Effective

• Higher doses (10 mg) may cause receptor desensitization or saturation, potentially disrupting normal circadian signaling 3
• Morning grogginess and "hangover" effects are more common with higher doses due to melatonin's half-life extending into morning hours 3
• Start with 3 mg for adults and titrate only if ineffective after 1-2 weeks 3, 1

Timing is Critical

• For DSWPD, administer 1.5-2 hours before desired bedtime (typically 19:00-21:00 for adults) 1
• Morning or afternoon administration will worsen circadian misalignment 3
• Immediate-release formulations are more effective than slow-release for sleep onset 1

Safety Considerations and Contraindications

Use with Caution:

• Warfarin users: Potential drug interactions reported 3, 1, 5
• Epilepsy patients: Case reports suggest caution 3, 1, 5
• Patients with impaired glucose tolerance: Melatonin associated with impaired glucose tolerance after acute administration 3, 5

Common Adverse Effects:

• Daytime sleepiness, headache (0.74%), and dizziness (0.74%) 3, 5
• Gastrointestinal upset more frequent at higher doses 3
• No serious adverse reactions documented across all age groups when used at appropriate doses 3, 1, 5

Product Quality Concerns

Melatonin is regulated as a dietary supplement in the U.S., raising significant concerns about purity and reliability of stated doses. 3, 1

• Choose United States Pharmacopeial Convention Verified formulations for reliable dosing and purity 3, 1, 5
• Different formulations may lead to variable efficacy between brands 3

Duration of Treatment

• For chronic insomnia: Maximum 3-4 months due to insufficient long-term safety data 3, 1
• For circadian rhythm disorders: May be used longer-term as these conditions require ongoing chronobiotic therapy 3
• In pediatric populations with autism spectrum disorders: Safe use documented up to 24 months 3
• Periodic reassessment every 3-6 months is indicated for long-term use 3