What are the indications for 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 is NOT recommended for primary insomnia in adults or irregular sleep-wake rhythm disorder in elderly patients with dementia. 1, 2

Primary Evidence-Based Indications

Delayed Sleep-Wake Phase Disorder (DSWPD)

Adults:

• The American Academy of Sleep Medicine suggests melatonin for adults with DSWPD, with or without depression (weak recommendation) 2
• Dosing: 3-5 mg taken between 19:00-21:00 for at least 28 days 3
• Efficacy: Increases total sleep time by 56 minutes and decreases sleep latency by 37.7 minutes in adults without depression 3, 2

Children and Adolescents WITHOUT Comorbidities:

• Weight-based dosing of 0.15 mg/kg administered 1.5-2.0 hours before habitual bedtime 1, 3, 2
• High-quality evidence shows reduction in initial sleep latency by 38-44 minutes 1
• Treatment duration as short as 6 nights has demonstrated effectiveness 3

Children and Adolescents WITH Psychiatric Comorbidities (including autism):

• Fast-release melatonin at 3 mg if <40 kg or 5 mg if >40 kg 1, 3, 2
• Administered at 18:00-19:00 for 4 weeks 3, 2
• High-quality evidence shows mean dim light melatonin onset (DLMO) advanced by 54.22 minutes and sleep onset time reduced by 36.57 minutes 1

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

• Melatonin regulates sleep-wake patterns in blind patients compared with placebo 4
• This represents one of the most convincing evidence bases for melatonin use 4

REM Sleep Behavior Disorder

• Dosing ranges from 3-12 mg at bedtime 5, 3
• This indication is supported by clinical practice patterns 5

Conditions Where Melatonin is NOT Indicated

Primary Insomnia in Adults

• The American Academy of Sleep Medicine suggests AGAINST using melatonin for primary insomnia (weak recommendation) 3, 2
• Meta-analyses show only minimal effects on sleep onset, maintenance, or quality 3
• 2 mg doses showed insufficient efficacy for sleep onset, maintenance, or quality 3

Irregular Sleep-Wake Rhythm Disorder (ISWRD) in Elderly with Dementia

• The American Academy of Sleep Medicine suggests clinicians AVOID melatonin for ISWRD in older people with dementia (weak recommendation against) 1
• Evidence shows no improvement in total sleep time 1
• Potential for harm: detrimental effects on mood and daytime functioning have been observed 1, 5
• Risk-benefit ratio suggests potential harms outweigh benefits 1

Dosing Algorithm by Indication

Start with lowest effective dose:

• Adults with DSWPD: Begin with 3 mg immediate-release, titrate in 3 mg increments if needed (maximum 15 mg) 5, 3
• Children with DSWPD (no comorbidities): 0.15 mg/kg taken 1.5-2 hours before bedtime 1, 3
• Children with DSWPD and psychiatric comorbidities: 3 mg (<40 kg) or 5 mg (>40 kg) 1, 3
• REM sleep behavior disorder: 3-12 mg at bedtime 5, 3

Timing considerations:

• For DSWPD in adults: 19:00-21:00 3
• For DSWPD in children without comorbidities: 1.5-2 hours before habitual bedtime 1, 3
• For DSWPD in children with psychiatric comorbidities: 18:00-19:00 3

Critical Safety Considerations

Contraindications and Cautions:

• Use with caution in patients taking warfarin due to potential interactions 5, 3, 2
• Use with caution in patients with epilepsy 5, 3, 2
• Avoid in elderly patients with dementia and ISWRD 1, 5

Common Adverse Effects:

• Daytime sleepiness (1.66%), headache (0.74%), and other sleep-related effects (0.74%) 2
• Morning grogginess and "hangover" effects more common with higher doses 5
• Gastrointestinal upset reported more frequently at higher doses 5
• Melatonin has been associated with increased depressive symptoms 2

No serious adverse reactions documented across all age groups when used at appropriate doses 5, 3

Important Clinical Caveats

Formulation matters:

• Immediate-release formulations are more effective than slow-release for sleep onset 3
• Choose United States Pharmacopeial Convention Verified formulations for reliable dosing 5, 3
• Melatonin is regulated as a dietary supplement in the US, raising concerns about purity and reliability of stated doses 5

Lower doses may be more effective:

• Higher doses (10 mg) may cause receptor desensitization or saturation 5
• Start with 3 mg and increase only if ineffective after 1-2 weeks 5

Long-term use considerations:

• Long-term safety data beyond several months is limited 5
• The American Academy of Sleep Medicine recommends against long-term use for chronic insomnia due to insufficient safety and efficacy data 5
• For circadian rhythm disorders requiring ongoing therapy, periodic attempts to reduce frequency and dose are indicated 5

Pediatric safety:

• No significant differences in pubertal development observed in children using melatonin (mean dose ~3 mg) for approximately 3 years compared to non-users 5
• Long-term safety data in children is limited but available evidence is reassuring 5