What is the recommended initial dosage and treatment approach for starting melatonin (melatonin) therapy?

Melatonin Prescription to Start

The American Academy of Sleep Medicine recommends against using melatonin for chronic insomnia in adults, but if prescribing for circadian rhythm disorders or REM sleep behavior disorder, start with 3 mg of immediate-release melatonin taken 1.5-2 hours before desired bedtime. 1, 2

Key Guideline Position on Melatonin

The 2017 American Academy of Sleep Medicine clinical practice guideline explicitly states that clinicians should NOT use melatonin as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults, based on trials of 2 mg doses showing benefits approximately equal to harms. 1 This is a weak recommendation with very low quality evidence, indicating harms may outweigh benefits for chronic insomnia. 1

However, melatonin IS recommended for specific conditions:

• REM sleep behavior disorder: 3-12 mg at bedtime 1
• Circadian rhythm disorders (delayed sleep-wake phase disorder, non-24-hour sleep-wake rhythm disorder): 3-5 mg daily 1, 2

Starting Dose Algorithm

For Adults with Circadian Rhythm Disorders or RBD:

Initial dose: 3 mg immediate-release melatonin 1, 2, 3

• Timing: Administer 1.5-2 hours before desired bedtime 2, 4
• Titration: If ineffective after 1-2 weeks, increase by 3 mg increments 2, 3
• Maximum dose: 15 mg for circadian disorders 2; up to 12 mg for RBD 1, 3

For Children (6-12 years):

Weight-based dosing for circadian disorders without comorbidities: 0.15 mg/kg (approximately 1.6-4.4 mg) 2

For children with psychiatric comorbidities:

• 3 mg if <40 kg 2
• 5 mg if >40 kg 2
• Timing: 1.5-2 hours before habitual bedtime 2

Why Lower Doses Are Often More Effective

Higher doses (10 mg) may cause receptor desensitization or saturation, potentially disrupting normal circadian signaling mechanisms. 2 The M1 and M2 receptor binding that suppresses REM sleep motor tone and renormalizes circadian features works optimally at lower concentrations. 2 Clinical trials show that 5 mg produces faster sleep onset than 0.5 mg, but doses above 5 mg appear no more effective. 5

Morning grogginess and "hangover" effects occur more commonly with higher doses due to melatonin's half-life extending into morning hours. 2 The relative ineffectiveness of 2 mg slow-release formulations suggests that a short-lived higher peak concentration works better than sustained lower levels. 5

Critical Safety Considerations and Contraindications

Use with Extreme Caution or Avoid:

• Patients taking warfarin: Potential drug interactions reported to WHO 1, 4
• Patients with epilepsy: Case reports suggest potential harm 1, 4
• Older adults with dementia: The American Academy of Sleep Medicine recommends avoiding melatonin for irregular sleep-wake rhythm disorder in this population due to lack of benefit and potential for detrimental effects on mood and daytime functioning 2
• Patients with impaired glucose tolerance or diabetes: Melatonin has been associated with impaired glucose tolerance in healthy individuals 2, 4

Product Quality Warning:

Melatonin is regulated as a dietary supplement in the US, raising significant concerns about purity and reliability of stated doses. 1, 2, 4, 3 Choose United States Pharmacopeial Convention Verified formulations for more reliable dosing and purity. 2, 4, 3

Duration of Treatment

Long-term use beyond 3-4 months is NOT recommended for chronic insomnia due to insufficient safety and efficacy data. 2 Most clinical trial data supports melatonin use lasting 4 weeks or less. 2

Exception: For circadian rhythm disorders requiring ongoing chronobiotic therapy, longer-term use may be appropriate with periodic reassessment every 3-6 months. 2

In pediatric populations with autism spectrum disorders, studies have documented safe use for up to 24 months with continued efficacy. 2

Common Adverse Effects

The most frequently reported adverse events in clinical trials:

• Daytime sleepiness (1.66%) 2, 6
• Headache (0.74%) 2, 6
• Dizziness (0.74%) 6
• Nausea (more frequent with higher doses) 2

These effects are generally mild to moderate and self-limiting. 6 No serious adverse reactions or life-threatening events have been documented in relation to melatonin use across age groups. 2, 6

Important Timing Caveat

If melatonin is taken at the wrong time (early in the day), it is liable to cause sleepiness and delay adaptation to local time. 5 Never advise taking melatonin in the morning or afternoon, as this will worsen circadian misalignment. 2

Drug Interactions to Monitor

• Photosensitizing medications: Recommend periodic ophthalmological and/or dermatological monitoring 4
• Concurrent medications affecting melatonin metabolism: May amplify effects of higher doses 2
• Alcohol: Avoid consumption as it interacts with melatonin 2
• Caffeine: Avoid excessive intake, particularly after 2:00 PM, as it counteracts melatonin's effects 2