What is the recommended initial dose of melatonin (melatonin) for therapeutic use?

Recommended Initial Melatonin Dose

Start with 3 mg of immediate-release melatonin taken 1.5-2 hours before desired bedtime for most adults and adolescents. 1, 2

Dosing Algorithm by Population

Adults and Adolescents

• Initial dose: 3 mg immediate-release melatonin administered 1.5-2 hours before target bedtime 1, 2
• If ineffective after 1-2 weeks, increase by 3 mg increments up to a maximum of 15 mg 1
• For delayed sleep-wake phase disorder specifically, 5 mg taken between 19:00-21:00 is recommended 2
• Most patients respond within the 3-6 mg range 3

Elderly Patients (>55 years)

• Prolonged-release melatonin 2 mg has shown benefit in this age group 2
• However, immediate-release formulations at 3 mg remain the standard starting point, as slow-release appears less effective for sleep onset 1, 2

Children (6-12 years)

• Without comorbidities: 0.15 mg/kg (typically 1.6-4.4 mg) taken 1.5-2 hours before habitual bedtime 1, 2, 3
• With psychiatric comorbidities or autism: 3 mg if <40 kg, 5 mg if >40 kg 1, 2

Why Lower Doses Are More Effective

Melatonin works through M1 and M2 receptor binding, and higher doses (≥10 mg) can cause receptor desensitization or saturation, potentially disrupting normal circadian signaling. 1

• Clinical trials demonstrate that 10 mg doses are associated with more frequent adverse effects including morning headache, morning sleepiness, and gastrointestinal upset 1
• Morning grogginess and "hangover" effects occur more commonly with higher doses due to melatonin's half-life extending into morning hours 1
• The pharmacologic 3 mg dose can induce hypothermia and cause plasma melatonin to remain elevated into daylight hours, while 0.3 mg physiologic doses avoid this 4

Timing and Formulation

• Administer 1.5-2 hours before desired bedtime for optimal circadian phase-shifting effect 1, 2
• For parasomnias, administration 30-60 minutes before bedtime is appropriate 3
• Use immediate-release formulations rather than slow-release, as the latter are less effective for sleep onset 1, 2
• Taking melatonin at the wrong time (early in the day) can cause sleepiness and delay adaptation to local time 5

Critical Safety Considerations

• Use caution in patients taking warfarin or those with epilepsy due to potential interactions 1, 2, 5
• No serious adverse reactions have been documented at appropriate doses across age groups 1, 2
• Common mild side effects include morning headache (0.74%), dizziness (0.74%), and gastrointestinal upset 1

Important Caveats About Product Quality

Melatonin is regulated as a dietary supplement in the U.S., not as a medication, raising significant concerns about purity and reliability of stated doses. 1, 3

• Choose United States Pharmacopeial Convention Verified formulations when possible for more reliable dosing 1, 3
• Melatonin concentration of marketed preparations varies widely between product labels and manufacturers 6

When NOT to Use Melatonin

• Avoid in older people with dementia for irregular sleep-wake rhythm disorder due to lack of benefit and potential for harm, including detrimental effects on mood and daytime functioning 1
• The American Academy of Sleep Medicine suggests against using melatonin for primary insomnia in adults (weak recommendation) due to minimal efficacy 2

Dose Titration Strategy

If the initial 3 mg dose is ineffective after 1-2 weeks and no adverse effects occur:

• Increase by 3 mg increments 1, 3
• Maximum recommended dose is typically 12-15 mg 2, 3
• For REM sleep behavior disorder specifically, doses range from 3-12 mg at bedtime 1, 2