What dose of melatonin (melatonin) is considered harmful?

What Dose of Melatonin is Harmful?

No specific dose of melatonin has been definitively established as "harmful" in the traditional toxicological sense, as no deaths or life-threatening adverse events have been documented even at supraphysiological doses; however, doses above 10-15 mg increase the risk of adverse effects like morning grogginess, headache, and receptor desensitization without providing additional therapeutic benefit. 1, 2

Understanding the Dose-Response Paradox

The key issue with melatonin is not acute toxicity but rather diminishing returns and increased side effects at higher doses:

• Higher doses (≥10 mg) cause receptor desensitization or saturation, potentially disrupting normal circadian signaling mechanisms rather than enhancing sleep 1
• Lower doses (3 mg) are often more effective than higher doses because they work with the body's natural receptor systems rather than overwhelming them 1
• The American Academy of Sleep Medicine recommends a maximum of 15 mg, with dose titration in 3 mg increments only if the initial 3 mg dose proves ineffective after 1-2 weeks 1

Adverse Effects by Dose Range

Standard Doses (0.15-5 mg)

• Minimal adverse effects with the most common being daytime sleepiness (1.66%), headache (0.74%), and dizziness (0.74%) 3
• These effects are generally mild to moderate and resolve spontaneously 3

Higher Doses (≥10 mg)

• Increased frequency of morning headache and morning sleepiness due to melatonin's half-life extending into morning hours 1
• Gastrointestinal upset reported more frequently 1
• Impaired motor function can occur 1
• Meta-analysis showed a 40% increase in adverse events (drowsiness, headache, dizziness) compared to placebo at doses ≥10 mg 2

Special Populations at Higher Risk

Patients Who Should Use Lower Doses or Avoid Melatonin:

• Patients with epilepsy: Use with caution based on case reports of potential seizure risk 4, 5
• Patients taking warfarin: Potential drug interactions reported to WHO 4
• Patients with liver disease: Enhanced sensitivity to melatonin requiring lower doses 1
• Older adults with dementia: Should avoid melatonin for irregular sleep-wake rhythm disorder due to detrimental effects on mood and daytime functioning 1
• Patients on photosensitizing medications: Require periodic ophthalmological/dermatological monitoring 4

Metabolic and Psychiatric Concerns

• Impaired glucose tolerance has been associated with acute melatonin administration in healthy women 4
• Increased depressive symptoms reported in some individuals, warranting caution in patients with mood disorders 4, 5

Practical Safety Algorithm

Starting dose:

• Adults: 3 mg immediate-release, 1.5-2 hours before bedtime 1, 5
• Children without comorbidities: 0.15 mg/kg 1
• Children with psychiatric comorbidities: 3 mg if <40 kg, 5 mg if >40 kg 1

If ineffective after 1-2 weeks:

• Increase by 3 mg increments 1
• Maximum recommended dose: 15 mg 1
• Do not exceed 15 mg as higher doses increase adverse effects without improving efficacy 1

Long-Term Safety Considerations

• Long-term safety data beyond several months is limited, though available evidence suggests good tolerability 1
• Most studies monitored subjects for only 4 weeks or less, with the longest duration being 29 weeks 3
• No serious or life-threatening adverse events have been documented in available literature 1, 3, 2

Critical Caveats

• Melatonin is regulated as a dietary supplement in the US, raising concerns about purity and reliability of stated doses 1
• Choose United States Pharmacopeial Convention Verified formulations for more reliable dosing 1, 4
• Document all concurrent medications before recommending melatonin to review for potential interactions 4
• Monitor for enhanced sedation, blood pressure changes, and mood alterations when using with interacting medications 4