Is melatonin safe for use in children?

Melatonin Safety in Children

Melatonin is generally safe for children with sleep disorders when used at appropriate doses, though long-term safety data remains limited and it should be used with caution. 1, 2

Evidence for Safety in Children

• Melatonin has been studied in children with Delayed Sleep-Wake Phase Disorder (DSWPD) and found effective with a moderate level of evidence at appropriate doses 1
• No serious adverse reactions have been documented in relation to melatonin use in children 1, 2
• Acute toxicity studies in animals showed toxic effects only at extremely high doses (>400 mg/kg), thousands of times higher than recommended doses 3
• Long-term studies (1.0-10.8 years) found no substantial deviation in children's development regarding sleep quality, puberty development, and mental health scores 3
• A questionnaire-based study assessing Tanner stages in children/adolescents using melatonin for approximately 3 years showed no significant differences in pubertal development compared to non-users 2

Recommended Dosing for Children

• For children with DSWPD without comorbidities, a weight-based dose of 0.15 mg/kg is recommended 1, 4
• For children with DSWPD and psychiatric comorbidities (like ADHD), fast-release melatonin at 3-5 mg is recommended 1, 2
• Weight-based approach: 3 mg if <40 kg and 5 mg if >40 kg has shown effectiveness 1, 2
• Timing: Administration 1.5-2.0 hours before habitual bedtime for optimal effect 1, 2
• Lower doses may be more effective than higher doses due to potential receptor desensitization with higher doses 2, 4

Common Side Effects and Precautions

• Morning grogginess and "hangover" effects are more commonly reported with higher doses 2, 5
• Gastrointestinal upset has been reported at higher doses 2
• Use with caution in patients taking warfarin or those with epilepsy due to potential interactions 2, 5
• Melatonin has been associated with impaired glucose tolerance in healthy women after acute administration 5
• Melatonin has been associated with increased depressive symptoms in some individuals 5

Monitoring and Treatment Duration

• Regular monitoring for effectiveness and side effects is recommended 5, 6
• Consider treatment breaks at least once a year (preferably during summer holidays) 3
• Clinical audits show that only 13% of children on long-term melatonin treatment have documented planned treatment breaks 6
• For children without comorbidities, as little as 6 nights of treatment has demonstrated effectiveness 1, 4
• For children with psychiatric comorbidities, a 4-week treatment duration is recommended 4

Important Caveats

• Melatonin is regulated as a dietary supplement in the US, raising concerns about purity and reliability of stated doses 2, 4
• Choose United States Pharmacopeial Convention Verified formulations when possible for more reliable dosing 2, 5
• Non-pharmacological interventions (sleep hygiene, behavioral therapies) should be tried first before initiating melatonin 6, 7
• Recent European expert guidance recommends low-dose melatonin for children over 2 years old only after sleep hygiene and behavioral interventions have failed 7
• A registry-based study found concerning trends of long-term melatonin use in children, with increasing doses over time despite limited long-term safety data 8

Clinical Algorithm for Melatonin Use in Children

1. Start with non-pharmacological interventions (sleep hygiene, behavioral therapies) 6, 7
2. If ineffective, consider melatonin at appropriate dose:
   • Children without comorbidities: 0.15 mg/kg 1
   • Children with psychiatric comorbidities: 3 mg (<40 kg) or 5 mg (>40 kg) 1, 2
3. Administer 1.5-2.0 hours before habitual bedtime 1, 2
4. Monitor effectiveness and side effects regularly 5, 6
5. Plan for treatment breaks at least annually 3
6. Reassess need for continued treatment 6