What is the duration of action of melatonin (melatonin)

Duration of Action of Melatonin

Melatonin typically has a short half-life of 40-60 minutes with effects lasting 3-5 hours for immediate-release formulations, while sustained-release formulations may extend effects to 6-8 hours. 1

Pharmacokinetics and Duration of Action

Immediate-Release Melatonin

• Half-life: 40-60 minutes
• Duration of action: 3-5 hours
• Peak plasma levels: Reached within 1 hour after ingestion
• Effects on sleep onset: Most pronounced in the first 3 hours after administration

Sustained-Release Melatonin

• Duration of action: 6-8 hours
• Provides more consistent blood levels throughout the night
• Less effective for sleep onset but may better maintain sleep through the night 1

Factors Affecting Duration of Action

1. Formulation type:

   • Fast-release formulations act quickly but have shorter duration
   • Controlled-release formulations extend the duration of action 1

2. Dosage:

   • Higher doses (3-5 mg) produce more pronounced and potentially longer-lasting effects
   • Optimal dose appears to be around 4 mg for maximum sleep-promoting effects 2

3. Individual metabolism:

   • Liver and kidney function affect clearance rates
   • Caution needed in patients with impaired hepatic or renal function 1

4. Age:

   • Older adults may experience longer duration due to decreased clearance
   • Children may metabolize melatonin differently than adults 3

Clinical Applications Based on Duration

For Sleep Onset Issues

• Immediate-release formulations (0.3-5 mg) taken 30 minutes to 2 hours before desired sleep time
• Most effective when taken 3 hours before desired bedtime 2

For Sleep Maintenance Issues

• Sustained-release formulations may be more appropriate
• 5 mg dose shows significant improvement in sleep efficiency throughout the night in older adults 3

For Circadian Rhythm Disorders

• Timing is critical for phase-shifting effects
• For DSWPD (Delayed Sleep-Wake Phase Disorder):
  • Adults: 5 mg taken between 19:00-21:00 for 28 days 1
  • Children/adolescents: 0.15 mg/kg taken 1.5-2 hours before habitual bedtime 1

Morning Melatonin Levels and Offset

• Melatonin's effects typically dissipate by morning in healthy individuals

• Elevated morning melatonin levels may indicate:

  • Inappropriate timing of administration
  • Excessive dosage
  • Delayed melatonin offset (DLMOff) 4

• Morning bright light exposure (5,000+ lux for 30 minutes) is the most effective intervention for suppressing any residual morning melatonin 4

Common Pitfalls and Caveats

• Incorrect timing: Taking melatonin at the wrong time can disrupt circadian rhythms rather than help
• Overdosing: Higher doses don't necessarily improve efficacy beyond 4-5 mg 2
• Quality control issues: Melatonin products often contain varying amounts of active ingredient from labeled concentrations 5
• Drug interactions: Potential interactions with warfarin and anticonvulsants 6
• Daytime drowsiness: May occur if taken too late at night or at excessive doses

Special Populations

• Children with ADHD/psychiatric comorbidities: Fast-release melatonin (3-5 mg) shows efficacy with effects lasting throughout the night 1
• Older adults: 5 mg dose increases sleep efficiency during both biological day and night, primarily by increasing Stage 2 non-REM sleep 3
• Jet lag: Most effective when taken close to target bedtime at destination (10pm-midnight) with effects lasting through the night 6

Remember that while melatonin is generally considered safe for short-term use, long-term effects have not been thoroughly studied, particularly at higher doses. The American Academy of Sleep Medicine provides weak recommendations for melatonin use in circadian rhythm disorders, suggesting its benefits outweigh potential harms 1.