What are the risks associated with long-term use of melatonin (N-acetyl-5-methoxytryptamine)?

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Last updated: May 10, 2025View editorial policy

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From the Guidelines

Long-term melatonin use is not recommended due to insufficient evidence on its safety and efficacy, and potential risks such as daytime drowsiness, headaches, and interactions with other medications 1.

Risks and Considerations

  • Potential concerns include daytime drowsiness, headaches, dizziness, and mild depression
  • Regular use might disrupt the body's natural melatonin production, potentially leading to dependency
  • Melatonin may interact with certain medications, including blood thinners, immunosuppressants, and diabetes medications
  • Additional risks exist for specific populations, such as pregnant women, vulnerable individuals with depression, and children and adolescents

Recommendations

  • Use the lowest effective dose (typically 0.5-3mg) for the shortest duration necessary
  • Consult with a healthcare provider to address underlying sleep issues rather than relying on supplements indefinitely
  • Melatonin is best used short-term for specific situations like jet lag or temporary sleep difficulties

Evidence

  • The FDA has approved pharmacologic therapy for short-term use (4 to 5 weeks), and patients should not continue using the drugs for extended periods 1
  • Observational studies have shown that hypnotic drugs may be associated with infrequent but serious adverse effects, such as dementia, serious injury, and fractures 1
  • Evidence is insufficient to evaluate the balance of the benefits and harms of long-term use of pharmacologic treatments in adults with chronic insomnia disorder 1

From the Research

Risk of Long-Term Melatonin Use

  • The risk of long-term melatonin use has been found to be minimal in several studies 2, 3.
  • Melatonin at low to moderate dosages (approximately 5-6 mg daily or less) appears to be safe for long-term use 2.
  • Long-term usage of melatonin may benefit certain patient populations, such as those with autism spectrum disorder 2.
  • However, it is widely agreed that the long-term effects of taking exogenous melatonin have been insufficiently studied and warrant additional investigation 2.
  • Some studies have found no difference between exogenous melatonin and placebo in terms of long-term negative effects 2, 3.

Comparison with Other Treatments

  • Melatonin has been compared to other treatments for insomnia, such as cognitive behavioral therapy (CBT-I) and ramelteon 4, 5, 6.
  • CBT-I has been found to be an effective treatment for adults with chronic insomnia, with clinically meaningful effect sizes 5.
  • Ramelteon has been found to be efficacious for the acute and long-term management of insomnia disorder in adults, with large effect sizes 6.
  • Melatonin has been found to be efficacious compared to placebo for insomnia symptoms, with small to medium effect sizes 6.

Factors Affecting Efficacy

  • The efficacy of melatonin and ramelteon may be affected by factors such as age, with older adults (mean age ≥55) showing larger effect sizes for PR melatonin 6.
  • The dosage and formulation of melatonin may also affect its efficacy, with prolonged release (PR) melatonin showing small to medium effect sizes 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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