The use of prolonged-release melatonin in circadian medicine: a systematic review

source extracted confidence: high 2026-04-09
#melatonin #humans #delayed-action-preparations #sleep-initiation-and-maintenance-disorders #circadian-rhythm

The use of prolonged-release melatonin in circadian medicine: a systematic review

Del et al., 2024 | Minerva Med | Systematic Review

Citation

Del Casale Antonio, Arena Jan F, ... Girardi Paolo. The use of prolonged-release melatonin in circadian medicine: a systematic review. Minerva Med. 2024-Apr;115(2):125-142. doi:10.23736/S0026-4806.24.09303-0

Abstract

INTRODUCTION: Melatonin, a hormone produced by the pineal gland, regulates the sleep-wake cycle and is effective in restoring biological rhythms. Prolonged-release melatonin (PRM) is designed to mimic the natural physiological pattern of melatonin release. In circadian medicine, PRM can be used to treat sleep and circadian rhythm disorders, as well as numerous organic diseases associated with sleep disorders. EVIDENCE ACQUISITION: This systematic review analyzed 62 studies and adhered to the PRISMA guidelines, examining the effectiveness of PRM in organic pathologies and mental disorders. EVIDENCE SYNTHESIS: The main evidence concerns primary insomnia in subjects over the age of 55, showing significant improvements in sleep quality. In neurodevelopmental disorders, there is evidence of a positive impact on sleep quality and quality of life for patients and their caregivers. PRM shows efficacy in the treatment of sleep disorders in mood disorders, schizophrenia, and neurocognitive disorders, but requires further confirmation. The additional use of PRM is supported for the withdrawal of chronic benzodiazepine therapies. The tolerability and safety of PRM are excellent, with ample evidence supporting the absence of tolerance and dependence. CONCLUSIONS: Overall, PRM in circadian medicine is an effective chronopharmaceutical for restoring the sleep-wake rhythm in patients with insomnia disorder. This efficacy may also extend to sleep disorders associated with mood, neurodevelopmental and neurocognitive disorders, suggesting a further potential role in insomnia associated with various organic diseases.

Key Findings

Overall, PRM in circadian medicine is an effective chronopharmaceutical for restoring the sleep-wake rhythm in patients with insomnia disorder. This efficacy may also extend to sleep disorders associated with mood, neurodevelopmental and neurocognitive disorders, suggesting a further potential role in insomnia associated with various organic diseases.

Outcomes Measured

  • sleep quality

Population

Field Value
Population insomnia disorder
Sample Size 62
Age Range See abstract
Condition insomnia

MeSH Terms

  • Melatonin
  • Humans
  • Delayed-Action Preparations
  • Sleep Initiation and Maintenance Disorders
  • Circadian Rhythm
  • Sleep Disorders, Circadian Rhythm
  • Neurodevelopmental Disorders
  • Mood Disorders
  • Sleep Wake Disorders
  • Sleep Quality
  • Neurocognitive Disorders

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Systematic Review, Journal Article
  • Vertical: melatonin

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09