CURRENT EVIDENCE ON THE USE OF MELATONIN FOR PRIMARY INSOMNIA COMPARED TO BENZODIAZEPINES

Authors

  • Valéria Goulart Viana Author
  • Daniel Gomes Fialho Author
  • Talyta Rodriguez Doratiotto Furia Author
  • Ramon Brasileiro Duarte Author
  • Felipe Dall Oglio Furlan Author
  • Caio de Lima Ferreira Author
  • João Eugênio Henrique Heidemann e Silva Author
  • Patrícia Lemos dos Santos Author
  • André Gustavo Sampaio Costa Author
  • Katiucia Sá Silva Author
  • Mariáh França Guimarães Meirelles de Paula Author
  • Jackellyne Alves Peres Gomes Author
  • Josinalva Pereira Souza Author
  • Lucas Rezende Author
  • Silvia Regina Maciel Fonseca Author
  • Ana Carla Ribeiro Arrais Author
  • Leonardo Franco de Almeida Author
  • Zayan Vilela Cid Tavares de Oliveira Author
  • João Pedro Reggi Author
  • Leonardo Soares da Silva Author

DOI:

https://doi.org/10.56238/levv16n54-139

Keywords:

Melatonin, Primary Insomnia, Benzodiazepines, Sleep Therapy, Clinical Pharmacology

Abstract

Primary insomnia is one of the most prevalent sleep disorders in the adult population, characterized by difficulty in initiating or maintaining sleep, resulting in significant impairments to health, cognitive performance, and quality of life. Benzodiazepines and GABA-A receptor agonists, known as Z-drugs, are widely used in the pharmacological treatment of insomnia; however, their long-term use is associated with tolerance, dependence, and cognitive impairment. Melatonin, an endogenous hormone responsible for regulating the sleep–wake cycle, has been studied as a safe and physiological therapeutic alternative. This study aimed to analyze the most recent scientific evidence on the efficacy and safety of melatonin and its melatonergic agonists compared to benzodiazepines in the treatment of primary insomnia. An integrative literature review was conducted based on studies published between 2015 and 2025 in PubMed, SciELO, ScienceDirect, and Scopus databases. The results demonstrated that melatonin shows moderate efficacy in sleep onset and maintenance, with a superior safety profile and absence of dependence potential, making it a suitable therapeutic option, especially for elderly and polymedicated patients. It is concluded that melatonin represents a promising, effective, and safe pharmacological alternative for the management of primary insomnia, contributing to more rational clinical practices aligned with evidence-based medicine.

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References

ATKIN, T. et al. Agomelatine for the treatment of generalized anxiety disorder: a systematic review and meta-analysis. Journal of Affective Disorders, v. 235, p. 141–150, 2018.

AULD, F. et al. Evidence for the efficacy of melatonin in the treatment of primary adult sleep disorders. Sleep Medicine Reviews, v. 34, p. 10–22, 2017.

BARDIN, L. Análise de conteúdo. São Paulo: Edições 70, 2016.

BRASIL. Conselho Nacional de Saúde. Resolução nº 510, de 7 de abril de 2016. Dispõe sobre as normas aplicáveis a pesquisas em Ciências Humanas e Sociais. Brasília: Ministério da Saúde, 2016.

CARDINALI, D. P. et al. Assessing the efficacy of melatonin to curtail benzodiazepine/Z drug abuse. Pharmacological Research, v. 109, p. 12–23, 2016.

CHEUNG, J. M. Y. et al. Comparative short-term safety and efficacy of hypnotics: a quantitative risk–benefit analysis. Journal of Sleep Research, e14088, 2023.

CRESCENZO, F. et al. Comparative effects of pharmacological interventions for insomnia disorder in adults: a systematic review and network meta-analysis. The Lancet, v. 400, p. 170–184, 2022.

GIL, A. C. Métodos e técnicas de pesquisa social. 7. ed. São Paulo: Atlas, 2019.

HASSINGER, A. B. et al. Selecting a pharmacotherapy regimen for patients with chronic insomnia. Expert Opinion on Pharmacotherapy, v. 21, n. 8, p. 1035–1043, 2020.

KIM, H. K.; YANG, K. Melatonin and melatonergic drugs in sleep disorders. Translational and Clinical Pharmacology, v. 30, p. 163–171, 2022.

LAKATOS, E. M.; MARCONI, M. A. Fundamentos de metodologia científica. 8. ed. São Paulo: Atlas, 2017.

MORERA-FUMERO, A.; FERNÁNDEZ-LÓPEZ, L.; ABREU-GONZÁLEZ, P. Melatonin and melatonin agonists as treatments for benzodiazepines and hypnotics withdrawal in patients with primary insomnia. Drug and Alcohol Dependence, n. 107994, 2020.

OXFORD CENTRE FOR EVIDENCE-BASED MEDICINE. Levels of Evidence (March 2011). University of Oxford, 2011. Disponível em: https://www.cebm.ox.ac.uk/resources/levels-of-evidence. Acesso em: 23 nov. 2025.

PARK, Y.-M. et al. Efficacy and safety of prolonged-release melatonin for primary insomnia in elderly patients. Chronobiology in Medicine, v. 5, n. 1, p. 25–33, 2023.

RIEMANN, D. et al. European guideline for the diagnosis and treatment of insomnia. Journal of Sleep Research, v. 26, n. 6, 2017.

SALAHUB, C. et al. Melatonin for insomnia in medical inpatients: a narrative review. Journal of Clinical Medicine, v. 11, n. 4, 2022.

SCHROECK, J. L. et al. Review of safety and efficacy of sleep medicines in older adults. Clinical Therapeutics, v. 38, n. 11, p. 2340–2372, 2016.

VIGO, D. E.; CARDINALI, D. P. Melatonin and benzodiazepine/Z-drug abuse. In: CARDINALI, D. P. (ed.). Psychiatry and Neuroscience Update. Cham: Springer, 2018. p. 233–248.

WANG, L. et al. A network meta-analysis of the long- and short-term efficacy of sleep medicines in adults and older adults. Neuroscience & Biobehavioral Reviews, v. 131, p. 489–496, 2021.

WHITTEMORE, R.; KNAFL, K. The integrative review: updated methodology. Journal of Advanced Nursing, v. 52, n. 5, p. 546–553, 2005.

Published

2025-11-26

How to Cite

VIANA, Valéria Goulart et al. CURRENT EVIDENCE ON THE USE OF MELATONIN FOR PRIMARY INSOMNIA COMPARED TO BENZODIAZEPINES. LUMEN ET VIRTUS, [S. l.], v. 16, n. 54, p. e10399, 2025. DOI: 10.56238/levv16n54-139. Disponível em: https://periodicos.newsciencepubl.com/LEV/article/view/10399. Acesso em: 13 feb. 2026.