ROLE OF MELATONIN IN THE MANAGEMENT OF SLEEP DISORDERS IN SCHIZOPHRENIA: A LITERATURE REVIEW

Andrzej Wydrych; Patryk Pindlowski; Ewa Wietrzykowska; Piotr Trojan; Maja Kuklo; Aleksandra Karolak; Agata Karasiewicz; Marta Kras; Aleksandra Tomczyk; Michał Olkowski

doi:10.31435/ijitss.4(48).2025.4153

Andrzej Wydrych Independent Public Complex of Health Care Facilities in Płońsk, Płońsk, Poland https://orcid.org/0009-0004-8466-2892
Patryk Pindlowski Hospital of Our Lady of Perpetual Help in Wołomin, Wołomin, Poland https://orcid.org/0009-0008-2474-860X
Ewa Wietrzykowska Municipal Polyclinical Hospital, Olsztyn, Poland https://orcid.org/0009-0009-5510-9007
Piotr Trojan Independent Public Complex of Health Care Facilities in Płońsk, Płońsk, Poland https://orcid.org/0009-0007-7956-4704
Maja Kuklo Clinical Hospital of the Ministry of Internal Affairs and Administration with the Warmia–Mazury Oncology Centre in Olsztyn, Olsztyn, Poland https://orcid.org/0009-0006-4008-647X
Aleksandra Karolak Medical University of Białystok, Białystok, Poland https://orcid.org/0009-0007-1179-1126
Agata Karasiewicz Otwock County Hospital – Otwock County Health Centre, Otwock, Poland https://orcid.org/0009-0003-2301-267X
Marta Kras Independent Group of Public Ambulatory Care Institutions Warsaw-Ochota, Warsaw, Poland https://orcid.org/0009-0006-9605-1866
Aleksandra Tomczyk University Clinical Hospital No. 2 in Łódź, Łódź, Poland https://orcid.org/0009-0009-6030-3939
Michał Olkowski Independent Public Complex of Health Care Facilities in Płońsk, Płońsk, Poland https://orcid.org/0009-0000-2942-3822

DOI: https://doi.org/10.31435/ijitss.4(48).2025.4153

Keywords: Melatonin, Schizophrenia, Sleep Disorders, Circadian Rhythms, Psychiatric Illnesses

Abstract

Introduction and Objective: Sleep and circadian rhythm disturbances are highly prevalent in Schizophrenia and significantly impact symptom severity, disease progression, and treatment outcomes. Schizophrenia, a chronic and disabling mental illness affecting approximately 1% of the global population, is particularly associated with pronounced sleep abnormalities. Over 80% of patients with schizophrenia experience reduced sleep efficiency and delayed sleep onset. These disturbances are closely linked to worsening psychotic symptoms, cognitive dysfunction, and diminished quality of life. This review aims to explore the role of melatonin in these disruptions and its potential as an adjunctive treatment in Schizophrenia.

Materials and methods: Articles in PubMed, GoogleScholar, ScienceDirect databases were retrieved by the authors. The authors searched with keywords: melatonin, schizophrenia, sleep disorder, circadian rhythms, psychiatric disease. Articles between 2000 and 2024 were included.

Results: Randomized controlled trials show that prolonged-release melatonin (2–10 mg, 1–2 hours before bedtime) improves sleep latency, efficiency, and duration in schizophrenia. Melatonin, immediate-release, has variable findings; low doses (<1 mg) are used to treat circadian disorders, while higher doses (3–12 mg) are used to treat insomnia. Melatonin will also improve benzodiazepine withdrawal insomnia and help habituate to sleep in a novel environment. It is tolerable with mild but occasional side effects, but larger, high-quality trials are needed.

Conclusions: Melatonin is of great promise as an adjunct to sleep and circadian disturbance treatment in schizophrenia and related psychiatric illnesses, but more extensive research must be conducted to confirm its long-term safety and clinical efficacy.

References

Andrabi, S. S., Vishnoi, S., Kaushik, M., Parveen, K., Tabassum, H., Akram, M., & Parvez, S. (2019). Reversal of schizophrenia-like symptoms and cholinergic alterations by melatonin. Archives of Medical Research, 50(5), 295–303. https://doi.org/10.1016/j.arcmed.2019.08.005

Arendt, J., & Aulinas, A. (2000). Physiology of the pineal gland and melatonin. In K. R. Feingold et al. (Eds.), Endotext. MDText.com, Inc. https://www.ncbi.nlm.nih.gov/books/NBK550972/

Baandrup, L., Fagerlund, B., Jennum, P., Lublin, H., & Glenthøj, B. Y. (2013). Melatonin for treatment of sleep disturbances in schizophrenia: A randomized, double-blind, placebo-controlled trial. Acta Psychiatrica Scandinavica, 127(1), 81–82. https://doi.org/10.1111/acps.12016

Baandrup, L., Glenthøj, B. Y., & Jennum, P. J. (2016). Objective and subjective sleep quality: Melatonin versus placebo add-on treatment in patients with schizophrenia or bipolar disorder withdrawing from long-term benzodiazepine use. Psychiatry Research, 240, 163–169. https://doi.org/10.1016/j.psychres.2016.04.031

Bastos, M. A. V., Jr., Oliveira Bastos, P. R. H., Portella, R. B., Soares, L. F. G., Conde, R. B., Rodrigues, P. M. F., Jr., & Lucchetti, G. (2019). Pineal gland and schizophrenia: A systematic review and meta-analysis. Psychoneuroendocrinology, 104, 100–114. https://doi.org/10.1016/j.psyneuen.2019.02.024

Behrouzian, F., Abdi, L., Nazarinasab, M., Moghaddam Sadegh, A., Anoosheh, S., & Moradi, M. (2023). Evaluating the effect of melatonin on positive and negative symptoms of schizophrenic patients: A randomized placebo-controlled study. Iranian Journal of Psychiatry, 18(2), 119–126. https://doi.org/10.18502/ijps.v18i2.12362

Chan, M. S., Chung, K. F., Yung, K. P., & Yeung, W. F. (2017). Sleep in schizophrenia: A systematic review and meta-analysis of polysomnographic findings in case-control studies. Sleep Medicine Reviews, 32, 69–84. https://doi.org/10.1016/j.smrv.2016.03.001

Chauhan, S., Barbanta, A., Ettinger, U., & Kumari, V. (2023). Pineal abnormalities in psychosis and mood disorders: A systematic review. Brain Sciences, 13(5). https://doi.org/10.3390/brainsci13050827

Feybesse, C., Chokron, S., & Tordjman, S. (2023). Melatonin in neurodevelopmental disorders: A critical literature review. Antioxidants, 12(11). https://doi.org/10.3390/antiox12112017

Garfinkel, D., Zisapel, N., Wainstein, J., & Laudon, M. (1999). Facilitation of benzodiazepine discontinuation by melatonin: A new clinical approach. Archives of Internal Medicine, 159(20), 2456–2460. https://doi.org/10.1001/archinte.159.20.2456

González-Rodríguez, A., Haba-Rubio, J., Usall, J., Natividad, M., Soria, V., Labad, J., & Monreal, J. A. (2022). Hormone targets for the treatment of sleep disorders in postmenopausal women with schizophrenia: A narrative review. Clocks & Sleep, 4(1), 52–65. https://doi.org/10.3390/clockssleep4010007

Javitt, D. C. (2023). Cognitive impairment associated with schizophrenia: From pathophysiology to treatment. Annual Review of Pharmacology and Toxicology, 63, 119–141. https://doi.org/10.1146/annurev-pharmtox-051921-093250

Maiti, R., Mishra, B. R., Jena, M., Mishra, A., & Nath, S. (2021). Effect of haloperidol and risperidone on serum melatonin and GAP-43 in patients with schizophrenia: A prospective cohort study. Clinical Psychopharmacology and Neuroscience, 19(1), 125–134. https://doi.org/10.9758/cpn.2021.19.1.125

Manoach, D. S., Thakkar, K. N., Stroynowski, E., Ely, A., McKinley, S. K., et al. (2010). Reduced overnight consolidation of procedural learning in chronic medicated schizophrenia is related to specific sleep stages. Journal of Psychiatric Research, 44, 112–120. https://doi.org/10.1016/j.jpsychires.2009.06.011

Manoach, D. S., & Stickgold, R. (2019). Abnormal sleep spindles, memory consolidation, and schizophrenia. Annual Review of Clinical Psychology, 15, 451–479. https://doi.org/10.1146/annurev-clinpsy-050718-095754

Minich, D. M., Henning, M., Darley, C., Fahoum, M., Schuler, C. B., & Frame, J. (2022). Is melatonin the "next vitamin D"?: A review of emerging science, clinical uses, safety, and dietary supplements. Nutrients, 14(19). https://doi.org/10.3390/nu14193934

Mishra, A., Maiti, R., Mishra, B. R., Jena, M., Nath, S., & Sahu, P. (2020). Effect of add-on ramelteon therapy on sleep and circadian rhythm disruption in patients with schizophrenia: A randomized controlled trial. European Neuropsychopharmacology, 31, 109–118. https://doi.org/10.1016/j.euroneuro.2019.11.008

Monteleone, P., Natale, M., La Rocca, A., & Maj, M. (1997). Decreased nocturnal secretion of melatonin in drug-free schizophrenics: No change after subchronic treatment with antipsychotics. Neuropsychobiology, 36(4), 159–163. https://doi.org/10.1159/000119377

Moon, E., Kim, K., Partonen, T., & Linnaranta, O. (2022). Role of melatonin in the management of sleep and circadian disorders in the context of psychiatric illness. Current Psychiatry Reports, 24(11), 623–634. https://doi.org/10.1007/s11920-022-01369-6

Morera-Fumero, A. L., & Abreu-Gonzalez, P. (2013). Role of melatonin in schizophrenia. International Journal of Molecular Sciences, 14(5), 9037–9050. https://doi.org/10.3390/ijms14059037

Naguy, A. (2022). Therapeutic use of melatonin in schizophrenia—More than meets the eye! World Journal of Psychiatry, 12(3), 533–535. https://doi.org/10.5498/wjp.v12.i3.533

Palagini, L., Manni, R., Aguglia, E., Amore, M., Brugnoli, R., Bioulac, S., Bourgin, P., Micoulaud Franchi, J. A., Girardi, P., Grassi, L., Lopez, R., Mencacci, C., Plazzi, G., Maruani, J., Minervino, A., Philip, P., Royant Parola, S., Poirot, I., Nobili, L., … Geoffroy, P. A. (2021). International expert opinions and recommendations on the use of melatonin in the treatment of insomnia and circadian sleep disturbances in adult neuropsychiatric disorders. Frontiers in Psychiatry, 12, 688890. https://doi.org/10.3389/fpsyt.2021.688890

Potanin, S. S., & Morozova, M. A. (2021). Oxidative stress in schizophrenia as a promising target for psychopharmacotherapy. Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova, 121(9), 131–138. https://doi.org/10.17116/jnevro2021121091131

Shamir, E., Laudon, M., Barak, Y., Anis, Y., Rotenberg, V., Elizur, A., & Zisapel, N. (2000). Melatonin improves sleep quality of patients with chronic schizophrenia. Journal of Clinical Psychiatry, 61(5), 373–377. https://doi.org/10.4088/jcp.v61n0509

Shamir, E., Rotenberg, V. S., Laudon, M., Zisapel, N., & Elizur, A. (2000). First-night effect of melatonin treatment in patients with chronic schizophrenia. Journal of Clinical Psychopharmacology, 20(6), 691–694. https://doi.org/10.1097/00004714-200012000-00017

Shen, J., Li, X., Zhong, Y., Zhang, J., Qin, H., Chen, F., & Zhao, X. (2025). Neuroendocrine characterization into schizophrenia: Norepinephrine and melatonin as promising biomarkers. Frontiers in Endocrinology, 16, 1551172. https://doi.org/10.3389/fendo.2025.1551172

Stummer, L., Markovic, M., & Maroney, M. E. (2018). Pharmacologic treatment options for insomnia in patients with schizophrenia. Medicines, 5(3). https://doi.org/10.3390/medicines5030088

Sun, C. H., Zheng, W., Yang, X. H., Cai, D. B., Ng, C. H., Ungvari, G. S., Li, H. Y., Wu, Y. J., Ning, Y. P., & Xiang, Y. T. (2017). Adjunctive melatonin for tardive dyskinesia in patients with schizophrenia: A meta-analysis. Shanghai Archives of Psychiatry, 29(3), 129–136. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5579456/

Takahashi, T., Nakamura, M., Sasabayashi, D., Nishikawa, Y., Takayanagi, Y., Nishiyama, S., Higuchi, Y., Furuichi, A., Kido, M., Noguchi, K., & Suzuki, M. (2019). Reduced pineal gland volume across the stages of schizophrenia. Schizophrenia Research, 206, 163–170. https://doi.org/10.1016/j.schres.2018.11.032

Tan, D. X., Xu, B., Zhou, X., & Reiter, R. J. (2018). Pineal calcification, melatonin production, aging, associated health consequences and rejuvenation of the pineal gland. Molecules, 23(2). https://doi.org/10.3390/molecules23020301

Tuft, C., Matar, E., Menczel Schrire, Z., Grunstein, R. R., Yee, B. J., & Hoyos, C. M. (2023). Current insights into the risks of using melatonin as a treatment for sleep disorders in older adults. Clinical Interventions in Aging, 18, 49–59. https://doi.org/10.2147/CIA.S361519

Waite, F., Myers, E., Harvey, A. G., Espie, C. A., Startup, H., Sheaves, B., & Freeman, D. (2015). Treating sleep problems in patients with schizophrenia. Behavioural and Cognitive Psychotherapy, 44(3), 273–287. https://doi.org/10.1017/S1352465815000430