Systematic Reviews
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatr. Aug 19, 2021; 11(8): 463-476
Published online Aug 19, 2021. doi: 10.5498/wjp.v11.i8.463
Therapeutic use of melatonin in schizophrenia: A systematic review
Cathy Duan, Zoe M Jenkins, David Castle
Cathy Duan, Zoe M Jenkins, David Castle, Department of Psychiatry, University of Melbourne, Parkville 3010, VIC, Australia
Zoe M Jenkins, David Castle, Mental Health Service, St. Vincent's Hospital, Melbourne 3065, VIC, Australia
David Castle, Centre for Complex Interventions, Centre for Addictions and Mental Health, Toronto ON M6J 1H4, Canada
David Castle, Department of Psychiatry, University of Toronto, Toronto ON M5S, Canada
Author contributions: Duan C and Castle D designed the research; Duan C performed the search; Duan C and Jenkins ZM extracted the data and wrote the paper; Castle D supervised the paper; all authors read and approved the final manuscript.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zoe M Jenkins, BSc, Research Fellow, Mental Health Service, St. Vincent's Hospital, 46 Nicholson Street, Fitzroy, Melbourne 3065, VIC, Australia. zoe.jenkins@svha.org.au
Received: February 24, 2021
Peer-review started: February 24, 2021
First decision: July 4, 2021
Revised: July 12, 2021
Accepted: July 29, 2021
Article in press: July 29, 2021
Published online: August 19, 2021
ARTICLE HIGHLIGHTS
Research background

Schizophrenia is a chronic psychiatric condition consisting of positive and negative symptoms causing significant impacts on life. Current treatment includes second-generation antipsychotics (SGAs), the use of which is associated with side effects including: increased metabolic risk, sleep dysfunction and extrapyramidal side effects (EPS). Exogenous melatonin has been demonstrated to attenuate sleep dysfunction in the general population, however its indication in schizophrenia has been relatively unexplored. The proven antioxidant and neuroprotective effects of melatonin suggest potential for therapeutic benefit in adjunctive treatment of schizophrenia, especially in attenuating side effects associated with SGAs.

Research motivation

Current therapeutic treatment for schizophrenia often causes side effects including increased cardiovascular and metabolic risk, sleep dysfunction and EPS. Adjunctive use of melatonin has been suggested to benefit sleep disturbances, however its indication in schizophrenia has remained unclear. Therefore, we synthesized the current evidence for the effect of adjunctive use of melatonin on any outcome in individuals with schizophrenia.

Research objectives

To synthesize clinical trials conducted to date that have investigated the use of melatonin as an adjunctive therapy for individuals with schizophrenia in improving any therapeutic outcome.

Research methods

A systematic literature search was conducted on MEDLINE (Ovid), Embase, PsychINFO, PubMed, CINAHL and Cochrane Library for clinical trials using melatonin as an adjunctive therapy that included a group of patients with schizophrenia. PRISMA guidelines were adhered to and the Cochrane risk-of-bias tool for randomized controlled trials was used by two authors to assess the trials independently, with consensus confirmed by a third reviewer.

Research results

A total of 15 trials were included for qualitative synthesis after assessing for eligibility and removing duplicates. The trials assessed the following primary outcomes: sleep (n = 6), metabolic profile (n = 3), tardive dyskinesia (n = 3), cognitive function (n = 2) and benzodiazepine discontinuation (n = 1).

Research conclusions

Positive outcomes were demonstrated for the use of melatonin in improving sleep efficiency and certain metabolic outcomes, specifically in first-episode patients initiating antipsychotic treatment. Currently, there is limited therapeutic indication for the use of melatonin in treatment of tardive dyskinesia, cognitive function or facilitating benzodiazepine discontinuation. Limitations included small sample sizes and no standardization of the duration and/or dosage of adjunctive melatonin used.

Research perspectives

Future studies are required to confirm these improvements, determine the pharmacokinetic interactions of melatonin with specific antipsychotic medications and develop a standardized duration and dosage of adjunctive melatonin treatment. Moreover, a long-term safety and efficacy profile remains to be determined.