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
Processing time: 169 Days and 3.8 Hours
Abstract
BACKGROUND

Sleep dysfunction is a common problem in people with schizophrenia, and side effects of treatment often exacerbate metabolic and cardiovascular risk and may induce extrapyramidal side effects. Melatonin (N-acetyl-5-methoxytryptamine) is an endogenously produced hormone which has demonstrated direct and indirect antioxidant and neuroprotective effects. Previous studies have explored the use of exogenous melatonin in improving sleep outcomes in the general population, yet indications for use in schizophrenia are unclear.

AIM

To synthesize the evidence from clinical trials investigating prescribed melatonin as an adjunctive therapy in patients with schizophrenia.

METHODS

A systematic literature review of MEDLINE (Ovid), Embase, PsychINFO, and PubMed on the 27/08/20; and CINAHL and Cochrane Library databases, was conducted. Inclusion criteria were: a peer-reviewed clinical trial published in English; included a group of patients with schizophrenia; used melatonin as an adjunctive therapy; and reported any outcome of any duration. Exclusion criteria were: neurodegenerative diseases, primary sleep disorders, co-morbid substance use or animal studies.

RESULTS

Fifteen studies were included in the current review with the following primary outcomes: sleep (n = 6), metabolic profile (n = 3), tardive dyskinesia (n = 3), cognitive function (n = 2) and benzodiazepine discontinuation (n = 1).

CONCLUSION

Adjunctive melatonin therapy has some positive outcomes for sleep, metabolic profile and tardive dyskinesia in patients with schizophrenia. No beneficial effect of melatonin was observed on outcomes of cognition or benzodiazepine discontinuation. Future studies utilizing larger samples and investigations specifically comparing the effect of melatonin as adjunctive therapy with different antipsychotics in patients with schizophrenia are required.

Keywords: Schizophrenia; Melatonin; Clinical trials; Sleep; Metabolic syndrome; Tardive dyskinesia

Core Tip: This systematic review synthesized the results of clinical trials that have investigated the effect of exogenous melatonin as adjunctive therapy for patients with schizophrenia. Some positive outcomes were demonstrated for sleep improvement and attenuating antipsychotic-induced metabolic side effects. Future investigations are required to determine differential effects of melatonin when used in conjunction with a range of antipsychotic medications.