Therapeutic use of melatonin in schizophrenia: A systematic review

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.

Automated summary

Adjunctive melatonin therapy has positive outcomes for sleep, metabolic profile, and tardive dyskinesia in patients with schizophrenia, but no beneficial effects on cognition and benzodiazepine discontinuation were observed. Further studies with larger sample sizes and specific comparisons are needed to determine the effect of melatonin as adjunctive therapy with different antipsychotics in patients with schizophrenia.