Abstract
Introduction: The administration of melatonin and melatonin receptor agonists (MRA) may result in a small improvement in sleep quality among middle-aged and older adults living with neurocognitive disorders, but debate remains as to whether effects are clinically meaningful. The purpose of this PROSPERO-registered systematic review and meta-analysis (CRD42022373972) was to synthesise evidence from randomized controlled trials (RCTs) of melatonin or MRA against placebo and other interventions for the treatment of sleep disturbances in adults with neurocognitive disorders.
Method: CENTRAL, MEDLINE, EMBASE, AMED, CINAHL and PsycINFO were systematically searched on November 4th 2022, examining the effect of melatonin and MRA on sleep efficiency: the percentage of time spent asleep while in bed. Results were analysed using Review Manager 5.4. Risk of bias was assessed using RoB 2 and the certainty of evidence was assessed with the GRADE framework.
Results: Among the 1,579 references evaluated, 13 RCTs were selected, corresponding to 16 studies, none including MRA, with a total of 592 patients. Compared with placebo, bright light treatment, or clonazepam, sleep efficiency significantly improved with melatonin administration (MD = 2.85, 95% CI: 0.88 to 4.81, p = 0.004). In subgroup analyses, only low doses of melatonin (< 5 mg) yielded a statistically significant improvement to sleep efficiency (MD = 3.81, 95% CI: 1.13 to 6.49, p = 0.005, I2 = 34%), and melatonin administration statistically significantly improved sleep efficiency in patients with Mild Cognitive Impairment, Parkinson's Disease, or Multiple Sclerosis (MD = 3.27, 95% CI: 0.11 to 6.43, p = 0.04, I2 = 41%), but not patients with Alzheimer's Disease. We found the overall quality of evidence to be moderate according to GRADE.
Conclusion: Melatonin may modestly ameliorate sleep quality in patients with neurocognitive disorders by improving sleep efficiency, which may be clinically significant to patients and those who care for them.