Melatonin for the treatment of dementia

Abstract

Background There are a number of studies that suggest a relationship between decline of melatonin function and the symptoms of dementia. Objectives The review assessed the evidence of clinical effectiveness of melatonin in the treatment of symptoms of dementia. Relevant primary outcomes were cognition, mood, behaviour, functions of daily living, and safety of melatonin use and secondary outcomes were quality of life, morbidity, mortality and length of time to institutionalization and caregiver stress. Search methods The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS were searched on 29 June 2009 using the terms: MELATONIN and N-ACETYL-5-METHOXYTRYPTAMINE. The CDCIG Specialized Register contains records from all major health care databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS) as well as from many trials databases and grey literature sources. The search of June 2009 retrieved several studies for consideration by the authors. Selection criteria All relevant, randomized controlled trials in which orally administered melatonin in any dosage was compared with a control group for the effect on managing cognitive, behavioral (excluding sleep), and mood disturbances of people with dementia of any degree of severity. Data collection and analysis Two to three reviewers independently assessed the retrieved articles for relevance and risk of bias, and extracted data from the selected studies. Statistically significant differences in end-points or changes in outcomes from baseline to end of treatment between the melatonin and control groups were examined. Each study was summarized using a measure of effect (e.g. mean difference) and meta-analyses were conducted when appropriate. Main results Five studies met the inclusion criteria. The pooled estimates of MMSE cognitive and ADAS-cognitive change scores from three of these studies revealed non-significant cognitive effects for melatonin treatment. In two of these studies, significant improvements in psychopathological behaviours (e.g., decreased mood symptoms of depression, anxiety and apathy and decreased behavior symptoms of hallucinations, delusions, agitation, irritability, and appetite disturbances), were found from meta-analysis of the change scores from the NPI (7 weeks, 2.5 mg melatonin), and ADAS non-cognitive (4 weeks, 3 mg melatonin) scales. Sensitivity analyses found similar results to those of the original meta-analyses, and thus, supported the effect estimates for non-significant cognitive outcomes. Individual study estimates for treatment effect of 2.5 mg melatonin at one year demonstrated a significant worsening of mood (e.g. decrease in positive affect) as measured by the Philadelphia Geriatric Centre Affect Rating Scale (positive). The remainder of the treatment effects for mood, behavior, and function of daily living were non-significant. There were no reported adverse effects associated with melatonin use. Authors' conclusions The analyses did not support the use of melatonin for treatment of cognitive impairment associated with dementia. Meta-analysis of psychopathologic behavior scale scores suggested that melatonin may be effective in treating these dementia-related disturbances.