Efficacy of melatonin supplementation for sleep quality, depression, and fatigue in patients with breast cancer: A systematic review and meta-analysis.
Melisha Koirala, Aakash Pandit55
Background: Breast cancer patients frequently experience a cluster of debilitating symptoms, including sleep disturbances, depression, and cancer-related fatigue, which persist during and after treatment. Melatonin, an endogenous hormone regulating circadian rhythms with antioxidant properties, has been proposed as a supportive therapy. However, clinical trials have yielded inconsistent findings regarding its symptomatic benefits. This meta-analysis aims to evaluate the efficacy of melatonin compared to placebo in improving sleep quality, depressive symptoms, and fatigue in breast cancer patients. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. Eligible studies compared oral melatonin supplementation with placebo in patients with breast cancer. Primary outcomes included sleep quality (measured by the Pittsburgh Sleep Quality Index [PSQI]), depression, and fatigue. Data were pooled using a random-effects model in Review Manager (RevMan) due to anticipated heterogeneity. Effect sizes were reported as Mean Differences (MD) for sleep quality and Standardized Mean Differences (SMD) for depression and fatigue, with 95% Confidence Intervals (CI). Heterogeneity was quantified using the I 2 statistic. Results: Seven RCTs involving a total of 568 patients were included in the pooled analysis. For sleep quality, analysis of three trials (N=186) showed no statistically significant improvement with melatonin compared to placebo (MD -9.13; 95% CI -23.87 to 5.62; P = 0.22), with extreme heterogeneity (I 2 = 99%). Regarding depressive symptoms (five trials, N=337), the pooled analysis indicated a trend towards reduction that did not reach statistical significance (SMD -0.42; 95% CI -0.96 to 0.12; P = 0.13), accompanied by high heterogeneity (I 2 = 83%). Similarly, no significant reduction in fatigue scores was observed across four trials (N=435) (SMD -0.21; 95% CI -0.91 to 0.50; P = 0.57), with substantial heterogeneity (I 2 = 92%). Conclusions: Current aggregated evidence does not support a significant therapeutic benefit of melatonin supplementation for improving sleep quality, depression, or fatigue in breast cancer patients. The analysis is limited by high heterogeneity, likely driven by variations in dosing, treatment duration, and baseline symptom severity. While individual studies suggest potential benefits, routine clinical use cannot be recommended based on current pooled data. Further standardized, large-scale trials are required to identify specific subgroups that may benefit.