Efficacy of antidepressant drugs in the treatment of depression in Alzheimer disease patients: A systematic review and network meta-analysis

Background: Depression is considered as one of the most common neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) patients. Prescription of antidepressants is a current clinical practice well-established as the first-line treatment for such patients. Our study was aimed at systematically examining the evidence on the efficacy of antidepressants in the treatment of depression in AD patients. Methods: We conducted a network meta-analysis of randomized controlled trials retrieved by systematic search of the Cochrane Central Register of Controlled Trials, PubMed, Embase, and CNKI databases. Primary outcomes included mean depression score and safety. Secondary outcomes were cognition. The surface under the cumulative ranking curve was performed to estimate a ranking probability for different treatments. Results: A total of 25 studies including 14 medications met the inclusion criteria. Compared with placebo, only mirtazapine (standard mean deviation [SMD], -1.94; 95% confidence interval [CI], -3.53 to -0.36; p < 0.05) and sertraline (SMD, -1.16; 95% CI, -2.17 to -0.15; p < 0.05) showed a slightly better effect in treating symptoms of depression. Clomipramine increased risk of adverse events than placebo (odds ratio, 3.01; 95% CI, 1.45 to 4.57; p < 0.05). In terms of cognitive function, there was no statistically significant difference between antidepressants and placebo. Conclusion: Overall, in the short-term treatment, these data suggest that commonly used antidepressants sertraline and mirtazapine should be considered as an alternative treatment for depression in AD patients. However, more high-quality trials with large samples and longer following-up are proposed.