Objective: The efficacy and tolerability of idalopirdine, a selective 5-hydroxytryptamine6 receptor antagonist, in patients with Alzheimer's disease (AD) is uncertain. A systematic review and meta-Analysis of randomized controlled trials (RCTs) testing idalopirdine for patients with AD was performed.Methods: We included RCTs of idalopirdine for patients with AD and used Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) scores as a primary measure.Results: Four RCTs with 2,803 patients with AD were included. There was no significant difference in ADAS-cog between the idalopirdine and placebo groups [mean difference (MD) =-0.41, P = 0.32, I 2 = 62%]. However, significant heterogeneity remained. Sensitivity analysis revealed that idalopirdine was more effective than placebo for ADAS-cog in the high dose and moderate AD subgroups (high dose subgroup: MD =-2.15, P = 0.005, moderate AD subgroup: MD =-2.15, P = 0.005). Moreover, meta-regression analysis showed that idalopirdine effect size for ADAS-cog was associated with mean dose (coefficient,-0.0289), ADAS-cog at baseline (coefficient,-0.9519), and proportion of male participants (coefficient, 0.2214). For safety outcomes, idalopirdine was associated with a higher incidence of at least one adverse event and increased γ-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, and vomiting than placebo. There were no significant differences in other secondary outcomes between both treatments.Conclusions: Idalopirdine is not effective for AD patients and is associated with a risk of elevated liver enzymes and vomiting. Although idalopirdine might be more effective at high doses and in moderate AD subgroups, the effect size is small and may be limited.
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