Objective: The association between the 1438A/G,102T/C and rs7997012G/A polymorphisms of HTR2A and the efficacy and safety of antidepressants (ADs) in the treatment of depression was controversial. That controversy was not only across studies but also across three previous meta-analyses. The aim of the current meta-analysis was to reanalyze the influence of HTR2A genetic polymorphisms on the efficacy and safety of antidepressants in the treatment of depressive disorder by adding lots of newly published literatures in recent 10 years and previous literatures omitted by previous meta-analyses. Method: PubMed, EMBASE, Web of Science, the Cochrane Library, Clinical Trials.gov, and four Chinese literature databases (CNKI, Wan Fang, VIP and Sino Med) were searched. The efficacy outcomes included repression rate and remission rate. The safety outcomes included incidents of antidepressant-induced side effects. Meta-analysis was performed using the Revman statistical software. The odds ratio (OR) and 95% confidence interval (95% CI) was applied to estimate the efficacy and safety of antidepressants in the treatment of depression. Results: The meta-analysis included 42 studies, 29 studies was on the treatment efficacy, 15 studies was on the side effects. We found significant associations between the response rate and 1438A/G polymorphism (16 cohort studies, 1931 subjects) in dominant genetic model (GG + GA vs AA: OR: 1.40, 95% CI: 1.121.76; P = 0.003), Then , We also found the significant association between the rs7997012G/A polymorphism (9 cohort studies,1434 subjects) and the remission rate in all genetic models (GG vs AA + GA: OR: 1.30, 95% CI: 1.011.66; P = 0.04; GG + GA vs AA: OR: 2.20, 95% CI: 1.533.16; P < 0.0001; GG vs AA: OR: 2.73, 95% CI: 1.784.17; P < 0.00001); Finally, the significant association between the 102T/C polymorphism (8 cohort studies, 804 subjects) and the ADs-induced side effects in recessive genetic model (TT + TC vs CC: OR: 0.57, 95% CI: 0.40.83; P = 0.003) and in homozygote genetic model (TT vs CC: OR: 0.54, 95% CI: 0.290.99; P = 0.05) was also found. Conclusion: Our meta-analysis firmly supported HTR2A 1438A/G polymorphisms are correlated with the response rate and rs7997012G/A polymorphisms are in connection with the remission rate. Moreover, our analysis also provided empirical evidence that HTR2A 102T/C may be correlated with the ADs-induced side effects. Keywords: depression, HTR2A genetic polymorphism, treatment outcome, side effect, meta-analysis
