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PLoS One. 2017 Oct 5;12(10):e0185865. doi: 10.1371/journal.pone.0185865. eCollection 2017.

Short-term efficacy and tolerability of venlafaxine extended release in adults with generalized anxiety disorder without depression: A meta-analysis.

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Department of Neurology, Neuroscience Centre, the First Teaching Hospital of Jilin University, Changchun, China.
China-Japan Union Hospital of Jilin University, Changchun, China.
Department of Epidemiology and Biostatistics, School of Public Health of Jilin University, Changchun, China.



Although efficacy of venlafaxine extended release (XR) for generalized anxiety disorder (GAD) has been reported in previous analyses in 2002 and 2004, the sample size was rather small and estimate of safety or tolerability was not clear. The present analysis had the advantage of large sample size and provided evidence for tolerability.


Literature databases were searched, including Pubmed, Embase, Cochrane Central Register of Controlled Trials, Web of science and clinical trials. 10 eligible articles were finally selected and data was extracted and logged into the Review Manager 5.3 by two independent authors. The risk of bias was evaluated by the Cochrane Collaboration's Risk of Bias Tool and the stability of the results was assessed by sensitivity analysis. The publication bias was assessed by funnel plot and Egger's/Begg's test using Stata Version 12.0 software.


In the current meta-analysis, 10 articles (14 studies) satisfying the inclusion criteria were analyzed. As efficacy outcomes, our findings indicated venlafaxine XR was significantly more effective than placebo according to mean change of the Hamilton Rating Scale for Anxiety total scores [mean difference = 3.31, 95% confidence interval(CI) 1.44-5.18, P = 0.0005], response [odds ratio(OR) = 1.83, 95%CI 1.58-2.12, P<0.00001], and remission (OR = 2.55, 95%CI 1.36-4.78, P = 0.003). In terms of tolerability, the most frequently reported treatment-emergent adverse events were nausea, dry mouth, dizziness, insomnia, somnolence, and headache. In addition, discontinuation due to all-cause (OR = 1.17, 95%CI 0.92-1.49, P = 0.19) was not significantly different between the two groups, whereas discontinuation due to adverse events was statistically higher in the venlafaxine XR group compared with the placebo treatment (OR = 2.80, 95%CI 2.21-3.54, P<0.00001) and discontinuation due to inefficacy was lower in venlafaxine than placebo treatment (OR = 0.26, 95%CI 0.17-0.40, P<0.00001). There was no significant publication bias and sensitivity analysis showed that our analysis exhibited high stability.


We concluded that venlafaxine XR (75-225 mg/day) is an effective and well-tolerated pharmacological treatment option for adult patients with GAD.

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