Clinical efficacy and safety of fluoxetine in generalized anxiety disorder in Chinese patients

Background: Generalized anxiety disorder (GAD) is a prevalent, disabling disease and is highly comorbid with other psychiatric disorders both in Western countries and the People's Republic of China. Fluoxetine, a selective inhibitor of serotonin reuptake (SSRI), is widely utilized in the management of GAD in clinical practice despite the lack of strong evidence. This article reviews fluoxetine trials to investigate fluoxetine's efficacy and tolerability in Chinese patients with GAD. Methods: A literature review was conducted using the following databases up to and including April 2013: Chinese BioMedical Literature, China National Knowledge Infrastructure, EMBASE, MEDLINE, and PsycINFO. We selected clinical studies that utilized fluoxetine for GAD in which all participants were Chinese. Results: Fifteen open-label, non-placebo trials were identified and analyzed; eleven anxiolytics were compared with fluoxetine separately. Short-term efficacy of fluoxetine had been established in these open-label, head-to-head controlled trials. Fluoxetine had rapid onset of action (approximately 1-2 weeks) and seemed to be effective in maintenance treatment. Fluoxetine was generally well-tolerated with the most common side effect of dry month and nausea. Compared to other anxiolytic agents, fluoxetine was equivalent with all of the comparative anxiolytics in terms of efficacy except mirtazapine which showed conflicting results with fluoxetine in two studies. In terms of side effects, fluoxetine was better tolerated than diazepam, doxepine, and amitriptyline, less tolerated than escitalopram, and had similar tolerability with duloxetine as well as alprazolam. Conclusion: Given the high risk of bias of the included studies, the overall small sample size of the studies, the lack of placebo control groups as well as the lack of certain clinically meaningful outcomes, it is not possible to recommend fluoxetine as a reliable first-line treatment in Chinese patients with GAD. Furthermore, no definitive implications for clinical practice in choosing anxiolytics can be drawn from this review. Trials with larger sample sizes, better quality, longer duration, and more clinically meaningful outcomes are needed in future research. Keywords: fluoxetine, generalized anxiety disorder, clinical trials, Chinese, prevalence