Pregabalin for generalized anxiety disorder: an updated systematic review and meta-analysis

Generalized anxiety disorder (GAD), characterized by pervasive and highly distressing anxiety and worries, is associated with severe impairment. Although numerous agents from various drug classes are available to treat GAD, as many as 50% of patients have inadequate response, constituting an important medical frontier. In the face of this challenge, new pharmacological alternatives need to be further studied aiming at clinical improvement and better quality of life for patients. To assess the efficacy of pregabalin (PGB) compared with placebo for amelioration of anxiety symptoms in patients with GAD. A systematic literature search was performed using databases such as MEDLINE and EMBASE and other sources. The main outcome was Hedges' g for continuous scores. We used a random-effects model. Heterogeneity was evaluated with the I (moderate heterogeneity was assumed if I was >50% and high heterogeneity if I was >75%) and the χ-test (P<0.10 for heterogeneity). Publication bias was evaluated using the funnel plot. Meta-regression was performed using the random-effects model. For safety evaluation, we compared patients' dropout rates. We included eight randomized-controlled trials (n=2299) in our study, comparing the use of PGB in different dosages and placebo. In terms of the main outcome, PGB was found to be superior to the placebo group (Hedges' g=0.37; 95% confidence interval 0.30-0.44). The funnel plot assessment showed a low risk of publication bias. Between-study heterogeneity was not significant (I=0%), strengthening our results. Meta-regression showed no particular influence of any variable on the results. A categorical analysis of safety, using dropout as the most severe possible outcome, was carried out. No difference between PGB and placebo groups was observed in terms of the dropout rates. PGB was superior to placebo for the amelioration of GAD symptoms. In addition, the dropout rate was not significantly higher than that of the placebo groups. PGB was comparable to benzodiazepines in clinical response, but had lower dropout rates than benzodiazepine.