Systematic Review of Pharmacotherapy for Generalized Anxiety Disorder Highlights Efficacious Options

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Although there are a number of effective treatment choices available for generalized anxiety disorder, venlafaxine, pregabalin, escitalopram, and duloxetine appear to be first-line choices.

Multiple effective drug therapies are available for the treatment of adults with generalized anxiety disorder (GAD), according to results from a large contemporary review published in the Lancet. Of the options, researchers’ meta-analysis showed that duloxetine, pregabalin, venlafaxine, and escitalopram were more efficacious than placebo, with relatively good acceptability.

In this systematic review and network meta-analysis, researchers searched major databases for studies that included adults who were treated with a minimum of 2 commercially available drug therapies or placebo for GAD. After applying the search criteria, the investigators identified 1992 studies that included a total of 89 randomized trials. The trials included 25,441 patients randomly assigned to 22 different active drugs or placebo. The primary outcomes measured were efficacy and tolerability of available drug options, which were compared using network analysis. Among the agents included, changes in efficacy were measured using the Hamilton Anxiety Rating Scale

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After analysis, the researchers found that escitalopram (mean difference [MD], −2.45; 95% credible interval [CrI], −3.27 to −1.63), venlafaxine (MD, −2.69; 95% CrI, −3.50 to −1.89), duloxetine (MD, −3.13; 95% CrI, −4.13 to −2.13), and pregabalin (MD, −2.79; 95% CrI, −3.69 to −1.91) showed better efficacy vs placebo. In addition, the researchers reported that these agents were well-tolerated compared with placebo.

The antipsychotic quetiapine showed the greatest change in Hamilton Anxiety Rating Scale score (MD, −3.60; 95% CrI, −4.83 to −2.39), but was not well-tolerated vs placebo.

Researchers added that sertraline, fluoxetine, and buspirone are also possible first-line alternatives, but the evidence for their use is limited by small study samples. “For patients for whom first-line choices have been unsuccessful at ameliorating symptoms, agomelatine might be considered on the basis of data available from our review,” they continued.

“[O]ur findings suggest that there are several viable options for the treatment of generalised anxiety disorder. There are differences in the efficacy and acceptability profiles across these options, and the best choice might not be uniform across patients,” the researchers concluded.


Slee A, Nazareth I, Bondaronek P, Liu Y, Cheng Z, Freemantle N. Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis. Lancet. 2019;393(10173):768-777.