Generalized anxiety disorder (GAD) is a significant and common mental illness with a lifetime prevalence of 3.7%. Regardless of the complexity of treatment decisions for GAD, few studies have conducted systematic comparisons of the efficacies of varying interventions. Thus, this study performed a valid network meta-analysis (NMA) of randomized controlled trials (RCTs) to synthesize direct and indirect evidence for alternative interventions for GAD. We searched four major bibliographic databases, the Cochrane Central Register of Controlled Trials, Embase, PsycINFO, and PubMed, for published RCTs of adult patients with a diagnosis of GAD and allowed for all comorbidities. A total of 91 articles (14,812 participants) were identified in the final NMA. The results showed that all pharmacological treatments except for serotonin modulators and second-generation antipsychotics had greater effects than placebo: norepinephrine–dopamine reuptake inhibitors (standardized mean difference (SMD) −1.84, 95% credible interval −3.05 to −0.62), noradrenergic and specific serotonergic antidepressants (−0.91, −1.62 to −0.20), melatonergic receptor agonists (−0.68, −1.15 to −0.21), selective serotonin reuptake inhibitors (SSRIs; −0.67, −0.90 to −0.43), azapirones (−0.58, −1.00 to −0.17), anticonvulsants (−0.56, −0.85 to −0.28), serotonin–norepinephrine reuptake inhibitors (SNRIs; −0.54, −0.79 to −0.30), and benzodiazepines (BZDs; −0.40, −0.65 to −0.15). Most psychological and self-help interventions exerted greater effects than the waitlist group. However, no psychological interventions had greater effects compared with the psychological placebo. Overall, most pharmacological interventions had larger effect sizes than psychological interventions, and most psychological interventions showed larger effect sizes than self-help interventions.
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