Electronic Thesis and Dissertation Repository

Thesis Format



Master of Science


Epidemiology and Biostatistics


Guaiana, Giuseppe.

2nd Supervisor

Martin, Janet.



Objectives: To assess the efficacy and acceptability of antidepressants compared to placebo among adults with a primary diagnosis of generalized anxiety disorder (GAD). Methods: Five electronic databases and 2 trial registries were searched to identify studies for inclusion. The risk of bias version 1 tool was used to assess the risk of bias. A random-effects meta-analysis was conducted using RevMan web. Results were presented using forest plots. Results: 38 studies (12,570 participants) were included. Very low-quality evidence showed a benefit for antidepressants over placebo in the rate of treatment response (RR, 1.39: 95% CI: 1.27, 1.52) and no differences in acceptability (RR, 1.02: 95% CI: 0.92, 1.12). These results were consistent across different classes of antidepressants. Conclusion: Higher quality of evidence is needed. Future studies should be more transparent with their methodology and outcome reporting and future reviews may include patients with comorbidities and explore other sources of heterogeneity.

Summary for Lay Audience

Objectives: Generalized anxiety disorder (GAD) is a common mental health condition and is characterized by excessive worry about everyday events. Treatments include various psychological and pharmacological approaches. Antidepressant medications are a common pharmacological treatment for GAD and studies have shown their benefit over placebo (inactive treatment). This review provides an updated summary of all the evidence available on this topic. Specifically, the objectives were: (i) to evaluate the efficacy of antidepressants compared to placebo in reducing the symptoms of GAD; (ii) to assess the acceptability of antidepressants compared to placebo (the total number of people dropping out from each group); and (iii) to investigate adverse effects of antidepressants compared to placebo. Methods: Online databases and trial registries were searched. Studies were included if they randomly assigned participants into one of two groups that received an antidepressant or placebo. The studies had to be among adults with a primary diagnosis of GAD, and without serious comorbid medical conditions. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool was used to assess the quality of evidence. Results: 38 studies with 12,570 participants were included. Antidepressants may be more effective than placebo at reducing symptoms of GAD, and in achieving treatment response and remission. Antidepressants may have similar acceptability to placebo but may be less well tolerated as more people reported experiencing adverse effects and more people taking antidepressant treatment dropped out due to adverse effects. Some specific adverse effects such as sleepiness/drowsiness were more frequently reported among antidepressants and limited evidence suggested a similar number of people experiencing agitation/anxiety and suicide wishes/gestures/attempts between the antidepressant and placebo groups. Limited evidence also suggested a benefit of antidepressants over placebo in improving quality of life. Conclusion: The findings of this review should be interpreted with caution due to the very-low quality evidence that was found. The applicability of this review was also limited to patients with a primary diagnosis of GAD and without other serious medical conditions. Clinicians and patients should jointly decide on the treatment regime that will most closely meet the needs and values of the patient.