Evidence-based review of clinical outcomes of guideline-recommended pharmacotherapies for generalized anxiety disorder

Can J Psychiatry. 2012 Aug;57(8):470-8. doi: 10.1177/070674371205700805.


Objective: To quantify the rates of clinical outcomes of Canadian Psychiatric Association (CPA) guideline-recommended pharmacotherapies for generalized anxiety disorder (GAD) by drug classification within each treatment line.

Methods: Evidence from original research cited by the CPA was included. Pooled analyses, duplicates, and studies with nonextractable data were excluded. Response, remission, and baseline-endpoint or mean reductions scores of the Hamilton Anxiety Rating Scale (HARS) were extracted. The Cochrane Collaboration's computer program, Review Manager, version 5, with a random effects model, was used to pool results.

Results: A total of 50 articles were cited as evidence for managing GAD by the CPA. There was sufficient evidence of remission with first- or third-line agents to pool reported rates, and with agents from all 3 treatment lines to pool response rates and reduction in HARS scores. The mean range of effect size varied considerably from study to study within each treatment line. Comparison of pooled remission rates between first- and second-line agents was not possible. While the range of values by drug and drug class overlapped, the summary results for the probability of response and reduction in HARS scores was greater for first-line, compared with second-line, treatments. Drug components for third-line treatments were heterogeneous and produced mixed results.

Conclusion: Despite the abundance of evidence in its totality presented in the CPA guidelines, there is inadequate evidence to formulate recommendations based on the pooled results from this study alone. However, such analysis provides an additional resource for clinicians to make more effective treatment decisions for individual patients with GAD.

Publication types

  • Review

MeSH terms

  • Anti-Anxiety Agents / adverse effects
  • Anti-Anxiety Agents / classification
  • Anti-Anxiety Agents / therapeutic use*
  • Anticonvulsants / adverse effects
  • Anticonvulsants / therapeutic use
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use
  • Anxiety Disorders / diagnosis
  • Anxiety Disorders / drug therapy*
  • Anxiety Disorders / psychology
  • Benzodiazepines / adverse effects
  • Benzodiazepines / therapeutic use
  • Drug Therapy, Combination
  • Evidence-Based Medicine*
  • Guideline Adherence*
  • Humans
  • Personality Inventory
  • Serotonin Uptake Inhibitors / adverse effects
  • Serotonin Uptake Inhibitors / therapeutic use
  • Treatment Outcome


  • Anti-Anxiety Agents
  • Anticonvulsants
  • Antidepressive Agents
  • Serotonin Uptake Inhibitors
  • Benzodiazepines