Efficacy of drug treatments for generalised anxiety disorder: systematic review and meta-analysisBMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d1199 (Published 11 March 2011) Cite this as: BMJ 2011;342:d1199
- David Baldwin, professor of psychiatry and honorary consultant psychiatrist1,
- Robert Woods, senior research executive2,
- Richard Lawson, statistician2,
- David Taylor, professor of psychopharmacology3
- 1University of Southampton Faculty of Medicine, University Department of Psychiatry, Academic Centre, Southampton SO14 3DT, UK
- 2Complete Medical Group, Macclesfield SK10 1AQ
- 3King’s College London, London SE1 9NH
- Correspondence to: D Baldwin
- Accepted 20 January 2011
Objective To appraise the evidence for comparative efficacy and tolerability of drug treatments in patients with generalised anxiety disorder.
Design Systematic review of randomised controlled trials. Primary Bayesian probabilistic mixed treatment meta-analyses allowed pharmacological treatments to be ranked for effectiveness for each outcome measure, given as percentage probability of being the most effective treatment. Secondary frequentist mixed treatment meta-analyses conducted with random effects model; effect size reported as odds ratio and 95% confidence interval.
Data sources Medline, Embase, BIOSIS, PsycINFO, Health Economic Evaluations Database, National Health Service Economic Evaluation Database, and Database of Abstracts of Reviews of Effects via DataStar, and Cochrane Database of Systematic Reviews via Cochrane Library (January 1980 to February 2009).
Eligibility criteria Double blind placebo controlled randomised controlled trials; published systematic reviews and meta-analyses of randomised controlled trials. Randomised controlled trials including adult participants (aged ≥18) receiving any pharmacological treatment for generalised anxiety disorder.
Data abstraction methods Titles or abstracts reviewed initially, followed by review of full text publications for citations remaining after first pass. A three person team conducted screening; an independent reviewer checked a random selection (10%) of articles screened. Data extracted for meta-analysis were also independently reviewed.
Main outcome measures Proportion of participants experiencing ≥50% reduction from baseline score on Hamilton anxiety scale (HAM-A) (response), proportion with final HAM-A score ≤7 (remission), proportion withdrawing from trial because of adverse events (tolerability).
Results The review identified 3249 citations, and 46 randomised controlled trials met inclusion criteria; 27 trials contained sufficient or appropriate data for inclusion in the analysis. Analyses compared nine drugs (duloxetine, escitalopram, fluoxetine, lorazepam, paroxetine, pregabalin, sertraline, tiagabine, and venlafaxine). In the primary probabilistic mixed treatment meta-analyses, fluoxetine was ranked first for response and remission (probability of 62.9% and 60.6%, respectively) and sertraline was ranked first for tolerability (49.3%). In a subanalysis ranking treatments for generalised anxiety disorder currently licensed in the United Kingdom, duloxetine was ranked first for response (third across all treatments; 2.7%), escitalopram was ranked first for remission (second across all treatments; 26.7%), and pregabalin was ranked first for tolerability (second across all treatments; 7.7%).
Conclusions Though the frequentist analysis was inconclusive because of a high level of uncertainty in effect sizes (based on the relatively small number of comparative trials), the probabilistic analysis, which did not rely on significant outcomes, showed that fluoxetine (in terms of response and remission) and sertraline (in terms of tolerability) seem to have some advantages over other treatments. Among five UK licensed treatments, duloxetine, escitalopram, and pregabalin might offer some advantages over venlafaxine and paroxetine.
Contributors: DB and DT provided specialist input regarding the research question and scope of the analyses, performed critical review of results, and assisted in the development of the manuscript from first draft to final submitted version. RL was involved in finalising the scope of the analyses, first and second pass screening of articles, and data selection stages of the systematic review. In addition, he performed all statistical analyses and assisted in drafting the manuscript. RW was involved in first and second pass screening of articles and in data selection stages of the systematic review and assisted in drafting the manuscript. All authors approved the final version of the manuscript. Gillian Sibbring is an employee of Complete Medical Group who undertook project management and critical review of the manuscript during all stages of its preparation. DB is guarantor.
Funding: This study was funded by Lundbeck, who commissioned RL, RW, and Gillian Sibbring at Complete Medical Group to conduct the systematic review and meta-analysis, and prepare the manuscript. Lundbeck had input in the concept and design of the study, but it was conducted and reported independently of the company and the authors had final responsibility for the decision to submit for publication.
Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that DT, RL, and RW have support from Lundbeck for the submitted work; DB holds or has held research grants (on behalf of the University of Southampton) from Cephalon, Eli Lilly, F Hoffmann-La Roche, GlaxoSmithKline, Lundbeck, Organon, Pfizer, Pharmacia, and Wyeth; he has neither received nor will seek financial reimbursement for his role in this study; DT holds or has held research grants (on behalf of King’s College London) from Servier; he has received financial recompense for the time spent away from his paid employment to contribute to this study; when the work was conducted, both RL and RW were employees of Complete Medical Group, who received funding from Lundbeck to conduct the study and prepare the manuscript (RL is no longer an employee of Complete Medical Group). DB has had specified relationships in the previous 3 years with Asahi Kasei Pharma, AstraZeneca, Cephalon, Eli Lilly, F Hoffmann-La Roche, GlaxoSmithKline, Lundbeck, Organon, Pharmacia, Pierre Fabre, Pfizer, Servier, Sumitomo, and Wyeth; DT has had specified relationships in the previous 3 years with Eli Lilly, Informa Healthcare, Lundbeck, Pfizer, and Servier. As an employee of Complete Medical Group, RL has received funding in the previous 3 years from AstraZeneca.
Ethical approval: Not required.
Data sharing: Technical appendix, statistical code, and dataset available from Gillian Sibbring at Complete Medical Group ().
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