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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

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Efficacy of drug treatments for generalised anxiety disorder: systematic review and meta-analysis

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Review published: .

CRD summary

The authors concluded that fluoxetine (for efficacy) and sertraline (for tolerability) seemed to have advantages over other treatments for generalised anxiety disorder. The authors' conclusions reflected the evidence presented; however, given the unknown quality of the included trials and the potential risk of error and bias in the review processes, their conclusions should be interpreted with caution.

Authors' objectives

To evaluate the effectiveness and tolerability of drug treatments for generalised anxiety disorder.

Searching

MEDLINE, EMBASE, BIOSIS Previews, PsycINFO, Health Economics Evaluation Databases (HEED), NHS EED, DARE, and Cochrane Database of Systematic Reviews were searched from January 1980 to February 2009. Search terms were reported; a full search strategy was provided in an online appendix (see URL for Additional Data). Reference lists of relevant systematic reviews, meta-analyses and pooled analyses were also searched. However, there was no specific search for unpublished material.

Study selection

Eligible for inclusion in the review were double-blind placebo-controlled phase II, III or IV randomised controlled trials (RCTs) of any duration, of any active drug treatment for generalised anxiety disorder in adults (aged 18 years or over).

Outcomes of interest were response, remission and tolerability of drug treatments. Response was defined as the proportion of patients who experienced a reduction of at least 50% from their baseline HAM-A score. Remission was defined as the proportion of patients with a final Hamilton Anxiety scale (HAM-A) score of 7 or more. Tolerability was defined as the percentage of patients withdrawing from the trial due to adverse events.

In included trials, duration of treatment ranged from four to 24 weeks. Active treatments included duloxetine, escitalopram, fluoxetine, lorazepam, paroxetine, pregabalin, sertraline, tiagabine and venlafaxine. Although the authors stated that only placebo controlled trials were eligible for inclusion in the review, two trials did not have a placebo arm. There was limited data on patient characteristics. Included trials had inclusion criteria of HAM-A scale scores of ≥18 or ≥20. Most included trials were conducted in the USA or Europe.

The authors initially stated that three people were involved in the process of study selection and an independent reviewer checked a random selection of 10% of selected articles. The authors later stated that a single reviewer assessed publications for data selection.

Assessment of study quality

The authors did not state whether they assessed study quality.

Data extraction

Data were extracted using intention to treat (ITT), or last observation carried forward where this was not possible, in order to calculate odds ratios (OR) and 95% confidence intervals (CI). If data on withdrawals were not reported in the paper, the review authors did not seek to obtain them from the study authors.

The authors did not state how many reviewers performed data extraction.

Methods of synthesis

Odds ratios were combined in a Bayesian mixed treatment comparison analysis, which allowed treatments to be ranked based on the probability of each treatment being the most effective for each outcome measure. A random-effects model was used. Vague prior parameters were used. Each analysis consisted of 20,000 iterations, with an initial burn-in period of 1,000 iterations. The model was checked for convergence. Initial values used were varied and tested in the models. A frequentist mixed treatment comparison was performed as a secondary analysis.

Subgroup analysis was performed for UK licensed drug treatments for generalised anxiety disorder only.

Publication bias was assessed using the Begg's test.

Results of the review

Twenty-seven RCTS were included in the analysis. Sample sizes ranged from 46 to 1,849 patients (where reported).

Response (23 RCTs): Fluoxetine had the greatest probability of being the most effective treatment for response (probability 62.9%). A subgroup analysis of treatments licensed for generalised anxiety disorder in the UK showed that duloxetine had the highest probability of the being the most effective treatment in terms of response (2.7%).

Remission (16 RCTs according to data in tables, 14 RCTs according to figures in text): Fluoxetine had the greatest probability of being the most effective treatment for remission (probability 60.6%). A subgroup analysis of UK licensed treatments for generalised anxiety disorder showed that escitalopram had the greatest probability of being the most effective treatment in terms of remission (26.7%).

Tolerability (23 RCTs): Sertraline had the greatest probability (49.3%) of being the most effective treatment in terms of tolerability (i.e. associated with lowest percentage of withdrawals due to adverse events), and lorazepam the least (probability not specified). A subgroup analysis of UK licensed treatments for generalised anxiety disorder showed that pregabalin had the greatest probability of being the most effective treatment in terms of tolerability (7.7%), and duloxetine the least (probability not specified).

No evidence for publication bias was found except for withdrawals due to adverse events (p=0.005)

Authors' conclusions

Fluoxetine (in terms of efficacy) and sertraline (in terms of tolerability) seem to have advantages over other treatments. Among five UK licensed treatments, duloxetine, escitalopram and pregabalin might offer some advantages over venlafaxine and paroxetine.

CRD commentary

The review addressed a clear research question and was supported by detailed inclusion criteria. The search strategy included a number of databases. However, there was no specific attempt to locate unpublished material, so relevant studies may have been missed. It was unclear exactly how the study selection process was performed, which made it unclear whether this process was subject to reviewer error or bias. The authors did not report using methods designed to reduce reviewer bias and error for the process of data extraction.

There was no apparent trial assessment, so it was not possible to determine the reliability of the results. There were limited data on patient characteristics, which made it difficult to determine whether it was appropriate to combine the studies in the analyses. Two trials included in the review did not appear to meet the specified inclusion criteria, in that they did not have a placebo arm. The analysis for remission was based on a smaller subset of the included trials than the other two outcomes, so there may be fundamental differences between trials that reported data for remission compared with those that did not.

The authors' conclusions reflected the evidence presented; however, given the lack of quality assessment and the potential risk of error and bias in the review processes, their conclusions should be interpreted with caution.

Implications of the review for practice and research

Practice: The authors did not state any implications for practice.

Research: The authors stated that a more complex model with incorporation of covariate effects could be implemented in further work to elucidate and adjust for other factors that might have an impact on parameters, as these would manage any variation between the direct and indirect evidence. The authors also state that as little published evidence on patient reported outcomes, such as quality of life in generalised anxiety disorder, was identified; this could inform the rationale for further research investigating comparative effectiveness of treatments used in generalised anxiety disorder over the longer term.

Funding

Lundbeck.

Bibliographic details

Baldwin D, Woods R, Lawson R, Taylor D. Efficacy of drug treatments for generalised anxiety disorder: systematic review and meta-analysis. BMJ 2011; 342: d1199 . [PubMed: 21398351]

Other publications of related interest

Correction: Efficacy of drug treatments for generalised anxiety disorder: systematic review and meta-analysis. BMJ 2011; 342:d1718

Indexing Status

Subject indexing assigned by NLM

MeSH

Adult; Aged; Anti-Anxiety Agents /adverse effects /therapeutic use; Anxiety Disorders /drug therapy; Humans; Middle Aged; Treatment Outcome; Young Adult

AccessionNumber

12011001650

Database entry date

23/03/2011

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

Copyright © 2014 University of York.
Bookshelf ID: NBK81714

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