Home > DARE Reviews > Selective serotonin reuptake inhibitors...

PubMed Health. A service of the National Library of Medicine, National Institutes of Health.

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

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

Selective serotonin reuptake inhibitors for unipolar depression: a systematic review of classic long-term randomized controlled trials

D Deshauer, D Moher, D Fergusson, E Moher, M Sampson, and J Grimshaw.

Review published: 2008.

CRD summary

The review concluded that the evidence supported the current recommendation that antidepressant treatment should continue for six to eight months following initial recovery, but there was no evidence to provide guidance for longer term treatment. Given the potential for bias in the included trials and review process, and the variability among trials, the authors' conclusions should be interpreted with caution.

Authors' objectives

To compare the efficacy and acceptability of long-term treatment of selective serotonin re-uptake inhibitors (SSRIs) versus placebo in patients with moderate to severe depression.

Searching

An updated search of MEDLINE and EMBASE was undertaken to May 2007. The Cochrane Central Register of Controlled Trials was also searched for articles published between 2003 and 2007. The search was restricted to articles published in English. Search terms were reported. In addition, reference lists of included studies were manually searched.

Study selection

Randomised controlled trials (RCTs) that compared selective serotonin re-uptake inhibitors (SSRIs) monotherapy versus placebo in patients (aged 18 years or over) diagnosed with major depression (according to the Diagnostic and Statistical Manual of Mental Disorders) were eligible for inclusion. Eligible trials were required to include treatment of at least six months and could include a one to two weeks placebo run-in period. Patients with comorbidity were eligible.

The primary outcomes of interest were response to treatment (ie. 50% improvement from baseline in depression score), remission (as defined by a conventional remission cut-off point, eg. score of 7 or less on the Hamilton rating scale for depression), and total number of drop-outs (to measure overall treatment acceptability). Secondary outcomes were quality of life, the number of patients needing rescue therapy (hospitalisation, psychotherapy), the number of patients self-harming, and patient back to work status.

The included trials were of patients aged between 18 and 89 years with major depressive disorder (with or without alcohol dependence) and depression after myocardial infarction or stroke. Included patients were recruited from a North American hospital, an addiction treatment unit, academic and community clinics, and stroke centres. Inclusion and exclusion criteria varied among the included trials. Some patients had a history of recurrent depression. SSRIs included daily doses of sertraline (50 to 200mg) or citalopram (20 to 60mg), or paroxetine (20mg). Most of the included trials lasted six months, but two trials lasted 6.5 months and eight months. Most of the included trials were funded by pharmaceutical companies.

Two reviewers screened studies for inclusion, with disagreements resolved by consensus among three other reviewers.

Assessment of study quality

The Cochrane risk-of-bias tool was used to assess trial quality, including criteria on randomisation, allocation concealment, blinding, completeness of outcome data, selectiveness of outcome reporting, and 'other' biases. For each criterion, trials were rated as having high, low or unclear risk of bias.

The authors did not state how many reviewers performed the validity assessment.

Data extraction

Two reviewers independently extracted primary outcome data to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Where data were missing for primary outcomes, the published last-observation-carried-forward approach was used. Secondary outcomes were presented as a narrative synthesis and in tables.

Methods of synthesis

Where clinically appropriate, odds ratios and 95% confidence intervals were combined using a random-effects model. Statistical heterogeneity was assessed using the I2 statistic.

Subgroup analysis was undertaken to assess patients with versus without comorbidities.

Publication bias was assessed through visual inspection of a funnel plot.

Results of the review

Six RCTs were included in the review (n=1,299 patients; range 83 to 369). There was a slight discrepancy between the number of patients reported in the forest plot and table; the figure from the forest plot has been cited in this abstract. The mean drop-out rate was 48% (range 27 to 77%). Four RCTs had unclear randomisation (two were at low risk of bias). Three RCTs had unclear allocation concealment (three were at low risk). Two RCTs had unclear blinding (four were at low risk). All the RCTs had unclear selective outcome reporting. Four RCTs were at high risk of bias for incomplete outcome data. Four RCTs were unclear for 'other' biases (two were at low risk of bias). Overall, trials were rated as being at moderate risk of bias.

selective serotonin re-uptake inhibitors (SSRIs) showed a statistically significantly greater improvement in response to treatment at six to eight months compared with placebo (OR 1.66, 95% CI 1.12 to 2.48; six RCTs), but there was evidence of statistical heterogeneity (I2=63.9%). Similar results were reported for patients with depression and no comorbidities (OR 2.13, 95% CI 1.11 to 4.08; I2=76.8%; three RCTs), but there was no statistical difference among patients with comorbidities (three RCTs) and no evidence of statistical heterogeneity.

There was no statistically significant difference in remission rates between patients receiving SSRIs and those receiving placebo (four RCTs). Subgroup analysis showed similar findings for patients with comorbidities (two RCTs), but in patients without comorbidities the remission rate was significantly higher in patients receiving SSRIs (OR 2.06, 95% CI 1.41 to 3.01; I2=0%; two RCTs).

There were no statistically significant differences between patients receiving SSRIs and those receiving placebo in the measure of overall acceptability (total drop-outs) and no evidence of statistical heterogeneity.

There was no evidence of publication bias according to funnel plots.

Secondary outcomes were reported in the review, but were somewhat limited by the poor reporting in the included trials.

Authors' conclusions

The evidence available supported the current recommendation that antidepressant treatment should continue for six to eight months following initial recovery, but there was no evidence to provide guidance for longer term treatment.

CRD commentary

The review question and supporting inclusion criteria were clearly defined. Appropriate sources were searched for relevant studies, but it was unclear whether attempts were made to locate unpublished data; there was no evidence of publication bias. The search was restricted by language, so language bias may have been introduced. The authors undertook study selection and data extraction in duplicate, but it was unclear whether this was true for quality assessment, which meant that reviewer error and bias could not be ruled out.

The authors assessed the quality of the trials, but these were rated to be at moderate risk of bias. The authors acknowledged the methodological limitations of the included trials and that none reported data beyond 12 months. There were considerable differences among trials in terms of inclusion and exclusion criteria and variability among outcome measurement tools; there was some evidence of statistical heterogeneity, suggesting that pooling of the results may not have been appropriate. The authors highlighted the limitations of using the last-observation-carried-forward approach and issues around commercial sponsorship of the trials.

Given the potential for bias in the included trials and review process, and the variability among trials, the authors' conclusions should be interpreted with caution.

Implications of the review for practice and research

Practice: The authors stated that the patients in the included trials may not be representative of those seen in everyday practice. They also stated that longer term treatment should only be provided in selected cases and should take into consideration the uncertainties surrounding the practice.

Research: The authors stated that longer term trials are needed to assess the use of SSRIs in depression and should use clinically relevant outcomes for all patients with depression, including those who experience spontaneous remission.

Funding

University of Ottawa Research Chair.

Bibliographic details

Deshauer D, Moher D, Fergusson D, Moher E, Sampson M, Grimshaw J. Selective serotonin reuptake inhibitors for unipolar depression: a systematic review of classic long-term randomized controlled trials. CMAJ: Canadian Medical Association Journal 2008; 178(10): 1293-1301. [PMC free article: PMC2335186] [PubMed: 18458261]

Indexing Status

Subject indexing assigned by NLM

MeSH

Depressive Disorder /drug therapy; Humans; Outcome Assessment (Health Care); Placebos; Quality of Life; Randomized Controlled Trials as Topic; Research Design; Serotonin Uptake Inhibitors /therapeutic use

AccessionNumber

12008103936

Database entry date

01/12/2010

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.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 18458261

PubMed Health Blog...

read all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...