Effectiveness of paroxetine in the treatment of acute major depression in adults: a systematic re-examination of published and unpublished data from randomized trials

Background: Concern has been raised about the efficacy of antidepressant therapy for major depression in adults. We undertook a systematic review of published and unpublished clinical trial data to determine the effectiveness and acceptability of paroxetine. Methods: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register, the Cochrane Central Register of Controlled Trials, the Glaxo-SmithKline Clinical Trial Register, MEDLINE and EM BASE up to December 2006. Published and unpublished randomized trials comparing paroxetine with placebo in adults with major depression were eligible for inclusion. We selected the proportion of patients who left a study early for any reason as the primary outcome measure because it represents a hard measure of treatment effectiveness and acceptability. Results: We included in our review 29 published and 11 unpublished clinical trials, with a total of 3704 patients who received paroxetine and 2687 who received with placebo. There was no difference between paroxetine and placebo in terms of the proportion of patients who left the study early for any reason (random effect relative risk [RR] 0.99, 99% confidence interval [CI] 0.88 - 1.11). Paroxetine was more effective than placebo, with fewer patients who did not experience improvement in symptoms of at least 50% (random effect RR 0.83, 99% CI 0.77 - 0.90). Significantly more patients in the paroxetine group than in the placebo group left their respective studies because of side effects (random effect RR 1.77, 95% CI 1.44 - 2.18) or experienced suicidal tendencies (odds ratio 2.55, 95% CI 1.17 - 5.54). Interpretation: Among adults with moderate to severe major depression in the clinical trials we reviewed, paroxetine was not superior to placebo in terms of overall treatment effectiveness and acceptability. These results were not biased by selective inclusion of published studies.