Paroxetine Versus Placebo and Other Agents for Depressive Disorders: A Systematic Review and Meta-Analysis

Objective: To compare paroxetine with placebo and other antidepressants across multiple efficacy and tolerability outcomes.

Data sources: Searches were conducted in MEDLINE (1966-2004), EMBASE (1980-2004), CINAHL (1982-2004), all Evidence-Based Medicine Reviews (1991-2004), HealthSTAR (1975-2004), BIOSIS (1980-2004), and PsycINFO (1840-2004). Medical Subject Headings (MeSH) included “paroxetine” OR “Paxil”exploded. The searches were not restricted by language, publication type, or study design.

Study selection: A study report was included if it described a randomized trial of paroxetine versus placebo or other antidepressants for patients with depressive disorders. Records were screened independently by 2 reviewers under the supervision of another reviewer.

Dataextraction: Three investigators abstracted data, including study design, trial characteristics, and psychiatric assessment tools, using a prespecified form. Two investigators assessed quality of reporting using Jadad’s scale.

Data synthesis: We included 62 unique randomized controlled trials. Paroxetine yielded consistently and significantly better remission (rate difference [RD]: 10% [95% CI = 6 to 14]), clinical response (RD: 17% [95% CI = 7 to 27]), and symptom reduction (effect size: 0.2 [95% CI = 0.1 to 0.3]) than placebo. Such consistency in the evidence base was not observed between paroxetine and other antidepressants. Pairwise comparisons of paroxetine and venlafaxine, mirtazapine, mianserin, or fluoxetine yielded inconsistent results across efficacy outcomes. Controlled-release paroxetine was the only antidepressant with significantly fewer dropouts due to adverse events than immediate-release paroxetine (RD: 5% [95% CI = 0.1 to 11]).

Conclusions: There were no significant and valid differences between paroxetine and other antidepressants to suggest that multiple modes of action improve clinical outcomes.