Common adverse events associated with an SSRI: meta-analysis of early paroxetine data

Purpose We wanted to determine to what extent adverse drug effects associated with a selective serotonin reuptake inhibitor (SSRI) were known but not assessed before application for registration of paroxetine. Methods With a special permit from the Norwegian Ministry of Health, we obtained reports from 82 clinical trials presented by the paroxetine license holder in 1989. There were 17 double blind, placebo controlled clinical trials with parallel design with 903 patients on paroxetine and 592 on placebo. Altogether 32 adverse effects showed a risk difference (RD) between paroxetine and control groups of more than 0.5%. We did a meta-analysis for each of these adverse effects. We then compared the outcome with the frequencies stated in the Summary of Product Characteristics (SPC) at the time of registration and those reported in the current SPC. Results At the time of registration 19 of the adverse effects were statistically significant. Only eight of these adverse effects were listed as being common in the first SPC from 1989. Five out of the nineteen adverse effects are not mentioned in the current SPC. Among them are headache with RD 5.4%, decreased libido RD 2.6%, nervousness RD 2.0% and paresthesia RD 1.7%. Conclusions Frequently occurring adverse reactions that are included in today's SPC for paroxetine were evident and documented already in the early studies accompanying the application for marketing authorization in 1989. Some other adverse effects observed then are still not mentioned in the SPC of today. Meta-analyses of adverse effects should be mandatory at the stage of first registration of a drug. Copyright (c) 2008 John Wiley & Sons, Ltd.