Background: Clinical trials are often not published and adverse effects are often under-reported. Access to unredacted clinical trials is vital for independent researchers. In 2011 the Nordic Cochrane Centre got access to unredacted antidepressant trials from the European Medicines Agency (EMA), including 29 trials conducted in healthy volunteers. We wished to examine adverse effects (AEs) of SSRIs in healthy volunteers.
1. A systematic review and meta-analysis of AEs of selective serotonin reuptake inhibitors in healthy volunteer studies, particularly activating effects and other AEs that can predispose to suicide.
Specific for EMA trials:
2. A comparison of unredacted CSRs with published articles to investigate the selectivity of reporting.
3. A comparison of protocols with CSRs to investigate if protocol planned assessments were carried out.
Methods: Searching for supplemental studies on PubMed and Embase for the systematic review. Eligibility criteria were set up. Studies were screened and relevant data extracted. Descriptive statistics were used to describe the included studies, and Peto OR for meta-analysis.
Results: A systematic review of ~ 150 healthy volunteer studies on antidepressants showed under-reporting of AEs. About one-third of studies did not mention AEs or their absence; 14 studies were eligible for meta-analysis, this showed that the incidence of AEs doubled when compared to placebo (Peto OR 2.20, 95% CI 1.35 to 3.59; P < 0.002). Only half the EMA trials (N = 29) were published (N = 15), and a mere few of these detailed AEs data fully (N = 2). Nine published articles had investigated AEs in their CSRs, but less than half (N = 4) reported these AEs, though these four studies all reported AEs partially. Result for objective 3 is pending.
Conclusions: We investigated the AEs of antidepressants in healthy volunteer studies. A systematic review of about 150 studies shows that about a third of all trials omit AE data and the meta-analysis shows that the incidence of the AEs possibly predisposing to suicide is doubled. Analysis of the EMA trials shows selective publication and inadequate reporting of AEs.