Antidepressants and suicidality: A re-analysis of the re-analysis

A recent study by Hengartner and Plöderl describes a strong increase for suicides (odds ratio (OR) of 2.83, 95% CI=1.13-9.67) and suicide attempts (OR=2.38 95%, CI=1.63-3.61) in antidepressant treated patients as compared to placebo. The authors re-analyzed data presented by Khan et al. who found no drug-placebo differences in suicide and suicide attempt rates. Hengartner and Plöderl base their findings on calculating the OR from a 2×2 table of the sum of the events and the totals of the sample sizes across studies. We here argue that pooling data from all drugs may not be the adequate approach.

We applied a meta-analytical approach to account for between-drug variance and conducted several statistical analyses as a sensitivity analysis. We argue that a more suitable approach for finding an overall effect from several observations is a meta-analytical approach namely the Mantel-Haenszel method without continuity correction.

Our analysis leads to different conclusions as opposed to Hengartner and Plöderl. With the recommended method we estimate an OR of 1.98, 95% CI 0.71-5.50 for suicides and 1.63 (95%CI=1.09-2.43) for suicide attempts.

The conducted analysis was restricted to the data available from the previous studies. Possibly, a more extensive search of the literature would lead to different results. However, we showed that re-analysing the re-analysis with several different approaches underlines the necessity of sensitivity analysis.

We could show that, in the case of rare events, the data is very sensitive to different analytical approaches underlining the importance of further investigations.