A meta-analysis of selective serotonin reuptake inhibitors in acute coronary syndrome: cause for concern

In a recent report in the Journal of Psychopharmacology, Mazza et al. (2010) performed a meta-analysis of studies that compared antidepressant therapy using selective serotonin reuptake inhibitors (SSRIs) with placebo in patients with an acute coronary syndrome (ACS). Mazza et al. found that SSRIs did not produce a significant improvement in symptoms of depression compared with placebo, a conclusion that is surprising in light of findings from a previous review (Thombs et al., 2008). The authors also found that SSRI treatment resulted in fewer re-hospitalizations compared with placebo, and that there were no SSRI–placebo differences for major adverse cardiac events, mortality, or myocardial infarction. Unfortunately, an examination of this meta-analysis shows an alarming number of errors in data extraction that we believe should prompt retraction of this report. Mazza et al. coded results from the CREATE trial by Lespérance et al. (2007) as statistically significant in favour of the placebo group, whereas the study actually showed the opposite. This error almost certainly resulted from a misreading of Table 2 of the Lespérance et al. publication as depression symptom scores rather than as changes in depression scores. If the CREATE results had been coded correctly as positive, rather than negative, Mazza et al. would have found that SSRIs had a statistically significant, albeit small, effect on depressive symptoms. Mazza et al. also incorrectly extracted re-hospitalization data from the SADHART trial (Glassman et al., 2002). In their report, Mazza et al. indicate that 131 of 369 patients in SADHART were re-hospitalized, including 55 of 186 patients who were administered sertraline and 76 of 183 who were administered placebo. As described in the text and depicted in Table 5 of the original SADHART publication, however, only 73 of 369 patients were re-hospitalized and/or died: 32 of 186 in the sertraline group and 41of 183 in the placebo group. Mazza et al. variably used fixed effects or random effects models in their analyses, depending on observed betweenstudy statistical heterogeneity. Experts in meta-analysis, however, emphasize that the decision to use fixed effects or random effects models should not be based on statistical heterogeneity, but rather an a priori understanding of whether or not all included studies share a common effect size. This only occurs when all included studies are functionally identical and do not differ in any way that might be expected to have an influence on effect sizes (Borenstein et al., 2009). Given the clinical and methodological heterogeneity in the small number of studies analyzed by Mazza et al. (e.g., depression measures, type of SSRI and maximum dose, patient characteristics), the random effects model should have been used in all of their analyses. When we re-analyzed the data reported in Mazza et al. for re-hospitalization using RevMan with a random effects model and the correct data from SADHART, there was no significant difference between SSRI and placebo for re-hospitalization. Meta-analyses are cited more than any other study design (Patsopoulos et al., 2005) and are among the most important resources used in grading evidence for practice guidelines and other policy statements (Harbour and Miller, 2001). With this in mind, and in light of the serious flaws in data extraction and analysis in the study by Mazza et al., we believe that this report should be retracted so that incorrect treatment and/or policy decisions are not based on erroneous conclusions.