**What are the chances for personalized treatment with antidepressants?** Introduction Finding subgroups of patients who especially benefit from pharmacological depression treatment is important, given the small treatment effects of antidepressants (AD) observed in randomized placebo controlled trials (RCT), and the relevance of personalized medicine. However, such research efforts can only be fruitful if there really are certain patients who respond particularly well to AD. The aim of this paper was to test this critical assumption. Methods Variance ratios (VR) and coefficients of variance ratios (CVR) calculated from a large, systematic review of RCT were meta-analytically combined. This included 163 studies and 51,137 patients. The analysis was repeated for classes of AD and specific AD. Results Variance ratios (VR = 1.01, CI 0.99-1.02) and coefficient of variance ratios (CVR = 0.82, CI 0.80-0.84) of the AD-treatment arms were comparable or smaller than in placebo-arms. Similar results were observed for classes of AD and for specific AD. Discussion/Conclusion The lacking increase of treatment outcome in the AD versus placebo groups in RCTs indicates that no specific subgroup of patients responds considerably better to AD. Thus, the quest for personalized treatment with AD is likely unsuccessful. However, our findings are no final proof and data using other research designs are needed.