Progress in Elucidating Biomarkers of Antidepressant Pharmacological Treatment Response: A Systematic Review and Meta-analysis of the Last 15 Years

G. Voegeli, M. L. Cléry-Melin, N. Ramoz, P. Gorwood

Antidepressant drugs are widely prescribed, but response rates after 3 months are only around one-third, explaining the importance of the search of objectively measurable markers predicting positive treatment response. These markers are being developed in different fields, with different techniques, sample sizes, costs, and efficiency. It is therefore difficult to know which ones are the most promising. Our purpose was to compute comparable (i.e., standardized) effect sizes, at study level but also at marker level, in order to conclude on the efficacy of each technique used and all analyzed markers. We conducted a systematic search on the PubMed database to gather all articles published since 2000 using objectively measurable markers to predict antidepressant response from five domains, namely cognition, electrophysiology, imaging, genetics, and transcriptomics/proteomics/epigenetics. A manual screening of the abstracts and the reference lists of these articles completed the search process. Executive functioning, theta activity in the rostral Anterior Cingular Cortex (rACC), and polysomnographic sleep measures could be considered as belonging to the best objectively measured markers, with a combined d around 1 and at least four positive studies. For inter-category comparisons, the approaches that showed the highest effect sizes are, in descending order, imaging (combined d between 0.703 and 1.353), electrophysiology (0.294-1.138), cognition (0.929-1.022), proteins/nucleotides (0.520-1.18), and genetics (0.021-0.515). Markers of antidepressant treatment outcome are numerous, but with a discrepant level of accuracy. Many biomarkers and cognitions have sufficient predictive value (d ≥ 1) to be potentially useful for clinicians to predict outcome and personalize antidepressant treatment.