Emotion-induced frontal α asymmetry predicts relapse after discontinuation of antidepressant medication

Background One in three patients relapse after antidepressant discontinuation. Thus, the prevention of relapse after achieving remission is an important component in the long-term management of Major Depressive Disorder (MDD). However, no clinical or other predictors are established. Frontal reactivity to sad mood as measured by fMRI has been reported to relate to relapse independently of antidepressant discontinuation and is an interesting candidate predictor. Methods Patients (n=56) who had remitted from a depressive episode while taking antidepressants underwent EEG recording during a sad mood induction procedure prior to gradually discontinuing their medication. Relapse was assessed over a six-months follow-up period. 35 healthy controls were also tested. Current source density of the EEG power in the α band (8-13Hz) was extracted and alpha-asymmetry was computed by comparing the power across two hemispheres at frontal electrodes (F5 and F6). Outcomes Sad mood induction was robust across all groups. Reactivity of α -asymmetry to sad mood did not distinguish healthy controls from patients with remitted MDD on medication. However, the 14 (25%) patients who relapsed during the follow-up period after discontinuing medication showed significantly reduced reactivity in α -asymmetry compared to patients who remained well. This EEG signal provided predictive power (69% out-of-sample balanced accuracy). Interpretation A simple EEG-based measure of emotional reactivity may have clinical utility in the management of antidepressant discontinuation. Funding Swiss National Science Foundation project grant 320030L_153449 / 1 to QJMH, Stiftung Deutsche Depressionshilfe to HW and QJMH, a Deutsche Forschungsgemeinschaft (DFG) grant (WA 1539/5-1) to HW, EMDO Stiftung to QJMH and the René and Susanne Braginsky Foundation and Clinical Research Priority Programme “Molecular Imaging” at the University of Zurich to KES. ### Competing Interest Statement QJMH acknowledges support by the UCLH NIHR BRC. QJMH has also obtained fees and options for consultancies for Aya Technologies and Alto Neuroscience and research grant funding from Koa Health, Wellcome Trust and Carigest S.A. All other authors declare no conflicts of interest. The funders had no role in the design, conduct or analysis of the study and had no influence over the decision to publish.