Emotion-induced frontal α asymmetry as a candidate predictor of relapse after discontinuation of antidepressant medication

Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 May 10:S2451-9022(24)00134-4. doi: 10.1016/j.bpsc.2024.05.001. Online ahead of print.

Abstract

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 and a positive predictive value of 0.75).

Interpretation: A simple EEG-based measure of emotional reactivity may have potential to contribute to clinical prediction models of antidepressant discontinuation. Given the very small sample size, this finding must be interpreted with caution and requires replication in a larger study.