EEG Abnormalities Are Associated With Poorer Depressive Symptom Outcomes With Escitalopram and Venlafaxine-XR, but Not Sertraline: Results From the Multicenter Randomized iSPOT-D Study

Rationale Limited research is available on electrophysiological abnormalities such as epileptiform EEG or EEG slowing in depression and its association with antidepressant treatment response. Objectives We investigated the association between EEG abnormalities and antidepressant treatment response in the international Study to Predict Optimized Treatment in Depression (iSPOT-D). Methods Of 1008 participants with major depressive disorder randomized to escitalopram, sertraline, or venlafaxine-XR, 622 completed 8 weeks of treatment per protocol. The study also recruited 336 healthy controls. Treatment response was established after 8 weeks using the 17-item Hamilton Rating Scale for Depression (HRSD₁₇). The resting-state EEG was assessed at baseline with eyes closed. EEG abnormalities including epileptiform activity, EEG slowing, and alpha peak frequency (APF) were scored for all subjects, blind to treatment outcome. Results Patients and controls did not differ in the occurrence of EEG abnormalities. Furthermore, in the per protocol sample the occurrence of epileptiform EEG and EEG slowing (as a combined marker) were associated with a reduced likelihood of responding to escitalopram (P = .019; odds ratio [OR] = 3.56) and venlafaxine-XR (P = .043; OR = 2.76), but not sertraline (OR = 0.73). The response rates for this "any EEG abnormality" groups versus the "no-abnormality" group were 33% and 64% for escitalopram and 41% and 66% for venlafaxine-XR, respectively. A slow APF was associated with treatment response only in the sertraline group (P = .21; d = .027). Conclusions EEG abnormalities are associated with nonresponse to escitalopram and venlafaxine-XR, but not sertraline, whereas a slow APF is associated to response for sertraline only.