Brain functional changes during placebo lead‐in and changes in specific symptoms during pharmacotherapy for major depression

Objective: Brain functional changes during placebo lead‐in have been associated with antidepressant response in clinical trials for major depressive disorder (MDD); however, the relationship between such non‐pharmacodynamic changes in brain function and changes in specific symptoms is unknown. Method: Fifty‐eight adults with MDD completed a 1‐week single‐blind placebo lead‐in preceding 8 weeks of double‐blind randomized treatment with fluoxetine or venlafaxine (n = 30) or placebo (n = 28). Brain functional change during lead‐in was assessed using quantitative electroencephalographic (qEEG) prefrontal theta‐band cordance. Symptoms were assessed using the Symptom Checklist‐90‐Revised (SCL‐90‐R). Results: The multiple regression model examining the qEEG parameter in relation to SCL‐90‐R subscales was significant [F_(9,9) = 4.27, P = 0.021, R² = 0.81] in females, with a significant association for the interpersonal sensitivity subscale (beta coefficient = 1.94, P = 0.001). Conclusion: Prefrontal neurophysiologic change during placebo lead‐in may indicate subsequent antidepressant‐related improvement in symptoms of interpersonal sensitivity.