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

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. 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). The multiple regression model examining the qEEG parameter in relation to SCL-90-R subscales was significant [F-(9,F-9) = 4.27, P = 0.021, R-2 = 0.81] in females, with a significant association for the interpersonal sensitivity subscale (beta coefficient = 1.94, P = 0.001). Prefrontal neurophysiologic change during placebo lead-in may indicate subsequent antidepressant-related improvement in symptoms of interpersonal sensitivity.