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

Acta Psychiatr Scand. 2009 Apr;119(4):266-73. doi: 10.1111/j.1600-0447.2008.01305.x. Epub 2008 Dec 9.


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, R(2) = 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / physiopathology*
  • Cyclohexanols / therapeutic use*
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / physiopathology*
  • Depressive Disorder, Major / psychology
  • Diagnostic and Statistical Manual of Mental Disorders
  • Double-Blind Method
  • Electroencephalography
  • Female
  • Fluoxetine / therapeutic use*
  • Humans
  • Male
  • Serotonin Uptake Inhibitors / therapeutic use*
  • Severity of Illness Index
  • Venlafaxine Hydrochloride


  • Cyclohexanols
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Venlafaxine Hydrochloride