Changes in brain function (quantitative EEG cordance) during placebo lead-in and treatment outcomes in clinical trials for major depression.
OBJECTIVE
Decreases in prefrontal electroencephalogram (EEG) cordance that are detectable as early as 48 hours after the start of medication have been related to clinical outcome in treatment trials for major depressive disorder. The relationship between brain changes during the placebo lead-in phase and medication treatment outcome is unknown. The authors hypothesized that decreases in prefrontal cordance during the placebo lead-in phase would be associated with better clinical outcome in subjects treated with antidepressants.


METHODS
Data were pooled examining 51 adults with major depressive disorder from two independent double-blind placebo-controlled trials. A 1-week single-blind placebo lead-in phase preceded 8 weeks of randomized treatment with medication (fluoxetine 20 mg or venlafaxine 150 mg) or placebo. The authors obtained quantitative EEG cordance measures at baseline and at the end of the placebo lead-in period. Relationships between regional cordance changes at the end of the placebo lead-in period and clinical outcome (the final 17-item Hamilton Rating Scale for Depression scores) were examined using multiple linear regression analysis.


RESULTS
As hypothesized, decreases in prefrontal cordance during the placebo lead-in period were associated with lower final Hamilton depression scale scores in subjects randomly assigned to medication. Prefrontal changes explained 19% of the variance in final Hamilton depression scale scores.


CONCLUSIONS
Neurophysiological changes during a placebo lead-in period may serve as nonpharmacodynamic biomarkers of eventual treatment outcomes in clinical trials for major depressive disorder.
Hunter
Aimee M
AM
Semel Institute for Neuroscience and Human Behavior at UCLA, 760 Westwood Plaza, Rm. 37-359, Los Angeles, CA 90024-1759, USA. amhunter@ucla.edu
Leuchter
Andrew F
AF
Morgan
Melinda L
ML
Cook
Ian A
IA
D000328:Adult; D015415:Biomarkers; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D001931:Brain Mapping; D003511:Cyclohexanols / Q000494:pharmacology / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000188:drug therapy*; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects* / Q000706:statistics & numerical data*; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D010919:Placebos; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012044:Regression Analysis; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D013826:Theta Rhythm / Q000187:drug effects / Q000706:statistics & numerical data; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride
D015415:Biomarkers; D003511:Cyclohexanols; D005473:Fluoxetine; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride