Changes in brain function of depressed subjects during treatment with placebo.
OBJECTIVE
It has been proposed that 50%-75% of the efficacy of antidepressant medication represents the placebo effect, since many depressed patients improve when treated with either medication or placebo. This study examined brain function in depressed subjects receiving either active medication or placebo and sought to determine whether quantitative electroencephalography (QEEG) could detect differences in brain function between medication and placebo responders. Both QEEG power and cordance, a new measure that reflects cerebral perfusion and is sensitive to the effect of antidepressant medication, were examined.


METHODS
Fifty-one subjects with major depression were enrolled in one of two independent, 9-week double-blind, placebo-controlled studies in which either fluoxetine (N=24) or venlafaxine (N=27) was the active medication. Serial QEEG recordings were performed during the course of treatment. After 9 weeks, the blind was broken and subjects were classified as medication responders, placebo responders, medication nonresponders, or placebo nonresponders.


RESULTS
No significant pretreatment differences in clinical or QEEG measures were found among the four outcome groups. Placebo responders, however, showed a significant increase in prefrontal cordance starting early in treatment that was not seen in medication responders (who showed decreased cordance) or in medication nonresponders or placebo nonresponders (who showed no significant change). There was no significant change in QEEG power during treatment.


CONCLUSIONS
These findings suggest that "effective" placebo treatment induces changes in brain function that are distinct from those associated with antidepressant medication. If these results are confirmed, cordance may be useful for differentiating between medication and placebo responders.
Leuchter
Andrew F
AF
UCLA Neuropsychiatric Institute, Los Angeles, CA 90024-1759, USA. afl@ucla.edu
Cook
Ian A
IA
Witte
Elise A
EA
Morgan
Melinda
M
Abrams
Michelle
M
D000328:Adult; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D003511:Cyclohexanols / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect; D000069470:Venlafaxine Hydrochloride
D003511:Cyclohexanols; D005473:Fluoxetine; D000069470:Venlafaxine Hydrochloride