Saturday, March 9, 2013
Placebo Response in Randomized Controlled Trials of Antidepressants for Pediatric Major Depressive Disorder
The increasing publicity of how antidepressants usually perform
no better than placebo is causing more concern, for example
larger and more widely distributed trials seem to be erasing
some of the few benefits over placebo they have.
Am J Psychiatry 166:1, January 2009
This article is featured in this month’s AJP
and is discussed in an editorial by Dr. Emslie (p. 1).
Placebo Response in Randomized Controlled Trials of
Antidepressants for Pediatric Major Depressive Disorder
Jeffrey A. Bridge, Ph.D.
Boris Birmaher, M.D.
Satish Iyengar, Ph.D.
Rémy P. Barbe, M.D.
David A. Brent, M.D.
The authors examined char-
acteristics and predictors of response to placebo in all available reports of short-
term randomized controlled trials of anti-
depressants for pediatric major depres-
Response, defined as a score
on the improvement item of the Clinical
Global Impression scale, and potential
predictors were extracted from 12 pub-
lished and unpublished randomized con-
trolled trials of second-generation antide-
pressants in participants 6–18 years of
age with major depression.
The single best predictor of the
proportion of patients taking placebo
who responded to treatment was the
number of study sites. Baseline severity of
illness also emerged as a significant in-
verse predictor of placebo response, al-
though the strength of this relationship
was diminished when number of sites
was controlled for. After one large fluoxe-
tine trial was excluded, younger partici-
pants showed a higher placebo response
rate than older adolescents. Higher pla-
cebo response rates in more recent stud-
ies were explained by an increasing trend
toward large multisite trials and by publi-
cation delays and failures to publish some
The recent shift toward
large multisite trials of antidepressant
medications for pediatric major depres-
sion may be contributing to an increasing
incidence of response to placebo. Phar-
macotherapy studies of pediatric depres-
sion that carefully recruit patients with at
least moderately severe depression may
be more informative and efficient than
many trials conducted to date. Such stud-
ies should have sufficient power to deter-
mine whether age moderates medication
and placebo response.