Placebo Response in Randomized Controlled Trials of Antidepressants for Pediatric Major Depressive Disorder

http://ajp.psychiatryonline.org/data/Journals/AJP/3879/09aj0042.PDF

 

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.   

 

 

 

Article

42

Am J Psychiatry 166:1, January 2009

ajp.psychiatryonline.org

This article is featured in this month’s AJP

Audio

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.

Objective:

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-

sive disorder.

Method:

Response, defined as a score

≤

2

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lished and unpublished randomized con-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.

Results:

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

negative trials.

Conclusions:

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.