Background
We assessed whether increasing the minimum prerandomization Hamilton Depression Rating
Scale (HAM-D) score to enrich the severity of the depressed sample affects antidepressant
trial outcome.
Methods
Using the Food and Drug Administration Summary Basis of Approval reports, we examined
outcome data from 51 clinical trials (11,270 depressed patients) evaluating 10 investigational
antidepressants.
Results
Using four categories of trials with increasing minimum HAM-D entry trial criteria,
we found no statistically significant relationship between prerandomization categories
and trial outcome overall. Although there were minor differences in trial outcome
among the three categories with the lowest entry criteria (mean 49%, range, 44.4%–50.0%),
the antidepressant trials requiring the highest prerandomization HAM-D score (≥ 20
HAM-D 17) had the lowest frequency of positive outcomes (20%), χ2 = 4.04, df =1, p = .04. Paradoxically, high entry criteria requirements failed to increase reliably
actual mean total prerandomization HAM-D scores, although mean total prerandomization
HAM-D scores and use of flexible dosing were associated with higher rates of positive
outcome. A greater placebo response was seen in trials requiring higher prerandomization
depressive symptoms.
Conclusions
In summary, requiring higher prerandomization depressive symptoms was not associated
with an increased rate of favorable outcomes among these 51 antidepressant trials.
Key Words
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Article info
Publication history
Published online: December 06, 2006
Accepted:
August 19,
2006
Received in revised form:
July 19,
2006
Received:
May 17,
2006
Identification
Copyright
© 2007 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
