Relationship between depression severity entry criteria and antidepressant clinical trial outcomes.

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 (> or = 20 HAM-D 17) had the lowest frequency of positive outcomes (20%), chi(2) = 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.