Antidepressant-placebo differences in 16 clinical trials over 10 years at a single site: role of baseline severity

Antidepressant-placebo differences observed in randomized double-blind, placebo-controlled clinical trials have always been relatively small and have further declined during the past three decades. During this same time, a decrease in patient severity of symptoms at baseline has occurred. The current study was designed to examine antidepressant-placebo difference scores and baseline severity of depression over a 10-year period in a sample of depressed patients enrolled at a single clinical trial site.

We analyzed data from a total of 462 patients who participated in 16 clinical trials at the Northwest Clinical Research Center, Bellevue, WA between 1995 and 2004. NWCRC collaborated with study sponsors to unblind the randomization codes from 16 trials for 293 patients assigned to antidepressants and 169 patients assigned to placebo.

The mean total baseline HAM-D17 scores were relatively high and stable (mean of 24.7, range 22.2-27.4). The outcome, as measured by changes in mean total HAM-D17 scores between antidepressant and placebo, were similar and were not related to the year of the conduct of the trial. Furthermore, the baseline severity of depressive symptoms, and BMI played a significant role in the outcome with antidepressants and not with placebo.

Our results show that no diminution of drug-placebo difference occurs over time when baseline severity remains constant. As such, they support the importance of depression severity as a determinant of antidepressant-placebo difference.