Magnitude of change with antidepressants and placebo in antidepressant clinical trials using structured, taped and appraised rater interviews (SIGMA-RAPS) compared to trials using traditional semi-structured interviews.
BACKGROUND
Although newer interview methods such as Structured Interview Guide for the Montgomery-Asberg Depression Rating Scale (SIGMA; MADRS) with audiotaping and Rater Applied Performance Scale (RAPS) appraisal have been introduced to improve reliability of ratings in antidepressant clinical trials, there is limited evidence that these methods actually improve trial outcome.


OBJECTIVE
The objective of this study uis to evaluate outcome in four similarly designed trials of two recently approved antidepressants: two trials randomly used taped SIGMA interviews with RAPS appraisal and two trials used traditional semi-structured MADRS interviews.


METHODS
We reviewed data from patients who were screened (N = 243) and randomized (N = 148), evaluating the magnitude of change with placebo and antidepressants on mean total MADRS score.


RESULTS
Depressed patients assigned to placebo in trials using taped SIGMA interviews with RAPS appraisal had a significantly larger MADRS change score (M = -11.5 ± 12.7) compared to patients assigned to placebo in trials using traditional semi-structured interviews (-5.4 ± 8.9; F(df = 1.57) = 5.58, p = 0.022). The error variance was also significantly larger in the placebo arm of trials using SIGMA interviews (F = 5.43, p = 0.023). Depressed patients assigned to antidepressants had similar outcome in all of the four trials.


CONCLUSIONS
The recently suggested modifications in obtaining clinical data in antidepressant trials such as taped SIGMA interviews with RAPS rating appraisals may in fact result in a higher magnitude of placebo response and a lower magnitude of antidepressant-placebo differences compared to the traditional methods of collecting clinical data. These results were unexpected and indicate the necessity to test new methods prospectively, no matter how intuitively sensible they seem, prior to their implementation.
Northwest Clinical Research Center, 1951 152nd Pl. NE Suite #200, Bellevue, WA, 98007, USA, akhan@nwcrc.net.
Arif
A
Khan
James
J
Faucett
Walter A
WA
Brown
D000328:Adult; D000928:Antidepressive Agents / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology; D003521:Cyclopropanes / Q000494:pharmacology; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D000078764:Milnacipran; D017063:Outcome Assessment, Health Care / Q000592:standards*; D010879:Piperazines / Q000494:pharmacology; D015990:Placebo Effect; D011569:Psychiatric Status Rating Scales / Q000592:standards*; D016032:Randomized Controlled Trials as Topic / Q000592:standards*; D000069503:Vilazodone Hydrochloride
D000928:Antidepressive Agents; D001572:Benzofurans; D003521:Cyclopropanes; D007211:Indoles; D010879:Piperazines; D000078764:Milnacipran; D000069503:Vilazodone Hydrochloride