MIDAS Project Publication Abstracts
Posternak, M.A., Zimmerman, M., Miller, I., &
Keitner, G. A reevaluation of the exclusion criteria used in antidepressant
efficacy trials. American Journal of Psychiatry, 2005, 159,
191-200.
Objective: Antidepressant efficacy trials (AETs) employ
multiple exclusion criteria that are designed primarily to maximize
drug-placebo differences. These exclusion criteria were implemented
prior to having undergone rigorous testing, however, and it is unclear
whether they accomplish their intended goal. In the present report,
we sought to review the current state of knowledge regarding treatment
response rates in individuals who are typically excluded from AETs.
Method: After reviewing 31 AETs published between 1994 and
1998, we identified 10 commonly used exclusion criteria. A computerized
MEDLINE and manual search was then performed, and all studies evaluating
the efficacy of antidepressant medications in populations of subjects
typically excluded from AETs were reviewed. Results: Three
exclusion criteria: short episode duration, mild severity of illness,
and positive response during the placebo lead-in phase are utilized
primarily to reduce placebo response rates. Of these, there exists
only preliminary evidence suggesting that a short episode duration
may be associated with less robust drug-placebo response rates.
The 7 other exclusion criteria we identified including various psychiatric
comorbidity, chronic duration of illness, medical comorbidity, and
prior nonresponse to treatment are utilized because such individuals
are believed to have lower response rates to somatic therapy. While
often true, such individuals also appear to have lower response
rates to placebo, and there is little evidence to suggest that drug-placebo
differences are any less robust in these individuals. Conclusions:
Studies to date suggest that many of the standard exclusion
criteria currently being employed in AETs may not be achieving their
intended goal. The practice of excluding subjects with particular
clinical profiles, which greatly reduces the generalizability of
AETs, appears to lack empirical support.
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