Methodological issues in clinical trials of antidepressant medications: perspectives from psychotherapy outcome research.

Despite their widespread use, the specific efficacy of antidepressant medications has been a source of debate in recent years. Examination of the literature reveals that a significant proportion of the benefit produced in antidepressant trials is duplicated in pill placebo conditions. Furthermore, early trials utilizing active placebos, or medications that mimic the common side effects of antidepressants, showed even smaller differences as compared with active medications. We examine issues surrounding the use of placebo control conditions in antidepressant trials, including the pros and cons of active placebos. We conclude that similar challenges are faced by psychotherapy outcome researchers who have focused more on the separation of specific from nonspecific treatment factors and on the effects of researcher allegiance and patient expectancy on outcome. Within this context, recommendations for improving future antidepressant research are discussed. Copyright 2005 S. Karger AG, Basel.