Therapeutic effect of follow-up assessments on antidepressant and placebo response rates in antidepressant efficacy trials: meta-analysis.

Background: It remains unclear how much various factors contribute to the placebo response.

Aims: To estimate the therapeutic impact of follow-up assessments on placebo response in antidepressant trials.

Method: Double-blind, placebo-controlled antidepressant trials that reported weekly changes in Hamilton Rating Scale for Depression (HRSD) scores over 6 weeks were selected. Included studies (n=41) were divided into those that conducted four, five or six follow-up assessments. Reductions in HRSD scores as a function of the different follow-up schedules were compared.

Results: An extra follow-up visit at week 3 was associated with a 0.86 further reduction in HRSD score; an extra visit at week 5 was associated with a 0.67 further reduction. These effects represented approximately 34-44% of the placebo response that occurred over these time frames. Two additional visits were associated with twice the reduction in HRSD score than one, suggesting that the therapeutic impact of assessment visits is cumulative and proportional. A comparable therapeutic effect was also found in participants receiving active medication.

Conclusions: Follow-up assessments in antidepressant treatment trials incur a significant therapeutic effect for participants on placebo, and this represents about 40% of the placebo response.