Does Study Design Influence Clinical Outcome?

Medline and the Cochrane Database were searched to identify RCTs of antidepressants for major depression approved by the Food and Drug Administration. Included studies enrolled outpatient participants aged 18-65, lasted 6-12 weeks, compared an antidepressant to placebo or another antidepressant and were published in English after 1985. Excluded trials enrolled inpatients, pregnant women and subjects with psychosis or mania.

Mixed-effects logistic regression models including study type (placebo-controlled or comparator) and study duration (6, 8 or 12 weeks) as fixed effects determined whether these factors affected response and remission rates. In the 90 trials analyzed, the odds of depression response (OR = 1.79, 95% CI = 1.45-2.17, p < 0.001) and remission (OR 1.53, 95% CI = 1.11-2.11, p < 0.001) were significantly higher in comparator relative to placebo-controlled trials. Trials lasting 8 (OR = 1.37, CI = 1.14-1.64, p = 0.001) and 12 (OR = 1.52, CI = 1.12-2.07, p = 0.008) weeks had significantly greater response rates than 6-week trials without differing themselves.

Response and remission rates to antidepressants are significantly affected by study type and duration. Clinicians and researchers must consider the study design when interpreting and designing RCTs of antidepressant medications, researchers urge.