Does study design influence outcome?. The effects of placebo control and treatment duration in antidepressant trials.
BACKGROUND
Clinicians and researchers synthesize data from randomized controlled trials (RCTs) of antidepressants to make conclusions about the efficacy of medications for depression. All treatments include nonspecific factors in addition to the specific effects of drugs, and study design may influence patient outcomes via nonspecific factors. This study investigated whether placebo control and treatment duration affect the outcome in antidepressant RCTs.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Rutherford
Bret R
BR
Department of Psychiatry, Columbia University and the New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA. brr8@columbia.edu
Sneed
Joel R
JR
Roose
Steven P
SP