• DOI:10.1002/14651858.CD003012.PUB2
• Corpus ID: 16163815

Active placebos versus antidepressants for depression.

@article{Moncrieff2004ActivePV,
  title={Active placebos versus antidepressants for depression.},
  author={Joanna Moncrieff and Simon Wessely and Rebecca Hardy},
  journal={The Cochrane database of systematic reviews},
  year={2004},
  volume={1},
  pages={
          CD003012
        }
}

• J. Moncrieff, S. Wessely, R. Hardy
• Published 26 January 2004
• Psychology, Medicine
• The Cochrane database of systematic reviews

BACKGROUND
Although there is a consensus that antidepressants are effective in depression, placebo effects are also thought to be substantial. Side effects of antidepressants may reveal the identity of medication to participants or investigators and thus may bias the results of conventional trials using inert placebos. Using an 'active' placebo which mimics some of the side effects of antidepressants may help to counteract this potential bias.

OBJECTIVES
To investigate the efficacy of antidepressants when compared with 'active' placebos.

SEARCH STRATEGY
The Cochrane Collaboration Depression, Anxiety and Neurosis review groups's search strategy was used to search MEDLINE (1966-2000), PsychLIT (1980-2000) and EMBASE (1974-2000) and this was last done in July 2000. Reference lists from relevant articles and textbooks were searched and 12 specialist journals were handsearched up to 1996.

SELECTION CRITERIA
Randomised and quasi randomised controlled trials comparing antidepressants with active placebos in people with depression.

DATA COLLECTION AND ANALYSIS
Since many different outcome measures were used a standard measure of effect was calculated for each trial. A subgroup analysis of inpatient and outpatient trials was conducted. Two reviewers independently assessed whether each trial met inclusion criteria.

MAIN RESULTS
Nine studies involving 751 participants were included. Two of them produced effect sizes which showed a consistent and statistically significant difference in favour of the active drug. Combining all studies produced a pooled estimate of effect of 0.39 standard deviations (confidence interval, 0.24 to 0.54) in favour of the antidepressant measured by improvement in mood. There was high heterogeneity due to one strongly positive trial. Sensitivity analysis omitting this trial reduced the pooled effect to 0.17 (0.00 to 0.34). The pooled effect for inpatient and outpatient trials was highly sensitive to decisions about which combination of data was included but inpatient trials produced the lowest effects.

REVIEWER'S CONCLUSIONS
The more conservative estimates from the present analysis found that differences between antidepressants and active placebos were small. This suggests that unblinding effects may inflate the efficacy of antidepressants in trials using inert placebos. Further research into unblinding is warranted.