Active placebos versus antidepressants for depression (Cochrane Review)
Moncrieff J, Wessely S, Hardy R
A substantive amendment to this systematic review was last made on 27 July
1998. Cochrane reviews are regularly checked and updated if necessary.
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 [my emphasis].
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 [my emphasis]. 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.
Reviewers' 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.
Citation: Moncrieff J, Wessely S, Hardy R. Active
placebos versus antidepressants for depression (Cochrane Review). In: The Cochrane Library, Issue 1 2003. Oxford: Update
This is an
abstract of a regularly updated, systematic review prepared and maintained by the Cochrane Collaboration. The full text of
the review is available in The Cochrane Library (ISSN 1464-780X).