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Meta-analysis of trials comparing antidepressants with active placebos

Published online by Cambridge University Press:  02 January 2018

Joanna Moncrieff ,
Simon Wessely  and
Rebecca Hardy
Joanna Moncrieff*
Affiliation:
Sector of Epidemiology and General Practice, Institute of Psychiatry, London
Simon Wessely
Affiliation:
Department of Psychological Medicine, Kings Cortege School of Medicine and Dentistry, London
Rebecca Hardy
Affiliation:
Department of Epidemiology and Public Health, University College London Medical School, London
*
Joanna Moncrieff. Section of Epidemiology and General Practice. Institute of Psychiatry, De Crespigny Parle. London SES 8AF
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Abstract

Background

Unblinding effects may-introduce bias into clinical trials. The use of active placebos to mimic side-effects of medication may therefore produce more rigorous evidence on the efficacy of antidepressants.

Method

Trials comparing antidepressants with active placebos were located. A standard measure of effect was calculated for each trial and weighted pooled estimates obtained. Heterogeneity was examined and sensitivity analyses performed. A subgroup analysis of in-patient and out-patient trials was conducted.

Results

Only two of the nine studies examined produced effect sizes which showed a consistent significant difference in favour of the active drug. Combining all studies produced pooled effect size estimates of between 0.41 (0.27–0.56) and 0.46 (0.31–0.60) with high heterogeneity due to one strongly positive trial. Sensitivity analyses excluding this and one other trial reduced the pooled effect to between 0.21 (0.03–0.38) and 0.27 (0.10–0.45).

Conclusions

Meta-analysis is very sensitive to decisions about exclusions. Previous general meta-analyses have found combined effect sizes in the range 0.4–0.8. The more conservative estimates produced here suggest that unblinding effects may inflate the efficacy of antidepressants in trials using inert placebos.

Type
Papers
Information
The British Journal of Psychiatry , Volume 172 , Issue 3 , March 1998 , pp. 227 - 231
Copyright
Copyright © 1998 The Royal College of Psychiatrists 

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Footnotes

†

See Commentary, pp. 232–234 this issue.

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