Placebo controls in clinical trials: concerns about use in relapse prevention studies in schizophrenia
BMJ 2016; 354 doi: https://doi.org/10.1136/bmj.i4728 (Published 09 September 2016) Cite this as: BMJ 2016;354:i4728
- Robin Emsley, Sarah Turoff, endowed chair in schizophrenia research1,
- W Wolfgang Fleischhacker, professor2,
- Silvana Galderisi, professor3,
- Lisa J Halpern, director of recovery services4,
- Joseph P McEvoy, professor5,
- Nina R Schooler, professor6
- 1Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Tygerberg Campus 8000, Cape Town, South Africa
- 2Department of Psychiatry and Psychotherapy, Medical University Innsbruck, Innsbruck, Austria
- 3Department of Psychiatry, University of Naples, Naples, Italy
- 4Vinfen, Cambridge, MA, USA
- 5Department of Psychiatry and Health Behavior, Georgia Regents University, Augusta, Georgia, USA
- 6State University of New York, Brooklyn, NY, USA
- Correspondence to: R Emsley rae{at}sun.ac.za
The use of placebos in clinical trials has major policy implications for ethical conduct across all of medicine and is relevant to clinicians, patients, drug development, and regulatory agencies. This article focuses on the use of placebos in relapse prevention studies in schizophrenia. However, the issues discussed are similar to those encountered in many other clinical trial situations. These include underestimating the risk of harm associated with trial participation, the risk of coercion, insufficient awareness of the risks by participants, and the risk of loss of trust between the patient and doctor.
While the debate around using placebos in clinical trials of schizophrenia is long running, several developments make it imperative to readdress the topic. Firstly, new research has reported deleterious effects of relapse,1 challenging the previous assumption that relapse is not associated with a risk of lasting harm. Secondly, new questions have been raised about the need for maintenance treatment in schizophrenia.2 Thirdly, ethical standards have evolved, with reduced tolerance of exposure of participants to risk and greater respect of patient autonomy. Finally, and most importantly, recent publications from both the European Medicines Agency and US Food and Drug Administration continue to encourage the use of placebos in schizophrenia trials.
Maintenance medication for schizophrenia
The place of maintenance antipsychotic treatment in schizophrenia has been questioned for two reasons.2 The drugs have potentially serious adverse effects, and preliminary and uncontrolled evidence suggests that in some patients gradual dose reduction and, where feasible, discontinuation may be associated with better long term outcome.3 However, stopping antipsychotic treatment is associated with very high rates of relapse, even after a single episode of psychosis.4 Relapses may be associated with undue patient …
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