Debate at Critical Psychiatry Network Annual Conference 13 June 2003
"Antidepressants are no better than placebos"
The National Institute for Clinical Excellence (NICE) (www.nice.org.uk) was set up as a Special Health Authority of the National Health Service (NHS) in England and Wales on 1 April 1999. Its role is to provide patients, health professionals and the public with authoritative, robust and reliable guidance on current "best practice". For example, it has recently published guidelines for the treatment and management of schizophrenia.1 It is currently preparing a clinical guideline for patients and clinicians on the management of depression.2 This guideline will provide advice on effective care using evidence from clinical trials and economic analyses and will include appropriate use of pharmacological treatments, such as antidepressants. Guidance will be based on the best evidence available to the guideline development group, led by the National Collaborating Centre for Mental Health.3 Consultation on the final draft of the guideline is scheduled to start in October 2003. The expected date of issue is February 2004.
The debate about whether antidepressants are any better than placebos at the Critical Psychiatry Network Annual Conference on 13 June 2003 (www.criticalpsychiatry.co.uk/AnnualConference2003.htm) is therefore timely. It may seem to be a very sceptical position to question the effectiveness of antidepressants, which are in widespread accepted clinical use, but there is at least sufficient eminent academic opinion to legitimately raise the issue.
The motion is proposed by Professor Irving Kirsch, Professor of Psychology, University of Connecticut, USA.5 He has previously been involved in two conferences connected to this theme at the University of Nevada, Reno. The first in 2000 was entitled "Causes, Treatments, and Politics of Depression: How Much do we Really Know?"6 It debated the merits of biological versus psychosocial models of depression.7, 8 It also discussed the flaws and biases in research on antidepressant drugs. The second "Rumble in Reno II" debated the clinical implications of the U.S. Food and Drug Administration (FDA) antidepressant trials.9 It featured a debate between Kirsch and Michael Thase, Professor of Psychiatry at the University of Pittsburgh Medical Center.10, 11
Kirsch concludes from his research that much of the apparent therapeutic benefit of antidepressants may derive from amplification of placebo responding by convincing patients that they are receiving a potent drug.12 Placebos are found to be approximately 75% as effective as antidepressant medications across all outcome studies in which it is possible to measure pre-post effect sizes. Analysis of the New Drug Application (NDA) data sets sent to the FDA by the manufacturers of the six most widely prescribed antidepressants has shown that although the response to antidepressants was substantial, the response to inert placebo was almost as great.13 More than half of the clinical trials sponsored by the pharmaceutical companies failed to find significant drug/placebo difference, and there were no advantages for higher doses of antidepressants. These data reinforce the argument that the small size of the average drug/placebo difference is an artifact associated with the breaking of the blind in clinical trials and of questionable clinical significance. The small magnitude of the so-called antidepressant effect in clinical trials should be more widely known. Kirsch proposes the development of nondeceptive methods of eliciting the placebo effect in treatment of depression. Psychotherapies may accomplish their effects by changing expectations, but unlike placebos, they do so without deception.14 The point is that the effectiveness of antidepressants has not been demonstrated empirically.
The motion is seconded by Joanna Moncrieff, Senior Lecturer in Social and Community Psychiatry at University College London and co-chair of the Critical Psychiatry Network (www.criticalpsychiatry.co.uk). She discusses "The Antidepressant Debate" in an editorial in the British Journal of Psychiatry.15 In particular, she highlights the methodological problems of antidepressant trials, including the evidence for the amplification of the placebo effect from studies comparing antidepressants with active placebos.16, 17 The antidepressant effect does not seem to be specific to identified antidepressants as other drugs not classed as antidepressants have been shown to have positive effects in depression in controlled clinical trials. Moncrieff suggests that the interests of the pharmaceutical industry and the psychiatric profession have helped to establish the notion of the efficacy and specificity of antidepressant drugs.18
The conclusions of Kirsch and Moncrieff are controversial. To right a more conventional balance to the debate, the motion is opposed by eminent psychiatrists: David Goldberg, Professor Emeritus, Institute of Psychiatry, King's College, London and Phil Cowen, Professor of Psychopharmacology, University of Oxford. David Goldberg has had a long and distinguished career in psychiatry, including being Professor of Psychiatry and Director of Research and Development at the Maudsley Hospital, London. Phil Cowen leads the Psychopharmacology Research Group in the Department of Psychiatry at the University of Oxford and has a particular interest in the role of brain serotonin, a neurotransmitter implicated in depression.
The debate will be chaired by Raj Persaud, Consultant Psychiatrist at The Maudsley Hospital. He currently presents All in the Mind on BBC Radio 4 (http://www.bbc.co.uk/radio4/science/allinthemind.shtml).
Is the debate just tilting at windmills erected by Kirsch and Moncrieff? The proposers of the motion may be the imaginary enemies of Goldberg and Cowen's Don Quixote and Sancha Panchez, but the debate is designed to engender public interest in an academic issue that will affect the outcome of the NICE guidelines on the management of depression.
Entry to the debate costs £25 and a printable booking form is available online. The debate is the end of a full one day conference programme entitled "The limits of psychiatry". Further details are available at http://www.critpsynet.freeuk.com/AnnualConference2003.htm.
__