© 2003 The Royal College of Psychiatrists
Correspondence |
The antidepressant debate should move on
Neuroscience and Psychiatry Unit, University of Manchester, Room G809 Stopford Building, Oxford Road, Manchester M13 9WL, UK
Mental Health Partnership of Bolton, Salford & Trafford, Cranwell House, Manchester, UK
In her editorial, ‘The antidepressant debate’, Moncrieff (2002) provocatively questioned the orthodox view that antidepressants are efficacious (i.e. work under clinical trial conditions) in the treatment of depressive illness. Questioning accepted views is valuable but Moncrieff missed the real question, which relates to effectiveness, that is when are antidepressants useful clinically? The efficacy argument at the head of her critique, based on individual, often old and poor-quality, studies flies in the face of consistent findings of antidepressant efficacy in systematic reviews and meta-analyses (e.g. Anderson et al, 2000). Even the argument of bias due to unblinding because of side-effects is contradicted by her own meta-analysis, which showed a significant benefit for antidepressants over ‘active’ placebo (Moncrieff et al, 1998). Even more compelling is the evidence from continuation/maintenance studies which show that antidepressants have a robust effect in reducing rates of relapse and recurrence (Carney et al, 2001), a cumulative effect over months or years. Explaining this by a placebo effect is difficult to accept, or else demands re-evaluation of the nature of placebo.
This is not to say that ‘negative’ studies, where antidepressants are no better than placebo, should be ignored. An important factor is probably related to severity of depression. Khan et al (2002) found that the proportion of studies favouring antidepressants over placebo increased with the severity of depression; the response to placebo declined with increasing severity whereas that to antidepressants increased. This raises the fundamental question of when (i.e. at what severity) in real life practice does someone with depression clearly benefit from antidepressant drug treatment. Put another way, is the current trend to wider use of antidepressants for milder depression justified? This can only be answered empirically in appropriate naturalistic trials, and even then will require value judgement about the size of the benefit.
Perhaps the most worrying aspect of Moncrieff's editorial was the implication that we should take either a psychosocial or a physical approach to the treatment of depression. Surely we should have put this rather tired dualist view of psychiatry behind us by now? A holistic view combining drug and psychological treatments is to be preferred and evidence is accumulating that this leads to better outcomes. To conclude, a balanced view of the evidence for antidepressants firmly places them as an established and important therapeutic option (alongside others) in the treatment of depression, with their role becoming more central with increasing severity. The true debate is about the best way to use them.
I.M.A. and P.M.H. have both received honoraria for speaking, been members of advisory boards, received research grants and had support for attending scientific meetings from several pharmaceutical companies involved in the manufacture and marketing of antidepressants.
REFERENCES
- Anderson, I. M., Nutt, D. J. & Deakin, J. F. W.
(2000) Evidence-based guidelines for treating depressive
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[Abstract/Free Full Text] - Carney, S., Geddes, J., Davies, C., et al (2001) Duration of treatment with antidepressants (Cochrane review). Journal of Psychopharmacology, 15 (suppl.), A10.
- Khan, A., Leventhal, R. M., Khan, R. K., et al (2002) Severity of depression and response to antidepressants and placebo: an analysis of the Food and Drug Administration database. Journal of Clinical Psychopharmacology, 22, 40–45.[CrossRef][Medline]
- Moncrieff, J. (2002) The antidepressant debate.
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[Free Full Text] - Moncrieff, J., Wessely, S. & Hardy, R.
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[Abstract/Free Full Text]
Author's reply
Royal Free and University College Medical School, University College London, Department of Psychiatry and Behavioural Sciences, Wolfson Building, 48 Riding House Street, London WIN 8AA, UK
I would like to make some comments on the points raised by Kirov & Korszun and Anderson & Haddad. They both cite evidence from continuation and maintenance studies, but this is likely to be more flawed than evidence from acute treatment studies. In studies of long-term treatment, patients who have responded to acute treatment are randomised to continue active drugs or to be withdrawn to an inert placebo. However, it cannot be assumed that the state of having had treatment withdrawn is equivalent to never having had treatment in the first place. It is known that there is a discontinuation reaction with all classes of antidepressants (Haddad et al, 1998). The symptoms of this reaction may themselves be mistaken for relapse, or they may unblind participants and predispose them to relapse because of fears of discontinuing treatment. This is likely to be a particular problem given that the initial sample of patients comprises people responsive to treatment who are therefore likely to have high expectations of the benefits of treatment.
In addition, the evidence on antidepressant effects and severity is complex. The majority of studies that show that increased efficacy correlates with increased severity are studies of out-patients. In in-patients, more-severe depression has been shown to respond less well to antidepressants than moderate depression does, independently of the presence of psychotic symptoms (Kocsis et al, 1990). In our meta-analysis we found no significant differences from placebo in in-patient studies (Moncrieff et al, 1998), which is in line with results from other large landmark in-patient studies such as the Medical Research Council study and the National Institute for Mental Health study described in my editorial (Moncrieff, 2002).
Finally, if the benefits of antidepressants are so obvious, it seems surprising to me that we have little evidence that the burden of depressive illness is reducing in line with the vast expansion in antidepressant prescribing. In contrast, long-term incapacity related to depression has been rising rapidly both in absolute terms and in relation to other conditions (Moncrieff & Pommerleau, 2000).
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[Abstract/Free Full Text] - Moncrieff, J. (2002) The antidepressant debate.
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[Free Full Text] - Moncrieff, J. & Pommerleau, J. (2000)
Trends in sickness benefits in Great Britain and the contribution of mental
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[Abstract/Free Full Text] - Moncrieff, J., Wessely, S. & Hardy, R.
(1998), Meta-analysis of trials comparing antidepressants
with active placebos. British Journal of Psychiatry,
172,
227–231.
[Abstract/Free Full Text]
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