SYMPOSIA
SYMPOSIA
SYMPOSIA
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Abstracts of the Invited Speakers<br />
DEBATES<br />
[MD-02]<br />
Antidepressants are useful in the treatment of depression: the case for the motion<br />
Ian Anderson<br />
Neuroscience and Psychiatry Unit, University of Manchester, UK<br />
E-mail: ian.anderson@manchester.ac.uk<br />
The group of drugs we call antidepressants have been available for nearly 60 years and are the first available physical treatment for<br />
depression that became accepted by the public and clinicians alike. However in the last decade, associated with the rise of evidencebased<br />
medicine and a concern about the medicalisation of distress, there has been a questioning and re-evaluation of their efficacy<br />
and place in the treatment of depression. This has occurred against the backdrop of increasing distrust of ‘Big Pharma’ and emphasis<br />
on psychological treatment approaches. I will be addressing some of the main challenges that have been put forward questioning the<br />
usefulness of antidepressants, ranging from the denial that depression is a disorder that can be treated by physical means, to the argument<br />
that there is no pharmacological or empirical evidence for a clinically useful benefit over psychologically-mediated placebo effects. To<br />
do this I will touch on recent developments in the understanding of how antidepressants might directly influence the processing by the<br />
brain of emotional material, consider the evidence that direct pharmacological effects are necessary to maintain the therapeutic effects of<br />
antidepressants and review the empirical evidence for clinically important efficacy from treatment trials in depression. I will conclude that<br />
while antidepressants are certainly not a panacea, denying their place in treating depression is based on prejudice rather than objective<br />
appraisal of the evidence.<br />
Key words: Depression, antidepressants, placebo, efficacy<br />
Bulletin of Clinical Psychopharmacology 2011;21(Suppl. 2):S38<br />
[MD-02]<br />
Have clinically significant benefits of antidepressants been demonstrated?<br />
Irving Kirsch<br />
Associate Director, Program in Placebo Studies (PiPS) and Lecturer in Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Professor Emeritus of<br />
Psychology, University of Hull & University of Connecticut<br />
E-mail: I.Kirsch@hull.ac.uk<br />
Despite their widespread use, clinically significant benefits of antidepressants have not been demonstrated for most of the patients to<br />
whom they are prescribed. Meta-analyses of complete data sets consistently show a drug-placebo difference in improvement on the<br />
Hamilton Rating Scale for Depression (HAMD) of approximately two points, which is well below the 3-point difference set by the National<br />
Institute for Health and Clinical Excellence (NICE) as a criterion of clinical significance (1).<br />
Drug placebo differences increase with increasing severity of depression, but reach clinical significance only for 10% of the patients to<br />
whom they are prescribed (2). Defenders of antidepressants claim that depression scores are inflated by researchers who are anxious to<br />
qualify patients for clinical trials. To the extent that this is true, it compromises the clinical trial data leading to drug approval, but even if<br />
these trials are discarded, the absence of negative evidence does not constitute positive evidence of effectiveness.<br />
Discontinuation studies show a relapse rate of approximately 50% when patients are switched to placebo. However, approximately<br />
half of the relapses may be due to prior administration of the active agent. In extension trials, in which responders are kept on<br />
placebo, the relapse rate is only 25% (3). These data suggest that antidepressants might induce a biological vulnerability to relapse.<br />
Consistent with this hypothesis, a meta-analysis of tryptophan depletion studies indicates that the risk of becoming depressed after<br />
acute lowering of serotonin levels is greatest between three and six months after discontinuation of an antidepressant (4). It is also<br />
consistent with the results of the STAR-D trial, which was designed to be more representative than typical clinical trials of what<br />
happens in clinical practice. Following successful treatment in the STAR-D trial, 93% of patients either relapsed or dropped out of the<br />
trial within a year (5). Taken together, these data suggest that in the long run, rather than helping depressed people, antidepressants<br />
may make them worse.<br />
S38 Bulletin of Clinical Psychopharmacology, Vol: 21, Supplement: 2, 2011 - www.psikofarmakoloji.org