SYMPOSIA

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