Placebo Effect: Antidepressants at it Again
How much does it matter for patients to believe they will get well?
Thanks to the work of Dr. Irving Kirsch, we now know that the majority of the effect of antidepressants is attributable to the “active placebo effect” or the belief that receiving a memified brain-chemical-corrector will actually help alleviate symptoms. As I discuss in this post, evaluation of published and unpublished data, in two metanalysis, demonstrated a non-clinically significant difference between placebo and antidepressants.
A fascinating new study entitled The Role of Patient Expectancy in Placebo and Nocebo Effects in Antidepressant Trials further explores the power of belief in psychiatric treatment. Two fluoxetine (generic Prozac) discontinuation studies including 673 (48-51% of each group) diagnosed depressed outpatients were treated to remission (3 weeks of HDRS< 7) in an open-label (they knew they were receiving fluoxetine) trial over 12 weeks.
At the 12 week point, all patients were informed that they would be randomized to placebo or continued fluoxetine.
The study identified that change in the first 3 weeks was correlated ( r = -0.46-48, P<.001) with change post-randomization. Impressively, participants continued on fluoxetine and those on placebo BOTH developed worsening depressive symptoms suggestive of two significant interpretations:
1. The initial effect was attributable to placebo since all patients knew they were receiving treatment (open label)
2. The loss of benefit with the introduction of the possibility of being randomized to placebo is the undoing of the placebo effect, or the nocebo effect.
The role of study design (open, placebo controlled, comparator) has been demonstrated to influence patient beliefs about outcomes, and therefore outcomes.
The power of belief and faith in the efficacy of medical treatments cannot be dismissed, and should be leveraged for the implementation of benign, non-habit forming treatments with the potential to confer benefit. The use of medications associated with short and long-term side effects, that primarily ride the placebo effect represents an ethically questionable practice that should be exposed for what it is.
I review some of the primary fallacies underlying current psychiatric practice, celebrate the great thinkers who have pulled th wool from our eyes, and propose a more enlightened approach to treatment in this short talk.
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