In the Lancet recently it has been suggested we need a fundamental change in appraising placebo in psychiatry research (Burke, 2023).
Why? In the Alpha-Stim Anxiety Insomnia and Depression cranial electrotherapy stimulation trial, Richard Morriss and colleagues reported no significant difference in their primary depression outcome between active and sham groups.
Although not the headline of the article, 41% of recruited patients who received sham stimulation had remission of their depression. This remarkable result adds to the growing list of neurotechnology trials in psychiatry demonstrating very large responses in their placebo arms.
For example, the largest recent sham-controlled trial of transcranial magnetic stimulation for treatment-resistant depression showed a similarly impressive 37% remission rate in the sham transcranial magnetic stimulation group.
Morriss and colleagues rightfully conclude that active stimulation was no more effective than sham stimulation; but do not consider more deeply how the placebo response might have contributed to the beneficial effect of sham stimulation.
A broader issue is that structured interrogation of placebo responses is not embedded in our research appraisal schema. Placebo effects have largely been considered an inconvenience in clinical research, and rarely find their way into formal medical training.
However, over the past decade, neuroscience research has increasingly demonstrated the robust neurobiological impacts of placebo effects, and their ability to meaningfully modulate brain circuits and neurotransmitter systems. Thus, a patient’s depressive symptoms improve in the therapeutic context of potentially receiving novel brain stimulation, because expectancies changed their brain.
