Commentary on Mishra et al. (2010): Transcranial magnetic stimulation effects on craving: impressive therapy or therapeutic impressions?
Article first published online: 14 DEC 2009
© 2010 Society for the Study of Addiction. No claim to original US government works
Volume 105, Issue 1, page 56, January 2010
How to Cite
TRAFTON, J. A. (2010), Commentary on Mishra et al. (2010): Transcranial magnetic stimulation effects on craving: impressive therapy or therapeutic impressions?. Addiction, 105: 56. doi: 10.1111/j.1360-0443.2009.02835.x
- Issue published online: 14 DEC 2009
- Article first published online: 14 DEC 2009
- study design
With their clinical trial of repetitive transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex, Mishra and colleagues unveil an exciting, novel, high-tech approach to the treatment of alcohol dependence . Ten daily sessions of TMS reduced alcohol craving during the month following treatment in patients who received active versus sham TMS. The exact mechanisms of this treatment (i.e. its impact on circuits, neural firing patterns and plasticity, and addiction processes) are unclear, but biologically plausible. Promising to validate undeniably Alan Leshner's credo that ‘addiction is a brain disease’ to the world, this early clinical trial will rightfully generate interest and excitement .
Nevertheless, these same features of the intervention (i.e. involving a large, fancy machine that produces obvious effects on the brain) also make it the perfect placebo, and should temper our enthusiasm until follow-up studies are conducted. The fact that the main effects of the intervention were on craving, a subjective experience, with only non-significant trends towards change in objective behavioral measures, raises suspicion. We know that subjective symptoms, such as pain, and their associated brain activity are highly susceptible to modulation by placebo, suggestion and cognitive reframing (e.g. [3,4]) and pain and drug craving are generated by shared neural circuits . Craving is the substance use outcome for which we should expect the most robust placebo effects.
Placebo is considered most often in medication trials, but impressive-seeming technology can also produce dramatic placebo effects. For example, demonstrating the power of technological placebo, Goldring and colleagues  produced a more than 30-point drop in blood pressure, symptomatic improvement and even behavioral changes in hypertensive subjects using an utterly fake, but impressive-appearing ‘electron gun’-based therapy delivered by a sympathetic nurse. The ‘electron gun’ consisted of a cone pointed at subjects' hearts, attached to a large metal coil that glowed red, crackled and emitted sparks, and an oscilloscope displaying wave patterns. With its clearly perceptible effects, it seems likely that TMS would be capable of inducing similarly powerful placebo effects.
Given these concerns, it will be crucial that carefully controlled follow-up studies are conducted to both prove the efficacy of this new intervention and delineate the mechanism underlying its impact. Future studies must compare the effectiveness of TMS of the right dorsolateral prefrontal cortex to TMS of other brain sites not believed to be involved in addictive behavior. This will not only demonstrate the site specificity of the effect and provide hints at mechanism, but also blind participants more truly to their treatment assignment and control for placebo effects. As the authors honestly relate, sensations produced by sham TMS were mild compared to actual TMS. Cleaning up elements of the clinical trial will also increase confidence in the intervention; follow-up trials will need to be strictly randomized, and the background treatment standardized. The poorly described and individualized use of a mix of evidence-based and non-evidence-based pharmacotherapies for alcohol use in this trial could have biased results, for example. This study opens the door for new approaches to treatment for addictive disorders, but begs for additional study to replicate findings, assess effects on drinking behavior, validate that TMS is the active component of the intervention and determine mechanism.