Provocation of symptoms may increase the effectiveness of repetitive transcranial magnetic stimulation

Provocation of symptoms may increase the effectiveness of repetitive transcranial magnetic stimulation

A new study inJama PsychiatryThe case that symptom provocation can significantly improve the clinical effectiveness of repetitive transcranial magnetic stimulation (RTMS), a noninvasive brain stimulation method used to treat depression, obsessive-compulsive disorder (OCD), and nicotine dependence.

The study was conceived, designed and supervised by Heather Burrell Ward, MD, assistant professor of psychiatry and behavioral sciences and director of neuromodulation research, in collaboration with Simon Vandekar, PhD, associate professor of biostatistics, and Daniel Bello and Megan Jones, two graduate students in their respective laboratories.

This is the first large-scale meta-analysis to examine whether deliberately symptomatic symptoms immediately prior to administration of RTMs improve treatment outcomes.

"FDA-approved protocols for OCD and nicotine dependence include a 'symptom challenge' immediately prior to administration of RTMs," Ward said. "For OCD, this involves provoking obsessive thoughts. So if someone has an obsession about hygiene, you could have them put them in a trash can immediately before receiving RTMs. For nicotine addiction, this involves provoking nicotine cravings.

"There is some evidence that activating a brain circuit immediately before using RTMs makes the RTMs more effective. However, this evidence comes from small studies and has never been analyzed in large numbers to draw definitive conclusions. We therefore conducted a systematic review with meta-analysis, a study that has detailed results from many previous studies to invest in the effect of symptom provisis. Because they are results across all studies to provide a more reliable estimate of an effect than any single study alone. “

Across the analysis, symptom provocation did not significantly improve clinical response – which is often measured by reductions in OCD symptoms or cigarette consumption. However, RTMS was almost twice as effective when symptom provocation was used compared to not used, suggesting that symptom provocation may improve response to RTMs.

It was surprising to see that despite different RTMS protocols, targets and provocation methods, symptom provocation appeared to improve both OCD and nicotine dependence. “

Heather Burrell Ward, MD, assistant professor of psychiatry and behavioral sciences

Ward added that it is also possible that symptom provocation has different effects in different populations.

"For example, some studies suggest that people with schizophrenia, unlike the general population, do not have cigarettes when presented with smoking-related images," she said. “In this case, symptom provocation might not be suitable for RTMs for nicotine dependence in schizophrenia.”

Ward, who is currently the principal investigator of a clinical trial comparing RTMS interventions for nicotine use in people with and without schizophrenia, sees these as important questions going forward.

"While this meta-analysis is incredibly valuable to the field in suggesting that symptom provocation can improve the clinical response to RTMs, it is important that prospective, randomized, controlled trials be conducted that directly test whether symptom provocation improves the response to RTMs," she said. "These should be done for OCD and nicotine addiction, as well as other disorders, including other substance use disorders, and other RTMS targets. Perhaps there are some brain circuits that need to be activated immediately before modulation and others that don't. Interestingly, when RTMS is used to treat depression, we don't provoke depressive symptoms.

“As a psychiatrist who administers RTMS in clinical and research settings, I want to know exactly what I need to do to make RTMs as effective as possible for my patients. There is so much left for us to learn about ways to optimize RTMS treatment, and Vanderbilt is a leader in this area. “

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