Searching for a New TMS Target in Schizophrenia, With Andrew Pines, MD

Andrew Pines identified efficacy, meaning whether the target reduced symptoms, as the principal unanswered question in an ongoing randomized controlled trial of a transcranial magnetic stimulation (TMS) target for schizophrenia. Earlier TMS trials in schizophrenia had shown the treatment to be safe, with adverse effects typically less burdensome than those of antipsychotics. Headache occurred in some patients, and seizure risk was very rare, usually quoted at 1 in 30,000 to 1 in 50,000 treatments.¹

Pines anticipated benefit for patients who had experienced heavy medication side effects or whose symptoms limited daily functioning. In depression, TMS effects reportedly lasted 1.5 to 2 years, based on anecdotal patient reports and a retrospective review of the group's own records for returning patients. A single course lasting that long could also be cost-effective for underserved populations.

The main limitation was that the trial was ongoing, so efficacy could not yet be judged.² The mechanism of TMS also remained poorly understood. "We say that it's affecting a brain network, and we can find these connections using functional connectivity or sometimes using white matter tractography, but that doesn't say a lot about the mechanism of actually what's occurring," Pines said.

Electroconvulsive therapy (ECT) had long been an effective treatment for depression and psychosis, but it carries stigma, Pines acknowledged. It is performed differently than in popular depictions in films and literature. Thought it is most often not first-line for patients, it could be lifesaving for many, including those with psychosis. ECT also remains nonfocal, inducing a seizure across the entire brain. "What we want to do is help to identify changes that are associated with ECT that are correlated with improvement in psychosis," Pines said. Identifying such changes could show whether targeting ECT differently would be more helpful and cause fewer side effects.

Dr Pines is a psychiatrist at Mass General Brigham and an instructor at Harvard Medical School.

References

1. Rossi S, Antal A, Bestmann S, et al. Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: expert guidelines. Clin Neurophysiol. 2021;132(1):269-306.

2. Dlabač-de Lange JJ, Knegtering R, Aleman A. Repetitive transcranial magnetic stimulation for negative symptoms of schizophrenia: review and meta-analysis. J Clin Psychiatry. 2010;71(4):411-418.