Bilateral Repetitive Transcranial Magnetic Stimulation as a Treatment for Suicidality: Study Outcomes and Future Directions

The concept of suicidality, which includes suicidal thoughts, behaviors, and actions, is being talked about more frequently in both scientific and lay circles. Suicidality is a major public health concern, and we know that individuals suffering from mental illness are at an elevated risk for suicide, given that 90% of individuals who complete suicide have a psychiatric illness. Yet, while we can effectively characterize suicidality in many of our patients, we do not have adequate treatments for this potentially lethal symptom. Known anti-suicidal treatments for mood disorders—electroconvulsive therapy, lithium, and possibly ketamine—are limited to specific clinical indications. With recent innovations in brain stimulation treatments for psychiatric illnesses, my colleagues and I decided to conduct a secondary analysis to determine whether repetitive transcranial magnetic stimulation (rTMS)—an effective treatment for depression—could be useful in treating suicidality too.

Prior to our analysis, a few small trials (Desmyter et al [2014], George et al, and Desmyter et al [2016]) tested rTMS targeted to the left dorsolateral prefrontal cortex (DLPFC) to treat suicidality, but the results were inconclusive. Our group’s study is unique in that we had a much larger group of patients (N=156) than the aforementioned trials, and we assessed both left DLPFC and bilateral DLPFC stimulation. Bilateral stimulation in our study was high frequency left DLPFC stimulation (10 Hz) and low frequency right DLPFC stimulation (1 Hz) (see Blumberger et al [2012] and Blumberger et al [2016]).

What do our results show? Essentially, bilateral rTMS was significantly better than placebo at eliminating suicidal ideation in patients with depression, and left DLPFC stimulation was not better than placebo. We also found that patients’ improvement in suicidality was not highly correlated to remission from depression as a whole. This is exciting from a clinical standpoint and may also make sense from a neuroscientific lens, as the right DLPFC, targeted by bilateral rTMS but not unilateral left rTMS, is implicated in the pathophysiology of suicidality.

Further reading on this topic has led me to believe that, rather than being a ‘suicide-specific’ target per se, treatment of the right DLPFC with rTMS may be affecting psychological or neurophysiological paradigms highly linked with suicidality. For instance, patients with suicidality may have problems with behavioral inhibition, executive functioning, cognitive control, or memory retrieval traced to abnormal right DLPFC function. This way of thinking is in line with Research Domain Criteria and will likely guide our group’s future research in the application of brain stimulation treatments to manage suicidality in patients. If we can think of suicidality as a treatable transdiagnostic entity affecting not only patients with depression but also those with psychotic illnesses, personality disorders, and anxiety disorders, among others, we may be able to reduce suffering and save the lives of many.

I’m curious to hear your thoughts on our future directions and conceptualization of the right DLPFC and its connection to suicidality.

Acknowledgement: Weissman would like to thank Zafiris J. Daskalakis, MD, PhD, FRCP(C) (Temerty Centre for Therapeutic Brain Intervention, and Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, University of Toronto, Ontario, Canada) for his assistance in the development of this blog entry. In the last 5 years, Dr Daskalakis has received research and equipment in-kind support for an investigator-initiated study through Brainsway, Inc. and Magventure, Inc.

Financial disclosure:Dr Weissman has no relevant personal financial relationships to report.