Brain Trust: An Interventional Psychiatry Deep Dive With Lisa Harding, MD

BRAIN TRUST: CONVERSATIONS IN PSYCHOPHARMACOLOGY
Series Editor Joseph F. Goldberg, MD

Joseph F. Goldberg, MD, in this installment of "Brain Trust: Conversations in Psychopharmacology," sits down with Lisa Harding, MD, at the Jersey City Psychiatry conference to discuss interventional psychiatry and how to select among treatments for difficult-to-treat depression.

Interventional psychiatry is often understood to encompasses a particular arm of the field—electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), intravenous ketamine or esketamine, and vagus nerve stimulation—but is not a specifically accredited specialty. Training has also not kept pace with many interventional techniques: "You can graduate a psychiatry residency without ever having mapped a patient with TMS. You could graduate residency without having to put in an IV on a patient to do intravenous esketamine," Harding said.

Concerning ECT as a treatment option, response rates ranged from 50% to 90%, varying by indication and severity. Most clinicians started with up to 6 right unilateral treatments and switched to bilateral placement for nonresponse, although severe catatonia might warrant bilateral placement initially. Prior ECT courses deserved the same scrutiny as medication dose and titration, Harding highlighted.

No head-to-head trials of ECT, TMS, and vagus nerve stimulation exist, so patient preference, occupational burden, access, and treatment setting often drove selection. For severely ill patients, ECT and ketamine acted fastest, with ECT producing improvement within the first 6 treatments, whereas TMS and vagus nerve stimulation required weeks to months. Intravenous ketamine was noninferior to ECT in a randomized trial.¹ Harding said she favored ECT for patients experiencing more severe symptoms in the short term.

Durability remained the central gap with these treatments. An estimated 80% to 90% of patients continued to experience depression after acute response, and no data guided whether relapse during maintenance warranted reinduction. Esketamine was the exception, with up to 6 years of open-label safety data and no new signals.²

For TMS techniques, accelerated theta burst TMS delivered 10 sessions per day, separated by 50 minutes, over 5 days, with functional magnetic resonance imaging–guided targeting. The protocol, however, is proprietary, experimental, and often not covered by insurance. "You are asking a patient to pay $30,000 out of pocket for a treatment that I don't know is durable," Harding said.

Looking forward, Harding identified artificial intelligence–assisted diagnosis, rather than neuromodulation, as a promising route to improved patient outcomes.

Dr Goldberg is a clinical professor of psychiatry at The Icahn School of Medicine at Mount Sinai in New York, NY and the immediate-past president of the American Society of Clinical Psychopharmacology.

Dr Harding is a psychiatrist and on the faculty at Yale University School of Medicine.

References

1. Anand A, Mathew SJ, Sanacora G, et al. Ketamine versus ECT for nonpsychotic treatment-resistant major depression. N Engl J Med. 2023;388(25):2315-2325.

2. Zaki N, Chen LN, Lane R, et al. Safety and efficacy with esketamine in treatment-resistant depression: long-term extension study. Int J Neuropsychopharmacol. 2025;28(6):pyaf027.