Emerging Neuromodulation and Pharmacotherapy for Treatment-Resistant Depression

Charles DeBattista, MD, offered an overview of emerging neuromodulation technologies and pharmacological developments for treatment-resistant depression (TRD) at the Southern California Psychiatry Conference. DeBattista is the keynote speaker at this year’s conference, sharing clinical and practical tips from his area of expertise.

DeBattista identified accelerated transcranial magnetic stimulation (TMS) protocols as among the most immediately clinically relevant advances, noting that they are increasingly becoming standard practice and offer the potential to achieve meaningful antidepressant effects more rapidly than conventional protocols. He cited the Stanford Accelerated Intelligent Neuromodulation Therapy (known as SAINT) protocol—a 5-day, fMRI-guided, high-dose intermittent theta burst stimulation approach developed at Stanford—as a leading example of this direction.¹ He also described a broader landscape of neuromodulation innovations, including focused ultrasound, CyberKnife, and deep brain stimulation, acknowledging that while some remain highly experimental, others are currently available.

On pharmacological development, DeBattista devoted considerable attention to psychedelics, noting that 1 or more agents in this class are likely to receive US Food and Drug Administration approval within the next 1 to 2 years. He characterized their most distinctive potential feature as the possibility of producing persistent antidepressant effects from a single or small number of administrations. However, he cautioned against overinterpretation of early enthusiasm, noting practical barriers including restricted prescriber access, adverse effect risk, and the likelihood that these agents will not be suitable for all patients.

DeBattista emphasized that diagnostic precision remains an underappreciated driver of treatment outcomes in patients presenting with apparent TRD. He argued that time constraints in clinical practice contribute to missed comorbidities—including subtle psychotic features and bipolar spectrum illness—that significantly affect long-term prognosis and treatment selection.²

Dr DeBattista is professor of psychiatry and behavioral sciences at Stanford University School of Medicine and director of the Depression Research Clinic at Stanford.

References

1. Cole EJ, Stimpson KH, Bentzley BS, et al. Stanford Accelerated Intelligent Neuromodulation Therapy for treatment-resistant depression. Am J Psychiatry. 2020;177(8):716–726.

2. McInnes LA, Qian JJ, Gargeya RS, et al. A retrospective analysis of ketamine intravenous therapy for depression in real-world care settings. J Affect Disord. 2022;301:486–495.