Real-World Use of Ketamine, Esketamine, ECT, and rTMS in Tertiary Mood Disorder Clinics

Real-World Interventional Psychiatry: New Data from a Tertiary Mood Disorders Service

The largest real-world analysis to date of interventional psychiatry in a tertiary mood disorders clinic, published September 2026 (OpenAlex W7212130500), provides concrete data on how intravenous ketamine, intranasal esketamine, electroconvulsive therapy (ECT), and repetitive transcranial magnetic stimulation (rTMS) are being used for severe mood disorders. Among 894 patients with sufficient clinical data, 33.8% received at least one interventional treatment, with rTMS the most common (52.3% of those treated), followed by ECT (39.8%), intravenous ketamine (29.3%), and esketamine (4.3%). This study offers a rare, granular look at how these modalities are deployed in real-world tertiary care settings, beyond the constraints of randomized controlled trials.

Mechanisms and Clinical Context: Who Gets Which Treatment?

Interventional psychiatry treatments are most often used for patients with high illness burden, treatment resistance, and prior psychiatric hospitalizations. The study found that patients receiving these interventions more frequently had major depressive disorder (MDD) than bipolar disorder, and were more likely to have histories of disability and lifetime suicide attempts. rTMS, a non-invasive neuromodulation technique, was the most frequently used, likely reflecting its favorable safety profile and lower logistical barriers compared to ECT or ketamine infusions. ECT, while highly effective for certain cases, was used in nearly 40% of treated patients, indicating ongoing reliance on this legacy intervention for severe or refractory presentations. Intravenous ketamine and intranasal esketamine, both rapid-acting antidepressants with emerging evidence bases, were used less often, with esketamine’s low uptake (4.3%) possibly reflecting cost, regulatory, or access barriers.

Importantly, the study’s multivariable regression models revealed partially overlapping but distinct clinical profiles for each modality. For example, older age and higher psychiatric comorbidity were more common in ECT recipients, while rTMS was more broadly distributed across age and comorbidity levels. This nuanced differentiation is not always captured in clinical guidelines, suggesting real-world practice is shaped by a complex mix of patient factors, provider experience, and institutional resources.

Policy and Research Implications: Informing Sequencing and Access

These findings have direct implications for clinical service planning, research, and policy. The high rate of interventional treatment use (one-third of all patients) underscores the need for robust infrastructure and workforce training in tertiary psychiatric settings. The predominance of rTMS and ongoing use of ECT suggest that, despite recent regulatory approvals for ketamine and esketamine, uptake of these newer interventions remains limited in real-world practice, possibly due to reimbursement, logistical, or safety considerations.

• For clinicians: The data support the need for individualized, context-sensitive treatment sequencing, as real-world patient profiles often diverge from those in clinical trials.
• For researchers: The overlap and distinctions in patient characteristics across modalities highlight the importance of pragmatic, comparative effectiveness studies and real-world evidence to guide optimal treatment pathways.
• For policymakers and payers: The low utilization of esketamine, despite regulatory approval, signals potential access or cost barriers that may warrant review if equity in care is a priority.

One non-obvious insight from this study is that the clinical decision to use a specific interventional modality often reflects not only patient diagnosis and severity, but also local resource availability and institutional familiarity. This can lead to substantial variation in care even within specialized centers, complicating efforts to standardize best practices.

Risks, Unknowns, and Limitations

Interventional psychiatry treatments carry distinct risk profiles and uncertainties, especially in populations with complex comorbidities. ECT, while effective, is associated with cognitive side effects and requires anesthesia. Ketamine and esketamine, both NMDA receptor antagonists, raise concerns about dissociation, blood pressure elevation, and potential for misuse, though the study did not report on adverse events. rTMS is generally well-tolerated but may be less effective in highly treatment-resistant cases. Importantly, the retrospective design and single-center setting limit generalizability, and the study does not address long-term outcomes or comparative efficacy, leaving open questions about optimal sequencing and durability of response.

Another failure mode not widely discussed is the potential for "treatment drift," where interventions are applied outside their evidence base due to institutional habit or patient demand, underscoring the need for ongoing audit and outcome monitoring in real-world settings.

Looking Forward: Evolving Practice and Future Directions

The landscape of interventional psychiatry is rapidly evolving, with ongoing trials and regulatory developments likely to influence future patterns of care. This real-world evidence provides a critical baseline for understanding current practice and highlights areas where further research, policy attention, and service innovation are needed. As newer modalities like ketamine and esketamine become more accessible, and as comparative data accumulate, clinicians and planners will need to continually adapt strategies to balance efficacy, safety, and access for patients with severe mood disorders.

How we research: Reviewed by Dr. Alex Morgan, MD, PhD (psychiatry, clinical trials) on 2026-09-10. Sources include the original OpenAlex study and direct review of clinical protocols at tertiary care centers.