Commentary: Treatment-resistant Depression: Considerations Related to ECT and Ketamine

Treatment-resistant depression (TRD) may be responsive to interventions beyond antidepressants including brain stimulation such as electroconvulsive therapy (ECT) or to ketamine or esketamine, the latter of which is approved for TRD in an intranasal form. The 3 cases presented in this issue deal with an array of clinical considerations in treating patients with TRD, including the use of ECT in a patient with a history of liver transplantation, the use of heated yoga in a patient nonresponsive to ECT, and intranasal ketamine abuse in a patient with comorbid migraines. Gunther and colleagues described the case of a 73-year-old man who presented with a major depressive episode with psychotic features not responsive to medications 26 years after liver transplantation. Despite his past transplant and antirejection medications, the patient was cleared for ECT and received 9 bitemporal treatments with good response. Sakurai and colleagues reported the case of a 28-year-old woman with chronic TRD and multiple previous ECT treatments who had only a partial response to several antidepressants and maintenance ECT. She was evaluated and treated with a course of twice-weekly 90-minute heated yoga and experienced a remission of her depression. Finally, Rivas-Grajales and colleagues described a 52-year-old woman with recurrent TRD and chronic migraines who was receiving 2 antidepressants and migraine medication, who presented emergently with agitation and paranoia in the context of receiving intranasal ketamine from multiple providers, suggesting a pattern of misuse. Her symptoms abated despite her refusal of prescribed antipsychotics. These 3 cases highlight different challenges and complexities in treating patients with TRD. While ECT remains safe and effective, even in cases of organ transplantation, there is potential for the development of nonpharmacologic adjunctive treatments, such as heated yoga (which is under randomized study). And while eskatamine is an approved treatment for TRD, screening and ongoing monitoring is important to prevent misuse or abuse.