Esketamine for Treatment Resistant Depression

In this episode, Dr Anita Clayton and experts discuss long-term results from esketamine trial and their approach to treatment.

Once remission is achieved, panelists stressed that treatment should not simply stop — particularly in TRD, where recurrence is a question of when, not if. Maintenance esketamine, dosed flexibly from weekly to every four weeks, was highlighted through the SUSTAIN3 study, which followed nearly 700 patients over five years and demonstrated sustained and even improving remission rates at week 112. Randomized withdrawal data further confirmed that continuing esketamine plus an antidepressant significantly lengthened time to recurrence compared to an antidepressant alone.

Panelists emphasized that apparent relapse should prompt thorough reassessment of contributing factors — including hormonal changes, cannabis use, emerging metabolic conditions, and new medical diagnoses. One striking case illustrated how pursuing a fatigue complaint in a depressed patient led to a previously undetected diagnosis of chronic lymphocytic leukemia, underscoring that ongoing medical vigilance is irreplaceable.

Psychotherapy was endorsed as an important force multiplier alongside pharmacotherapy, particularly for patients who become hypervigilant to sadness after achieving remission — a phenomenon likened to the anxiety of early cancer survivorship. Panelists agreed that measurement-informed care, close monitoring, and encouraging patients to report early warning signs remain the cornerstones of durable long-term TRD management.

In the next episode, ”Drug-Drug Interactions and Alcohol Use in Treatment Resistant Depression,” panelists discuss the critical but often overlooked impact of drug-drug interactions, CBD, and alcohol use on TRD treatment outcomes, emphasizing non-judgmental, context-driven questioning as essential to uncovering these hidden barriers to recovery.