DURABILITY OUTCOMES IN TREATMENT RESISTANT DEPRESSION

In major depressive disorder, treatment resistance is associated with reduced probability of achieving short-term benefit from sequential antidepressant interventions and increased probability of relapse if short-term benefit is achieved. This workshop will review existing data and present new findings regarding the durability of benefit of 4 novel interventions for treatment-resistant depression (TRD): transcranial magnetic stimulation (TMS), (es)ketamine (KET), vagus nerve stimulation (VNS) and psychedelics. Dr. Wilson will review existing data on the durability of benefit following response to TMS including new information on frequency, timing and retreatment outcomes in patients who relapsed after responding or remitting in their index TMS course. Dr. Rosenblat will review evidence on the durability of antidepressant response to KET, both with KET discontinuation and as a maintenance strategy. He will present new findings from an extensive database from his program. Dr. Conway will review evidence regarding durability of benefit with VNS and present new findings from the RECOVER trial on clinical outcomes after 2 years of active VNS plus treatment as usual. The findings address durability and late emergence of benefit for symptom severity, daily function, and quality-of-life outcomes. Dr. Suppes will address recent findings for durability of response to psychedelics with a focus on her study in Veterans. To our knowledge, the durability of benefit of treatments for TRD has never been the topic of a scientific symposium at any meeting. Indeed, much attention has focused on the impact of these interventions on the likelihood of short-term response and remission, despite the fact that treatment resistance is strongly linked to risk of relapse. This symposium will address a critical clinical challenge and populationbased need, namely optimal long-term care in TRD. By addressing the timing and predictors of relapse/recurrence, this symposium will have implications for mechanistic issues regarding neuroplastic processes that may contribute to sustained benefit.

Learning Objective 1: Participants will be able to identify best practices to capture durability outcomes in treatment resistant depression.

Learning Objective 2: Participants will be able to cite three reasons why durability is key to adopting novel interventions in treatment resistant depression.

References

Conway CR, Rush AJ, Gordon C, Preskorn SH, Sackeim HA, Aaronson ST, McIntyre RS, Lee YL, Shy O, Tran Q, Way J, Bunker MT. An examination of symptoms, function and quality of life as conjoint clinical outcome domains for treatmentresistant depression. J Mood Anxiety Disord. 2025 Apr 14;10:100121. doi: 10.1016/j.xjmad.2025.100121. PMID: 40657595; PMCID: PMC12243987. Ellis S, Bostian C, Donnelly A, Feng W, Eisen K, Lean M, Conlan E, Ostacher M, Aaronson S, Suppes T. Long-term outcomes of single-dose psilocybin for U.S. military Veterans with severe treatment-resistant depression - 12-month data from an open-label pilot study. J Affect Disord. 2025 Nov 15;389:119655. doi: 10.1016/j.jad.2025.119655. Epub 2025 Jun 9. PMID: 40499827.