Abstract
Objective: Treatment-resistant depression (TRD) affects one-third of patients with major depressive disorder, leading to increased morbidity, health care costs, and suicide risk. TRD lacks a standardized definition, complicating treatment selection. Current guidelines often group treatments broadly without clear prioritization, and evidence gaps persist, particularly regarding newer interventions and real-world clinical complexity. A simulated case-based discussion, modeling a modified Delphi consensus, was conducted to offer a clinical perspective to this gap.
Participants: A panel of 10 psychiatrists, directly engaged in the treatment of TRD at the Mayo Clinic Depression Center, participated in the surveys.
Evidence: Results represent expert opinion from participants. The process included an initial group review of TRD, where participants reviewed and presented a summary on each TRD treatment option, followed by discussion.
Process: Using a structured clinical vignette of a patient with TRD after 3 antidepressant trials, statements regarding next-step treatments were created through iterative ranking of options. Six vignette variations reflecting common clinical considerations (eg, metabolic disease, age) were included. Agreement was measured in 3 anonymous survey rounds, with group discussions in between.
Conclusions: Strong consensus emerged recommending augmentation with second-generation antipsychotics, transcranial magnetic stimulation, and ketamine/ esketamine as next-step treatments in the base vignette. Treatment preferences shifted to include nonaugmentative antidepressants and electroconvulsive therapy based on changes in patient characteristics. This study highlights the importance of tailoring treatment strategies for TRD to patient factors that extend beyond conventional guideline tiers. Integrating multidisciplinary perspectives and patient preferences holds promise for enhancing therapeutic selection and advancing personalized care in TRD.
J Clin Psychiatry 2026;87(1):25cs16066
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