Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM): Study Design and Treatment Characteristics of the First 396 Participants Randomized

Objective: Evidence from clinical trials comparing effectiveness and safety of pharmacological strategies in older adults unresponsive to first-line antidepressants is limited. The study, Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM), tests three hypotheses concerning pharmacotherapy strategies for treatment-resistant late-life depression: 1) augmentation strategies will provide greater improvement than switching monotherapies; 2) augmentation strategies will have lower tolerability and more safety concerns than switching monotherapies; and 3) age will moderate the effectiveness and safety differences between treatment strategies. The authors describe the methodology, processes for stakeholder engagement, challenges, and lessons learned in the early phases of OPTIMUM. Methods: This pragmatic randomized clinical trial located in five North American regions will enroll 1,500 participants aged 60 years and older unresponsive to two or more antidepressant trials. The authors evaluate two strategies (medication augmentation versus switch) using four medications (aripiprazole, bupropion, lithium, and nortriptyline) via a stepwise, prespecified protocol. Primary outcomes include: 1) symptom remission (Montgomery Asberg Depression scale <= 10); 2) psychological well-being, comprising positive affect, general life satisfaction, and purpose; and 3) safety (rates of serious adverse events and prevalence of falls and fall-related injuries). Results: To date, 396 participants have been randomized. The authors report on four challenges: 1) engagement and recruitment; 2) increasing polypharmacy in older adults, resulting in potentially hazardous scenarios; 3) reporting adverse events and procedure standardization across sites; and 4) dissemination of results. Conclusion: Solutions to these challenges, including early inclusion of stake holders, will inform future pragmatic studies in older adults with depression.