Pilar Cristancho1, Emily Lenard2, Eric J Lenze2, J Philip Miller3, Patrick J Brown4, Steven P Roose4, Carolina Montes-Garcia4, Daniel M Blumberger5, Benoit H Mulsant5, Helen Lavretsky6, Bruce L Rollman7, Charles F Reynolds8, Jordan F Karp8. 1. Department of Psychiatry (PC, EL, EJL), Healthy Mind Lab, School of Medicine, Washington University in St. Louis, St. Louis. Electronic address: cristanchopimiento.l@psychiatry.wustl.edu. 2. Department of Psychiatry (PC, EL, EJL), Healthy Mind Lab, School of Medicine, Washington University in St. Louis, St. Louis. 3. the Division of Biostatistics (JPM), School of Medicine, Washington University in St. Louis, St. Louis. 4. the Department of Geriatric Psychiatry (PJB, SPR, CMG), Program on Healthy Aging and Late Life Brain Disorders, New York State Psychiatric Institute, Columbia University Medical Center, New York. 5. the Centre for Addiction and Mental Health and Department of Psychiatry (DMB, BHM), University of Toronto, Toronto. 6. the Semel Institute for Neuroscience and Human Behavior (HL), University of California, Los Angeles. 7. the Department of Medicine and Center for Behavioral Health and Smart Technology (BLR), University of Pittsburgh School of Medicine, Pittsburgh. 8. the Department of Psychiatry (CFR, JFK), University of Pittsburgh School of Medicine, Pittsburgh.
Abstract
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.
RCT Entities:
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.
Authors: Luis Agüera-Ortiz; María Dolores Claver-Martín; María Dolores Franco-Fernández; Jorge López-Álvarez; Manuel Martín-Carrasco; María Isabel Ramos-García; Manuel Sánchez-Pérez Journal: Front Psychiatry Date: 2020-05-20 Impact factor: 4.157
Authors: Joanna Abraham; Katherine J Holzer; Emily M Lenard; Kenneth E Freedland; Bethany R Tellor Pennington; Rachel C Wolfe; Theresa A Cordner; Ana A Baumann; Mary Politi; Michael Simon Avidan; Eric Lenze Journal: BMJ Open Date: 2022-08-23 Impact factor: 3.006