This is a proposal for a career development program preparing for study of psychiatric issues and interventions for people near the end-of-life, specifically major depressive disorders. The public health burden of issues such as depression at the end-of-life is enormous, not only for the patients, but also their loved ones. Improved psychiatric care and interventions in this population would improve the lives of over a million people a year, allowing patients and families to be engaged in their final hours together, rather than to spend them in misery. Current evidence-based interventions for depression do not work fast enough or frequently enough for patients with only weeks to live. Small studies and our pilot have provided initial evidence for the safety and efficacy of methylphenidate for rapidly treating depression in hospice settings. A mentoring team led by Drs. Dilip Jeste and Charles von Gunten will guide the development of the Candidate in the transformation from a successful basic scientist to a patient-oriented researcher and clinical trialist, with a special focus on conducting clinical trials in vulnerable and medically-ill populations. The overall goal is to develop the candidate into an independent scientist who would obtain R01 funding in a new and critically important area, psychiatric hospice care. This proposal is consistent with the NIMH strategic plan of strengthening the application of mental health interventions in diverse care settings by examining community and intervention delivery approaches, how they may affect intervention outcomes, and potentially providing a knowledge base to move evidence-based interventions into practice.
SPECIFIC AIMS : In patients receiving hospice care with a current major depressive episode, a 28-day double-blind, comparator controlled, flexible dose trial of methylphenidate vs. escitalopram monotherapy will be conducted to assess both: 1) the comparative efficacy and onset of action, and 2) the comparative safety and tolerability of using these medications for treating major depressive episodes in this population. We hypothesize that treatment with methylphenidate will both: 1) Reduce the severity of depressive symptoms and 2) Induce a response of major depressive episodes significantly faster than escitalopram. Methods: A 28-day double-blind, comparator controlled, flexible dose trial of methylphenidate monotherapy vs. escitalopram monotherapy investigating the safety, tolerability, efficacy, and time to efficacy for the treatment of major depression in patients receiving hospice care will be conducted. Dose will be titrated to tolerable effects or side-effects in the first fifteen days. Patients will remain on the final stable dose for the remainder of the study. Conclusions: There are very few psychiatrists working in end-of-life care, and even fewer who are investigators. Funding this proposal will give me the experience necessary to improve the science of recognizing and treating psychiatric issues at the end-of-life. Effective treatments have significant relevance for patients, their loved ones, and caregivers. Should the results of this trial favor use of methylphenidate, the findings will be used to design larger, randomized, multi-site, and controlled trials. The results may also be used to design studies of patients receiving pre-hospice care and/or of caregivers of all three populations.

Public Health Relevance

The goal of this proposal is to train me to become a clinical trialist and improve upon current psychopharmacological treatments for depression in patients receiving hospice care. Depression in patients receiving hospice care is highly prevalent, and the current evidence-based interventions for depression do not work fast enough or frequently enough for patients with only weeks to live. This study proposes a 28-day double-blind, comparator controlled, flexible dose trial of methylphenidate vs. escitalopram monotherapy to assess: 1) the comparative efficacy and onset of action of methylphenidate vs. escitalopram for treating major depressive episodes, and 2) the comparative safety and tolerability of using methylphenidate vs. escitalopram in patients receiving hospice care.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23MH091176-05
Application #
8485678
Study Section
Interventions Committee for Adult Disorders (ITVA)
Program Officer
Hill, Lauren D
Project Start
2013-11-01
Project End
2015-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
5
Fiscal Year
2014
Total Cost
$179,263
Indirect Cost
$13,279
Name
University of California San Diego
Department
Psychiatry
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Thomas, Lori P Montross; Meier, Emily A; Irwin, Scott A (2014) Meaning-centered psychotherapy: a form of psychotherapy for patients with cancer. Curr Psychiatry Rep 16:488
Fairman, Nathan; Irwin, Scott A (2013) Palliative care psychiatry: update on an emerging dimension of psychiatric practice. Curr Psychiatry Rep 15:374
Irwin, Scott A; Pirrello, Rosene D; Hirst, Jeremy M et al. (2013) Clarifying delirium management: practical, evidenced-based, expert recommendations for clinical practice. J Palliat Med 16:423-35
Empeno, Jessica; Raming, Natasha T J; Irwin, Scott A et al. (2013) The impact of additional support services on caregivers of hospice patients and hospice social workers. Omega (Westport) 67:53-61
Irwin, Scott A; Iglewicz, Alana; Nelesen, Richard A et al. (2013) Daily oral ketamine for the treatment of depression and anxiety in patients receiving hospice care: a 28-day open-label proof-of-concept trial. J Palliat Med 16:958-65
Irwin, Scott A; Mausbach, Brent T; Koo, Derek et al. (2013) Association between hospice care and psychological outcomes in Alzheimer's spousal caregivers. J Palliat Med 16:1450-4
Burton, Cynthia Z; Twamley, Elizabeth W; Lee, Lana C et al. (2012) Undetected cognitive impairment and decision-making capacity in patients receiving hospice care. Am J Geriatr Psychiatry 20:306-16
Rao, Sanjai; Ferris, Frank D; Irwin, Scott A (2011) Ease of screening for depression and delirium in patients enrolled in inpatient hospice care. J Palliat Med 14:275-9
Irwin, Scott A; Montross, Lori P; Bhat, Reshma G et al. (2011) Psychiatry resident education in palliative care: opportunities, desired training, and outcomes of a targeted educational intervention. Psychosomatics 52:530-6
Montross, Lori; Winters, Kathryn D; Irwin, Scott A (2011) Dignity therapy implementation in a community-based hospice setting. J Palliat Med 14:729-34

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