Introduction: This is a proposal to continue a career development program for the study ofpsychiatric issues and interventions for people near the end-of-life, specifically major depressivedisorders. The public health burden of issues such as depression at the end-of-life is enormous,not only for the patients, but their loved ones. Improved psychiatric care and interventions in thispopulation would improve the lives of over a million people a year, allowing patients and families tobe 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 patientswith only weeks to live. Small studies and our pilot work have provided initial evidence for thesafety and efficacy of methylphenidate for rapidly treating depression in hospice settings. Amentoring team continuing to be led by Dilip Jeste and Charles von Gunten will guide thedevelopment of the candidate in the transformation from a successful basic scientist to anindependent patient oriented researcher and clinical trialist, with a special focus on conductingclinical trials in vulnerable and medically-ill populations. The overall goal is to develop thecandidate into an independent scientist who would obtain RO1 funding in a new and criticallyimportant area, psychiatric hospice and palliative care. This proposal is consistent with theNIMH strategic plan of strengthening the application of mental health interventions in diversecare settings by examining community and intervention delivery approaches , how they mayaffect intervention outcomes, and potentially providing a knowledge base to move evidence-based interventions into practice.
SPECIFIC AIMS : In patients receiving hospice care with acurrent major depressive episode, a 28-day double-blind, comparator controlled, flexible dosetrial of methylphenidate vs. citalopram monotherapy was conducted to assess both: 1) thecomparative efficacy and onset of action, and 2) the comparative safety and tolerability of usingthese medications for treating major depressive episodes in this population. We hypothesizedthat treatment with methylphenidate would both: 1) Reduce the severity of depressivesymptoms and 2) Induce a response of major depressive episodes significantly faster thancitalopram. Methods: A 28-day double-blind, comparator controlled, flexible dose trial ofmethylphenidate monotherapy vs. citalopram monotherapy investigating the safety, tolerability,efficacy, and time to efficacy for the treatment of major depression in patients receiving hospicecare was conducted. Doses were titrated to tolerable effects or side-effects in the first fifteendays. Patients remained on the final stable dose for the remainder of the study. As noted in theprogress reports, this trial was a useful tool for training about clinical trial issues; however, thetrial itself was cancelled due to lack of enrollment. Several other studies have been completedinvestigating ketamine for the rapid treatment of depression in hospice patients, as well asstudies of cognitive impairments, hospice caregiver stress, and suicide in hospice patients.Conclusions: There are very few psychiatrists working in end-of-life care, and even fewer whoare investigators. Continued funding of this proposal will give me the rest of the experiencenecessary to improve the science of recognizing and treating psychiatric issues at the end-of-lifeand become and independent investigator. Effective treatments have significant relevance forpatients, their loved ones, and caregivers. Under this award, several studies have beencompleted looking at various psychiatric issues affecting those in hospice care, including twoinvestigating the use of ketamine for the rapid treatment of depression in hospice patients. Theresults of these investigations will now be used for the remainder of this award to design andpilot larger-scale randomized controlled studies of patients with serious advanced illnessesreceiving pre-hospice (palliative) care.

Public Health Relevance

The goal of this proposal is to train me to become a clinical trialist and an independentinvestigator to improve help upon current psychopharmacological treatments for depression andother psychiatric issues in patients with advanced illness. Depression in these patients is highlyprevalent; and the current evidence-based interventions for depression do not work fast enoughor frequently enough for patients with limited prognoses. During this proposal and to serve theaim of my career development; several studies were conducted; including a 28-day double-blind; comparator controlled; flexible dose trial of methylphenidate vs. citalopram monotherapywas attempted to assess: 1) the comparative efficacy and onset of action of methylphenidatevs. citalopram for treating major depressive episodes; and 2) the comparative safety andtolerability of using methylphenidate vs. citalopram; in patients with serious and advancedmedical illnesses; such as cancer.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
Application #
Study Section
Interventions Committee for Adult Disorders (ITVA)
Program Officer
Hill, Lauren D
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Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Diego
Schools of Medicine
La Jolla
United States
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Mausbach, Brent T; Irwin, Scott A (2017) Depression and healthcare service utilization in patients with cancer. Psychooncology 26:1133-1139
Montross-Thomas, Lori P; Scheiber, Caroline; Meier, Emily A et al. (2016) Personally Meaningful Rituals: A Way to Increase Compassion and Decrease Burnout among Hospice Staff and Volunteers. J Palliat Med 19:1043-1050
Mausbach, Brent T; Schwab, Richard B; Irwin, Scott A (2015) Depression as a predictor of adherence to adjuvant endocrine therapy (AET) in women with breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat 152:239-46
Iglewicz, Alana; Morrison, Katherine; Nelesen, Richard A et al. (2015) Ketamine for the treatment of depression in patients receiving hospice care: a retrospective medical record review of thirty-one cases. Psychosomatics 56:329-37
Montross-Thomas, Lori P; Irwin, Scott A; Meier, Emily A et al. (2015) Enhancing legacy in palliative care: study protocol for a randomized controlled trial of Dignity Therapy focused on positive outcomes. BMC Palliat Care 14:44
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
Farokhpay, Reza; Thomas, Lori P Montross; Meier, Emily A et al. (2014) Self-reflections on mortality among hospice patients? J Palliat Med 17:879
Pottie, Colin G; Burch, Karen A; Thomas, Lori P Montross et al. (2014) Informal caregiving of hospice patients. J Palliat Med 17:845-56
Fairman, Nathan; Thomas, Lori P Montross; Whitmore, Stephanie et al. (2014) What did I miss? A qualitative assessment of the impact of patient suicide on hospice clinical staff. J Palliat Med 17:832-6
Montross, Lori P; Meier, Emily A; De Cervantes-Monteith, Kelly et al. (2013) Hospice staff perspectives on Dignity Therapy. J Palliat Med 16:1118-20

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