Improving Psychiatric Interventions at the End of Life -
Project Summary / Abstract:
Introduction: This is a proposal to continue a career development program for the 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 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 work have provided initial evidence for the
safety and efficacy of methylphenidate for rapidly treating depression in hospice settings. A
mentoring team continuing to be led by Dilip Jeste and Charles von Gunten will guide the
development of the candidate in the transformation from a successful basic scientist to an
independent 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 RO1 funding in a new and critically
important area, psychiatric hospice and palliative 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. citalopram monotherapy was 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 hypothesized
that treatment with methylphenidate would both: 1) Reduce the severity of depressive
symptoms and 2) Induce a response of major depressive episodes significantly faster than
citalopram. Methods: A 28-day double-blind, comparator controlled, flexible dose trial of
methylphenidate monotherapy vs. citalopram monotherapy investigating the safety, tolerability,
efficacy, and time to efficacy for the treatment of major depression in patients receiving hospice
care was conducted. Doses were titrated to tolerable effects or side-effects in the first fifteen
days. Patients remained on the final stable dose for the remainder of the study. As noted in the
progress reports, this trial was a useful tool for training about clinical trial issues; however, the
trial itself was cancelled due to lack of enrollment. Several other studies have been completed
investigating ketamine for the rapid treatment of depression in hospice patients, as well as
studies 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 who
are investigators. Continued funding of this proposal will give me the rest of the experience
necessary to improve the science of recognizing and treating psychiatric issues at the end-of-life
and become and independent investigator. Effective treatments have significant relevance for
patients, their loved ones, and caregivers. Under this award, several studies have been
completed looking at various psychiatric issues affecting those in hospice care, including two
investigating the use of ketamine for the rapid treatment of depression in hospice patients. The
results of these investigations will now be used for the remainder of this award to design and
pilot larger-scale randomized controlled studies of patients with serious advanced illnesses
receiving pre-hospice (palliative) care.
