Clinical Management of Treatment Resistant
Depression
Rosemary Payne, M.S.N.
Senior Supervisory Nurse Manager
Clinical Center
National Institute of Health
Lawrence Park, M.D.
Medical Director
Experimental Therapeutics & Pathophysiology Branch (ETPB)
National Institute of Mental Health
Outline
• NIH-CC Model of Care
Rosemary Payne, MSN
–
–
–
–
Mission
Dimensions of Practice
Nursing Demographics
Research Participation
• Treatment of TRD
Lawrence Park, MD
–
–
–
–
–
Depression Statistics
TRD
Treatment Algorithm
Alternative Treatments
Investigative Treatments
NIH-CC – Clinical Research Nurse (CRN)
Model of Care
• Clinical Nursing Research Leadership– Sr. Supervisory Nurse – Nurse Manager
– Team Leader – Clinical Manager
• Clinical Research Team– Protocol Coordinator
– Primary Nurse
– Associate Nurse
• Clinical Research Support–
–
–
–
Clinical Research Nurse – per diem
Patient Care Technician
Behavioral Health Technician
Research Support Assistant – Unit Clerk
Mission/Vision of NIH-CC-CRN Team
Mission
•
•
•
Provided clinical care for patients participating in clinical research studies conducted by
investigators within the Intramural Research Program at the National Institutes of
Health.
As integral research team members, we provide support for the design, coordination,
implementation and dissemination of clinical research by NIH investigators, with a focus
on patient safety, continuity of care and informed participation.
We are also committed to supporting the NIH effort to train the next generation of
clinical researchers and provide national leadership for the clinical research enterprise.
Vision
•
•
•
The Clinical Center leads the Nation in developing a specialty practice model for Clinical
Research Nursing.
This model will define the roles and contributions of nurses who practice within the
clinical research enterprise, as they provide care to research participants and support
accurate, reliable and ethical study implementation.
We will also develop and disseminate practice documents, standards and management
tools for implementing clinical research nursing across a wide continuum of practice
settings.
The Art/Science of
Clinical Research Nursing
Dimensions of Practice
Study
Management
Clinical
Practice
Care
Coordination
and
Continuity
Human
Subjects
Protection
Contribution
to the Science
Clinical Research Nurse Demographics
• Education Preparation
– Inpatient – 70% Bachelor of Science or higher
– Outpatient – 88% Bachelor of Science or higher
• Years of Clinical Research Nurse Experience
– Inpatient – 7 to 30 years
– Outpatient – 5 to 35 years
• Multi-cultural and inclusionary
• Specialty and advance practice
Research Participant
• Individualized research and nursing plan of
care.
• Interdisciplinary team approach to research,
stabilization and reintegration.
• Collaboration and/or referral to community
providers and supports.
• Structured community outings and access to
other ancillary support services (social workers,
recreational/rehabilitation therapists,
nutritionists, pharmacists and chaplains)
Research Subject Demographics
•
•
•
•
Local – Maryland/DC/Virginia
National geography
Ages 18-65, based on eligibility
Multicultural and diverse
Acknowledgements
•
•
•
•
John Gallin, MD – Clinical Center Director
Clare Hastings, PhD, Chief Nursing Officer
Barbara Jordan, PhD, Service Chief – NBHP
Rosemary Payne, MSN, Sr. Supervisory
Nurse Manager
• Victoria Liberty, BSN, Clinical Manager
• Roger Brenholtz, MSN, Clinical Manager
• Brenda Justement, MSN, Clinical Manager
Depression: The Need for Improved Treatments
Depression: Adverse Effects
• Disruption to
Problems with Current Antidepressants:
•
•
Low remission rates
Questionable efficacy in bipolar
depression
Lag of onset of antidepressant effects
personal,
family, and social life
• Occupational
•
impairment
• Risk of suicidal
behavior
Next generation antidepressant
Rapid onset: Hours/day
Euthymic
Lag of onset:
10-14 weeks
Standard antidepressant
(Monoaminergic)
Depressed
Major Depressive Episode
Initiate Treatment
Courtesy of Carlos Zarate Jr, MD
Lessons from STAR*D
Treatment Algorithms
Treatment Resistant Depression
Trivedi et al. (Am J Psychiatry, 2006); Rush et al. (NEJM, 2006)
STEP-BD
Study 1. Acute Phase BP Depression
• Discontinuation rate
– 34% both groups
• Remission transient
~15% both group
• Durable recovery (8w)
– 24% active
– 27% placebo
• TEAS rate (switching)
– 10% active
– 11% placebo
From: Thase ME. STEP-BD and Bipolar Depression: What Have
We Learned? Current Psychiatry Reports. 2007,9:497-503.
Augmentation Strategies
Augmentation
Evidence Added $
Rating* Monthly
lithium 900 mg (to TCA)
A
2
T3 25 ug (to TCA)
A
3
mirtazapine 15 mg
A/B
18
buspirone 40 mg
B
4
Wellbutrin SR 300 mg
B
42
Zyprexa 10 mg
B
172
Provigil 200 mg
B/C
110
nortriptyline 100 mg
C
2
pindolol 10 mg
C
2
lithium 900 mg (to SSRI)
C
2
T3 25 ug (to SSRI)
C
3
Effexor XR 150 mg
C
54
other atypicals
C
70-158
*Thase ME.
CNS Spectrums
2004;9(11):808821.(updated)
A= >1 RCTs
B= 1 RCT, plus c
C= Case series,
anecdotal report,
expert opinion
D= Anecdotal
reports but
experts have not
endorsed
Electroconvulsive Therapy (ECT)
• Oldest, most effective
treatment for depression
• Mechanism of action
unknown
• Seizure a necessary
component of treatment
• General anesthesia
required
• Confusion/memory loss
potential side effects
• Relapse a major issue
NeuroStar TMS
O’Reardon JP et al. Efficacy and Safety of TMS in the Acute Treatment of Major Depression: A Multisite RCT. Biol
Psychiatry 2007:62:1208-16
Other Pharmacological Strategies
• New Antidepressants
– Vortioxetine
– Levomilnacipran
– Vilazodone
• Atypical Antipsychotic Augmentation
– Olanzapine (UP, with fluoxetine)
– Quetiapine (UP adjunctive)
– Aripiprazole (UP adjunctive)
– Lurasidone (BP monotherapy/adjunctive)
Investigational Treatments
Ketamine (NMDA Antagonists)
Courtesy of Carlos Zarate Jr, MD
30
HAMD Following a Single
Ketamine Infusion
Response: 50% decrease in HAMD
80
% Participants Responding
Hamilton Depression Rating Scale (HAMD)
Rapid Antidepressant Effect of Ketamine in
Unmedicated Treatment Resistant MDD (n=18)
25
20
15
10
5
*
** **
Placebo
Ketamine
***
***
***
0
70
Monoaminergic
Antidepressant
71%
62-65%
60
53%
50
40
35%
56%
58%
53%
35%
30
20
13%
10
0
-60 40 80 110 230 Day Day Day Day
1 2
7
3
Minutes
Zarate et al. Arch Gen Psychiatry 2006
Courtesy of Carlos Zarate Jr, MD
Time
40
80 110 230 Day Day Day Day
7
2
3
1
Minutes
8
Weeks
***p<0.001, **p<0.01, *p<0.05
Rapid Antidepressant Effect of Ketamine in
Treatment Resistant Bipolar (BP) Depression
First BP Study of Ketamine (n=18)
Ketamine
Placebo
MADRS
40
40
35
35
30
30
25
25
20
15
20
*** *** *** *** *** *** ***
15
*** ***
***
***
***
***
*
10
10
5
Replication BP study (n=15)
-60 40 80 110 230 DayDay Day Day Day Day
1 2 3 7 10 14
0
Minutes
0
Time
Diazgranados et al. Arch Gen Psych 2010
Courtesy of Carlos Zarate Jr, MD
5
-60 40 80 110 230 DayDay Day Day Day Day
1 2 3 7 10 14
Minutes
Zarate et al. Biol Psych 2012
***p<0.001, **p<0.01, *p<0.05
Acknowledgement
Research Subjects and their families
NIMH/ETBP Staff
Extramural Collaborations
Carlos Zarate
R. Machado-Vieira
Allison Nugent
Maura Furey
Min Park
Mark Niciu
Erica Richards
Jenny Vande Voort
Tyler Ard
Elizabeth Ballard
Wally Duncan
Niall Lally
Immaculata Ukoh
Rezvan Ameli
Nancy Brutsche
Intramural Research Program, NIMH
Office of the Clinical Director, NIMH
7SE, OP4, 7SW, NCF staff
MEG/MRI/MRS/PET/SSCC Cores
Todd Gould, Robert Schwartz (MD
Psych Rsrch)
Vistagen Therapeutics
Rima Kaddurah-Daouk (Duke
University)
Gustavo Turecki (McGill University)
Per Svenningsson (Karolinska
Institutet)
Paul Greengard (Rockefeller
University)
Brian Roth (University of North
Carolina)
Michael Perlis,Philip Gehrman,David
Dinges (UPenn)
RAPID Fast-Fail Trials
Thank You!
Rosemary Payne, MSN
rosemary.payne@nih.gov
Lawrence Park, MD
lawrence.park@nih.gov
Kalene Dehaut, MSW
Social Worker/Outreach Recruiter
Office of the Clinical Director, NIMH
kalene.dehaut@nih.gov