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Clinical Management of Treatment Resistant Depression
Rosemary Payne, M.S.N.Senior Supervisory Nurse Manager
Clinical CenterNational 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 TRDLawrence 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 TeamMission• 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
Clinical Practice
Care Coordination
and Continuity
Contribution to the Science
Human Subjects
Protection
Study Management
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
Euthymic
Depressed
Next generation antidepressant
Lag of onset:10-14 weeks
Rapid onset: Hours/day
• Disruption to personal, family, and social life• Occupational impairment• Risk of suicidal behavior
Depression: Adverse Effects Problems with Current Antidepressants:
• Low remission rates• Questionable efficacy in bipolar
depression• Lag of onset of antidepressant effects
Standard antidepressant(Monoaminergic)
Major Depressive Episode
Initiate Treatment
Depression: The Need for Improved Treatments
Courtesy of Carlos Zarate Jr, MD
Lessons from STAR*DTreatment Algorithms
Treatment Resistant Depression
Trivedi et al. (Am J Psychiatry, 2006); Rush et al. (NEJM, 2006)
STEP-BDStudy 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 StrategiesAugmentation Evidence
Rating*Added $ Monthly
lithium 900 mg (to TCA) A 2T3 25 ug (to TCA) A 3mirtazapine 15 mg A/B 18buspirone 40 mg B 4Wellbutrin SR 300 mg B 42Zyprexa 10 mg B 172Provigil 200 mg B/C 110nortriptyline 100 mg C 2pindolol 10 mg C 2lithium 900 mg (to SSRI) C 2T3 25 ug (to SSRI) C 3Effexor XR 150 mg C 54other atypicals C 70-158
*Thase ME. CNS Spectrums 2004;9(11):808-821.(updated)
A= >1 RCTsB= 1 RCT, plus cC= Case series, anecdotal report, expert opinionD= 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 TreatmentsKetamine (NMDA Antagonists)
Courtesy of Carlos Zarate Jr, MD
Rapid Antidepressant Effect of Ketamine in Unmedicated Treatment Resistant MDD (n=18)
Zarate et al. Arch Gen Psychiatry 2006
0
5
10
15
20
25
30
PlaceboKetamine
-60 80 23011040 Day1
Day3
Day2
Day7
Time
*
** ********
***
0
10
20
30
40
50
60
70
80
80 23011040 Day3
Day2
Day7
8Weeks
13%
71%
53%58%56%
35%
53%
62-65%
35%
Response: 50% decrease in HAMDHAMD Following a Single Ketamine Infusion
Ham
ilto
n D
epre
ssio
n R
atin
g S
cale
(H
AM
D)
% P
arti
cip
ants
Res
po
nd
ing Monoaminergic
Antidepressant
Day1
***p<0.001, **p<0.01, *p<0.05
MinutesMinutes
Courtesy of Carlos Zarate Jr, MD
Rapid Antidepressant Effect of Ketamine in Treatment Resistant Bipolar (BP) Depression
Diazgranados et al. Arch Gen Psych 2010 Zarate et al. Biol Psych 2012
Replication BP study (n=15)First BP Study of Ketamine (n=18)
0
5
10
15
20
25
30
35
MA
DR
S
-60 80 23011040 Day1
Day3
Day2
Day7
Day10
Day14 0
5
10
15
20
25
30
35
40
****** *** ******
****
-60 80 23011040 Day1
Day3
Day2
Day7
Day10
Day14
****** ************ ***
Time
KetaminePlacebo
***p<0.001, **p<0.01, *p<0.05
MinutesMinutes
Courtesy of Carlos Zarate Jr, MD
Acknowledgement
NIMH/ETBP StaffCarlos ZarateR. Machado-VieiraAllison NugentMaura FureyMin ParkMark NiciuErica RichardsJenny Vande VoortTyler ArdElizabeth BallardWally DuncanNiall LallyImmaculata UkohRezvan AmeliNancy BrutscheIntramural Research Program, NIMHOffice of the Clinical Director, NIMH7SE, OP4, 7SW, NCF staffMEG/MRI/MRS/PET/SSCC Cores
Extramural CollaborationsTodd Gould, Robert Schwartz (MD Psych Rsrch)Vistagen TherapeuticsRima 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
Research Subjects and their families
Thank You!
Rosemary Payne, [email protected]
Lawrence Park, [email protected]
Kalene Dehaut, MSWSocial Worker/Outreach Recruiter
Office of the Clinical Director, NIMH