CUMMING SCHOOL OF MEDICINE
Departments of Clinical Neurosciences & Psychiatry
Deep Brain Stimulation
For Treatment Resistant Depression
Sandra Golding on behalf of Drs. Zelma Kiss &
Raj Ramasubbu & the AIHS CRIO-DBS Team
October 23, 2014
Depression: Background
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What is DBS?
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What is DBS?
 DBS has revolutionized the treatment of movement
disorders:
— Essential tremor (1987)
— Parkinson’s disease (1993)
— Dystonia (1997)
— Is approved to treat epilepsy in Canada (2012)
 DBS is under investigation for:
— OCD, depression, Tourette’s & other psychiatric conditions
— Eating disorders: anorexia nervosa, obesity
— Drug-addiction
— Other neurologic conditions
— Restoration of motor & sensory impairments: stroke
rehabilitation
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Advantages of DBS
MEDICATION
DEEP BRAIN STIMULATION
All of brain-body exposed to drug
Local effect
More side effects
Fewer side effects
Continuously on
Individualized stimulation
Costly
Economic over the long term
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Advantages of DBS
— Can be tested in a RCT double blind manner
— Can be switched on and off
— Can be coupled with functional neuroimaging
— Can record activity from implanted DBS leads while they
patient performs emotional cognitive or motor tasks
— We have some idea about potential mechanisms of action
— Reversible
— Stimulation dose can be adjusted
— No cognitive side effects. No personality changes
• from Krack et al, TINS 2010
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Advantages of DBS
ELECTROCONVULSIVE THERAPY (ECT)
DEEP BRAIN STIMULATION (DBS)
Cognitive side effects possible
No cognitive side effects
Needs general anaesthesia
Patient awake—local anaesthesia only
Expensive in the long run
Economic over the long run
Most people do not return to work
Most people do return to work
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SGC-DBS Studies
 Toronto study (Mayberg, Lozano, Kennedy) N=20
 Canadian multicentre study (2011) N=21
 Emory (USA) study (Holtzheimer, Mayberg, 2012)
N=10
 Spanish study (Puigdemone et al 2011) N=10
 Calgary study (Ramasubbu et al 2013) N=4
 German study (Merkel et al 2013) N=6
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Canadian 3 Centre Study Outcomes
 Significant reductions in depressive symptomatology
(reduction in the baseline HRSD-17 of 40% or more) in
62% of patients (29% response rate when defined as 50%
reduction in HDRS-17)
 Employment rate increased to 65% by year 1 & onward
 2 patients completed suicide (10%)
 2 patients attempted suicide (10%)
 6 patients hospitalized for worsening depression
 3 patients had hardware infections
 Battery replacement surgeries every 3-4 years
 No decline in memory/neuropsychology measures
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Calgary Pilot Study Outcomes
 Stimulus Optimization (first 12 weeks)
— Longer pulse widths showed 50% reduction on HAM-D
scores & increased positive affect
 Post-Optimization Phase
— 2/4 patients responded with 50% reduction in HAM-D
scores at week 36
— ¼ responded partially with 30% reduction in HAM-D score
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AIHS-CRIO Study
Clinical study:
Objectives/Hypothesis
Longer pulse width is
better than short pulse
width
PW
Add-on CBT will improve
clinical and functional
amplitude
outcome
Neural markers will predict
DBS responders & nonresponders
Stimulus pulses
+
0
-
Animal study:
Power = I2/R = (amp x freq x pw)2
Objectives/Hypothesis
Time of
1 cycle
Mechanisms of long pulse
(1/frequency)
R
width stimulation
ZHTKiss 2006
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AIHS-CRIO Study
 Inclusion Criteria:
— Unipolar recurrent, & bipolar MDD
— Failure of 4 medication treatments including augmentation
and combination
— ECT failure or requiring maintenance ECT (possibly)
— Psychotherapy failure
— Ages 20 - 60
 Exclusion Criteria:
— Psychosis, PTSD, OCD, Neurological disorders, severe
unstable medical conditions (heart, renal, liver failure),
Cardiac pace maker
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AIHS-CRIO Study Plan
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Surgery
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Surgery
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AIHS-CRIO Study Plan
 Assessments
— fMRI scan at baseline
— PET scan at baseline & 6 months
— Blood work for biomarkers at baseline & every 3 months
— Neuropsychological testing at baseline & 6 months
— MRI pre-surgery & 1 day post op
— CT scan at 3 months
— Monthly psychiatric assessments (16) including HAM-D,
HAM-A, MADRS, CGI, PANAS, CTQ
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Contact Information
 http://www.ucalgary.ca/dbs4depression/
 Research Coordinator
— Sandra Golding, BN RN MScHA
 403-210-6905
 sgolding@ucalgary.ca
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Collaborative Team Members

Collaborative Leads
— Rajamannar Ramasubbu MD, U of C
— Zelma Kiss MD PhD, U of C

Collaborative Members
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Aaron Mackie MD, U of C
Bradley Goodyear PhD, U of C
Catherine Lebel PhD, U of C
Christine Molnar, MD, U of C
Christopher Butson PhD, University of Utah
David Gobbi, Private Sector
Glenda MacQueen MD, U of C
Helen Mayberg MD, Emory University
Kartikeya Murari, PhD, U of C
Keith Dobson, PhD, U of C
Matthew Hill, PhD, U of C
Misha Eliasziw, PhD, Tufts University
Richard Frayne MD, U of C
Yves Starreveld, MD, U of C
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Current Calgary Study Outcomes
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Thank You
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