Deep Brain StimulationFor Treatment Resistant Depression

Sandra Golding on behalf of Drs. Zelma Kiss & Raj Ramasubbu & the AIHS CRIO-DBS Team October 23, 2014

CUMMING SCHOOL OF MEDICINEDepartments of Clinical Neurosciences & Psychiatry

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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

Stimulus pulses

ZHTKiss 2006

PW

Time of 1 cycle (1/frequency)

0

+

-

amplitude

Power = I2/R = (amp x freq x pw)2

R

Clinical study: Objectives/ Hypothesis

Longer pulse width is better than short pulse widthAdd-on CBT will improve clinical and functional outcomeNeural markers will predict DBS responders & non-responders

Animal study: Objectives/ Hypothesis

Mechanisms of long pulse width stimulation

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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— 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