1. 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 CUMMING SCHOOL OF MEDICINE Departments of Clinical Neurosciences & Psychiatry

2. Depression: Background CUMMING SCHOOL OF MEDICINE

3. What is DBS? CUMMING SCHOOL OF MEDICINE

4. 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 CUMMING SCHOOL OF MEDICINE

5. Advantages of DBS MEDICATIONDEEP BRAIN STIMULATION All of brain-body exposed to drugLocal effect More side effectsFewer side effects Continuously onIndividualized stimulation CostlyEconomic over the long term CUMMING SCHOOL OF MEDICINE

6. 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 CUMMING SCHOOL OF MEDICINE

7. Advantages of DBS ELECTROCONVULSIVE THERAPY (ECT)DEEP BRAIN STIMULATION (DBS) Cognitive side effects possibleNo cognitive side effects Needs general anaesthesiaPatient awake—local anaesthesia only Expensive in the long runEconomic over the long run Most people do not return to workMost people do return to work CUMMING SCHOOL OF MEDICINE

8. 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 CUMMING SCHOOL OF MEDICINE

9. 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 CUMMING SCHOOL OF MEDICINE

10. 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 CUMMING SCHOOL OF MEDICINE

11. AIHS-CRIO Study CUMMING SCHOOL OF MEDICINE

12. 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 CUMMING SCHOOL OF MEDICINE

13. AIHS-CRIO Study Plan CUMMING SCHOOL OF MEDICINE

14. Surgery CUMMING SCHOOL OF MEDICINE

15. Surgery CUMMING SCHOOL OF MEDICINE

16. 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 CUMMING SCHOOL OF MEDICINE

17. Contact Information CUMMING SCHOOL OF MEDICINE  http://www.ucalgary.ca/dbs4depression/ http://www.ucalgary.ca/dbs4depression/  Research Coordinator — Sandra Golding, BN RN MScHA  403-210-6905  sgolding@ucalgary.ca sgolding@ucalgary.ca

18. 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 CUMMING SCHOOL OF MEDICINE

19. Current Calgary Study Outcomes CUMMING SCHOOL OF MEDICINE

20. Thank You CUMMING SCHOOL OF MEDICINE