Y P Clinical Applications O of TMS C T & O Evidence in N Depression O D Adam Stern, M.D. E 2553480 S Director of Psychiatric Applications A Berenson-Allen Center for E Noninvasive Brain Stimulation, BIDMC L Instructor in Psychiatry P Harvard Medical School
Y P O Overview C T • TMS Basics in Psychiatry O N O • TMS studies in depression D E • Treatment program at BIDMC S A E L P
Y P O Disclosures C T Research has been supported by O N Harvard Catalyst / The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for O Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102) and financial contributions from Harvard University and its D affiliated academic health centers. The content is solely the responsibility of the author and does not necessarily represent the official views of Harvard E Catalyst, Harvard University and its affiliated academic healthcare centers, or the National Institutes of Health. S A NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation E L P
Y P Disclosures (cont.) O C • TMS has been approved for treatment in T O treatment-resistant depression though we N may discuss other uses which have not been FDA approved. O D • Some portion of the material has been E S shared by other members of the BA-CNBS A and are used with permission. E L P • I have no financial conflicts to report.
Y P What is the need for non-invasive brain stimulation? O C T O N O D E S A E L P
Y P Developments in Medical O Treatment of Depression C T 1900 O N 1 st century ’30s ’40s ’50s ’60s ’70s ’80s ’90s O D E S “Black Bile” ECT TCAs MAOIs SSRIs A E Heterocyclics Lithium Pharmacologic L Refinements P Courtesy of: ASCP Psychopharmacology Curriculum: “Electroconvulsive Therapy” 6
Y P What about Electroconvulsive therapy (ECT)? O C • Many decades of safety and efficacy data T O • Gold Standard for N treatment-resistant O depression D • Invasive stimulation E requiring anesthesia with S frequent cognitive adverse A effects E Image courtesy of: L http://www.nimh.nih.gov/health/topics/brain- • Enormous stigma P stimulation-therapies/brain-stimulation- therapies.shtml
Y P O C T O N O D E S A E L P A.T. Barker 1984
Y Electro-Magnetic Induction P O “ I think I got hold of a good thing ” C T O N O D E S A E M. Faraday L P 29 August 1831
Y Stimulation Coils P O C T O N O D E S A E L P
Equipment Y P Repetitive Stimulators O C T O N O D E S A E L P
Y P O Topographic resolution C T O N O D E S A E L P
Y P O C Stern AP, Cohen D. Neuropsychiatry 2013. T O N O D E S A E L P
Y Scalp to Brain Relation P O C T O N O D E S A E L P
Y TMS Parameters P O C T O N O D E S A E L P
Y rTMS: P Lasting Modulation of Cortical Activity O C TMS Sham TMS T O N O 1 Hz D TMS E S A 20 Hz E TMS L P Valero et al. 2002
Y Therapeutic Applications of P rTMS O C • Depression • PD T • Bipolar Disorder • Focal dystonia O • OCD • Epilepsy N • PTSD – Myoclonic epilepsy • Schizophrenia O – Focal status • Auditory Hallucinoses D epilepticus • Pain • Stuttering E – Visceral pain S • Tics – Atypical facial pain A • Neurorehabilitation – Phantom pain E – Neglect L P – Aphasia – Hand weakness
Y Potential Adverse Effects P O C • Common: T – Headache O – Auditory effects N • Rare O – Seizure induction D – Effects on Cognition – Mania E – Endocrine effects S A Safety Guidelines E L Monitoring P
Y P O C T O N O D E 2013_______ S Brainsway DeepTMS A E FDA L cleared P
Y rTMS in Depression P O C • Kolbinger et al. 1993, 95 T • Grisaru et al. 1994 O • George et al. 1996 N O D • Pascual-Leone et al. 1996 – Double Blind E – Multiple Control Conditions S – 17 patients A – 9/17 with ∂ HDRS > 50% E L P Lancet 1996
Y rTMS for depression treatment P Efficacy - Review O C T O N O D E S A E L P Gershon, Dannon and Grunhaus (Am J Psychiatry 2003; 160:835–845)
Y P O C T O N O D E S A E L P
Y P Sen ‐ Star Treatment Link O C 4 key functions: T O * Contact sensing to ensure treatment coil is positioned N correctly O * Magnetic field confirmation D to ensure patient receives desired treatment E * Surface field cancellation to S reduce stimulation of the A scalp E * Charge approximately $100 L P per treatment
Y P O Stimulation Parameters C T O 10 pulses/sec N 120% of motor threshold O D 3000 pulses/session E 4–6 weeks S A Iron-core coil E L P
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Y P Study 101 Trial Design O C Randomized, Double ‐ blind, Sham ‐ Controlled T Phase I Phase I I Phase I I I Drug-Free Acute Treatment Phase O Taper Phase 6 weeks 3 weeks Lead-I n N 7-10 days NeuroStar TMS Therapy O (N= 155) [TMS Taper D + Open-label n= 325 AD Mono-Rx] E Sham TMS S (N= 146) A Randomization E Primary Timepoint @ 4 weeks L Secondary Timepoint @ 6 weeks P Durability of Effect @ 9 weeks
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Y P How does TMS compare to other approaches O for treatment ‐ resistant depression? C T O N • Olanzapine/Fluoxetine (Thase, 2007): 0.33 O • Aripiprazole (Marcus, 2008): 0.34 D E • Neurostar TMS Therapy (Demitrack, 2009): 0.52 S A • Brainsway DeepTMS (Levkovitz, 2015): 0.76 E L • Electroconvulsive Therapy (UK ECT Review Group, 2003): 0.91 P
Y P Brainsway DeepTMS: A New Device O C T O N O D E S A E L P
Y P CONSORT O C T O N O D E S A E L P
Y P DeepTMS HDRS Change O C T O N O D E S A E L P Levkovitz, et al. World Psychiatry 2015;14:64–73
Y P O C T O N O D E S A E L P
Y Is this as good as it gets? Probably Not. P O HAM-D (rho=0.43**) C BDI (rho=0.51***) 100 T O depression score N % reduction 50 O D 0 E S -50 A -100 0 100 200 E % change MEP amplitude L Oliveira-Maia A, Press DZ, Pascual-Leone A. (preliminary/submitted): P Modulation of motor cortex excitability predicts antidepressant response to prefrontal cortex repetitive transcranial magnetic stimulation.
Y P What about Stim. Target? O C T O N O D E S A E L P
Y Patient Referral P O C • For patients with T O medication resistant N depression O • Must be under care of D psychiatrist E • Referral form on S A tmslab.org or call: E 667 ‐ 0307 L P
Y P Initial Evaluation O C • Referral from treating psychiatrist T O • Neurology N – Contraindications O – Effect of medication on TMS D • Psychiatry E – Caution if: Psychotic depression, bipolar, personality S disorders A – At least one adequate trial of antidepressant medication E L P
Y P O C T O N O D E S A E L P
Y P Consent O C • Discussion of on ‐ label vs. off ‐ label treatment T O N • Explanation of side ‐ effects O – Seizure D – Headache E – Neck pain S – Scalp pain A E L P
Y P Initiation Phase O C • Treatments daily (excluding weekends) T O • Various mood assessments N daily/weekly/monthly O • Minimum 2 weeks D • Maximum 4 ‐ 6 weeks E S A E L P
Y P Assessment tools O C • Beck, Hamilton, Analogue scale T O • Target symptoms N • Clinician evaluation of patient • Other sources of information (e.g. family, referring O psychiatrist) D • Side effects questionnaire E S A • Weekly meeting of all staff to discuss progress E L P
Y P Alternatives being investigated O C • Choosing protocol on clinical parameters T O (anxiety, risk of mania/sz) N • Using rs ‐ fMRI guidance for targeting O • Using anatomical MRI to help with intensity of D stimulation (particularly in elderly) E S • Plasticity measures as guide A • Others: mood induction, more than one E L session/day P
Y P O C T O N O D E S A E L P
Y P Maintenance Phase O C • Minimal evidence (absence of evidence, not evidence T O of absence) N • Relapse prevention O – Start with weekly treatment D – Gradually space out sessions E • “Watchful Waiting” S A – Patient presents when feeling worse E L P
Y P Cost O C • Insurance coverage depends on location T O – Medicare jurisdiction N – Private payers O • Additional fee for assessments D • Helping with billing, talking with payers E S A E L P
Y P O C T O N O D E S A E L P
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