Noninvasive Neuromodulation in Psychiatric Treatment: Current and Developing
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1 Noninvasive Neuromodulation in Psychiatric Treatment: Current and Developing Sarah H. Lisanby, MD J.P. Gibbons Professor and Chair Psychiatry & Behavioral Sciences
2 ECT TMS dtms Benefits Risks Critical knowledge gaps and needs for future work
3 ECT Source: STAR-D Trial Benefits Percent of people with Depression Responding Unparalleled efficacy Number of medication trials ECT
4 ECT Benefits Unparalleled efficacy Rapidly resolves suicide risk All Kellner Rights Reserved, Duke et Medicine al Am 2007 J Psychiatry 2005; 162: # of ECT Sessions Needed
5 Amnesia Score (%) Unilateral ECT Bilateral Benefits Risks Memory loss Reduced with unilateral electrode placement 10 0 Personal Impersonal Lisanby All Rights Reserved, Duke et Medicine al Arch Gen Psych 2000;57:381 Bilateral Unilateral
6 Benefits Risks Memory loss Reduced with unilateral electrode placement, and Ultrabrief pulse width ms 0.3 ms 1.5 ms Standard Pulse 1-2 ms Ultra-Brief Pulse ms Sackeim All Rights Reserved, Duke Medicine et 2007 al. Brain Stimulation 2008;1:71-83
7 MST Benefits Risks Critical knowledge gaps and needs for future work Novel strategies to protect memory Magnetic Seizure Therapy
8 ECT MST Benefits Risks Critical knowledge gaps and needs for future work Novel strategies to protect memory Magnetic Seizure Therapy More focal Electric fields in brain Lee et al. EMBC 2014
9 ECT MST Verbal Memory Benefits Risks Critical knowledge gaps and needs for future work Novel strategies to protect memory Magnetic Seizure Therapy More focal Electric fields in brain Superior cognitive outcomes McClintock et al. ACNP 2012
10 ECT Benefits Risks Critical knowledge gaps and needs for future work Novel strategies to protect memory Deeper understanding of mechanisms of action of seizures Remains the most potent antidepressant and suicide prevention strategy currently FDA approved
11 TMS Benefits Antidepressant efficacy Active TMS Sham Response O Reardon et al. Biol Psychiatry 2007
12 TMS Benefits Antidepressant efficacy Tool to target illness-related circuits Depression Targets Insel. All Rights Reserved, Scientific Duke Medicine 2007 American. 2010
13 TMS Benefits Antidepressant efficacy Tool to target illness-related circuits Lacks amnesia seen with ECT
14 TMS Benefits Risks Hearing loss / tinnitus Seizure Role of concomitant medications Medical comorbidities Substance use disorders Vulnerable populations seizure threshold lower in children, seizure risk higher in autism and after traumatic brain injury
15 TMS Benefits Risks Critical knowledge gaps and needs for future work Optimal dosage Spatial distribution
16 Coil Figure-8 E field Benefits Risks Critical knowledge gaps and needs for future work Optimal dosage Spatial distribution H-Coil Deng, Peterchev and Lisanby, 2008
17 Wide Variety of Coil Designs Deng, Lisanby, Peterchev. Brain Stim 2013
18 Wide Variety of Coil Designs Wide Variety of E-field Spatial Spread Deng, Brain Stim 2013
19 Focality/Depth Tradeoff of 61 Coils Fig 8 [Mod. from Deng, Lisanby & Peterchev, Brain Stim. 2013]
20 New approaches to shape field through coil design Single source multi-coil array Each loop is neighbored by a loop with current in the opposite direction, permitting field cancellation All Gomez Rights Reserved, Duke et Medicine al 2007 IEEE Transactions on Biomedical Engineering. 2013
21 New approaches to shape field through coil design Single source multi-coil array Each loop is neighbored by a loop with current in the opposite direction, permitting field cancellation Engineering challenges in implementation All Gomez Rights Reserved, Duke et Medicine al 2007 IEEE Transactions on Biomedical Engineering. 2013
22 Psychiatry & Behavioral Sciences New approaches to shape field through coil design Cervel Neurotech Deep Shaped-Field repetitive transcranial magnetic stimulator (DSF-rTMS) NCT Deng et al Stimulation 2013 All Rights Reserved, DukeBrain Medicine 2007 Tal Low Field Magnetic Stimulation (LFMS) NIMH RAPID, NCT
23 Psychiatry & Behavioral Sciences New approaches to shape field through coil design Cervel Neurotech Deep Shaped-Field repetitive transcranial magnetic stimulator (DSF-rTMS) NCT Deng et al Stimulation 2013 All Rights Reserved, DukeBrain Medicine 2007 NeoSync EEG Synchronized TMS Tal Low Field Magnetic Stimulation (LFMS) NIMH RAPID, NCT Rohan et al American Journal Psychiatry 2004 NCT
24 Conventional TMS ctms Pulse width control Benefits Risks Critical knowledge gaps and needs for future work Optimal dosage Spatial distribution Temporal characteristics Pulse shape Directionality control Peterchev, Jalinous, & Lisanby 2008
25 Unidirectional Bidirectional Benefits Risks Critical knowledge gaps and needs for future work Optimal dosage Spatial distribution Temporal characteristics Pulse shape Train parameters» Frequency, duration, directionality
26 Low Frequency Right versus High Frequency Left for Depression 8 Randomized Controlled Trial, 249 patients No detectable difference between low or high frequency Implications for practice as low frequency has lower seizure risk than high frequency Chen et al. Psychiatry Research. 2013
27 TMS Benefits Risks Critical knowledge gaps and needs for future work Optimal dosage Optimal patient selection Other indications Anxiety Disorders» OCD, PTSD Addictions Cognitive enhancement» TBI
28 Future Indications Under Investigation: PTSD Both low and high frequency effective Karsen et al. Brain Stimulation. 2014
29 TMS Benefits Risks Critical knowledge gaps and needs for future work Optimal dosage Optimal patient selection Concomitant therapies Pharmacological Nonpharmacological/behavioral
30 Non-Invasive Neuromodulation in Development for Psychiatric Treatment TDCS/tACS Benefits Remission Rate (%) Evidence for antidepressant effects Sham + placebo Sham + Sert tdcs + placebo tdcs + Sert wk 6 Brunoni et al JAMA Psychiatry 2013
31 Non-Invasive Neuromodulation in Development for Psychiatric Treatment TDCS/tACS Benefits Risks Excellent safety profile Critical knowledge gaps and needs for future work Mechanisms of action and optimizing dosimetry in space and time
32 Are we asking the right question? Extracellular Currents Endogenously Generated Exogenously Applied TMS TDCS/TACS Neural oscillations epiphenomenon or signal? Emerging role of abnormal neural oscillations in psychiatric disorders
33 Are we asking the right question? Extracellular Currents Endogenously Generated Exogenously Applied TMS Frohlich & Schmidt. Frontiers in Human Neuroscience 2013
34 Conclusions TMS here TMS now Spatial maps of neurocircuitry underlying disorders have guided spatial targeting for depression, but Temporal targeting is presently lacking, but of great potential impact Understanding the interaction between endogenous neural dynamics underlying psychiatric disorders and exogenously applied electrical currents represents a key knowledge gap in the development noninvasive neuromodulation for psychiatric disorders.
35 The Future for Devices in Psychiatry Now this is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning. Winston S. Churchill, The Bright Gleam of Victory November, 10, Mansion House, London.
36 Acknowledgements Psychiatry & Behavioral Sciences Brain Stimulation Engineering Lab Noninvasive Neuromodulation Neuroscience Neurocognitive Research Lab Andrew Krystal, MD, PhD Simon Davis, PhD Michael Koval, PhD Stefan Goetz, PhD David Murphy, MS Chris Sikes-Keilp, Jonathan Young, Pam Smith, Mark Mayo, Lis Bernhardt Angel Peterchev, PhD Bruce Luber, PhD Zhi-De Deng, PhD ECT Team: Drs Mankad, Moore, Dennis, Adams; ECT Nursing Williams Ward Attendings and Nursing Shawn McClintock, PhD Mustafa Husain, MD Rich Weiner, MD, PhD R01MH (PIs: Lisanby/Peterchev) R01 MH (PI: Lisanby) U01 MH (PIs: Kellner and Lisanby) K01 AG (PI: Luber, Mentor: Lisanby) R21 EB00685 (PIs: Lisanby & Peterchev) Brain & Behavior Foundation (Lisanby), Stanley Foundation (Lisanby/Husain)
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