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Transcranial Direct Current Stimulation (Tdcs): a Novel Therapeutic Treatment

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Transcranial Direct Current Stimulation (Tdcs): a Novel Therapeutic Treatment Transcranial direct current stimulation (tDCS): a novel therapeutic treatment Dr Donel Martin School of Psychiatry, UNSW . Leading tertiary referral clinic for brain stimulation treatment in Australia Sydney . Conducted first RCT of rTMS Neurostimulation in Australia in 1997 Centre . Conducted first RCT of tDCS in (SyNC) Australia in 2007 . Training courses on rTMS and tDCS since 2014 Transcranial Direct Current Stimulation (tDCS) Anode (+ve) Cathode (-ve) tDCS = small unidirectional current (1-2mA) Clinical translation potential of tDCS ‘Home-supervised’ tDCS ‘DIY’ tDCS tDCS: Lasting effects after stimulation 13 min 9 min 7 min 11 min 5 min Nitsche & Paulus (2001) tDCS: Applications (-2013) Bikson et al., 2016 Why tDCS for depression? control network Fitzgerald et al., 2010 Rayner et al., 2016 tDCS: Antidepressant effects (Brunoni et al., 2016) Active Sham OR CI NNT Response 34% 19% 2.44 1.38-4.32 7 Remission 23.1% 12.7% 2.38 1.22-4.64 9 tDCS: Effects on learning Reis et al., 2009 tDCS enhances rehabilitation after stroke Overall positive effect of tDCS + training compared to sham tDCS + training Positive effects found for subacute and chronic phases Kang et al., 2016 Transcranial direct current stimulation tDCS causes lasting modifications in neuronal excitability Promising antidepressant effects, though modest Can improve learning when applied during concurrent training/rehabilitation Excellent translation potential However… “Current evidence does not allow making any recommendation of Level A (definite efficacy) for any indication…” Lefaucheur et al., 2017. Evidence-based guidelines Large inter-individual variability in outcomes after tDCS (e.g., depression) Need to first optimise/individualise tDCS “dose” Acknowledgments Sydney Neurostimulation Centre (SyNC), Black Dog Institute Angelo Alonzo Nicholas Chand Veronica Galvez Ortiz Stevan Nikolin Vanessa Dong Giselle Lo Ada Wong Lucy McGuirk Divya Kumar Kevin Yeung Shani Lauf Colleen Loo Seeking Volunteers: Clinical trial in older adults (60-85) with Mild Memory Problems CONTACT: Donel Martin Ph: (02) 9382 8353 [email protected] Transcranial Magnetic Stimulation (TMS) a real alternative for Major Depression Disorder Dr Jason Pace What is Transcranial Magnetic Stimulation ? TMS technology was invented in 1985. Consists of a coil which is placed on a persons head and applies a pulsating magnetic energy to the cerebral cortex This subsequently induces electrical activity in the brain. rTMS is when TMS is delivered in a repeated sequence of pulsing magnetic energy that is applied for the treatment. While is comes from the school of brain stimulation, unlike ECT treatment, TMS does not involve inducing seizures and is administered to patients in an outpatient setting while fully awake and does not cause any cognitive impairment. What does rTMS treatment involve? An initial planning session to creates a customised treatment plan for the patient. Subsequent sessions last about 40 minutes. rTMS needs to be given at least 3 times a week. Treatment for acute depression requires 30 sessions. TMS can be given while patient are still taking medication. rTMS tolerability Typically patient experience some discomfort in the scalp locally over the treatment area. This may cause a mild headache post treatment. Despite some discomfort, patients rates rTMS as a very well tolerable and acceptable procedure. Studies show very few drop outs and clinically compliance is excellent. No systemic side effects. Very low risk of seizure. Who is a good candidate for rTMS ? TGA guidelines recommends - Treatment Resistant Depressive disorder Consider prior to ECT Consider if tolerating medication has been a problems Unipolar or Bipolar Depression Over 18 years and not pregnant is limited TMS for TRD is equally effective in patient >65yr. (Conelea et al Journal of Affective Disorders, Aug 2017) Effectiveness of TMS Carpenter et al.(Depress Anxiety 2012) in a multisite naturalistic study involving 307 patient from 42 clinics demonstrated 58% response rate and 37% remission rates, with the average patient receiving 28 treatment sessions. Antidepressant effect of TMS is independent of medication, a meta-analysis of 54 sham-controlled studies published between 1997–2013 (Kedzior et al, Neuropsychiatr Dis Treat. 2014). Over 15 meta-analyses of TMS for depression, including more recent randomised control studies all consistently show statistically significant efficacy. ( Perera et al, Brain Stimulation 9 (2016) TGA approved 2007, FDA approved 2008, RANZCP guidelines endorsed 2013, NICE indorsed 2016. Long Term Benefits of TMS Multisite, naturalistic observational study, shows improvement in depressive symptoms following a course of rTMS, was maintained over the 12 month period for both responders and remitters. (Dunner , Sackeim, Carpenter et al J Clin Psychiatry 2014). Philip et al (Brain Stimulation 2016) showed that 70% of patients having benefited from TMS remained well 12 months. More importantly 70% of patient that relapsed, responded as well and quicker to a retreatment with TMS. This suggests TMS can be potentially useful in maintenances treatment. Sydney TMS Started in December 2015 Treated 130 patients Offices in Castle Hill & St Leonards Accepting referrals for GPs and Psychiatrists for TRD patients only over 18yrs. Our Observation Mean age of 45.09 , Range 18-90 yrs Sex 59% male , 41% female. All Patients met diagnosis of Treatment resistant Major Depressive Disorder ( failed two adequate trails of medications) Average number of TMS sessions - 28 In addition to clinical observations we also conduct baseline and repeated HAM-D and MADRS ( every 10 sessions) mean HAM-D pre treatment score 16.13 (SD=7.32) mean MADRS pre treatment score 26.15 (SD=10.75). Outcomes so far. Analyses using SPSS was performed on data from 54 patients who completed at least 20 sessions. The level of statistical significance was set at p .05 Response – was defined as a 50% reduction in scores Remission -was defined as HAMD (total score ≤7) and MADRS (total score ≤9) Response or Remission 50% Response rate 41% Remission rates 28% These results reached statistically significance even with only 54 patient. Where to next for TMS treatment ? “Theta Burst “a new ultra high frequently TMS that is looking promising and reduces treatment times to 10 minutes so could reduce costs of treatment. More evidence is emerging regards safety of offering patients sessions in shorter intervals, eg 2-3 sessions daily safely. Other Conditions ; OCD - Kumar et al , Neuropsychiatry (London) (2016) Addictions- Gorelick et al Ann N Y Acad Sci. 2014 Oct Schizophrenia – Cochrane Review 2015- some evidence in reducing auditory hallucinations but generally quality of research is poor. Others…ADHD, Tourettes, Austism… very early work only Take Home……. TMS is NOT an experimental treatment, it is a Real treatment option and with over 20 years of research and international governing body endorsement, TRD = should consider TMS rather than ongoing medication trial and certainly prior to ECT TMS is not only good in acute treatment but maybe most useful as maintenance treatment for patient with chronic depression Patient tolerability and acceptance of TMS is excellent. PSYCHIATRY PERMINDER SACHDEV CENTRE FOR HEALTHY BRAIN AGEING (CHeBA) UNIVERSITY OF NEW SOUTH WALES & NEUROPSYCHIATRIC INSTITUTE THE PRINCE of WALES HOSPITAL SYDNEY • Psychiatric disorders are often chronic and difficult to treat Treatment Resistant Depression (TRD) Lack of adequate clinical response after 2 well-delivered treatments First treatment: 50% respond (35% remit)1 Second treatment: 20-25% respond (10-15% remit)2,3 Thus, over 20% of depressed patients have TRD About 10% of OCD is severe and disabling and resistant to treatment 1 Depression Guideline Panel. Vol. 1. 1993. 2 Fava M, et al. Psychiatr Clin North Am. 2003;26:457-494. 3 Rush AJ, Ryan ND. Current and emerging therapeutics for depression. In: Davis KL, et al (eds). 2002:1081-1095. How do we improve the treatment of psychiatric disorders? • Better use of existing treatments • New drugs • New psychological treatments • Neuromodulation – TMS – tDCS – VNS – DBS Neural circuits underlie all behaviour A ‘connectogram’ for an example healthy adult female subject The outermost ring shows the various brain regions arranged by lobe. The set of five rings (from the outside inward) reflect grey matter volume, area, thickness, curvature, and connectivity density. The lines inside of the circle represent the computed degrees of connectivity between segmented brain regions using diffusion tractography, with colour representing the relative fractional anisotropy of the connection. 1 5 O C T O B E R 2 0 1 5 | VO L 5 2 6 | N AT U R E | 3 7 7 The DeLong “Box” Models of Basal Ganglia Circuitry and Their Use in Guiding Deep-Brain Stimulation (DBS). N Engl J Med 2012;367: 1529-38. Functional networks in the intrinsic activity of the brain. Ann. N.Y. Acad. Sci. 1394 (2017) 31–54 C 2016 PSYCHOSURGERY Surgical planning of deep brain stimulation of the antero-medial globus pallidus interna in a patient with Tourette Syndrome MECHANISMS (1) Depolarization blockade: stimulation-induced alterations in the activation of voltage-gated currents that block neural output near the stimulating electrode (Beurrier et al., 2001) (2) Synaptic inhibition: indirect inhibition of neuronal output by activation of axon terminals that make synaptic connections with neurons near the stimulating electrode (Dostrovsky et al., 2000) (3) Synaptic depression:
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