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Research Applications and Off-Label Uses Simon Kung, M.D. Associate Professor of Psychiatry Mayo Clinic

Children and adolescents Anxiety Schizophrenia Addiction Bipolar depression Pregnancy Autism Tinnitus Pain

Double-blind randomized trial Bipolar depression Deep TMS study Double-blind randomized trial Improvement in Hamilton Depression Rating score  50 patients No difference in response or remission rates = 4 weeks 4 weeks 8 weeks Tavares, D. F., Myczkowski, M. L., Alberto, R. L., Valiengo, L., Rios, R. M., Gordon, P., ... & Lafer, B. (2017). Treatment of bipolar depression with deep TMS: results from a double-blind, randomized, parallel group, sham-controlled clinical trial. Neuropsychopharmacology, 42(13), 2593..

Open-Label Study 190 patients with depression Versus 50 patients with bipolar disorder Equal efficacy Both groups got better No treatment-induced mania Carnell, B. L., Clarke, P., Gill, S., & Galletly, C. A. (2017). How effective is repetitive transcranial magnetic stimulation for bipolar depression?. Journal of affective disorders, 209, 270-272.

Meta-analysis Sham Active treatment 181 bipolar patients (19 RCTs) Right and left dorsolateral prefrontal cortexes efficacious (19 RCTs) Right-sided treatment has superior efficacy.  Bilateral stimulation was not different from placebo. No difference in treatment-emergent mania McGirr, A., Karmani, S., Arsappa, R., Berlim, M. T., Thirthalli, J., Muralidharan, K., & Yatham, L. N. (2016). Clinical efficacy and safety of repetitive transcranial magnetic stimulation in acute bipolar depression. World Psychiatry, 15(1), 85-86.

Generalized Anxiety Disorder PTSD Meta-analysis Versus 377 patients 15 patients active TMS 25 patients sham 217 Active 160 Sham High or low frequency improved Decreased anxiety Panic Disorder Randomized controlled trials No benefit Dilkov, D., Hawken, E. R., Kaludiev, E., & Milev, R. (2017). Repetitive transcranial magnetic stimulation of the right dorsal lateral prefrontal cortex in the treatment of generalized anxiety disorder: a randomized, double-blind sham controlled clinical trial. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 78, 61-65. Yan, T., Xie, Q., Zheng, Z., Zou, K., & Wang, L. (2017). Different frequency repetitive transcranial magnetic stimulation (rTMS) for posttraumatic stress disorder (PTSD): A systematic review and meta-analysis. Journal of psychiatric research, 89, 125-135. Li, H., Wang, J., Li, C., & Xiao, Z. (2014). Repetitive transcranial magnetic stimulation (rTMS) for panic disorder in adults. The Cochrane Library.

Schizophrenia 2018 Meta-analysis (30 RCTs) Hallucinations and negative symptoms Modest nonsignificant worsening of positive symptoms 768 patients Higher frequency treatment More efficacious Greater than 3 weeks  Left prefrontal cortical site Kennedy, N. I., Lee, W. H., & Frangou, S. (2018). Efficacy of non-invasive brain stimulation on the symptom dimensions of schizophrenia: a meta-analysis of randomized controlled trials. European Psychiatry, 49, 69-77.

2015 Cochrane Review Not enough evidence to show that TMS was helpful for schizophrenia Nonrobust improvement of:  Clinical global impression Hallucinations Temporoparietal TMS Positive symptoms Dougall, N., McIntosh, A., & Ebmeier, K. P. (2006). Transcranial magnetic stimulation for schizophrenia. The Cochrane database of systematic reviews, (3).

Addiction Level 1 Class B Level 2 and Class B Level 3 and Class C Nicotine addiction Alcohol Heroin Food addiction Cocaine Methamphetamines Cannabis Pathological gambling We need to wait for more research Makani, R., Pradhan, B., Shah, U., & Parikh, T. (2017). Role of repetitive transcranial magnetic stimulation (rTMS) in treatment of addiction and related disorders: a systematic review. Current drug abuse reviews, 10(1), 31-43.

Autism Spectrum Disorder 2016 consensus group No evidence to use TMS clinically for autism Oberman, L. M., Enticott, P. G., Casanova, M. F., Rotenberg, A., Pascual‐Leone, A., McCracken, J. T., & TMS in ASD Consensus Group. (2016). Transcranial magnetic stimulation in autism spectrum disorder: challenges, promise, and roadmap for future research. Autism Research, 9(2), 184-203.

2014 Randomized Controlled Trial 28 patients Deep TMS Some reduction in anxiety No improvement in social relating Enticott, P. G., Fitzgibbon, B. M., Kennedy, H. A., Arnold, S. L., Elliot, D., Peachey, A., ... & Fitzgerald, P. B. (2014). A double-blind, randomized trial of deep repetitive transcranial magnetic stimulation (rTMS) for autism spectrum disorder. Brain Stimulation, 7(2), 206-211.

Single pulse TMS device Migraine Headache Acute Chronic US FDA-approved Single pulse TMS device Acute Prophylactic Migraine with aura Lipton, R. B., Dodick, D. W., Silberstein, S. D., Saper, J. R., Aurora, S. K., Pearlman, S. H., ... & Goadsby, P. J. (2010). Single-pulse transcranial magnetic stimulation for acute treatment of migraine with aura: a randomised, double-blind, parallel-group, sham-controlled trial. The Lancet Neurology, 9(4), 373-380.

Conflicting studies 2017 meta-analysis Single pulse TMS Acute migraine TMS did not help Conflicting studies Lan, L., Zhang, X., Li, X., Rong, X., & Peng, Y. (2017). The efficacy of transcranial magnetic stimulation on migraine: a meta-analysis of randomized controlled trails. The journal of headache and pain, 18(1), 86 Shirahige, L., Melo, L., Nogueira, F., Rocha, S., & Monte‐Silva, K. (2016). Efficacy of Noninvasive Brain Stimulation on Pain Control in Migraine Patients: A Systematic Review and Meta‐Analysis. Headache: The Journal of Head and Face Pain, 56(10), 1565-1596.

Adolescents ~ 40 patients Uncontrolled trials Some benefit and it is tolerable Case reports 14 – 21 years  Open label studies Magavi, L. R., Reti, I. M., & Vasa, R. A. (2017). A review of repetitive transcranial magnetic stimulation for adolescents with treatment-resistant depression. International Review of Psychiatry, 29(2), 79-88.

Pregnancy 30 patients 41% response rate No RCTs 10 patients Can help pregnant patients Felipe, R. D. M., & Ferrão, Y. A. (2016). Transcranial magnetic stimulation for treatment of major depression during pregnancy: a review. Trends in psychiatry and psychotherapy, 38(4), 190-197.

Will There Be Harm to the Baby?  1 case report of preterm labor at 36 weeks No other concerns about outcome for the baby More research is needed on TMS and safety in pregnancy Felipe, R. D. M., & Ferrão, Y. A. (2016). Transcranial magnetic stimulation for treatment of major depression during pregnancy: a review. Trends in psychiatry and psychotherapy, 38(4), 190-197.

Types of pain disorders Off-Label Uses for TMS Types of pain disorders Bipolar depression Older adolescents This is off-label use Discuss with patient Geriatric patients older than 70 years

Key Points There are numerous research studies regarding other psychiatric uses for TMS.  Off-label use for bipolar depression, adolescents, geriatric patients and certain types of pain.  There is not enough evidence for schizophrenia, addiction, autism, or tinnitus.

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