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

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

4. 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),

5. 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,

6. 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),

7. 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, 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, Li, H., Wang, J., Li, C., & Xiao, Z. (2014). Repetitive transcranial magnetic stimulation (rTMS) for panic disorder in adults. The Cochrane Library.

8. 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,

9. 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).

10. 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),

11. 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),

12. 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),

13. 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),

14. 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),

15. 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),

16. 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),

17. 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),

18. 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

19. 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.

20. Next Presentation TMS Summary