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2. Efficacy of TMS for Depression: Results from Clinical Trials
Simon Kung, M.D. Associate Professor of Psychiatry Mayo Clinic

3. Randomized Controlled Trials
301 participants
Neuronetics
2007
Device approval
190 participants 
NIMH
2010
BrainsWay 
deep TMS
2015
212 participants 
Device approval

4. Neuronetics Industry-Sponsored Randomized Trial
Moderate-to-severe depression 
Current episode less than 3 years
301 patients
No more than 4 antidepressant trials
Randomized
No intolerance to antidepressants
Sham
TMS
- Monday to Friday
- 40-minute session
- 6 weeks
- Left sided, 10 Hz at 120% of motor threshold
O’Reardon, J. P., Solvason, H. B., Janicak, P. G., Sampson, S., Isenberg, K. E., Nahas, Z., ... & Demitrack, M. A. (2007). Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biological psychiatry, 62(11),

5. Results Response Rates Remission Scores Rate (%) Rate (%) Time Time
8.4
6.8
19.4
11.6
23.9
15.1
5.2
2.7
9.0
8.2
17.4
8.2 25 25 20 20 15 15
= Active TMS
Rate (%)
Rate (%) 10 10
= Sham TMS 5 5
Week 2
Week 4
Week 6
Week 2
Week 4
Week 6
Time
Time
O’Reardon, J. P., Solvason, H. B., Janicak, P. G., Sampson, S., Isenberg, K. E., Nahas, Z., ... & Demitrack, M. A. (2007). Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biological psychiatry, 62(11),

6. NIMH-Sponsored Trial 190 patients Randomized study NIMH study
Neuronetics trial
Active sham
Blocked magnetic stimulation
MRI to locate the dorsolateral prefrontal cortex
3-6 weeks 
6 weeks
George, M. S., Lisanby, S. H., Avery, D., McDonald, W. M., Durkalski, V., Pavlicova, M., ... & Holtzheimer, P. E. (2010). Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Archives of general psychiatry, 67(5),

7. Results Remission rate Similar response rate Active TMS Sham
Nonremitters  5%
14%
Open label
Similar response rate
TMS
Odds ratio 4.2 
More likely to remit in active treatment
30% remission
George, M. S., Lisanby, S. H., Avery, D., McDonald, W. M., Durkalski, V., Pavlicova, M., ... & Holtzheimer, P. E. (2010). Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Archives of general psychiatry, 67(5),

8. BrainsWay Deep TMS Study
212 patients
18 Hz stimulation
20 sessions
over 4 weeks
Maintenance
biweekly 
for 12 weeks
Failed 1 to 4 antidepressants
1980 pulses/treatment 
Nontolerant to least 2
 antidepressants
~ 20 minutes
Levkovitz, Y., Isserles, M., Padberg, F., Lisanby, S. H., Bystritsky, A., Xia, G., ... & Hafez, H. M. (2015). Efficacy and safety of deep transcranial magnetic stimulation for major depression: a prospective multicenter randomized controlled trial. World Psychiatry, 14(1),

9. Results 45 years for active
Mean baseline Hamilton Depression Rating Score
Average age
47 years for sham 23
Results
Response rate
Remission rate
Outcome: change in Hamilton Depression Rating Score
Active
37%
30.4%
Improved 3.1 points
Sham
27.8%
15.8%
Protocol group, statistically significant
Levkovitz, Y., Isserles, M., Padberg, F., Lisanby, S. H., Bystritsky, A., Xia, G., ... & Hafez, H. M. (2015). Efficacy and safety of deep transcranial magnetic stimulation for major depression: a prospective multicenter randomized controlled trial. World Psychiatry, 14(1),

10. Open Label Real-World Study
Patient Characteristics
Female (%)
66.8
48.6 ± 14.2
307 patients
Age (years)
92.8
Recurrent illness course (%)
42 different sites
Prior ECT treatment (%)
5.2
Followed patients receiving TMS 
Number of antidepressant attempts in current episode
3.6
Carpenter, L. L., Janicak, P. G., Aaronson, S. T., Boyadjis, T., Brock, D. G., Cook, I. A., ... & Demitrack, M. A. (2012). Transcranial magnetic stimulation (TMS) for major depression: a multisite, naturalistic, observational study of acute treatment outcomes in clinical practice. Depression and anxiety, 29(7),

11. Results PHQ-9 End of acute phase response rate 56.4% Likelihood of
success with TMS
Remission rate
28.7%
Carpenter, L. L., Janicak, P. G., Aaronson, S. T., Boyadjis, T., Brock, D. G., Cook, I. A., ... & Demitrack, M. A. (2012). Transcranial magnetic stimulation (TMS) for major depression: a multisite, naturalistic, observational study of acute treatment outcomes in clinical practice. Depression and anxiety, 29(7),

12. How Long Does This Last? Durability Study
36.2% required more TMS
257 TMS patients
62.5% continued
to meet response criteria
Followed up
 1 year
53% responded or remitted
 55% to 75% still on medication
Dunner, D. L., Aaronson, S. T., Sackeim, H. A., Janicak, P. G., Carpenter, L. L., Boyadjis, T., ... & Lanocha, K. (2014). A multisite, naturalistic, observational study of transcranial magnetic stimulation for patients with pharmacoresistant major depressive disorder: durability of benefit over a 1-year follow-up period. The Journal of clinical psychiatry, 75(12),

13. “Do I Need Maintenance TMS?”
Maintenance TMS is useful. 
59 patients
Open-label studies 
Controlled studies
Responded to TMS
Not covered by US insurance companies
TMS maintenance
No further TMS
Relapse rate: 37.8%
Relapse rate: 81.8%
Richieri, R., Guedj, E., Michel, P., Loundou, A., Auquier, P., Lançon, C., & Boyer, L. (2013). Maintenance transcranial magnetic stimulation reduces depression relapse: a propensity-adjusted analysis. Journal of affective disorders, 151(1), Rachid, F. (2017). Maintenance Repetitive Transcranial Magnetic Stimulation (rTMS) for Relapse prevention in Patients with Depression: A Review. Psychiatry research.

14. Key Points
In randomized trials, active versus sham response rates are not impressive.
 The absolute remission rates are low—but twice as high for active compared to sham.
 In an open-label trial of about 300 patients, the response rate by PHQ-9 was about 56%.
 For durability, a small study of 120 patients at 1 year showed 62% were still in response; 36% needed more TMS, and 55% to 75% had to continue on medication. 

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