Transcranial magnetic stimulation (TMS)

Concept: TMS uses an electrically induced magnetic field to induce electrical currents that stimulate regions of the cerebral cortex (Perera et al, 2016).

• Repetitive pulses of electrical current are called repetitive TMS (rTMS)
• Can be delivered in high frequency (10 – 20Hz) that typically leads to increase in brain activity or low frequency (≤ 1Hz) which typically has the opposite effect (Brunoni et al, 2017).
  • In theory, depressed patients have left prefrontal hypoactivity and right prefrontal hyperactivity, thus treatments would be to aim to stimulate the left with high frequency rTMS or inhibit the right with low frequency rTMS (Brunoni et al, 2017)
• There are a variety of rTMS forms: priming low-frequency, bilateral, high-frequency, low-frequency, and theta burst have been found to be more effective than sham for treatment of MDD (Brunoni et al, 2017).

Treatment for MDD

• Eligible patients (Perera et al, 2016)
  • Insurance typically requires history of failing 2 – 4 antidepressant trials (due to lack of efficacy or intolerability of side-effects)
  • Moderate to severe MDD w/o psychosis
• Standard treatment regimen involves high frequency, left prefrontal rTMS 5 days / week over 4-6 weeks
• There has been concern for high relapse rates in patients who achieve remission (Carpenter et al, 2012; Dunner et al, 2014; Janicak et al, 2010).

Adverse effects (Perera et al, 2016)

• There is a very low risk of seizure associated with TMS
  • Patients with various neurological disorders (TBI, stroke, AD, myoclonus dystonia) did not have subclinical EEG abnormalities with application of TMS (Rossi et al, 2021)
  • Patients with epilepsy did demonstrate induction of epileptiform abnormalities with TMS, and thus patients at high risk of seizures (such as those with uncontrolled epilepsy) would require continuous EEG monitoring during TMS session (Rossi et al, 2021)
• Vasovagal syncope sometimes occurs in initial treatments.
• Due to an audible clicking sound, ear plugs are recommended to both the patient and the clinician administering the TMS.
• Mild scalp discomfort, though generally patients develop tolerance after 1-2 weeks
• Patients with implanted devices require extra caution (Rossi et al, 2021)
  • TMS with figure-8 coils is considered safe in patients with pacemakers, VNS systems, and spinal cord stimulators, as long as the coil is a safe distance away (>10cm)
  • TMS can be safely conducted in patients with implanted electrodes in CNS that are not connected to an implanted pulse generator (MRI compatible implants are more likely to be TMS safe)
  • In patients with DBS or cortical stimulation electrodes, TMS can induce currents causing unintended stimulation

References

Brunoni, A. R. et al. Repetitive Transcranial Magnetic Stimulation for the Acute Treatment of Major Depressive Episodes: A Systematic Review With Network Meta-analysis. JAMA Psychiatry 74, 143–152 (2017). https://pubmed.ncbi.nlm.nih.gov/28030740/

Carpenter, L.L. et al. Transcranial magnetic stimulation (TMS) for major depression: a multisite, naturalistic, observational study of acute treatment outcomes in clinical practice. Depress Anxiety. 2012 Jul;29(7):587-96. https://pubmed.ncbi.nlm.nih.gov/22689344/

Dunner D.L, et al. 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. J Clin Psychiatry. 2014 Dec;75(12):1394-401. https://pubmed.ncbi.nlm.nih.gov/25271871/

Janicak P.G, et al. Durability of clinical benefit with transcranial magnetic stimulation (TMS) in the treatment of pharmacoresistant major depression: assessment of relapse during a 6-month, multisite, open-label study. Brain Stimul. 2010 Oct;3(4):187-99. https://pubmed.ncbi.nlm.nih.gov/20965447/

Perera, T. et al. The Clinical TMS Society Consensus Review and Treatment Recommendations for TMS Therapy for Major Depressive Disorder. Brain Stimul. May-Jun 2016;9(3):336-346 https://pubmed.ncbi.nlm.nih.gov/27090022/

Rossi, S. et al. Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines. Clin Neurophysiol. 2021 Jan;132(1):269-306. https://pubmed.ncbi.nlm.nih.gov/33243615/