Continuing Education Activity

Repetitive transcranial magnetic stimulation (rTMS) is a safe and non-invasive treatment technique used to treat various psychiatric and neurological disorders. It involves the stimulation of specific deep brain regions by the production of high and low-intensity magnetic fields which modulates the cortical excitability. This activity reviews the use of rTMS for treatment-resistant depression, PTSD, OCD, Tourette syndrome, and various other movement disorders. It also illustrates the importance of an interprofessional team in evaluating and treating these conditions.

Objectives:

• Outline the indications for the use of repetitive transcranial magnetic stimulation.
• Describes the most common adverse effects associated with repetitive transcranial magnetic stimulation.
• Explains the equipment and the technique to use repetitive transcranial magnetic stimulation.
• Summarize how interprofessional team coordination can improve results when utilizing repetitive transcranial magnetic stimulation as a treatment option.

Introduction

Transcranial magnetic stimulation (TMS) is a non-invasive stimulation of brain tissue through the production of a high or low-intensity magnetic field thought to modulate cortical excitability. Repetitive transcranial magnetic stimulation (rTMS) refers to applying recurring TMS pulses to a specific brain region. rTMS has been studied as a potential treatment for several psychiatric and neurological disorders. The neuromodulatory effects depend on several stimulation parameters, including frequency, intensity, duration, cortical target, number of sessions, and patient factors such as age, disease state, medication trial, and individual symptoms. Broadly, rTMS has been classified as high-frequency (>1 Hz), which increases cortical excitability, and low-frequency (<1 Hz), which depresses cortical excitability.[1]

Anatomy and Physiology

rTMS is a brain-stimulation technique in which the patient is seated with a large wire coil positioned near the scalp. It generates rapidly changing magnetic pulses that induce an electric field, thereby modulating cortical excitability. It results in depolarization of the underlying brain region. Studies have shown that the beneficial effects of rTMS for treatment-resistant depression and posttraumatic stress disorder (PTSD) are achieved by targeting the left dorsolateral prefrontal cortex (LDPFC).[2][3] rTMS has also been used for the treatment of obsessive-compulsive disorder (OCD) and Tourette disorder by modulating the activity at the orbitofrontal cortex (OFC) and supplementary motor area (SMA). Since rTMS is non-invasive, the depth of penetration is not readily accessible for direct stimulation of the OFC. Therefore, SMA is stimulated for the treatment of OCD and Tourette disorder.[4]

The treatment dose is expressed as a percentage of the motor threshold and is individualized for each patient. Motor threshold is defined by the visible observed movement of the abductor pollicis brevis.[3] The use of rTMS in clinical neurophysiology involves recording motor evoked potentials (MEPs), which assess conduction through the descending corticospinal tracts. MEPs enable investigation of cortical motor control and corticospinal conduction time in clinical settings. rTMS has 2 classic paradigms: Low-frequency (1 Hz or less), which consists of continuous trains of single pulses, and High-frequency (>1 Hz), which consists of a burst of stimuli that typically lasts 5 to 10 seconds, separated by pauses of 30 to 60 seconds.[5]

Indications

The therapeutic potentials for rTMS have been demonstrated for the following:

• Treatment-resistant depression
• Obsessive-compulsive disorder
• Posttraumatic stress disorder
• Tourette disorder
• Chronic pain syndrome
• Generalized anxiety disorder (GAD) 
• Bipolar disorder
• Movement disorders such as Parkinson disease, functional tremors, focal epilepsy, cortical myoclonus, and spasticity.

Repetitive transcranial magnetic stimulation has been approved by the U.S Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD) since 2008. It is perceived as a treatment modality alternative to Electroconvulsive therapy (ECT). The first device was cleared for the treatment of MDD and targeted the left DLPFC. Later, the FDA approved 5 additional rTMS devices and expanded the indication for the initial rTMS device to include a broader patient population with treatment resistance to 1 or more antidepressant medications.

For chronic pain, studies have shown clear efficacy of high-frequency rTMS applied contralateral to the side of pain at the primary motor cortex (M1), and the FDA approved it by 2013. There is a possible efficacy for the use of HF-rTMS of the left DLPFC for schizophrenia, likely targeting the negative symptoms. Studies have shown possible usage of Low-frequency rTMS for tinnitus and auditory hallucinations(Left temporoparietal cortex). High-frequency rTMS, when applied sequentially to left DLPFC and superior medial frontal cortex (SMFC), showed promising results in reducing the craving in chronic smokers and thus helping in smoking cessation. The FDA approved marketing TMS for the treatment of OCD in 2018.[3][4][6][7][8]

Contraindications

Although rTMS is a non-invasive technique and its side effect profile is rare, it may induce seizures. Hence, it is not recommended for patients with epilepsy. Pre-existing neurological disease, adolescents, change in medication regimen, substance use during the rTMS course (especially during HF-rTMS)should also be taken into account, as they lower the seizure threshold. It is therefore necessary that services where rTMS is provided be well equipped to manage any seizure episode in patients.[9]

rTMS is a relatively well-tolerated treatment but may present with pain at the stimulation site, post-treatment headaches, neck pain, or toothache. Muscle twitching during treatment can also occur. Transient changes in the auditory threshold, hyperacusis, have been demonstrated due to the loud clicks produced during TMS pulses. Hence, hearing protection is mandatory. Metallic/electronic implants or cochlear implants that are in close contact with the TMS coil serve as an absolute contraindication.[5][9]

Equipment

TMS is based on the Faraday law of electromagnetic induction, consisting of a passage of high-intensity, brief current in a copper wire, which in turn converts into an extracranial magnetic field and generates an intracranial electrical current. The nature of the neural circuit activated by TMS depends upon the orientation and the type of TMS coil being used. It can be a round coil that is relatively more powerful, or it could be a figure-of-8-shaped coil that is more focal. The figure-of-8-shaped coil produces maximal current at the intersection, and thus it is also known as the double-cone coil. The H-coil configuration also allows a slower decay of the magnetic field.[5][10][11]

Preparation

The patient is prepared by undergoing a comprehensive physical examination, with possible laboratory tests. Psychiatric evaluation is done to discuss their symptoms of depression, with the antidepressant medication trials they have earlier used. It helps determine whether rTMS would be a suitable treatment option for them. The physician should ask the patient for any personal/family history of epilepsy or any other mental health disorder, such as substance abuse, bipolar disorder, or psychosis. Studies have shown that patients should be asked about any metal or implanted medical devices, such as stents, aneurysm clips, deep brain stimulators, pacemakers, cochlear implants for hearing, or any magnetic implants, because of the strong magnetic field produced during the procedure.[9]

Technique or Treatment

Transcranial magnetic stimulation is a noninvasive neuromodulation technique used for both diagnostic and therapeutic purposes. It can be administered using 3 protocols: 

• Single-pulse TMS (spTMS), where the motor cortex is stimulated, and muscle activation in the contralateral limb is monitored using electromyography. Single-pulse TMS, along with electromyography, is helpful for presurgical planning by corticospinal tract mapping.
• Paired-pulse TMS (ppTMS) is largely delivered over the motor cortex and is used to measure the cortical excitation: inhibition ratio. Two pulses are delivered consecutively at a fixed interstimulus interval and reveal the regional inhibitory or excitatory signaling strength.
• Repetitive TMS (rTMS) is delivered in trains lasting a couple of minutes and is commonly used to suppress neuropsychiatric symptoms. For pharmacoresistant depression and PTSD, a frequency of 10 to 20 Hz is used daily for 4 to 6 weeks at the LDPFC region. Magnetic pulses are delivered for 5 to 10 seconds, followed by a 30 to 60-second pause due to the risk of seizures and to prevent overheating.[11]

Repetitive transcranial magnetic stimulation can be performed as an outpatient procedure. The patient is taken to the treatment room and seated in a reclining chair, with earplugs provided for use during the session. An electromagnetic coil is placed against the patient's head and switched on and off repeatedly to generate TMS pulses. The patient reports a tapping sensation on the forehead, which is called mapping. The physician determines the required magnetic energy by increasing the dose and observing finger or hand twitching. During the process, the stimulus may be adjusted based on the individual's symptoms and side effects. After each treatment session, the patient can return to his/her routine daily activities.

Complications

The most common complication associated with rTMS is the likely induction of seizures. Although in patients without epilepsy, the risk of seizure induction is <0.01% per session. In patients suffering from epilepsy, the risk is higher, although less than 3% per session. However, less serious complications include local pain, mostly headache or neck pain, and transient tinnitus. Hyperacusis is another complication due to the loud clicks during rTMS sessions. Hence, hearing protection becomes essential during the sessions. The adverse effects are usually short-lived and mild. rTMS does not require sedation with anesthesia during the treatment. At times, the patient's inability to attend sessions also influences the patient's response to rTMS.[9][11]

Clinical Significance

For treatment-resistant MDD and PTSD, depressive symptoms likely improve or may go away entirely, although it may take a few weeks of rTMS sessions. After the rTMS treatment series, standard care for depression, such as psychotherapy or medication, can be recommended as an ongoing treatment to prevent relapse. However, the use of maintenance rTMS sessions remains under investigation. Still, studies have shown the beneficial effect of rTMS if depressive symptoms occur later on in patients, where this treatment was initially successful. This is known as re-induction.[12] rTMS has been used for the treatment of GAD and Bipolar Depression and is well-tolerated. However, treatment of mania has received mixed results.[3] 

Studies have shown that rTMS is safe and effective for stroke complications as well, and accelerates their recovery. Improvements in Parkinson disease, functional tremors, focal epilepsy, cortical myoclonus, dysarthria, and aphasia have also been studied.[13] For Tourette disorder and OCD, low-frequency rTMS has been used to control hyperexcitability, thereby controlling the symptoms.[4] High-frequency rTMS also reduces craving in patients who are chronic smokers, thus helping in smoking cessation.[8][14]

Enhancing Healthcare Team Outcomes

Repetitive transcranial magnetic stimulation is a noninvasive brain-stimulation technique that has shown promising results in diagnostic and therapeutic applications. A detailed mental and physical health examination is essential for physicians to determine whether rTMS would effectively treat a given individual. Treatment-resistant depression, PTSD, OCD, and Tourette disorder are among the few conditions for which rTMS has shown beneficial effects. The physician should be aware of the medications the patient initially tried. Additionally, one should consider whether the patient is misusing substances. 

A team of psychiatrists, psychologists, social workers, and primary care providers is involved and educates the patient regarding the importance of follow-up sessions. They note the medications the patient has tried and how the symptoms improved with those medications rather than with the rTMS sessions. Psychotherapy and medications are often continued as maintenance therapy after the success of rTMS therapy to prevent relapse. Social workers are assigned to determine whether these patients can work or drive to return to verify the effectiveness of their daily routines.

Communication becomes essential at all interprofessional levels to ensure adequate patient care. Places that provide rTMS services should be well equipped with measures to treat seizures. For any other side effects, referrals should be made to manage long-term outcomes and minimize the risk of medical error. Overall, studies have shown that rTMS is an effective treatment for neuropsychiatric disorders.

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References

1.

Wang X, Mao Z, Ling Z, Yu X. Repetitive transcranial magnetic stimulation for cognitive impairment in Alzheimer's disease: a meta-analysis of randomized controlled trials. J Neurol. 2020 Mar;267(3):791-801. [PubMed: 31760522]

2.

Baeken C, Brem AK, Arns M, Brunoni AR, Filipčić I, Ganho-Ávila A, Langguth B, Padberg F, Poulet E, Rachid F, Sack AT, Vanderhasselt MA, Bennabi D. Repetitive transcranial magnetic stimulation treatment for depressive disorders: current knowledge and future directions. Curr Opin Psychiatry. 2019 Sep;32(5):409-415. [PMC free article: PMC6688778] [PubMed: 31145145]

3.

Kozel FA. Clinical Repetitive Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder, Generalized Anxiety Disorder, and Bipolar Disorder. Psychiatr Clin North Am. 2018 Sep;41(3):433-446. [PubMed: 30098656]

4.

Mantovani A, Lisanby SH, Pieraccini F, Ulivelli M, Castrogiovanni P, Rossi S. Repetitive transcranial magnetic stimulation (rTMS) in the treatment of obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS). Int J Neuropsychopharmacol. 2006 Feb;9(1):95-100. [PubMed: 15982444]

5.

Lefaucheur JP. Transcranial magnetic stimulation. Handb Clin Neurol. 2019;160:559-580. [PubMed: 31277876]

6.

Taib S, Ory-Magne F, Brefel-Courbon C, Moreau Y, Thalamas C, Arbus C, Simonetta-Moreau M. Repetitive transcranial magnetic stimulation for functional tremor: A randomized, double-blind, controlled study. Mov Disord. 2019 Aug;34(8):1210-1219. [PubMed: 31180620]

7.

Lefaucheur JP, André-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder D, Devanne H, Di Lazzaro V, Filipović SR, Hummel FC, Jääskeläinen SK, Kimiskidis VK, Koch G, Langguth B, Nyffeler T, Oliviero A, Padberg F, Poulet E, Rossi S, Rossini PM, Rothwell JC, Schönfeldt-Lecuona C, Siebner HR, Slotema CW, Stagg CJ, Valls-Sole J, Ziemann U, Paulus W, Garcia-Larrea L. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol. 2014 Nov;125(11):2150-2206. [PubMed: 25034472]

8.

Chang D, Zhang J, Peng W, Shen Z, Gao X, Du Y, Ge Q, Song D, Shang Y, Wang Z. Smoking Cessation With 20 Hz Repetitive Transcranial Magnetic Stimulation (rTMS) Applied to Two Brain Regions: A Pilot Study. Front Hum Neurosci. 2018;12:344. [PMC free article: PMC6166007] [PubMed: 30319373]

9.

Taylor R, Galvez V, Loo C. Transcranial magnetic stimulation (TMS) safety: a practical guide for psychiatrists. Australas Psychiatry. 2018 Apr;26(2):189-192. [PubMed: 29338288]

10.

Hallett M. Transcranial magnetic stimulation: a primer. Neuron. 2007 Jul 19;55(2):187-99. [PubMed: 17640522]

11.

Damar U, Lee Kaye H, Smith NA, Pennell PB, Rotenberg A. Safety and Tolerability of Repetitive Transcranial Magnetic Stimulation During Pregnancy: A Case Report and Literature Review. J Clin Neurophysiol. 2020 Mar;37(2):164-169. [PubMed: 32142024]

12.

Rachid F. Maintenance repetitive transcranial magnetic stimulation (rTMS) for relapse prevention in with depression: A review. Psychiatry Res. 2018 Apr;262:363-372. [PubMed: 28951141]

13.

León Ruiz M, Rodríguez Sarasa ML, Sanjuán Rodríguez L, Benito-León J, García-Albea Ristol E, Arce Arce S. Current evidence on transcranial magnetic stimulation and its potential usefulness in post-stroke neurorehabilitation: Opening new doors to the treatment of cerebrovascular disease. Neurologia (Engl Ed). 2018 Sep;33(7):459-472. [PubMed: 27161423]

14.

Kwon HJ, Lim WS, Lim MH, Lee SJ, Hyun JK, Chae JH, Paik KC. 1-Hz low frequency repetitive transcranial magnetic stimulation in children with Tourette's syndrome. Neurosci Lett. 2011 Mar 29;492(1):1-4. [PubMed: 21256925]

Disclosure: Sukhmanjeet Kaur Mann declares no relevant financial relationships with ineligible companies.

Disclosure: Narpinder Malhi declares no relevant financial relationships with ineligible companies.