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 the 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 upon several stimulation parameters such as 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 the cortical excitability, and low frequency(<1 Hz), which depresses the cortical excitability.[1]

Anatomy and Physiology

The rTMS is a brain stimulation technique in which the patient is seated with a large wire coil positioned near to the scalp. It generates rapidly changing magnetic pulses that induce an electric field, having a modulatory effect on cortical excitability. It results in depolarization of the underlying region of the brain. Studies have shown the beneficial effects of rTMS for treatment-resistant depression and posttraumatic stress disorder (PTSD) are by targetting 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 so 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 reported as a percentage of the motor threshold(MT), and it is individualized for each patient. MT is defined by the visible observed movement of the abductor pollicis brevis.[3] The use of rTMS in clinical neurophysiology is by recording motor evoked potential (MEP), which assesses the conduction through the descending corticospinal tracts. MEPs allow the investigation of cortical motor control and corticospinal conduction time in the clinical setting. rTMS has two classic paradigms: Low-frequency (1Hz or less), which consists of continuous trains of single pulses, and High-frequency (>1 Hz) that consists of a burst of stimuli that usually last for 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, 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) by 2008. It is perceived as a treatment modality alternative to Electroconvulsive therapy (ECT). The first device was cleared for the treatment of MDD targeting the left DLPFC. Later, FDA approved 5 more rTMS devices and modified the initial rTMS device's indication to target the broader patient range suffering from treatment resistance with one or more antidepressant medication.

For chronic pain, studies have shown definite efficacy in the use of high-frequency rTMS 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. FDA approved marketing TMS for treatment of OCD in the year 2018.[3][4][6][7][8]

Contraindications

Although rTMS is a non-invasive technique and its side effect profile is rare, but it may induce seizures. Hence, it is not recommended for patients with epilepsy. Pre-existing neurological disease, adolescents, change in medication regime, 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 being provided, should be well equipped to deal with any seizure episode in patients.[9]

rTMS is relatively a well tolerable treatment but may present with pain at the stimulation site, posttreatment 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 pulse. 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-eight-shaped coil that is more focal. The figure-of-eight-shaped coil produces maximal current at the intersection, and thus it is also known as the double-cone coil. H-coil is another configuration that allows slower fall-off of the magnetic field.[5][10][11]

Preparation

The patient is prepared by undergoing a complete physical examination with possible lab tests. Psychiatric evaluation is done to discuss their symptoms of depression, with the antidepressant medication trials they have earlier used. It helps in determining if rTMS would make a good 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 the patient should be enquired for any metal or implanted medical devices such as stents, aneurysm clips, implanted deep brain stimulators, implanted electrical devices such as pacemakers, cochlear implants for hearing, or any magnetic implants due to the strong magnetic field produced during the procedure.[9]

Technique or Treatment

Transcranial magnetic stimulation is a unique stimulation protocol that has been used for both diagnostic and therapeutic purposes. It can be administered using three 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 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 used commonly 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 and turned off for another 30 to 60 seconds 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 is made to sit in a reclining chair with earplugs given to wear during the session. An electromagnetic coil is placed against the patient's head and is switched on-off repeatedly to produce the TMS pulses. A tapping sensation is felt on the forehead by the patient, and this is called mapping. The physician determines the amount of magnetic energy required by increasing the dose and noticing finger or hand twitch. During the process, the stimulus might be changed depending upon the individual 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 seizure. 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 follow-up for the sessions also determines 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 is still under research. 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's disease, functional tremors, focal epilepsy, cortical myoclonus, dysarthria, aphasia have also been studied.[13] For Tourette's 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 utilizes non-invasive brain stimulation and has shown promising results for diagnostic and therapeutic purposes. A detailed mental and physical health examination is essential for the physicians to understand if rTMS would effectively treat a certain individual. Treatment-resistant depression, PTSD, OCD, and Tourette's disorder are among the few where rTMS have shown beneficial effects. The physician should be aware of the medication trials the patient has initially tried. Also, one should consider if there is any substance misuse by the patient. 

A team of psychiatrists, psychologists, social workers, nurse practitioners, and primary care providers are involved and educate the patient regarding the importance of follow-up sessions. They note the medication trials the patient has tried and how the symptoms improved to the medication than to 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 manage if these patients can work or drive back to verify the effectiveness of their daily routine activities.

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-effect, referrals should be made to manage any long-term outcomes and minimize the need for medical error. In all, studies have shown that rTMS is an effective technique for treating neuropsychiatric disorders.

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References

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8.

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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]

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

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