Side Effects Of Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) is a neuromodulation and neurostimulation technique where magnetic pulses influence the activity of the nervous system. The magnetic pulses induce tiny electrical currents in the brain to stimulate nerve cells. If TMS pulses are given repetitively, it is called repetitive TMS (rTMS).

This treatment can lead to increased or decreased electrical activity in certain brain regions. Thus, causing behavioural changes which can be beneficial in treating certain conditions, such as various mental disorders. Although this treatment offers many beneficial effects, it is vital to understand the side effects associated with TMS. 

Understanding transcranial magnetic stimulation

TMS can be applied in three different ways: 

• Single-pulse - used to map the outputs of the motor cortex, to study the time taken for electrical impulses in the brain to be conducted, as well as the time taken for brain-behaviour relations
• Paired-pulse - can be delivered to a single area or two different areas of the brain using a single or multiple coils
• Repetitive pulse - can be achieved through regular repeated single TMS pulses

Research studies have shown that TMS may be a potential treatment for a variety of conditions, such as:

• Tinnitus
• Tics
• Epilepsy
• Parkinson's disease
• Stuttering
• Spasticity
• Dystonia
• Bipolar disorder
• Hallucinations
• Drug addiction
• Catatonia
• Post-traumatic stress disorder (PTSD)
• Acute mania
• Panic
• Depression
• Schizophrenia
• Obsessive-compulsive disorder (OCD)
• Migraine
• Neuropathic pain (nerve pain/neuralgia)
• Visceral pain
• Post-stroke rehabilitation (particularly to improve hand function)

Although TMS shows potential for treating a range of diseases, it is important to note, that the majority of the therapeutic uses listed above require further research to strengthen the claims.¹ Currently, TMS is approved by the Food and Drug Administration (FDA) for treating: 

• Major depression
• Migraines 
• OCD
• Nicotine addiction

Whereas in the UK, rTMS is approved by the National Institute for Health and Care Excellence for treating depression, but only for patients who do not respond well to antidepressants. 

Side effects 

Hearing

A small number of patients have found that their auditory thresholds (the lowest levels of sound an individual can hear) had increased after TMS.² In one patient, it was found that they had a permanent change in auditory thresholds. However, this individual did not use ear plugs whilst undergoing the procedure as well as a Hesed coil (H-coil) which can penetrate deeper into the brain.³

It should be noted that when hearing protection has been used, which is the majority of studies, there were no changes in hearing.^4,5,6,7 In a paediatric study to assess hearing safety, no changes were found in 18 patients who did not use hearing protection. However, the results of this study do not necessarily mean that changes in hearing are not a concern, as the study’s sample size was too small.⁸ 

Seizures 

The most severe short-term side effect of rTMS is seizures. There have been numerous reports of seizures as a result of rTMS, many of which were early studies before defined safety thresholds were implemented. Taking into account the large groups of patients that have been given rTMS since 1998 and the limited reports of seizures, it can be concluded that there is a very low risk of seizures. 

One study found that a patient with major depression developed seizures six hours after TMS. The patient was taking antidepressant drugs which could have heightened their risk of seizures.

The seizures in this patient could have also been a pseudoseizure, which is a seizure that is not related to abnormal brain activity. This conclusion was drawn based on a normal neurological exam and electroencephalogram (EEG). However, as the seizure occurred six hours after TMS, the relationship is not certain.⁹ 

Syncope

Vasovagal syncope is a type of fainting which can be attributed to physical discomfort or anxiety. It occurs as a result of a sudden drop in blood pressure or heart rate, which causes you to faint. It may be difficult to distinguish between syncope and seizure as the behaviours displayed overlap. For example, rigid tightening of the muscles and hallucinations.

The distinguishing feature that is used to classify syncope is regaining consciousness within seconds rather than minutes.¹⁰ As the preliminary measures for suspected syncope and seizures are the same, TMS treatment should be stopped straight away.¹

Headache, discomfort and local pain 

Single-pulse TMS is generally well tolerated among patients. Whereas, the most common side effect of rTMS is pain. The intensity of pain experienced differs on a patient-by-patient basis, this could be due to the: 

• Design of the coil
• Susceptibility of the individual
• Scalp location
• Frequency and intensity of stimulation

It should be noted that, in clinical trials assessing the use of TMS, less than two per cent of patients halted treatment due to pain. Some studies have assessed options to reduce pain, such as topical anaesthetics (e.g., injecting one per cent of lidocaine locally) or the use of styrofoam pads.¹¹ Additionally, the cause of the pain associated with TMS is unclear.

Taking this into account, patients should be warned that TMS could cause pain and discomfort. Patients may have persistent headaches occasionally after treatment which can be overcome through oral painkillers. However, TMS has not been associated with migraines.¹² 

Neuropsychological changes

TMS can lead to patients being able to perform better or worse at specified tasks (e.g., improved/delayed reaction time). These effects tend to occur after one application of rTMS and can occur via spontaneous suppression of electrical signals of the brain or neural noise (similar to static in a communicational system).¹³

These side effects are often moderate, so there aren’t safety concerns associated with them.¹⁴ In the case of psychiatric diseases, two studies found that the application of rTMS led to:¹⁵

• Difficulties in memory
• Extreme tiredness
• Difficulties concentrating (this side effect was found to be mild and temporary as well as very rare)

Importantly, it has been found that rTMS may lead to the placebo effect. Thus, it can be challenging to test functions which are dependent on subjective measures versus tests that have changes which can be quantified.^16,17 

Acute psychiatric changes

Some patients with depression, who receive high or low-frequency rTMS, have reported mania as a result of treatment. Mania is a mental state that can be attributed to periods of abnormal energy levels, elevated mood and activity.¹⁸ It has been reported that rTMS in patients with major depressive disorder has led to the induction of: 

• Anxiety
• Suicidal ideation
• Psychotic symptoms
• Insomnia
• Agitation^19,20

However, it is not known if these side effects are occurring at an elevated rate in association with other interventions or compared to the natural course of the disease. In normal patients, the side effects of suicidal ideation and psychotic symptoms are not associated with rTMS. 

Summary

Transcranial magnetic stimulation (TMS) is a promising therapeutic modality for various diseases and disorders. While TMS offers potential benefits, it's important to consider the side effects that may accompany treatment. These side effects can include changes in hearing, seizures, syncope, headaches, discomfort, localised pain, neuropsychological changes, or acute psychiatric alterations.

It's worth noting that these side effects, although possible, occur at a low rate and are generally manageable with proper monitoring and care. If you are considering this treatment, always consult your healthcare provider, they will provide further information and guidance.