Repetitive Transcranial Magnetic Stimulation for Depression Treatment

What is Transcranial Magnetic Stimulation?

Transcranial Magnetic Stimulation (TMS) is a non-invasive technique that uses a powerful electro-magnet placed on the scalp of a person to alter brain activity. Originally developed as a diagnostic tool for mapping brain function, TMS appears promising as a treatment for a variety of complex neuropsychiatric conditions, particularly major depression.

TMS induces an electromagnetic current in the underlying cortical neurons, which may explain its therapeutic effects. Repetitive TMS, using varying frequencies and intensities, can increase or decrease excitability in the cortical area directly targeted by the stimulation. Recent studies combining TMS and neuroimaging techniques, such as magnetic resonance imaging, demonstrate that the effects of TMS are not limited to the cortex but spread to functionally related subcortical structures. This finding provides a basis for using TMS to treat the pathologic neural activity that may underlie neuropsychiatric illness.

Repetitive transcranial magnetic stimulation, known as rTMS, can produce longer lasting changes for treatment of various neurological conditions (e.g. migraine, stroke, Parkinson's disease, dystonia, tinnitus) and psychiatric conditions (e.g. major depression, auditory hallucinations).

Clinicians and physicians are excited about the therapeutic applications of repetitive transcranial magnetic stimulation (r TMS) because it is non-invasive, unlike other implanted devices such as the Vagus Nerve Stimulation (VNS) System, and does not have the pain and potentially devastating side effects of Electroconvulsive Therapy (ECT or "shock therapy").

Effects on the Brain

The exact details of how TMS functions are still being explored. The effects of TMS can be divided into two types depending on the mode of stimulation:
  • Single or paired pulse TMS. The pulse(s) causes neurons in the neocortex under the site of stimulation to depolarise and discharge an action potential. If used in the primary motor cortex, it produces muscle activity referred to as a motor-evoked potential (MEP) which can be recorded on electromyography (EMG). If used on the occipital cortex, 'phosphenes' (flashes of light) might be detected by the subject. In most other areas of the cortex, the participant does not consciously experience any effect, but his or her behavior may be slightly altered (e.g. slower reaction time on a cognitive task), or changes in brain activity may be detected using Positron Emission Tomography or fMRI. Effects resulting from single or paired pulses do not outlast the period of stimulation. A review of TMS can be found in the Handbook of Transcranial Magnetic Stimulation.
  • Repetitive TMS (rTMS) produces effects which last longer than the period of stimulation. rTMS can increase or decrease the excitability of corticospinal or corticocortical pathways depending on the intensity of stimulation, coil orientation and frequency of stimulation. The mechanism of these effects is not clear although it is widely believed to reflect changes in synaptic efficacy akin to long-term potentiation (LTP) and long-term depression (LTD).

Single pulse TMS is regarded as safe although seizures following single pulse TMS stimulation have been reported in some patients with stroke or other disorders involving the central nervous system. Seizures from single or paired pulse TMS are rare, especially in patients without pre-existing conditions that affect the central nervous system such as epilepsy. rTMS has been reported to cause seizures in normal individuals at certain combinations of stimulation frequency and intensity. Guidlines have since been instituted regarding the maximum safe frequency and intensity combinations of rTMS.

Common adverse effects of TMS are:
  • Discomfort or pain from the stimulation of the scalp and associated nerves and muscles on the overlying skin. Discomfort is rarely a problem for single pulse TMS but some people may find rTMS quite uncomfortable.
  • Rapid deformation of the TMS coil produces a loud clicking sound which scales with stimulator intensity. The sound has been characterized as deceptively mild sounding and has the potential to affect hearing, given sufficient exposure (particularly relevant for rTMS). Hearing protection may be offered to prevent this.
  • rTMS in the presence of EEG electrodes can result in electrode heating and, in severe cases, skin burns.
FDA approval

In January 2007 FDA advisory panel said clinical trials failed to establish that the device was clinically effective. Although TMS-treated patients were twice as likely as sham-treated patients to show clinical benefit, some panel members said this effect was "small," "borderline," "marginal," and "of questionable clinical significance."

However, two years later, in October 8, 2008, a TMS device, NeuroStar, manufactured by Neuronetics Inc. has been approved for use by the Food and Drug Administration (FDA) in the United States for use in adult patients with major depression who have previously tried medication and not improved satisfactorily.

Most TMS use is currently done off label or under research protocols approved by hospital ethics boards and, in the US, often under Investigational Device Exemption from the U.S. Food and Drug Administration (FDA). The requirement for FDA approval for research use of TMS is determined by the degree of risk as assessed by the investigators, the FDA, and the local ethics authority.

Main Differences between ECT and TMS

  • ECT, also known as electroshock therapy, uses an electric shock to induce seizure. TMS uses a magnetic field to induce a much smaller electric current in a specific part of the brain without causing seizure or loss of consciousness.
  • ECT is extremely effective in treating severe depression. TMS is not so powerful. It is used to treat milder depression, and it works best in patients who have failed to benefit from one, but not two or more, antidepressant treatments.
  • TMS is much safer than ECT. Unlike ECT, TMS does not require sedation and is administered on an outpatient basis.

Patients undergoing TMS must be treated four or five times a week for four weeks.

Because your psychiatrist needs to determine how to most effectively administer treatment, your first session could last up to an hour and a half. You will be provided and asked to wear protective earplugs, as the system emits a tapping sound during operation.

Your psychiatrist will first perform a test to identify your motor threshold. The motor threshold is the amount of magnetic field strength that results in a movement of your right thumb. This test is important because it identifies the magnetic field strength that will be used in your treatment. This field strength is customized for each patient to deliver the correct treatment dose.

After this initial procedure, the doctor will determine the place on the head where the TMS treatment will be applied and the treatment coil will be moved to that location. This will allow you to receive optimal treatment.

The physician will then administer TMS Therapy over a 40-minute period. In 30-second intervals, the device will deliver rapid “pulses” of the magnetic fields. These will feel like tapping on your scalp. Some patients may find this tapping uncomfortable. Your physician may be able to make adjustments to reduce this discomfort.


The efficiency of repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression has been assessed in a number of acute treatment trials during the last 10 years. Little is known about the long-term impact of the treatment on the disorder and its effectiveness when applied for repeated relapses of depression over time. The majority of patients achieved a significant improvement in each treatment course with significant improvements achieved in patients treated with both low-frequency right-sided rTMS and high-frequency left-sided rTMS. While some of the trials produce controversial results, the widely accepted approach suggests that rTMS may have value in the treatment of episodes of depressive relapse with little reduction in efficacy over time.

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