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Repetitive Transcranial Magnetic Stimulation in Depression: A Changing Landscape

Repetitive Transcranial Magnetic Stimulation in Depression: A Changing Landscape


It is estimated that globally 121 million people suffer from clinical depression. Despite an extensive psychotherapeutic and pharmacological arsenal, many affected individuals continue to suffer while the burden on the health care system increases. Of the millions affected worldwide, 20% to 40% are resistant to pharmacological antidepressant treatments while another third show poor response.1 Many medications are associated with significant adverse effects (eg, weight gain, sexual dysfunction), and there is a recognized need for better treatment options for treatment-resistant depression.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive, nonconvulsive neurostimulation treatment. Approval of an rTMS device was granted by the FDA in October 2008. The approval was for 10 Hz stimulation of the left dorsolateral prefrontal cortex (DLPFC) as a treatment for major depression in patients who have not responded to only one antidepressant. rTMS has rather benign adverse effects—the most frequent are mild headache, nausea, and irritation at point of stimulation.2 The most serious adverse effect is the induction of a seizure, which is exceedingly rare, with an estimated incidence of less than 1 in 1000 patients.

Mechanism of action

Magnetism and electricity are intrinsically related to each other. Electrical currents generate magnetic fields (eg, magnetic resonance scanners), and conversely, magnetic fields elicit currents in conductors. rTMS takes advantage of this link and makes use of the electromagnetic induction phenomenon to elicit a focal current in brain tissue strong enough to trigger action potentials in neurons. And, it does so in a noninvasive fashion (ie, there is no need for a surgical intervention).

A coil made of an electrical conductor that is isolated by a plastic shell acts as the inductor. When pulses of current pass through the coil, a strong focal magnetic field is generated (on the order of 1.5 to 2 Tesla). This magnetic field crosses the skull and soft tissue unimpeded; the brain tissue acts as the conductor, and an electrical current is generated parallel to the current in the coil windings and in the opposite direction. The current induced is maximal at the focal point of the coil and diminishes with distance. It is sufficiently strong to cause neuronal polarization and depolarization in the volume lying 3 to 4 cm around the focal point. The entire procedure is carried out with no need for general anesthesia or prior procedural preparation (eg, intravenous line, heart rate or blood pressure monitoring), as opposed to other convulsive neurostimulation techniques, such as magnetic seizure therapy and electroconvulsive therapy.

A brief overview

Beginning in the 1980s, a series of positron emission tomography (PET) studies showed that glucose metabolism is reduced in a number of areas of the prefrontal cortex, including the DLPFC.3,4 Additional research using PET demonstrated that effective antidepressant treatment was correlated with reversing the hypoactivity in the prefrontal cortex.5,6 More recent studies using functional MRI (fMRI) and electroencephalographic recordings show that it is not only the DLPFC that changes its level of activation.7,8 A network of brain regions involved in cognitive control and emotion regulation, including the DLPFC, changes its activity in response to effective antidepressant treatment.

The large body of convergent evidence pointing at the DLPFC as a neuroanatomical location of interest in depression built a compelling and solid rationale for early studies using rTMS to target the DLPFC in depression treatment.9-11 Pilot studies then showed that rTMS to the left DLPFC was an effective treatment for a proportion of patients with major depressive episodes who had not responded to earlier antidepressant treatments. Indeed, a recent meta-analysis shows that rTMS is effective in 30% to 40% of individuals with treatment-resistant depression.12

Conventional rTMS protocols typically target the left DLPFC. The discharge frequency of stimulation (ie, the number of times the magnetic field is generated and the current induced on brain tissue) is usually at a frequency of 10 Hz; this high-frequency stimulation increases cortical excitability. Other protocols have targeted the right DLPFC using low-frequency stimulation at 1 Hz; this protocol decreases cortical excitability.

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