A New Treatment Option for Major Depression

Transcranial magnetic stimulation (TMS) is noninvasive focused brain stimulation that uses pulsed magnetic fields. The underlying mechanism depends on the principle of electromagnetic induction, the process (discovered by Faraday in 1839) by which electrical energy is converted into a magnetic field and vice versa.¹

Earlier prototypes of TMS date back to the beginning of the 20th century when Sylvanus P. Thompson (a hysics professor) reported the use of a large magnetic apparatus that could induce phosphenes from retinal stimulation. However, it was the design by Barker and colleagues in 1985 of a magnetic stimulator that was powerful enough to stimulate the cerebral cortex that led to the modern TMS era.

TMS devices use a dynamic or pulsed magnetic field of about 1.5 Tesla strength (of similar intensity to that of an MRI), which is generated by ultrabrief pulses of electrical current. The magnetic field can traverse the cranium to reach the cortex with virtually no impedance, unlike electrical stimulation of the scalp. At the cortex, the magnetic field is transformed (by virtue of electromagnetism) into a local electrical field that depolarizes neurons in the cortical region of interest. In contrast with the more global brain stimulation produced by electroconvulsive therapy, TMS produces focal stimulation of about 1 cm².

TMS can increase or reduce regional brain activity relative to baseline depending on the frequency of TMS pulses. Administered at a low frequency of 1 Hz or less (currently off label) TMS is believed to preferentially activate interneurons that release inhibitory neurotransmitters; it therefore may induce inhibition within regional neural circuitry. Fast frequency TMS (frequencies greater than 1 Hz, up to about 20 Hz) is believed to have primarily glutamergic or excitatory effects on neurotransmission. This is hypothesized to produce long-term potentiation and possible induction of neuroplasticity within neural circuits.

The FDA approved a TMS device in October, 2008 as a treatment option for patients with unipolar, nonpsychotic, major depression who have failed to respond to a single adequate antidepressant treatment during the current depressive episode. The FDA based its approval on data from a large (N = 301), industry-sponsored, multicenter randomized clinical trials of TMS applied at 10 Hz to the left prefrontal cortex for 20 to 30 sessions over 4 to 6 weeks.^2,3

The current FDA label and approval is narrow.⁴ The FDA label is silent on treatment of previous major depressive episodes: it does not matter if a patient had failed to respond to several antidepressant medications in previous episodes, it will still be “on-label” treatment as long as there has been only one antidepressant medication non-response in the current major depression episode. The use of TMS to treat bipolar depression or psychotic depression is off-label.

TMS is safe and well tolerated overall but there are some contraindications and cautions that need to be considered before treatment. The presence of nonremovable metallic objects within the head and implanted devices such as a deep brain stimulator or cochlear implant contraindicate use of TMS. Other implanted medical devices, such as cardiac pacemakers and vagus nerve implants, are also relative but not absolute contraindications. Underlying organic brain disease or a personal or close family history of epilepsy are viewed as significant cautions.

Patients are fully awake and aware throughout a TMS session: no sedation is necessary. Thus, patients return to normal activities immediately after the session and can drive themselves for treatment. TMS therapy is therefore compatible with continuing to work and maintaining one’s usual activities.

A large number of psychiatrists in private practice as well as academic medical centers now offer TMS as a clinical option to patients. To our knowledge, insurance coverage is currently determined on a case-by-case basis. For most patients, TMS is largely a self-pay option.

References:

References

1. Faraday M. Experimental Research in Electricity. Quartich (B). 1839.
2. O’Reardon JP, Solvason HB, Janicak PG, et al. Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biol Psychiatry. 2007;62:1208-1216.
3. Hines JZ, Lurie P, Wolfe SM. Post hoc analysis does not establish effectiveness of rTMS for depression. Neuropsychopharmacol. 2009;34:2053-2054.
4. Lisanby SH, Husain MM, Rosenquist PB, et al. Daily Left Prefrontal repetitive transcranial magnetic stimulation in the acute treatment of major depression: clinical predictors of outcome in a multisite, randomized controlled trial. Neuropsychopharmacology. 2009;34:522-534.