The Expanding Evidence Base for rTMS Treatment of Depression
The Expanding Evidence Base for rTMS Treatment of Depression
Purpose of Review Daily left prefrontal transcranial magnetic stimulation (TMS) for several weeks was first proposed as an acute treatment for depression in the early 1990s, and was Food and Drug Administration (FDA) approved in 2008. In the past year, several important studies have been published that extend our understanding of this novel treatment approach.
Recent Findings The first round of multisite clinical trials with TMS addressed whether prefrontal rTMS has efficacy and were conducted in carefully selected depressed patients who were antidepressant medication free. Several more recent studies assess the clinical effectiveness of TMS and report that about 35–40% of real-world patients who are commonly taking adjunctive antidepressants reach remission with a modest side effect profile. There are also new studies examining the durability of the TMS-induced antidepressant effect. Fifty-eight percent of TMS remitters remain remitted at 3-month follow-up.
Summary These recent studies suggest that daily left prefrontal TMS over several weeks as a treatment for depression not only appears to have efficacy in rigorous randomized controlled trials, but is effective in real-world settings, with remission in 30–40% of patients. The TMS antidepressant effect, once achieved, appears to be as durable as with other antidepressant medications or interventions. Much more research is needed, particularly with issues such as the TMS coil location, stimulation intensity and frequency, and dosing strategy.
Transcranial magnetic stimulation (TMS) is perhaps the most popular of the new brain stimulation techniques because its clinical effects are produced without the need for a craniotomy [as with deep brain stimulation (DBS)] or seizure induction [as with electroconvulsive therapy (ECT)]. As a focal, noninvasive form of brain stimulation, TMS produces limited side effects and can be used as either a therapy or a research tool (e.g., to measure how excitable the brain is or to produce a temporary lesion).
TMS uses an electromagnetic coil on the scalp to create an extremely potent (near 1.5 T) but brief (μs) magnetic field. This magnetic field enters the surface of the brain without interference from the skin, muscle, and bone. In the brain, the magnetic pulse encounters nerve cells and induces electrical current to flow. Thus, the magnetic field created from electrical energy in the coil passes through the skull and is converted back into electrical energy in the brain. It is for this reason that TMS is sometimes called 'electrodeless electrical stimulation'.
The idea of using TMS, or something akin to it, to alter neural function goes back to at least the early 1900s. In 1902 Pollacsek and Beer, psychiatrists working down the street from Sigmund Freud in Vienna, filed a patent to treat depression and neuroses with an electromagnetic device that looks surprisingly like today's TMS machines. The modern TMS era began in 1985 when Barker et al., working in Sheffield, England, created a focal electromagnetic device with sufficient power to induce currents in the spine. They quickly realized that their device could also directly and noninvasively stimulate the human brain, launching the modern TMS era.
Repetitive TMS or rTMS can create behaviors not seen with single pulses, including the potential risk of causing an unintended seizure. Worldwide, out of the 300 000 or more treatment or research sessions in the history of TMS, approximately 20 seizures have occurred. In the United States, since market introduction of the NeuroStar TMS Therapy system in October 2008, seven seizures have been reported out of 250 000 NeuroStar TMS treatment sessions in over 8000 patients. In five of the seven seizures, patients had concurrent use of medications that may have altered seizure threshold. The estimated risk of seizure under ordinary clinical use is approximately one in 30 000 treatments (0.003% of treatments) or one in 1000 patients (0.1% of patients) (M. Demitrack, Neuronetics, personal communication). This risk is less than or comparable to the risk of seizure associated with antidepressant medications. All TMS seizures have occurred during stimulation, rather than later, and have been self-limited with no sequelae. rTMS seizures are more likely to occur with certain combinations of TMS intensity, frequency, duration and interstimulus interval.
Abstract and Introduction
Abstract
Purpose of Review Daily left prefrontal transcranial magnetic stimulation (TMS) for several weeks was first proposed as an acute treatment for depression in the early 1990s, and was Food and Drug Administration (FDA) approved in 2008. In the past year, several important studies have been published that extend our understanding of this novel treatment approach.
Recent Findings The first round of multisite clinical trials with TMS addressed whether prefrontal rTMS has efficacy and were conducted in carefully selected depressed patients who were antidepressant medication free. Several more recent studies assess the clinical effectiveness of TMS and report that about 35–40% of real-world patients who are commonly taking adjunctive antidepressants reach remission with a modest side effect profile. There are also new studies examining the durability of the TMS-induced antidepressant effect. Fifty-eight percent of TMS remitters remain remitted at 3-month follow-up.
Summary These recent studies suggest that daily left prefrontal TMS over several weeks as a treatment for depression not only appears to have efficacy in rigorous randomized controlled trials, but is effective in real-world settings, with remission in 30–40% of patients. The TMS antidepressant effect, once achieved, appears to be as durable as with other antidepressant medications or interventions. Much more research is needed, particularly with issues such as the TMS coil location, stimulation intensity and frequency, and dosing strategy.
Introduction
Transcranial magnetic stimulation (TMS) is perhaps the most popular of the new brain stimulation techniques because its clinical effects are produced without the need for a craniotomy [as with deep brain stimulation (DBS)] or seizure induction [as with electroconvulsive therapy (ECT)]. As a focal, noninvasive form of brain stimulation, TMS produces limited side effects and can be used as either a therapy or a research tool (e.g., to measure how excitable the brain is or to produce a temporary lesion).
TMS uses an electromagnetic coil on the scalp to create an extremely potent (near 1.5 T) but brief (μs) magnetic field. This magnetic field enters the surface of the brain without interference from the skin, muscle, and bone. In the brain, the magnetic pulse encounters nerve cells and induces electrical current to flow. Thus, the magnetic field created from electrical energy in the coil passes through the skull and is converted back into electrical energy in the brain. It is for this reason that TMS is sometimes called 'electrodeless electrical stimulation'.
Brief History
The idea of using TMS, or something akin to it, to alter neural function goes back to at least the early 1900s. In 1902 Pollacsek and Beer, psychiatrists working down the street from Sigmund Freud in Vienna, filed a patent to treat depression and neuroses with an electromagnetic device that looks surprisingly like today's TMS machines. The modern TMS era began in 1985 when Barker et al., working in Sheffield, England, created a focal electromagnetic device with sufficient power to induce currents in the spine. They quickly realized that their device could also directly and noninvasively stimulate the human brain, launching the modern TMS era.
Seizure Risk
Repetitive TMS or rTMS can create behaviors not seen with single pulses, including the potential risk of causing an unintended seizure. Worldwide, out of the 300 000 or more treatment or research sessions in the history of TMS, approximately 20 seizures have occurred. In the United States, since market introduction of the NeuroStar TMS Therapy system in October 2008, seven seizures have been reported out of 250 000 NeuroStar TMS treatment sessions in over 8000 patients. In five of the seven seizures, patients had concurrent use of medications that may have altered seizure threshold. The estimated risk of seizure under ordinary clinical use is approximately one in 30 000 treatments (0.003% of treatments) or one in 1000 patients (0.1% of patients) (M. Demitrack, Neuronetics, personal communication). This risk is less than or comparable to the risk of seizure associated with antidepressant medications. All TMS seizures have occurred during stimulation, rather than later, and have been self-limited with no sequelae. rTMS seizures are more likely to occur with certain combinations of TMS intensity, frequency, duration and interstimulus interval.
