Advances in transcranial magnetic stimulation for managing major depressive disorders
The utility of TMS for treating depression continues to widen, as the technology is refined
Advantages of maintenance TMS over maintenance ECT include lower cost, fewer adverse effects (particularly cognitive deficits), and the ability to remain independent during the period of the treatment sessions.
TMS as an assessment tool for ECT response. TMS can be used to study excitability in cortical circuits. In a study, EEG potentials evoked by TMS before and after a course of ECT in 8 severely depressed patients revealed an increase in frontal cortical excitability, compared with baseline.20 Such findings support the ability of ECT to produce synaptic potentiation in humans. Furthermore, to the extent that depression presents with alterations in frontal cortical excitability, serial EEG-TMS measurements might be an effective tool to guide and monitor treatment progress with ECT, as well as other forms of therapeutic modulation.
Summing up: TMS and ECT. Although a definitive comparative study is needed, available evidence suggests that TMS might be an alternative treatment in a subgroup of patients who are referred for ECT. Factors that might warrant considering TMS over ECT include:
- patient preference
- fear of anesthesia
- concern about cognitive deficits
- stigma.
Although TMS might offer a workable alternative to ECT for acute and maintenance treatment of depression in selected patients, further refinement of the delivery of TMS is also needed to (1) enhance its efficacy and (2) identify clinical and biological markers to better define this select population.
Standard TMS treatment parameters
Superficial TMS. Superficial TMS for depression typically involves a single coil placed over the left dorsolateral prefrontal cortex. The standard, FDA-approved protocol includes stimulating at 110% of motor threshold with 75, 4-second trains at 10 Hz (ie, 40 stimulations) interspersed by 26-second intertrain intervals. Without interruption, a standard treatment session takes 37.5 minutes and delivers a total of 3,000 pulses. Most patients require 20 to 30 sessions, on a Monday-through-Friday schedule, to achieve optimal benefit.
This approach stimulates to a depth of approximately 2 or 3 cm. The coil usually is placed over the left dorsolateral prefrontal cortex because earlier studies indicated that decreased activity in this part of the brain correlates with symptoms of depression. When TMS is administered in a rapid repetitive fashion (at >1 Hz; typically, at 10 Hz), blood flow and metabolism in that area of the brain are increased. In addition, imaging studies indicate that trans-synaptic connections with deeper parts of the brain also allow modulation of other relevant neural circuits.
An alternate approach, less well-studied, involves low-frequency stimulation over the right dorsolateral prefrontal cortex. Parameters differ from what is used in left high-frequency dorsolateral prefrontal cortex TMS: frequency <1 Hz; train durations as long as 15 minutes; an intertrain interval of 25 to 180 seconds; 120 to 900 stimulations per train; and 2,400 to 18,000 total stimulations.
One hypothesis is that this low-frequency approach selectively stimulates inhibitory interneurons, decreases local neuronal activity and diminishes blood flow to deeper structures, such as the amygdala. Although right low-frequency TMS, compared with left high-frequency TMS, has potential advantages of better tolerability and decreased risk for seizures, its relative efficacy is unclear.
Deep TMS. Studies also are pursuing different coil configurations that allow for more direct stimulation of relevant structures (eg, prefrontal neuronal pathways associated with the reward system).
One of these coil designs (ie, the H-coil), coupled to a Magstim TMS stimulator, recently received FDA clearance for treatment-resistant depression. In the pivotal, sham-controlled study, patients received 20 treatment sessions over 4 weeks.21 The treatment protocol consisted of a helmet-like coil placed over the medial and lateral prefrontal cortex. Stimulation parameters included an 18-Hz frequency; stimulation intensity of 120% motor threshold; stimulation train duration of 2 seconds; and an intertrain interval of 20 seconds. The treatment sessions lasted 20.2 minutes and delivered a total of 1,980 stimulations.
Based on the 21-item HDRS, the active treatment coil group achieved a significantly greater decrease in baseline score (6.39 vs 3.28; P < .008); a greater response rate (37% vs 27.8%; P < .03); and a greater remission rate (30.4% vs 15.8%; P < .016) compared with the sham coil group.
Next, in what is the only randomized, controlled maintenance assessment to date, the same patients were followed for an additional 12 weeks, continuing blinded treatments twice weekly. At the end of the second phase, the active treatment group also demonstrated greater benefit than the sham group (P < .03). One seizure did occur, possibly related to excessive alcohol use; but this raises the question of whether treating at a higher frequency (18 Hz) with greater depth and less focality might increase the risk of seizure.
