To assess the potential advantages, as well as the relative safety, of this approach over standard TMS delivery, an adequately designed and powered trial comparing the H-coil and a single-coil device is needed.
Alternate TMS approaches
Efforts to improve the clinical effectiveness of TMS for treating depression include several approaches.
Theta burst stimulation (TBS) is a patterned form of TMS pulse delivery that utilizes high and low frequencies in the same stimulus train (eg, three 50-Hz bursts delivered 5 times a second). Such a pulse sequence can modulate long-term depression and long-term potentiation mechanisms that induce plasticity in areas such as the hippocampus.22
Intermittent TBS (iTBS) administers stimulations over a relatively brief duration (eg, 2 seconds) or intermittently (eg, every 10 seconds) for a specific period (eg, 190 seconds [600 pulses in total]) over the left dorsolateral prefrontal cortex. This technique induces long-term potentiation and produces effects similar to those of high-frequency TMS.
In contrast, continuous TBS (cTBS) administers a continuous train (eg, 40 seconds [600 total pulses]) over the right dorsolateral prefrontal cortex. This induces long-term depression and produces effects similar to low-frequency TMS.
Recent studies using different delivery paradigms have generated mixed results:
Study 1: Fifty-six patients with depression received active treatment; 17 others, a sham procedure.23 This study used 3 different conditions:
- a combination of low-frequency and high-frequency TMS stimulation, administered over the right and left dorsolateral prefrontal cortices, respectively
- a combination of iTBS over the left dorsolateral prefrontal cortex and cTBS over the right dorsolateral prefrontal cortex
- a sham procedure, in which no magnetic field was created.
Neither active treatment arm separated from the sham procedure based on change scores in the 21-item HDRS (P = not significant).
Study 2: Sixty treatment-resistant depression patients were assigned to cTBS, iTBS, a combination of the 2 procedures, or a sham procedure.24 After 2 weeks, the active treatment arms produced the greatest benefit, based on change in scores on the 17-item HDRS, which differed significantly among the 4 groups (F value = 6.166; P < .001); the iTBS and combination arms demonstrated the most robust effect.
There were also significantly more responders in the iTBS (40.0%) and combination groups (66.7%) than in the cTBS (25.0%) and sham groups (13.3%) (P < .010). A lower level of treatment refractoriness predicted a better outcome.
Study 3: Twenty-nine depressed patients were randomized to cTBS over the right dorsolateral prefrontal cortex or a sham procedure.25 Overall, there was no difference between groups; however, actively treated patients who were unmedicated (n = 3) or remained on a stable dosage of medication during treatment (n = 8) did experience a significantly greater reduction in the HDRS score.
Study 4: In a pilot trial, 32 depressed patients were randomized to 30 sessions of adjunctive combined iTBS plus cTBS or bilateral sham TBS.26 Based on reduction from the baseline Montgomery-Åsberg Depression Rating Scale score, 9 patients in the active treatment group and 4 in the sham group achieved response (odds ratio, 3.86; P < .048).
If at least comparable efficacy can be clearly demonstrated, advantages of TBS over standard TMS include a significantly reduced administration time, which might allow for more patients to be treated and reduce associated costs of treatment.27
Magnetic low-field synchronized stimulation is produced by rotating spherical rare-earth magnets that are synchronized to an individual’s alpha frequency. A recent 6-week, double-blind, sham-controlled trial (N = 202) reported that, in the intention-to-treat population, there was no difference in outcome between treatment arms. In patients who completed the study according to protocol (120 of 202), however, active treatment was significantly better in decreasing baseline HDRS score (P < .033).28
Magnetic seizure therapy (MST) is an experimental approach to treating patients with more severe depression that is resistant to medical therapy. The primary aim is to use TMS to induce a seizure, thus achieving the same efficacy as provided by ECT but without the adverse cognitive effects of ECT. With MST, the TMS device uses much higher stimulation settings to produce a seizure—the goal being to avoid direct electrical current to the brain’s memory centers.29
A pilot study considered the clinical and cognitive effects of MST in a group of 26 treatment-resistant depression patients (10 randomized; 16 open-label).30 Based on reduction in baseline HDRS scores at the end of the trial, 69% of patients achieved response and 46% met remission criteria; however, one-half of patients relapsed within 6 months.
Importantly, no cognitive adverse effects were observed. Furthermore, the antidepressant and anti-anxiety effects of MST were associated with localized metabolic changes in brain areas implicated in the pathophysiology of depression.