While some clinicians are using TBS off-label, a recent non-inferiority trial (N = 395) reported similar efficacy and safety comparing standard 10 Hz TMS to an iTBS protocol at 120% of resting motor threshold (both over the left DLPFC).8 This has led to FDA clearance of the TMS device adapted to provide iTBS in this trial.8
From a more practical perspective, TBS has the potential to reduce the number of pulses (eg, 600 vs 3,000) and the total number of sessions required, as well as the duration of treatment sessions (eg, 37.5 minutes to <5 minutes). This can accelerate the time to response and decrease patient and staff commitment, with resulting cost savings.9 Despite this recent progress, ongoing research still needs to clarify issues such as the risk/benefit profile, particularly in younger and older populations, as well as assessment of duration of initial benefit and appropriate maintenance strategies.
New devices
Another initiative is the development of alternative TMS equipment. For example, newer coil designs with enhanced cooling ability allow for a substantial decrease in the required inter-train interval duration between stimulation trains, thus shortening the total session duration by approximately 50% (eg, from 37.5 to 19 minutes). The use of different coil arrays (eg, the H-coil capable of deeper vs surface stimulation) may allow for more direct stimulation of relevant neurocircuitry (eg, cingulate cortex), possibly improving efficacy and shortening time to onset of benefit. However, in head-to-head comparisons with single-coil devices, enhanced efficacy for depression has not been clearly demonstrated. One caveat is that the increase in depth of magnetic field penetration results in a loss of focality, resulting in the stimulation of larger brain areas. This might increase the risk of adverse effects such as seizures.
Increasing durability of effect
Because high relapse and recurrence rates compromise the initial benefit of any antidepressant therapy, appropriate maintenance strategies are essential. Several studies have evaluated strategies to maintain the acute benefit of TMS for treatment-resistant depression.
One was a 6-month, open-label TMS durability of effect trial for acute responders (n = 99) in the pivotal registration study.5 During this study, all participants were given antidepressant medication monotherapy. In addition, with early indication of relapse, patients received a reintroduction of TMS sessions (32/99 patients; mean number of sessions = 14.3). With this protocol, approximately 84% re-achieved their response status. The overall relapse rate was approximately 13%.5
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