Are We Ready for TMS Maintenance?

Joan A. Camprodon, M.D.

Transcranial magnetic stimulation (TMS) is an established, noninvasive, and nonconvulsive neuromodulation technique initially developed in the mid-1980s as a tool to study human neurophysiology (1). Since that time, several diagnostic and therapeutic clinical applications for TMS have been developed that are part of the standard of care in neurology, neurosurgery, and psychiatry clinics around the world.

Notably, in 2008 the Food and Drug Administration (FDA) cleared the use of high-frequency repetitive TMS (rTMS) to the dorsolateral prefrontal cortex for the treatment of major depressive disorder (MDD) (2). Four TMS systems have since been cleared by the FDA and are commercially available for the treatment of depression in the United States. Although many insurance companies are now covering TMS treatments, there are significant differences across states.

Most clinical research efforts to date have focused on understanding the role of TMS as an acute treatment for depression. The largest multicenter naturalistic trial studied the effect of TMS on 307 patients who presented to 42 U.S.-based TMS clinics with persistent symptoms of MDD (3).

After a standard acute course of TMS, the response rate was 58 percent, and the remission rate was 37.1 percent, according to the primary outcome measure (Clinical Global Impressions-Severity [CGI-S] scale). When considering secondary measures (Patient Health Questionnaire [PHQ-9] and Inventory of Depressive Symptoms-Self Report [IDS-SR]), the response rate ranged from 41.5 percent to 58 percent and the remission rate ranged from 26.5 percent to 37.1 percent.

While these data are encouraging and a motivation to continue translational and clinical research efforts to further improve the acute efficacy of TMS, the clinical management of depression does not end after the initial acute course of treatment, even if successful. A longitudinal study of 257 adults with treatment-resistant depression found that 70.5 percent of patients who remit after a full course of TMS remain in remission a year later, and 62.5 percent of patients who respond retain the therapeutic benefit over the same period (4). This is not without additional treatment though: 36.2 percent of the patients followed in this study required more TMS during the one-year follow-up period, ranging from a couple booster sessions to an additional full course (the mean number of sessions was 16.2).

Interestingly, additional TMS was more likely in the subgroups that obtained initial benefit (42.1 percent of remitters and 61.4 percent responders versus 32.2 percent of partial responders and 19.5 percent of nonresponders). These data tell us two things: the effects of TMS are durable, and additional TMS after the acute course of treatment may have a role in keeping patients well.

What should we offer to patients after they have completed an acute course of TMS treatment, particularly if they responded? The current standard is to return patients to their outpatient providers for continued pharmacological and/or psychotherapeutic treatment, and if symptoms relapse, a new course of TMS can be considered. But similar to ECT, one could envision a relapse-prevention strategy that includes maintenance treatments after the acute course.

One study found that clustered TMS maintenance (five sessions over two days, done once a month) prevented relapse better than no maintenance (5). A different protocol designed as one session per week for two weeks, followed by one session every two weeks for two months, and finally one session per month for two months also proved to prevent relapse more effectively than lack of maintenance (6).

In contrast, another recent study reported that once-monthly TMS sessions may not be superior to “watchful waiting” for antidepressant-free MDD patients who responded to an acute course of TMS (7). This result, though negative, is important as it provides evidence for the limits of relapse prevention efficacy (that is, once-monthly TMS in medication-free patients may not be sufficient).

While determining the most effective maintenance protocol for TMS as well as the patients who are the most appropriate to receive it will require more research, a body of evidence is starting to grow in support of maintenance TMS as an effective strategy for relapse prevention. Appropriately powered clinical trials specifically designed to answer questions related to maintenance are needed, but in the meantime clinicians (and health insurance companies) need to make decisions about the most effective (and cost-effective) treatment choices for patients who are presenting for treatment today. ■