Durability of clinical benefit with transcranial magnetic stimulation (TMS) in the treatment of pharmacoresistant major depression: assessment of relapse during a 6-month, multisite, open-label study

Background

Although transcranial magnetic stimulation (TMS) can be an effective acute antidepressant treatment, few studies systematically examine persistence of benefit.

Objective

We assessed the durability of antidepressant effect after acute response to TMS in patients with major depressive disorder (MDD) using protocol-specified maintenance antidepressant monotherapy.

Methods

Three hundred one patients were randomly assigned to active or sham TMS in a 6-week, controlled trial. Nonresponders could enroll in a second, 6-week, open-label study. Patients who met criteria for partial response (i.e., >25% decrease from the baseline HAMD 17) during either the sham-controlled or open-label study (n = 142) were tapered off TMS over 3 weeks, while simultaneously starting maintenance antidepressant monotherapy. Patients were then followed for 24 weeks in a naturalistic follow-up study examining the long-term durability of TMS. During this durability study, TMS was readministered if patients met prespecified criteria for symptom worsening (i.e., a change of at least one point on the CGI-S scale for 2 consecutive weeks). Relapse was the primary outcome measure.

Results

Ten of 99 (10%; Kaplan-Meier survival estimate = 12.9%) patients relapsed. Thirty-eight (38.4%) patients met criteria for symptom worsening and 32/38 (84.2%) reachieved symptomatic benefit with adjunctive TMS. Safety and tolerability were similar to acute TMS monotherapy.

Conclusions

These initial data suggest that the therapeutic effects of TMS are durable and that TMS may be successfully used as an intermittent rescue strategy to preclude impending relapse.

Keywords: antidepressant, clinical trial, major depression, maintenance of effect, TMS, treatment resistance