In a controlled, pilot, maintenance trial, 67 unmedicated patients with treatment-resistant depression received an acute course of TMS.9 Forty-seven of the responders were then randomized to a 1-year follow-up trial with or without a scheduled monthly TMS session. All patients could receive reintroduction TMS if they met criteria for symptom worsening.
Both groups had a similar outcome. The number of patients who did not require TMS reintroduction was 9 of 23 (39%) in the scheduled TMS group vs 9 of 26 (35%) in the no-scheduled TMS group (P < .1). Although no difference was noted between groups, the authors commented that these preliminary results will help inform larger, more definitive trials. They concluded that both acute and maintenance TMS monotherapy might be an option—for some patients.
A long-term, naturalistic outcomes study followed 257 treatment-resistant depressed patients for 1 year after they responded to an acute course of TMS.10 In addition to most patients receiving ongoing maintenance medication, they also could receive reintroduction of TMS if symptoms became worse.
Compared with pre-TMS baseline, there was a statistically significant reduction in the mean total score on the CGI-S scale (primary outcome, P < .0001) at the end of acute treatment that was sustained at follow-up. Ninety-six patients (36.2%) required reintroduction of TMS and 75 of 120 (62.5%) who initially met response or remission criteria after acute treatment continued to meet response criteria after 1 year. The authors concluded that TMS demonstrated both a statistically and clinically meaningful durability of acute benefit during this time frame.
TMS and electroconvulsive therapy
For more than 75 years, ECT has consistently proved to be an effective treatment for major depressive disorder. Although the use of ECT has fluctuated over this period, one practice survey estimated that 100,000 patients receive ECT annually.11
ECT has limitations, however, including cost, the need for general anesthesia, and cognitive deficits that range from short-term confusion to anterograde and retrograde amnesia, which can persist for weeks beyond active treatment.12 Despite increasing awareness of mental illness, stigma also remains a significant barrier to receiving ECT.
TMS vs ECT. Several trials have directly compared ECT and TMS:
- A recent meta-analysis of 9 trials included 384 patients with depression who were considered clinically appropriate for ECT and were randomized to one or the other treatment.13 Both modalities produced a significant reduction in baseline HDRS score, but ECT (15.4 point reduction) was superior to TMS (9.3 point reduction) in the degree of improvement (P < .01).
- Another meta-analysis of 9 trials (N = 425) found ECT superior to TMS in terms of response (P < .03) and remission (P < .006) rates, based on improvement in the HDRS score.14 When psychotic depressed patients were excluded, however, TMS produced effects equivalent to ECT.
In contrast to what was seen with ECT, cognitive testing of patients who received TMS revealed no deterioration in any domain. Furthermore, one of the comparison studies observed a modest, but statistically significant, improvement in patient’s working memory-executive function, objective memory, and fine-motor speed over the course of TMS treatment.15
TMS plus ECT. A 2-week, randomized, single-blind, controlled pilot study (N = 22) examined the combination of TMS and ECT as acute treatment of depression.16 Patients were assigned to receive either unilateral non-dominant (UND) ECT 3 days a week or a combination of 1 UND ECT treatment followed by 4 days of TMS. At the conclusion of treatment, UND ECT plus TMS group produced comparable efficacy and fewer adverse effects compared with the UND ECT-only group.
TMS maintenance after acute ECT response. Most patients who are referred for ECT have a depressive illness characterized by repeated episodes and incomplete response to pharmacotherapy or psychotherapy, or both. The need for an effective maintenance strategy after the acute response is therefore critical. Medication or ECT, or both, are commonly used to maintain acute benefit but, regrettably, a recent systematic review of the durability of benefit with such strategies found a substantial percentage (approximately 50%) of patients relapsed within the first year.17
- In this context, a case series report found that 1 or 2 weekly, sequential, bilateral TMS treatments after a successful acute course of ECT maintained response in 5 of 6 patients over 6 to 12 months.18
- Another case series (N = 6) transitioned stable patients from maintenance ECT to maintenance TMS, primarily because of adverse effects with ECT.19 With a mean frequency of 1 TMS treatment every 3.5 weeks, all 6 patients remained stable for as long as 6 months. Subsequently, 2 patients relapsed—1 at 8 months and 1 at 9 months.