Neuromodulation describes any treatment that modifies or alters the activity of the nervous system. In the broadest sense, this term could be said to refer to pharmaceuticals, but the term generally is used to refer to treatments that use some form of electromagnetic stimulus. Advances in therapeutic neuromodulation now provide clinicians with various options beyond medication and psychotherapy to treat depression. Although electroconvulsive therapy (ECT) is the prototype therapeutic neuromodulation approach, many patients with treatment-resistant depression are not appropriate candidates or are unwilling to consider ECT because of its disadvantages. More recent alternatives provide a wide range of approaches, for example, transcranial magnetic stimulation (TMS) and vagus nerve stimulation (VNS), both of which have U.S. Food and Drug Administration (FDA) indications for management of more difficult-to-treat depressions. Other approaches, none of which has FDA clearance yet, include focal electrically administered seizure therapy (FEAST), magnetic seizure therapy (MST), deep brain stimulation (DBS), and transcranial direct current stimulation (tDCS). These approaches can be categorized based on the need for a surgical procedure (i.e., invasive vs. noninvasive) and the need to produce a seizure to achieve their clinical benefit (i.e., convulsive vs. nonconvulsive) (Table 7–1). In this chapter, we focus on the potential role of TMS relative to ECT. We provide a broad overview of the literature and make recommendations for patient selection. A full discussion of other emerging techniques is beyond the scope of this chapter, but brief descriptions are included at the end of the chapter to provide a broader context for understanding TMS. TMS is often compared with ECT. Although both treatments are forms of neuromodulation, they use very different technologies and methods of administration. ECT involves direct application of an electrical current via electrodes, whereas TMS uses a magnetic field to induce an electrical field without the use of electrodes. ECT stimulates the entire brain, from cortex to brain stem, whereas TMS stimulates only a small, localized area of the cortex. Because the therapeutic element of ECT is a generalized seizure, it must be modified by the use of anesthesia and neuromuscular blockade. TMS is nonconvulsive and noninvasive and is administered while a person is fully awake and is completely independent throughout the treatment course. This accounts for the very different risk and side-effect profiles of ECT and TMS, particularly effects on cognition. Studies have considered TMS as a potential acute treatment alternative to ECT; the use of TMS as an acute complementary strategy with ECT; the durability of clinical effect for TMS versus ECT; the role of TMS as a maintenance strategy after a successful acute course of ECT; the relative cost-effectiveness of TMS and ECT; and patient preference for TMS versus ECT. These topics are discussed in the following subsections. Table 7–1. Comparison of different forms of neuromodulation Seizure No seizure Noninvasive Electroconvulsive therapy (ECT)a Transcranial magnetic stimulation (TMS)a Magnetic seizure therapy (MST) Cranial electrotherapy stimulation (CES) Focal electrically administered seizure therapy (FEAST) Transcranial direct current stimulation (tDCS) External trigeminal nerve stimulation Transcutaneous auricular vagus nerve stimulation (taVNS) Invasive Deep brain stimulation (DBS)b Vagus nerve stimulation (VNS)a Epidural prefrontal cortical stimulation (EpCS) Note. Invasive is defined as requiring a surgical procedure. aProcedure has been cleared by the U.S. Food and Drug Administration for depression. bProcedure has been cleared by the U.S. Food and Drug Administration for Parkinson’s disease and OCD. Ten published studies directly compare TMS and ECT for patients with a major depressive episode deemed appropriate for ECT. Participants in these studies suffered primarily from unipolar depression, although some also had bipolar depression. All but two of the studies involved random assignment to either treatment, all but one used left-sided high-frequency TMS, and four used single-blind assessments. The studies varied in regard to the type of ECT and TMS devices, ECT electrode placement (i.e., bilateral, unilateral nondominant, unilateral nondominant switched to bilateral), and the number of sessions with either treatment approach. With these limitations in mind, the results of these studies are summarized as follows: five left-sided high-frequency trials (four randomized and one open) showed antidepressant equivalence between the two therapies; four left-sided high-frequency trials (three randomized and one open) showed superiority for ECT over TMS; and one right-sided low-frequency trial showed superiority for ECT over TMS. Of note, no trial results showed superiority for TMS over ECT. All trials, however, demonstrated either comparable or better tolerability with TMS, particularly regarding cognitive effects (e.g., Martis et al. 2003). Furthermore, by present standards, no trial provided an optimal course of TMS. Table 7–2 summarizes these trials in more detail. Despite methodological shortcomings, the studies provide preliminary guidance about the relative advantages and disadvantages of both approaches. In addition, three meta-analyses consider the acute benefit of TMS compared with ECT. The first meta-analysis (Micallef-Trigona 2014) considered nine trials (N=384) that met the author’s criteria for inclusion. Patients were randomly assigned to either treatment and assessed with the Hamilton Depression Rating Scale (HDRS). Although both treatment arms produced a significant decrease from baseline scores, ECT was superior to TMS in terms of total point reduction (i.e., 15.4 vs. 9.3, respectively; P<0.01). The second meta-analysis (Ren et al. 2014) considered nine trials (N=425). On the basis of HDRS change scores, ECT was superior to TMS in terms of response (P<0.03) and remission (P<0.01). When patients with psychotic symptoms were excluded, however, response and remission rates did not differ between the two groups. A third meta-analysis (Xie et al. 2013) considered nine trials (N=395). The authors reported that differing parameters significantly altered the response to TMS and suggested that this issue should be addressed in future studies that compare TMS with ECT. In a published pilot study, Pridmore (2000) compared unilateral nondominant ECT (UND ECT) with UND ECT plus TMS. Over the 2-week trial, one group (n=11) received UND ECT three times per week, and the second group (n=11) received one UND ECT session followed by four daily TMS sessions. Both groups experienced a comparable response, but the UND ECT plus TMS group experienced fewer adverse events. Two of the acute trials described in Table 7–2 also reported their patients’ clinical status after 6 months. Dannon et al. (2002) found no differences in the relapse rates (i.e., 20%) based on the HDRS-17 and the Global Assessment of Functioning (GAF) Scale in either the ECT (N=20) or TMS (N=21) groups. Eranti et al. (2007) also reported no difference between the ECT (N=22) and TMS (N=24) groups based on the HDRS-17 change scores. A more recent, large retrospective study considered 300 patients with recurrent major depression, half of whom received a course of TMS and half of whom received a course of ECT (Jin et al. 2016). Jin et al. reported that although the acute response rate was greater in the ECT group than in the TMS group (i.e., 58.7% vs. 46.0%; P<0.05), the survival rate was comparable between groups. Table 7–2. Comparative studies of transcranial magnetic stimulation (TMS) and electroconvulsive therapy (ECT) Outcome ECT (%) TMS (%) Commentsa Left-sided high-frequency TMS vs. ECT: acute randomized trials 16/20 (80%) 9/20 (45%) Response rate: HDRS-17 (≥50%); GAS (≥60) Unblinded assessments TMS comparable to UND/BL ECT in nonpsychotic major depression; up to 20 treatments 11/16 (69%) 11/16 (69%) Remission rate: HDRS-17 (≥8) Single-blind assessments UND ECT (mean=10.5 treatments); TMS (20 treatments) 6/14 (43%) 7/17 (41%) Response rate: HDRS-24 (≥50%; ≥8) Unblinded assessments 2–4 weeks of treatment; BL ECT 12/20 (60%) 6/20 (30%) 11/20 (55%) 6/20 (30%) Response rate: HDRS-17 (≥50%; <10); GAS (≥60) Remission rate: HDRS-17 (≤8) Single-blind assessments UND ECT (mean=10.5 treatments); TMS (20 treatments) 6/15 (40%) 10/20 (50%) Response rate: HDRS-17 (≥50%) Single-blind assessments UND/BL ECT (up to 4 weeks); TMS (20 treatments) 13/22 (59%) 4/24 (17%) Remission rate: HDRS-17 (≤8) Single-blind assessments UND/BL ECT (mean=6.3 treatments); TMS (mean=13.7 treatments) 68% improvement from baseline (n=40) 29% improvement from baseline (n=33) HDRS-21 Unblinded assessments BL ECT (10 treatments); TMS (10 treatments) Left-sided high-frequency TMS vs. ECT: acute open trials 62% mean improvement from baseline (n=14) 10% mean improvement from baseline (n=14) HDRS-17 Unblinded assessments UND ECT (6–12 treatments); TMS (10 treatments) 6/14 (43%) 7/16 (44%) Response rate: HDRS-17 (≥50%) Unblinded assessments UND ECT (mean=10 treatments); TMS (mean=10 treatments) Right-sided low-frequency TMS vs. ECT: acute randomized trial 26% higher rate of partial remission with ECT vs. TMS (P<0.04) TMS (n=30) ECT (n=30) HDRS-17 Unblinded assessments UND ECT (9 treatments); TMS (15 treatments) Note. BL ECT=bilateral ECT; GAS=Global Assessment Scale; HDRS=Hamilton Depression Rating Scale (17-item or 24-item version); UND/BL ECT=unilateral nondominant ECT switched to bilateral ECT; UND ECT=unilateral nondominant ECT. aFor response and remission rates, values within parentheses indicate criteria defining response. Given the high rates of relapse after an acute response to ECT, there is a need to develop effective maintenance strategies; Jelovac et al. (2013) provide an overview of current evidence with respect to relapse after acute ECT. Studies in adult and geriatric patients employed maintenance medication, ECT, or their combination and yielded mixed results (Kellner et al. 2006, 2016). Thus, no clear guidance is yet available on how to provide an optimally effective approach. Two case series have considered the relative long-term benefits of TMS as one such strategy for maintaining ECT benefit. The first case series included six patients (four with unipolar and two with bipolar depression) who were followed for 6–13 months and received once- or twice-weekly bilateral TMS maintenance treatments after a successful acute course of ECT (Noda et al. 2013). The authors reported that five of the six patients were able to maintain their response status during this time period, as supported by change in scores on the Quick Inventory of Depressive Symptomatology—Self-Report (QIDS-SR). In the second case series, six patients (five of whom had major depression) were transitioned from maintenance ECT to maintenance TMS (administered on average every 3.5 weeks) because of adverse events or patient preference (Cristancho et al. 2013). As demonstrated by change in scores on the Beck Depression Inventory (BDI) from the initiation of TMS therapy, all patients maintained their response or remission status for the first 6 months. Subsequently, two patients relapsed, one at 8 months and one at 9 months. The total observation period for individual patients ranged from 7 to 23 months. Although the data from these two studies are further supported by increasing clinical experience using TMS for maintenance purposes after ECT, definitive trials are needed to clarify the value of this approach. Jin et al. (2016) reported that TMS was less costly than ECT (P<0.05) and concluded, based on both clinical outcome and economic data, that TMS might be an alternative to ECT for some patients. In contrast, however, a group of researchers from Spain used a probabilistic sensitivity analysis, populating their model with data from various comparison trials of TMS and ECT (Vallejo-Torres et al. 2015). The primary outcome was quality-adjusted life years over a 12-month period. The authors concluded that ECT alone is likely to be a more cost-effective option than TMS alone or TMS followed by ECT, although this last strategy was the most clinically effective. In a retrospective medical record review, Magnezi et al. (2016) considered 81 patients with treatment-resistant major depression who had received TMS or ECT and found a trend in the group effect favoring ECT over TMS. Notably, however, the ECT patients experienced more adverse events, and TMS patients rated their treatment more favorably. There has not yet been a definitive, rigorously designed study using the optimal application of TMS for comparison with ECT. Thus, the existing data must be considered preliminary. Nevertheless, there is an increasing clinical utilization of TMS as a substitute or complementary strategy for patients deemed appropriate candidates for ECT, partly driven by patient preference. In the absence of better data, the existing literature indicates that at least a subgroup of depressed patients referred for ECT could potentially benefit from TMS as an alternative, especially if delivered using present-day treatment protocols. More clearly identifying this population is an important next step (Table 7–3). CLINICAL VIGNETTE The patient is a 42-year-old man with a 10-year history of treatment-resistant depression. After multiple failed medication trials and two hospitalizations, he fully recovered after a course of 12 bilateral ECT treatments. Rapid and repeated relapse, however, necessitated the use of maintenance ECT at a frequency of once every 2–3 weeks. Cognitive side effects interfered with the patient’s ability to work as a registered nurse for 3–4 days after each treatment. He then underwent a brief series of 10 consecutive daily left-sided 10-Hz TMS treatments, after which he was transitioned to maintenance TMS with one session every 2 weeks for 12 weeks. Treatment frequency was then decreased to once a month, allowing him to remain symptom free and to function at full capacity. After 6 months, sessions were administered on an as-needed basis. He remained in remission and off medication for 24 months with a single TMS treatment every 3 months.
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Transcranial Magnetic
Stimulation and Other
Neuromodulation
Therapies
TMS and ECT for Management of Depression
TMS VERSUS ECT FOR ACUTE TREATMENT
TMS COMBINED WITH ECT FOR ACUTE TREATMENT
TMS VERSUS ECT: DURABILITY OF CLINICAL EFFECT
TMS FOR MAINTENANCE TREATMENT AFTER ACUTE ECT RESPONSE
TMS VERSUS ECT: COST-EFFECTIVENESS
TMS VERSUS ECT: PATIENT PREFERENCE
SUMMARY
Related posts:
Clinical Applications and Patient Selection
Managing Patients After Transcranial Magnetic Stimulation How to Best Maintain Response and Remission
Transcranial Magnetic Stimulation for Disorders Other Than Depression
Transcranial Magnetic Stimulation Therapy for Treatment-Resistant Depression
Transcranial Magnetic Stimulation and Psychotherapy
Current FDA-Cleared TMS Systems and Future Innovations in TMS Therapy
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