Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for major depression: preliminary results of a randomized trial

Abstract

Background: Many severely depressed patients do not benefit from or tolerate existing treatments. Repetitive transcranial magnetic stimulation (rTMS) has been reported to benefit depression. We compared rTMS to electroconvulsive therapy (ECT) in severely ill, depressed patients.

Methods: Twenty-five patients with a major depression (unipolar or bipolar) deemed clinically appropriate for ECT were randomly assigned to rTMS (10–20 treatments, 10 Hz, 110% motor threshold applied to the left dorsolateral prefrontal cortex for a total of 10,000–20,000 stimulations) or a course of bitemporal ECT (4–12 treatments). The primary outcome measure was the 24-item Hamilton Depression Rating Scale (HDRS). The Brief Psychiatric Rating Scale (BPRS), Young Mania Rating Scale (YMS), and Clinical Global Impression scale (CGI) were secondary measures. Minimal rescue medications were utilized.

Results: Mean percent improvement on the baseline HDRS score did not significantly differ between the two treatments (i.e., 55% for the rTMS group vs. 64% for the ECT group [p = ns]). With response defined as a 50% reduction from baseline and a final score ≤ 8 on the HDRS, there was also no significant difference between the two groups. We did not observe any differences between groups on the secondary measures.

Conclusions: A 2–4 week randomized, prospective trial comparing rTMS to ECT produced comparable therapeutic effects in severely depressed patients.

Introduction

Depression is a common and serious illness afflicting 10% of all patients seeking treatment at primary health care facilities worldwide (World Health Organization 2000). Major depressive disorder (MDD) is associated with substantial personal and societal costs, owing to issues such as suicide, lost productivity, and the high rates of health service utilization Janicak et al 2001, Sturm and Wells 1995.

Since the 1950s, antidepressants have been the primary treatment approach for depressive disorders, and electroconvulsive therapy (ECT) has remained an option for patients refractory or intolerant to pharmacotherapy (Janicak et al 2001). Although there is strong support for antidepressant efficacy Janicak et al 1985, Janicak et al 1989, a substantial number of depressed patients do not benefit from or cannot tolerate psychopharmacotherapy or ECT (Janicak and Martis 1999). Furthermore, ECT has well-documented side effects, including short-term anterograde, retrograde, and autobiographical memory deficits; is costly; often requires hospitalization; and is associated with substantial social stigma Fink 1997, Janicak et al 1991. Given the pervasive nature of depression and the need for more effective, safer, and more socially acceptable therapeutic strategies, alternative approaches are being investigated, including repetitive transcranial magnetic stimulation (rTMS) Martis and Janicak 2000, Gates et al 1992, Hufnagel et al 1993, vagal nerve stimulation (Rush et al 2000), and bright-light therapy (Terman et al 2001).

Repetitive TMS utilizes an electrical current that passes through a metal coil applied to the scalp to produce fluctuating magnetic pulses George et al 1998, George et al 1998. Unlike electrical stimulation, these magnetic pulses enter the brain painlessly and unimpeded, causing neuronal depolarization in a localized area under the coil and possibly distal effects as well Barker et al 1987, Lisanby et al 2000a. Early observations in which this technique was used as a neurophysiological probe indicated that some neurology patients experienced mood elevation (Lisanby et al 2000a). The subsequent therapeutic application of transcranial magnetic stimulation (TMS) for depression has produced encouraging preliminary results Beedle et al 1998, Hallet and Cohen 1989. Furthermore, both human and animal studies have observed a number of similar effects induced by rTMS, ECT (or electroconvulsive shock), and antidepressants on the endocrine system, sleep parameters, and in certain behavioral and biochemical measures, all of which are associated with potential antidepressant properties Keck et al 2001, Krystal et al 2000, Lisanby et al 2000b, Szuba et al 2000.

Concurrent with these observations, several studies have explored the potential antidepressant effects of rTMS in humans. To date, much of the literature has centered on comparisons of rTMS to sham rTMS. Although there are significant methodological questions to be resolved Loo et al 2000, Lisanby et al 2001a, and not all reports have been positive (e.g., Loo et al 1999, Padberg et al 1999), most studies observed that patients treated with rTMS had a significantly better result than those receiving sham rTMS George et al 1997, George et al 2000, Kimbrell et al 1999, Klein et al 1999, Nahas et al 1998, Pascual-Leone et al 1996. Furthermore, although the literature reveals uncertainty as to what constitutes optimal rTMS parameters for the treatment of depression, we believe the existing data provide reasonable direction, and our choice of parameters for the present study reflects this literature (see Table 1 for a description of the parameters).

The relative efficacy of rTMS versus sham rTMS has also been studied in patients with drug treatment—resistant depression (TRD), albeit variably defined Avery 1999, Berman et al 2000, Figiel et al 1998, Greer 1998, Hoflich et al 1993, Loo et al 1999, Nahas et al 1998, Padberg et al 1999, Pascual-Leone et al 1996. Overall, the majority of studies have reported a positive outcome with rTMS for TRD (see Martis and Janicak 2000 for review).

There have also been favorable preliminary results in comparisons of rTMS to ECT for a more severely ill, often drug-resistant, heterogeneous group of patients typically seen in clinical practice Grunhaus et al 2000, Pridmore et al 2000. The aim of the present study was to extend these findings by comparing the efficacy of rTMS to ECT for patients with major depression for whom ECT would be considered appropriate in a general clinical setting. The issues that differentiated this study from earlier comparisons were the use of more aggressive rTMS parameters; administering ECT with bitemporal electrode placement; and minimizing the use of concurrent medication.