Background: Many severely depressed patients do not benefit from or tolerate xisting treatments. Repetitive transcranial magnetic stimulation (rTMS) has been re-ported 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 pre-frontal 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 therapeu-tic
effects in severely depressed patients. Biol Psychiatry
2002;51:659 ?667 © 2002 Society of Biological
Psychiatry
Key Words: rTMS, ECT, major depression, randomized
trial
Introduction
D
epression 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 substan-tial
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 electro-convulsive
therapy (ECT) has remained an option for
patients refractory or intolerant to pharmacotherapy (Jani-cak
et al 2001). Although there is strong support for
antidepressant efficacy (Janicak et al 1985, 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 antero-grade,
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 accept-able
therapeutic strategies, alternative approaches are be-ing
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 1998a). Unlike
electrical stimulation, these magnetic pulses enter the
brain painlessly and unimpeded, causing neuronal depo-larization
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, 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 depres-sion
(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 compari-sons
were the use of more aggressive rTMS parameters;
administering ECT with bitemporal electrode placement;
and minimizing the use of concurrent medication.