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Correspondence |
Harvard Center for Non-Invasive Brain Stimulation, Beth Israel Deaconess Medical Center and Harvard School, 330 Brookline Avenue, Boston, MA 02215, USA.
Correspondence: E-mail: ffregni{at}bidmc.harvard.edu
Schulze-Rauschenbach et al (2005) report an interesting study comparing electroconvulsive therapy (ECT) with repetitive transcranial magnetic stimulation (rTMS) for the treatment of major depression. They conclude that both are equally efficacious, but rTMS is associated with fewer cognitive side-effects.
Ultimately, a therapeutic plan that optimally helps a given individual cope with disability and recover can only be devised when the physician transcends the traditionally proven, generic insights about pathological anatomy, physiopathology and aetiology of disease, and identifies the unique characteristics of a specific patient. Therefore, therapeutic decisions should always consider the risk–benefit ratio of each treatment option for the specific patient and circumstances. The focus on differences in side-effect profile of rTMS and ECT in major depression by Schulze-Rauschenbach et al is thus most valuable.
In 2003 we conducted a similar study of which the authors appear to be unaware (O’Connor et al, 2003). We compared 14 patients with medication-refractory depression who underwent ECT with 14 who underwent rTMS. ECT had a significantly greater positive effect on mood than a 2-week trial of rTMS. The reason for this difference between our results and other published trials comparing rTMS with ECT (Janicak et al, 2002; Grunhaus et al, 2003; Schulze-Rauschenbach et al, 2005) is unclear. In our study, as in that of Schulze-Rauschenbach et al, ECT was applied unilaterally approximately three times per week for 2–4 weeks. We applied rTMS in sessions of 1600 stimuli at 10 Hz and 90% of motor threshold intensity to the left dorsolateral prefrontal cortex daily (Monday through Friday) for 2 consecutive weeks. Thus we employed ‘stronger’ parameters of rTMS than Schulze-Rauschenbach et al, who applied shorter trains and also limited stimulation to only 2 weeks. Nevertheless, in both studies ECT and rTMS may have been used at insufficient doses, since progression to bilateral ECT (UK ECT Review Group, 2003) or extension of daily rTMS to 3–4 weeks (Gershon et al, 2003; Rumi et al, 2005) were not considered.
In our study ECT exerted a deleterious but transient effect on various components of memory that was no longer detected 2 weeks after the end of treatment. However, there was evidence of persistent retrograde amnesia after ECT. Patients undergoing rTMS experienced only a modest reduction in the severity of depression but there was no evidence of anterograde or retrograde memory deficits and there was a remarkable suggestion of cognitive improvement even in those patients with no antidepressant benefits. These findings, as those of Schulze-Rauschenbach et al, suggest that the cognitive effects of rTMS might not be the consequence of the mood effects. The suggestion of independent effects of rTMS on mood and cognition also seems to be supported by a previous study of rTMS in major depression (Moser et al, 2002) and studies in patients with cerebrovascular (Rektorova et al, 2005) and Parkinson’s disease (Boggio et al, 2005). Boggio et al (2005) showed that 10 days of rTMS treatment (15 Hz, left dorsolateral prefrontal cortex) improved cognition and depression in patients with Parkinson’s disease, but this cognitive improvement was not correlated with mood change. Furthermore, there was no correlation between cognitive and motor function improvement. Thus, it appears that left prefrontal rTMS exerts differential effects on cognition, mood and motor function. Even in individuals without psychiatric illness, we have recently shown that suppression of the right hemisphere by slow rTMS can enhance verbal memory, while left-sided slow rTMS disrupts it (Kahn et al, 2005). Therefore, cognitive and antidepressant effects of rTMS may be the consequence of modulation of dissociable neural networks.
REFERENCES
Boggio, P. S., Fregni, F., Bermpohl, F., et al (2005) Effects of repetitiveTMS and fluoxetine on cognitive function in patients with Parkinson’s disease and concurrent depression. Movement Disorders, in press.
Gershon, A. A., Dannon, P. N. & Grunhaus, L.
(2003) Transcranial magnetic stimulation in the treatment of
depression. American Journal of Psychiatry,
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Grunhaus, L., Schreiber, S., Dolberg, O. T., et al (2003) A randomized controlled comparison of electroconvulsive therapy and repetitive transcranial magnetic stimulation in severe and resistant nonpsychotic major depression. Biological Psychiatry, 53, 324 –331.[CrossRef][Medline]
Janicak, P. G., Dowd, S. M., Martis, B., et al (2002) Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for major depression: preliminary results of a randomized trial. Biological Psychiatry, 51, 659 –669.[CrossRef][Medline]
Kahn, I., Pascual-Leone, A., Theoret, H., et al
(2005) Transient disruption of ventrolateral prefrontal
cortex during verbal encoding affects subsequent memory performance.
Journal of Neurophysiology,
94, 688
–698.
Moser, D. J., Jorge, R. E., Mones, F., et al
(2002) Improved executive functioning following repetitive
transcranial magnetic stimulation. Neurology,
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O’Connor, M., Brenninkmeyer, C., Morgan, A., et al (2003) Relative effects of repetitive transcranial magnetic stimulation and electroconvulsive therapy on mood and memory: a neurocognitive risk – benefit analysis. Cognitive and Behavioral Neurology, 16, 118 –127.
Rektorova, I., Megova, S., Bares, M., et al (2005) Cognitive functioning after repetitive transcranial magnetic stimulation in patients with cerebrovascular disease without dementia: a pilot study of seven patients. Journal of Neurological Sciences, 229–230, 157 –161.[CrossRef]
Rumi, D. O., Gattaz, W. F., Rigonatti, S. P., et al (2005) Transcranial magnetic stimulation accelerates the antidepressant effect of amitriptyline in severe depression: a double-blind placebo-controlled study. Biological Psychiatry, 57, 162 –166.[CrossRef][Medline]
Schulze-Rauschenbach, S. C., Harms, U., Schlaepfer, T. E.,
et al (2005) Distinctive neurocognitive effects of
repetitive transcranial magnetic stimulation and electroconvulsive therapy in
major depression. British Journal of Psychiatry,
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–416.
UK ECT Review Group (2003) Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet, 361, 799 –808.[CrossRef][Medline]
Department of Psychiatry, University of Bonn, Sigmund-Freud Strasse 25, 53105 Bonn, Germany.
Correspondence: E-mail: michael.wagner{at}ukb.uni-bonn.de
We are glad that Fregni et al share our interest in side-effect profiles of rTMS and ECT in major depression and thank them for their positive judgement of our work. They draw attention to their related study (O’Connor et al, 2003), which we regretfully overlooked when we wrote our article. They point to similarities between the studies, but speculate about the reasons for the discrepant findings regarding the clinical efficacy of rTMS. We believe the following methodological differences might contribute.
First, in the study by O’Connor et al (2003), the level of baseline depression was different in the treatment groups: those receiving rTMS were significantly less depressed than those receiving ECT. Furthermore, those treated with rTMS were medication-free for at least 2 weeks but those receiving ECT continued to receive antidepressant medication. Finally, the duration of treatment – and the interval between initial and follow-up measurements – tended to be longer (2–4 weeks) in the ECT group than in the rTMS group (2 weeks). These features most likely contributed to the better clinical efficacy of unilateral ECT compared with rTMS in the study by O’Connor et al, where not a single patient treated with rTMS showed a clinically significant (50% reduction in the Hamilton Rating Scale for Depression) response.
In contrast, those treated with either rTMS or ECT in our study were matched for baseline levels of depression. They were treated for about 5 weeks on average. Antidepressant medication was kept constant in both ECT and rTMS treatment arms, and both treatments were clinically effective in about half of the patients. In principle, a comparative study of side-effects of two treatments only seems to be relevant when both modalities have a measurable clinical effect.
We agree that the effects of rTMS on mood and cognition may be independent of each other, and may point to different neural networks mediating these effects. However, the better retrograde memory performance after treatment, even in patients lacking an antidepressant response to rTMS, reported by O’Connor et al, is not necessarily suggestive of such a dissociation. It might also be explained by test repetition effects, which were masked in the ECT group because of enduring memory impairments. A healthy control group assessed repeatedly can be used to control for this confounding variable. We noted that patients receiving rTMS did not show stronger improvements over time than the control group for any objective cognitive measure, effectively ruling out a genuine memory-enhancing effect of rTMS as used in our study.
With the development of magnetic seizure therapy as possibly yet another form of brain stimulation for depression, the issue of relative benefits, side-effects and the duration of both will need further careful assessment. We have highlighted some of the methodological issues to be considered when studying the effects of different treatments on cognition.
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| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
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