Positive predictors for antidepressive response to prefrontal repetitive transcranial magnetic stimulation (rTMS)

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Abstract

Repetitive transcranial magnetic stimulation (rTMS) is a brain stimulation technique which had recently been investigated as a putative antidepressant intervention. However, there is little agreement about clinically useful predictors of rTMS outcome. Therefore, the objective of the present study was to determine whether specific biographical, clinical, and psychopathological parameters are associated with the antidepressant response to rTMS in a large sample of 70 depressive patients. We performed a logistic regression analysis in 70 patients with major depressive disorder treated with rTMS of the left dorsolateral prefrontal cortex testing the predictive value of various domains of the depression syndrome as well as the variables episode duration, degree of treatment resistance, and CORE criteria. Response was defined as a 50% reduction of the initial Hamilton score (HAMD). After two weeks of treatment, 21% of the patients showed a response to rTMS. The binary logistic regression model correctly assigned 86.7% of the responders and 96.4% of the non-responders to their final response group. In the model, a high level of sleep disturbances was a significant predictor for treatment response to rTMS. Also, a low score of treatment resistance and a short duration of episode were positive predictors. These findings provide new evidence that especially pronounced sleep disturbances may be a significant clinical predictor of a response to rTMS. Prospective rTMS studies are necessary to validate the predictive value of the derived model.

Introduction

Affective disorders, especially major depression, are the most common psychological disorders, afflicting worldwide 10% of all patients seeking treatment at primary health care facilities (Lopez and Murray, 1998). Because major depression is associated with substantial personal and societal costs, owing suicide, lost productivity, and the high rates of health service utilization, it constitutes a major public health issue (Sturm and Wells, 1995). Especially chronic depression leads to disability with major economic costs (Hirschfeld et al., 2000).

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., 1985). Although there is strong support for antidepressant efficacy of these strategies, a substantial number of depressed patients do not benefit from or cannot tolerate psychopharmacotherapy and/or ECT (Janicak and Martis, 1999). As a less invasive alternative to ECT, repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) has been introduced and investigated over the past decade especially for those patients showing adverse effects, intolerance, and interactions that may lead to protracted, chronic courses with incomplete remission.

rTMS utilizes an electrical current that passes through a metal coil applied to the scalp to produce fluctuating magnetic pulses (George et al., 1999). Unlike electrical stimulation, these magnetic pulses enter the brain non-invasively and unimpededly, causing neuronal depolarization in a localized area under the coil and possibly distal effects as well (Lisanby and Belmaker, 2000).

Since 1993, the effectiveness of rTMS has been studied as a potential treatment for depression. To date, much of the literature has focussed on comparison of rTMS to sham rTMS. Although there are significant methodological questions to be resolved (Loo et al., 2000, Lisanby et al., 2001) and not all reports have been positive (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 (see for meta-analyses: Burt et al., 2002, Martin et al., 2003). Overall, there is a significant reduction in depressive symptomatology due to rTMS, but the clinical significance of the therapeutic changes were only modest (Berman et al., 2000, Burt et al., 2002, Schlaepfer et al., 2003, Loo and Mitchell, 2005).

Therefore, it remains an important issue to identify those features of the depressive syndrome that would predict response to rTMS (Loo and Mitchell, 2005). In accordance to previous reports (Conca et al., 2000, Holtzheimer et al., 2004), we described treatment resistance and episode duration as clinical features associated with response to rTMS (Bajbouj et al., 2005). Thus, the purpose of the present study was to identify and validate predictors for antidepressive response to prefrontal rTMS in a large sample of patients who met the criteria for major depressive disorders.

Section snippets

Subjects

Seventy out-patients from the Department of Psychiatry, Universitätsmedizin Berlin, Charité, Campus Benjamin Franklin, participated in this study. All patients were suffering from major depression or bipolar II disorder. 32 (45.7%) patients had a single episode, 30 (42.9%) recurrent depression, and 8 (11.4%) a bipolar II disorder. Of the bipolar II patients, only those with current depressive states were included. Diagnoses were established by experienced psychiatrists, based on a clinical

Results

All 70 subjects completed all treatment sessions without any drop-out. There were no major adverse events and rTMS treatments were generally very well tolerated. After two weeks of rTMS, 15 of 70 patients (21.4%) had an antidepressant response defined as a 50% reduction in the Hamilton rating scale (HAMD). The mean reduction of the initial HAMD score (28 items) was 62.8 ± 9.6% (means ± SD, range 50–80%) in the subgroup of responders and 7.9 ± 17.1% (range −34.5% to 46.2%) in the subgroup of

Discussion

Using repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex for two weeks, parameters predicting a future therapeutic response were studied. After examining the data from 70 patients, illness features were identified that distinguished between responders and non-responders. Specifically, general variables like short duration of episode and low level of treatment-resistance, and more specific clinical variables like high level of sleep disturbances showed

Acknowledgements

The authors are grateful to Rita Viernickel and Anne Weigand for technical assistance.

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