Elsevier

Psychiatry Research

Volume 126, Issue 2, 30 April 2004, Pages 123-133
Psychiatry Research

Repetitive transcranial magnetic stimulation: a putative add-on treatment for major depression in elderly patients

https://doi.org/10.1016/j.psychres.2003.10.006Get rights and content

Abstract

Repetitive transcranial magnetic stimulation (rTMS) is a recent putative treatment for affective disorders. Several studies have demonstrated antidepressant effects of rTMS in younger patients; we aimed to assess its effect in older outpatients with treatment-resistant major depression. Twenty-four outpatients (mean age=62 years, S.D.=12) with major depression were randomized for sham or real stimulation and received 10 daily rTMS sessions (20 Hz, 2-s trains, 28-s intertrain intervals, 100% of motor threshold) in addition to the antidepressant medication. For sham stimulation, the coil was tilted 90°. Depression severity was assessed using the Hamilton Depression Rating Scale, the Beck Depression Inventory, items from the NIMH self-rated symptom scale, and a visual analog depression scale. Mini-Mental Status Examination performance, memory, and executive and attentional functions were measured to control for cognitive side effects. Depression ratings revealed significant antidepressant effects within 2 weeks in both sham and real stimulation groups; however, there were no between-group differences. Treatment with rTMS was safe; adverse events were rare and not more prevalent in either group, and cognitive assessment did not show any deterioration. We were unable to demonstrate any additional antidepressant effects of real stimulation in elderly patients with treatment-resistant major depression. Therapeutic effects of rTMS in this clinically challenging patient group remain to be demonstrated.

Introduction

Studies of repetitive transcranial magnetic stimulation (rTMS) are of considerable interest for the understanding of the basic neurophysiology of mood generation and modulation. The first observation that transcranial magnetic stimulation might lead to mood alterations in healthy volunteers is more than a decade old (Bickford et al., 1987) and has been followed by numerous studies (for reviews, see Wassermann and Lisanby, 2001, Martin et al., 2003). Antidepressant properties of rTMS applied to the dorsolateral prefrontal cortex of depressed patients have been reported in controlled studies (Pascual-Leone et al., 1996, George et al., 1997, Klein et al., 1999, Loo et al., 1999, Padberg et al., 1999, Berman et al., 2000, George et al., 2000). All but one study found acute phase antidepressant effects (Loo et al., 1999). The comparison of these studies is difficult due to heterogeneous patient populations with respect to age and diagnosis and variable stimulation intensities and frequencies. Most authors used focal coils and applied rTMS at high frequency (>1 Hz) to left dorsolateral prefrontal cortex (DLPFC). Some studies used stimulation intensities above motor threshold (>100% of motor threshold) (e.g. Loo et al., 1999), whereas others used stimulation intensities below motor threshold (e.g. Berman et al., 2000). The very few studies assessing rTMS effects in relatively older patients were inconclusive with respect to antidepressant properties but point to a lesser effect than in younger patients (Figiel et al., 1998, Padberg et al., 1999). The explanation for this difference is not clear. Figiel et al. (1998) assumed that lesser antidepressant effects might be related to structural brain changes, often found in older depressed patients (Dahabra et al., 1998).

An effective treatment for elderly depressed patients is urgently required, as conventional pharmacological strategies are often hampered by drug resistance, intolerance, and interactions that may lead to protracted, chronic courses with incomplete remission (Thomas et al., 2003). Electroconvulsive therapy (ECT) is commonly used as a non-pharmacological antidepressant treatment (Manly et al., 2000) but requires anesthesia. Recent studies (Janicak et al., 2002, Grunhaus et al., 2003) suggested similar antidepressant effects of ECT and rTMS, and there is some evidence that rTMS may be associated with less amnestic impairment (Little et al., 2000, Kosel et al., 2003, O'Connor et al., 2003) than that associated with ECT. If this is confirmed for elderly patients, it will have important clinical implications, because age is a risk factor for cognitive impairment and the development of degenerative brain disorders.

The aim of this sham-controlled, parallel-group study was to investigate antidepressant properties of rTMS in relatively elderly depressed outpatients with treatment-resistant major depression and to monitor carefully for cognitive effects, both positive and negative, during treatment. To investigate a spectrum of different ages, patients aged 40–90 years were included. High frequency real or sham rTMS was applied daily over 2 weeks to the left DLPFC.

Section snippets

Subjects

Twenty-four patients were randomly included in either a sham or a real stimulation group and received 10 rTMS sessions on 2× five consecutive workdays within 2 weeks. To be eligible for the study, patients had to be in the age range of 40–90 years and fulfill criteria for treatment-resistant major depression (DSM-IV, ICD-10) (American Psychiatric Association, 1994). Diagnoses were obtained from an in-depth clinical interview using sections 6, 7 and 8 of the Schedules for Clinical Assessment in

Demographics

Table 1 summarizes the demographic data. There were no exclusions from the study after randomization. Groups did not differ with respect to age, gender, education, duration of the current episode or the number of previous episodes. Patients in the sham stimulation group were older at onset of the first episode (independent sample t-test, two-tailed: t=2.5, d.f.=22, P=0.02). Table 2 presents an overview of individual patient characteristics. All but one patient in the sham stimulation group was

Discussion

This parallel group study assessed effects of rTMS applied to the left DLPFC as an add-on treatment to medication in elderly drug-resistant depressed patients. In both the real and sham rTMS groups, depression improved in the range of 17–20% from baseline in observer ratings and self-ratings after 10 stimulation sessions. However, real rTMS did not have any additional antidepressant effects compared with sham rTMS. This finding is in agreement with one previous controlled study (Loo et al., 1999

Acknowledgments

This project was funded by grants 4038-044046 and 3231-044523 from the Swiss National Science Foundation to Dr Schlaepfer.

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