Repetitive transcranial magnetic stimulation: a putative add-on treatment for major depression in elderly patients
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.
References (39)
- et al.
A randomized clinical trial of repetitive transcranial magnetic stimulation in the treatment of major depression
Biological Psychiatry
(2000) - et al.
Structural and functional abnormalities in elderly patients clinically recovered from early- and late-onset depression
Biological Psychiatry
(1998) - et al.
‘Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician
Journal of Psychiatric Research
(1975) - et al.
A controlled trial of daily left prefrontal cortex TMS for treating depression
Biological Psychiatry
(2000) - et al.
A randomized controlled comparison of electroconvulsive therapy and repetitive transcranial magnetic stimulation in severe and resistant non-psychotic major depression
Biological Psychiatry
(2003) - et al.
Add-on rTMS for treatment of depression: a pilot study using stereotaxic coil-navigation according to PET data
Journal of Psychiatric Research
(2003) - et al.
Repetitive transcranial magnetic stimulation vs. electroconvulsive therapy for major depression: preliminary results of a randomized trail
Biological Psychiatry
(2002) - et al.
Sham TMS: intracerebral measurement of the induced electrical field and the induction of motor-evoked potentials
Biological Psychiatry
(2001) - et al.
Electroconvulsive therapy in old-old patients
American Journal of Geriatric Psychiatry
(2000) - et al.
Neurocognitive effects of repetitive transcranial magnetic stimulation in severe major depression
Clinical Neurophysiology
(2003)
Repetitive transcranial magnetic stimulation (rTMS) in pharmacotherapy-refractory major depression: comparative study of fast slow and sham rTMS
Psychiatry Research
Repetitive transcranial magnetic stimulation (rTMS) in major depression: relation between efficacy and stimulation intensity
Neuropsychopharmacology
Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression
Lancet
Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5–7, 1996
Electroencephalograpy and Clinical Neurophysiology
Therapeutic application of repetitive transcranial magnetic stimulation: a review
Clinical Neurophysiology
Cognitive deficits in depression: possible implications for functional neuropathology
British Journal of Psychiatry
Beck Depression Inventory: Manual
Magnetic stimulation of human peripheral nerve and brain: response enhancement by combined magnetoelectrical technique
Neurosurgery
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