Effects of antidepressant pharmacotherapy after repetitive transcranial magnetic stimulation in major depression: an open follow-up study.

An increasing number of clinical studies demonstrates antidepressant effects of repetitive transcranial magnetic stimulation (rTMS). However, limited data are available so far concerning the stability of these effects and the efficacy of subsequent maintenance therapy. Therefore, we examined whether antidepressant pharmacotherapy can stabilize clinical improvement after rTMS monotherapy. Twenty-six drug-free patients suffering from a major depressive episode (DSM-IV criteria) participated in an open rTMS trial over two weeks (10-13 sessions, 10 Hz, left prefrontal stimulation at 100% motor threshold intensity). Subsequently, the patients were followed up during standardized antidepressant pharmacotherapy with mirtazapine for a further 4 weeks. The interval between the last rTMS and the first day of pharmacotherapy varied between one and five days. After two weeks of rTMS monotherapy 39% of the patients responded to rTMS by at least 50% reduction in their Hamilton Rating Scale for Depression (HRSD) scores. Treatment interruption after rTMS resulted in a significant increase in the HRSD score of rTMS responders. The degree of the deterioration was dependent on the length of interval without treatment. However, this deterioration was reverted and the further clinical course stabilized by subsequent mirtazapine treatment. The overall response rate after rTMS and mirtazapine treatment (alone or in combination) was 77%. Our results suggest that (1) antidepressant pharmacotherapy is able to further improve the clinical response to rTMS and (2) that responders to rTMS monotherapy should receive subsequent psychopharmalogical treatment without interruption in order to avoid a deterioration of symptoms.

Repetitive transcranial magnetic stimulation (rTMS) in major depression: relation between efficacy and stimulation intensity.

Repetitive transcranial magnetic stimulation (rTMS) has been found to exert modest to substantial antidepressant effects in the majority of prior clinical studies. As effect sizes and stimulation conditions have varied greatly, controversy persists regarding effective stimulation parameters (e.g. intensity, frequency, localization). In the present controlled study, we investigated whether the antidepressant efficacy of rTMS may be related to the stimulation intensity applied. Thirty-one patients suffering from a pharmacotherapy-resistant major depressive episode were randomly assigned to three treatment groups receiving rTMS at different stimulation intensities: (1) intensity at the individual motor threshold (MT); (2) 90% subthreshold intensity; and (3) low intensity of standard sham rTMS. Each patient underwent 10 sessions of 10 Hz rTMS with 1500 stimuli/day over the left dorsolateral prefrontal cortex. Improvement of depressive symptoms after rTMS significantly increased with stimulation intensity across the three groups. A 30% to 33% reduction of baseline depression scores was observed after rTMS at MT intensity. Similarly, groups differed significantly regarding the clinical course after rTMS with the lowest number of antidepressant interventions and the shortest hospital stay in the MT intensity group. These findings support the hypothesis of a relationship between stimulation intensity of rTMS and its antidepressant efficacy.

Relation between responses to repetitive transcranial magnetic stimulation and partial sleep deprivation in major depression.

Repetitive transcranial magnetic stimulation (rTMS) has been found to ameliorate symptoms in major depression. However, its mechanism of action has to be further elucidated and the relationship between responses to rTMS and other antidepressant interventions except electroconvulsive therapy has not been investigated to date. Here we studied in an open trial whether the response to partial sleep deprivation may predict the clinical outcome of rTMS treatment. Thirty-three drug-free patients suffering from a major depressive episode underwent a partial sleep deprivation at least 5 days prior to rTMS and subsequently received 10 sessions of 10 Hz rTMS of the left prefrontal cortex. After rTMS a significant overall improvement of 32% on the Hamilton Rating Scale for Depression was observed. Forty-two percent of patients showed an antidepressant response after rTMS. Amelioration of depression after partial sleep deprivation was inversely correlated with improvement after rTMS. There was no clinically applicable predictive value of the response to partial sleep deprivation for the outcome after rTMS. Apparently, different subgroups of depressed patients respond to both interventions. Further studies are needed to characterize the response to rTMS by means of clinical and biological parameters.