[Repetitive transcranial magnetic stimulation in major depression: response factor]

Abstract

Objective: Repetitive transcranial magnetic stimulation (rTMS) is a brain stimulation technique that has been investigated as a novel treatment for psychiatric disorders, notably in major depression, and has shown statistically significant effects. The authors found it necessary to propose an up-to-date review of positive predictors for antidepressive response to repetitive transcranial magnetic stimulation.

Method: Based on an exhaustive consultation of Medline data, supplemented by a manual research, only works evaluating response factors of rTMS in major depression were retained.

Results: Twenty-nine studies were retained, including meta-analyses, reviews, randomized controlled trials and open trials. The most concordant data clearly indicate that a high score of treatment resistance, a long duration of current episode, advanced age, and psychotic symptoms are negative predictors for treatment response to rTMS. In the older patients, menopausal women are especially concerned. However, some parameters should be adapted to the degree of cortical atrophy such as intensity of stimulation or total number of rTMS sessions. Previous response to rTMS therapy seems to be a good predictor contrary to non-response to electroconvulsive therapy. Adjunctive antidepressant treatment shows greater responsiveness to rTMS contrary to benzodiazepine or anticonvulsant treatment. To our knowledge, no study compares unipolar and bipolar depression, the profile of depression is not established yet. Imaging studies show that TMS antidepressant responders differed from non-responders in inferior frontal activity, at baseline, and even more so following treatment. Furthermore, reduced baseline cerebral metabolism in cerebellar, temporal, anterior cingulate and occipital regions of the brain was correlated with improvement after two weeks of fast (20Hz) left dorsolateral prefrontal cortex (DLPFC) rTMS. Additionally, a right frontal region emerges with divergent polarity in the metabolic prediction of response to low rTMS. Inhibiting right DLPFC or stimulating DLPFC shows similar results, the choice on the side of stimulation does not seem determining. Bilateral stimulation for the moment does not seem superior to unilateral stimulation. Parameters of stimulation associated with effectiveness of rTMS are an intensity of stimulation higher than 100% of the motor threshold, a number of stimulations per sessions superior to 1000, and a full number of days of treatment greater than 10.

Discussion: Parameters of stimulation must be adapted according to the treated patients. For example, older patients who present cortical atrophy need higher intensity of stimulation. Other criteria could influence effectiveness of rTMS in the same way. Would it be necessary, for example, to adapt the duration or the intensity of stimulation according to the severity of the depressive episode or its duration of evolution? Do antecedents of resistance to a pharmacological treatment oblige us to stimulate differently? Few studies exceed 10 days of treatment; will longer duration of treatment be more effective? Also, we did not find any data on the interest of maintenance treatment among responders. Should the characteristics of the depressive disorder or its evolution require maintenance treatment? What will be its rhythm and its duration? Should we adapt rTMS parameters to abnormalities highlighted by functional neuroimagery? The prospects for work remain numerous.