Patterns of response to repetitive transcranial magnetic stimulation (rTMS) in major depression:: Replication study in drug-free patients

Background: Repetitive transcranial magnetic stimulation (rTMS) has been found to exert modest to moderate therapeutic effects in major depression, but mechanism of action and its clinical relevance have not been clarified yet. Previous trials have reported patterns of symptomatology predicting response to rTMS. As most patients also received concomitant antidepressant medication these response patterns may rather refer to combined treatment than rTMS alone. Thus, this study aims to replicate previous findings and explore patterns of response in drug-free patients. Methods: In the Munich-Berlin Predictor Study data of 79 patients from two open clinical trials evaluating effects of high-frequency rTMS of the left dorsolateral prefrontal cortex were pooled. Previous models predicting the response to rTMS [Fregni, F., Marcolin, M.A., Myczkowski, M., Amiaz, R., Hasey, G., Rumi, D.O., Rosa, M., Rigonatti, S.P., Camprodon, J., Walpoth, M., Heaslip, J., Grunhaus, L., Hausmann, A., Pascual-Leone, A., 2006. Predictors of antidepressant response in clinical trials of transcranial magnetic stimulation. Int. J. Neuropsychopharmacol. 9, 641-654; Brakemeier, E.L., Luborzewski, A., Danker-Hopfe, H., Kathmann, N., Bajbouj, M., 2007. Positive predictors for antidepressive response to prefrontal repetitive transcranial magnetic stimulation (rTMS). J. Psychiatr. Res. 41, 395-403.] were systematically tested and new explorative regression analyses were conducted. Results: Of the 79 patients, 34.2% showed an antidepressant response. Previous models could not be validated. Explorative regression analysis revealed a significant model with therapy resistance, HAMD items 1 (depressed mood), and 2 (feelings of guilt) as negative and retardation as positive predictors. Limitations: No controlled study; specific statistical issues; sample size; differences concerning patient population and stimulation parameters between study sites. Conclusions: In sum, this study does not confirm clinical valid and robust patterns being predictive for a response to rTMS in depression. The only exception is a high level of therapy resistance being associated with poor outcome. Future predictor studies should focus on large and homogenous samples of rTMS multicenter trials and include neurobiological variables. (C) 2007 Elsevier B.V All rights reserved.