Magnetic seizure therapy in treatment-resistant depression: clinical, neuropsychological and metabolic effects S. Kayser 1 , B. H. Bewernick 1 , A. Matusch 2 , R. Hurlemann 1 , M. Soehle 3 and T. E. Schlaepfer 1,4 * 1 Department of Psychiatry and Psychotherapy, University of Bonn, Germany 2 Institute of Neurosciences and Medicine (INM-2), Forschungszentrum Jülich, Germany 3 Department of Anaesthesiology and Intensive Care Medicine, University of Bonn, Germany 4 Departments of Psychiatry and Mental Health, The Johns Hopkins University, Baltimore, MD, USA Background. Magnetic seizure therapy (MST), despite being in an early phase of clinical research, has been demon- strated to be associated with antidepressant efficacy. However, safety, tolerability and efficacy data in connection with functional brain activity from larger samples are lacking. The aim of this study was to determine clinical and cog- nitive effects of MST and the influence of MST on regional brain glucose metabolism. Method. Twenty-six patients suffering from treatment-resistant depression (TRD) underwent MST. Ten patients under- went a randomized trial and 16 patients an open-label study design. The primary outcome criterion was the severity of depressive symptoms assessed with the Hamilton Depression Rating Scale (HAMD). Depressive symptoms, tolerability and cognitive safety, along with social functioning and quality of life parameters, were assessed using various rating scales. A clinical follow-up visit 6 months following the completion of a course of MST and [ 18 F]-fluorodeoxyglucose positron emission tomography (FDG-PET) scans of 12 patients were analysed. Results. A significant response to MST was demonstrated by 69% of the patient sample, with 46% meeting remission criteria. Anxiety ratings were significantly reduced in responders and their quality of life was improved. Half of the responders relapsed within 6 months. No cognitive side-effects were observed. FDG-PET scans showed a metabolic in- crease in the frontal cortex bilaterally and a decrease in the left striatum. Conclusions. Robust antidepressant and anti-anxiety efficacy of MST was demonstrated, and found to be associated with localized metabolic changes in brain areas that are strongly implicated in depression. Thus, MST presents an effec- tive, well-tolerated and safe treatment option for patients unable to respond to other forms of therapy for depression. Received 21 January 2014; Revised 9 August 2014; Accepted 14 August 2014; First published online 25 November 2014 Key words: Cognition, efficacy, magnetic seizure therapy, major depression, positron emission tomography. Introduction Major depression is usually recurrent, often life- threatening (Bertolote et al. 2004), and leads to dysfunc- tions of mood, motivation and cognition (Austin et al. 2001). In approximately 50% of patients, first-line anti- depressant treatment is ineffective and about a third of patients do not show a substantial antidepressant re- sponse, even after four treatment steps (Rush et al. 2006; Lisanby et al. 2009). Incomplete recovery or par- tial remission from depression is classified as treatment-resistant depression (TRD; Schlaepfer et al. 2012). In the field of treatment resistance, electrocon- vulsive therapy (ECT) is currently seen as the main treatment option (Krystal et al. 2000), with a remission rate of approximately 70% (Sackeim et al. 2000b; Petrides et al. 2001). However, because of the high re- lapse rates recorded (∼50%) (Sackeim et al. 2000a; Grunhaus et al. 2001; Azuma et al. 2007a), negative cog- nitive side-effects (Lisanby et al. 2000; Rose et al. 2003) and social stigma (Ottosson & Max Fink, 2004), ECT is often used as a last resort (Grunhaus et al. 2001). Therefore, there is an urgent need for new therapy strategies in cases of treatment-resistant forms of depression. A widely recognized shortcoming of ECT is its pro- pensity to be associated with cognitive side-effects (Bernstein et al. 1998; Fink, 2001), with about 55% of patients reporting cognitive impairments after ECT (Rose et al. 2003). These symptoms have a significant impact on a patient’s outcome (Austin et al. 2001), impairing functionality, basic autonomy and quality of life (Montgomery & Gale, 2008). * Address for correspondence: T. E. Schlaepfer, M.D., Department of Psychiatry and Psychotherapy, University Hospital, Sigmund- Freud-Straße 25, 53105 Bonn, Germany. (Email: schlaepf@jhmi.edu) Psychological Medicine (2015), 45, 1073–1092. © Cambridge University Press 2014 doi:10.1017/S0033291714002244 ORIGINAL ARTICLE