Thomas Wobrock1, Birgit Guse2, Joachim Cordes3, Wolfgang Wölwer3, Georg Winterer4, Wolfgang Gaebel3, Berthold Langguth5, Michael Landgrebe6, Peter Eichhammer5, Elmar Frank5, Göran Hajak7, Christian Ohmann8, Pablo E Verde8, Marcella Rietschel9, Raees Ahmed10, William G Honer11, Berend Malchow12, Thomas Schneider-Axmann12, Peter Falkai12, Alkomiet Hasan12. 1. Department of Psychiatry and Psychotherapy (TW, BG), Georg-August-Universtat Goettingen, Goettingen; Centre of Mental Health (TW), County Hospitals Darmstadt-Dieburg, Groß-Umstadt. Electronic address: t.wobrock@kreiskliniken-dadi.de. 2. Department of Psychiatry and Psychotherapy (TW, BG), Georg-August-Universtat Goettingen, Goettingen. 3. Department of Psychiatry and Psychotherapy, Heinrich-Heine University, Düsseldorf; Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich, Heine University, Düsseldorf. 4. Department of Psychiatry and Psychotherapy, Heinrich-Heine University, Düsseldorf; Charité-Universitätsmedizin Berlin, Berlin. 5. Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg. 6. Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg; Department of Psychiatry, Psychosomatics and Psychotherapy, kbo-Lech-Mangfall-Klinik, Agatharied. 7. Department of Psychiatry, Psychosomatics and Psychotherapy, Sozialstiftung Bamberg, Bamberg. 8. Coordination Centre for Clinical Trials, Heinrich-Heine University, Düsseldorf. 9. Department of Genetic Epidemiology in Psychiatry, Institute of Central Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim. 10. Institut für anwendungsorientierte Forschung und klinische Studien GmbH, Goettingen, Germany. 11. Department of Psychiatry and Institute of Mental Health, University of British Columbia, Vancouver, British Columbia, Canada. 12. Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universtat, Munich, Germany.
Abstract
BACKGROUND: Investigators are urgently searching for options to treat negative symptoms in schizophrenia because these symptoms are disabling and do not respond adequately to antipsychotic or psychosocial treatment. Meta-analyses based on small proof-of-principle trials suggest efficacy of repetitive transcranial magnetic stimulation (rTMS) for the treatment of negative symptoms and call for adequately powered multicenter trials. This study evaluated the efficacy of 10-Hz rTMS applied to the left dorsolateral prefrontal cortex for the treatment of predominant negative symptoms in schizophrenia. METHODS: A multicenter randomized, sham-controlled, rater-blinded and patient-blinded trial was conducted from 2007-2011. Investigators randomly assigned 175 patients with schizophrenia with predominant negative symptoms and a high-degree of illness severity into two treatment groups. After a 2-week pretreatment phase, 76 patients were treated with10-Hz rTMS applied 5 days per week for 3 weeks to the left dorsolateral prefrontal cortex (added to the ongoing treatment), and 81 patients were subjected to sham rTMS applied similarly. RESULTS: There was no statistically significant difference in improvement in negative symptoms between the two groups at day 21 (p = .53, effect size = .09) or subsequently through day 105. Also, symptoms of depression and cognitive function showed no differences in change between groups. There was a small, but statistically significant, improvement in positive symptoms in the active rTMS group (p = .047, effect size = .30), limited to day 21. CONCLUSIONS: Application of active 10-Hz rTMS to the left dorsolateral prefrontal cortex was well tolerated but was not superior compared with sham rTMS in improving negative symptoms; this is in contrast to findings from three meta-analyses.
RCT Entities:
BACKGROUND: Investigators are urgently searching for options to treat negative symptoms in schizophrenia because these symptoms are disabling and do not respond adequately to antipsychotic or psychosocial treatment. Meta-analyses based on small proof-of-principle trials suggest efficacy of repetitive transcranial magnetic stimulation (rTMS) for the treatment of negative symptoms and call for adequately powered multicenter trials. This study evaluated the efficacy of 10-Hz rTMS applied to the left dorsolateral prefrontal cortex for the treatment of predominant negative symptoms in schizophrenia. METHODS: A multicenter randomized, sham-controlled, rater-blinded and patient-blinded trial was conducted from 2007-2011. Investigators randomly assigned 175 patients with schizophrenia with predominant negative symptoms and a high-degree of illness severity into two treatment groups. After a 2-week pretreatment phase, 76 patients were treated with 10-Hz rTMS applied 5 days per week for 3 weeks to the left dorsolateral prefrontal cortex (added to the ongoing treatment), and 81 patients were subjected to sham rTMS applied similarly. RESULTS: There was no statistically significant difference in improvement in negative symptoms between the two groups at day 21 (p = .53, effect size = .09) or subsequently through day 105. Also, symptoms of depression and cognitive function showed no differences in change between groups. There was a small, but statistically significant, improvement in positive symptoms in the active rTMS group (p = .047, effect size = .30), limited to day 21. CONCLUSIONS: Application of active 10-Hz rTMS to the left dorsolateral prefrontal cortex was well tolerated but was not superior compared with sham rTMS in improving negative symptoms; this is in contrast to findings from three meta-analyses.
Authors: Leandro da Costa Lane Valiengo; Stephan Goerigk; Pedro Caldana Gordon; Frank Padberg; Mauricio Henriques Serpa; Stephanie Koebe; Leonardo Afonso Dos Santos; Roger Alberto Marcos Lovera; Juliana Barbosa de Carvalho; Martinus van de Bilt; Acioly L T Lacerda; Helio Elkis; Wagner Farid Gattaz; Andre R Brunoni Journal: JAMA Psychiatry Date: 2020-02-01 Impact factor: 21.596
Authors: A Hasan; T Wobrock; B Guse; B Langguth; M Landgrebe; P Eichhammer; E Frank; J Cordes; W Wölwer; F Musso; G Winterer; W Gaebel; G Hajak; C Ohmann; P E Verde; M Rietschel; R Ahmed; W G Honer; P Dechent; B Malchow; M F U Castro; D Dwyer; C Cabral; P M Kreuzer; T B Poeppl; T Schneider-Axmann; P Falkai; N Koutsouleris Journal: Mol Psychiatry Date: 2016-10-11 Impact factor: 15.992
Authors: Alkomiet Hasan; Birgit Guse; Joachim Cordes; Wolfgang Wölwer; Georg Winterer; Wolfgang Gaebel; Berthold Langguth; Michael Landgrebe; Peter Eichhammer; Elmar Frank; Göran Hajak; Christian Ohmann; Pablo E Verde; Marcella Rietschel; Raees Ahmed; William G Honer; Berend Malchow; Susanne Karch; Thomas Schneider-Axmann; Peter Falkai; Thomas Wobrock Journal: Schizophr Bull Date: 2015-10-03 Impact factor: 9.306