Journal
BIOLOGICAL PSYCHIATRY
Volume 77, Issue 11, Pages 979-988Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2014.10.009
Keywords
Brain stimulation; Evidence-based psychiatry; Negative symptoms; Randomized controlled trial; Repetitive transcranial magnetic stimulation; Schizophrenia
Categories
Funding
- Deutsche Forschungsgemeinschaft [FA-210/1]
- Alpine Biomed
- AstraZeneca
- Bristol-Myers Squibb
- Eli Lilly and Company
- I3G
- Janssen-Cilag
- Novartis
- Lundbeck
- Roche
- Sanofi-Aventis
- Otsuka
- Pfizer
- Cerbomed
- AOK (health insurance company)
- inomed
- Localite
- MagVenture
- MAG More
- neuroConn
- Syneika
- FBI-Medizintechnik
- Spitzer Arzneimittel
- DiaMedic
- Essex Pharma
- Lilly Deutschland
- Pfizer Neuroscience
- Janssen-Cilag GmbH
- Neuss
- Lilly Deutschland GmbH
- Bad Homburg
- Servier
- Munich
- ANM
- Autifony Therapeutics
- Merz
- Tinnitus Research Initiative
- German Research Foundation
- German Bundesministerium fur Bildung und Forschung
- American Tinnitus Association
- Deymed Diagnostic
- Actelion Pharmaceuticals
- Affectis Pharmaceuticals
- Bayerische Motorenwerke
- Bundesministerium fur Bildung und Forschung
- Bundesministerium fur Strahlenschutz
- Bristol-Meyers Squibb
- Cephalon
- Daimler Benz
- Deutsche Forschungsgesellschaft
- Elsevier
- EuMeCom
- Essex
- Georg Thieme
- Gerson Lerman Group Council of Healthcare Advisors
- GlaxoSmithKline
- Meda
- Merck
- Proctor Gamble
- Schering-Plough
- Sepracor
- Springer
- Urban Fischer
- Volkswagen
- Desitin
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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.
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