Background: Schizophrenia is a severe and often difficult to treat psychiatric illness. In many patients, negative symptoms dominate the clinical picture. Meta-analysis has suggested moderate, but significant effects of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on these symptoms. For treatment of depression a much shorter protocol - intermittent theta burst stimulation (iTBS) - has shown to be non-inferior to conventional high-frequency rTMS. This randomized, sham-controlled, rater-blinded clinical trial assesses the effects of conventional HF-rTMS as well as of iTBS of the left dorsolateral prefrontal cortex in comparison with sham. Methods: The study will be conducted at two psychiatric university hospitals in Germany and at two in the Czech Republic. Assuming an effect size of 0.64 to be detected with a power of 80%, the calculated sample size is 90 patients. Primary outcome will be the difference in the Scale for the Assessment of Negative Symptoms (SANS) score between each active arm and the sham arm at end of treatment.In addition, the trial investigates effects on depressive symptoms, cognitive performance and cigarette smoking. Recording magnetic resonance imaging (MRI) and electroencephalography (EEG) data will serve to assess whether treatment success can be predicted by neural markers and is related to specific neurobiological changes. Discussion: This is a clinical trial directly comparing 10 Hz-rTMS and iTBS in a sham-controlled manner in treating negative symptoms of schizophrenia. If successful, this would present an interesting treatment option for a chronic and severe condition that can be applied at most psychiatric hospitals and only takes up a few minutes per day. Trial registration number: This trial has been registered at clinicaltrials.gov, Identifier: NCT04318977. Data dissemination: Results from the trial shall be published in peer-reviewed journals and presented at meetings and conferences.

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