rTMS Add on Value for Amelioration of Negative Symptoms of Schizophrenia

In this randomized placebo-controlled study the efficacy of high-frequency rTMS and TBS are evaluated. The active study arms are high-frequency rTMS and iTBS of the left dorsolateral prefrontal cortex to treat negative symptoms in schizophrenia. The control arm will include the same number of patients as each active arm and includes both sham rTMS and sham iTBS in the same proportion as the active treatments.

Standards of the trial will be harmonized across four clinical centers with the aim to pool data for analysis. Each center is responsible for ethical approval and adherence to good clinical practice by itself (Sponsor).

Interim analysis: Several meta-analyses of the effect of rTMS/iTBS on negative symptoms in schizophrenia showing heterogeneous effect sizes have been published since begin of the trial. Thefore, an interim analysis after inclusion of at least 15 patients in each arm was added to the protocol. In case of null findings and low effect sizes (no differences of either rTMS or TBS vs. sham in the primary outcome), the trial will be terminated.

Inclusion criteria

• ICD-10: schizophrenia with primarily negative symptoms
• Age: 18-75 years
• at least 35 Points at the composite score of the SANS
• stabe medication during the last 2 weeks (at the investigator's discretion)
• written informed consent (by the patient or guardian)

Exclusion criteria

• clinically relevant unstable concomitant somatic diseases
• previous treatment by rTMS
• conditions in which TMS may not be applicated, as e.g., cardiac pacemakers or ferromagnetic implants
• history of epileptic seizures
• current substance or alcohol abuse, or clinically relevant comorbidity (according to M.I.N.I. interview)
• unacceptable concomitant medication (benzodiazepines in higher doses, e.g., Lorazepam > 2 mg/d, Diazepam > 10 mg/d)
• insufficient knowledge of the language of the country of the treatment site
• pregnancy and nursing period
• current statutory hospitalisation