Accelerated rTMS for Psychomotor Slowing

The goal of this clinical trial is to optimize the treatment of psychomotor slowing in patients with schizophrenia using Transcranial Magnetic Stimulation (TMS). A previous randomized controlled trial indicated that inhibitory stimulation over the supplementary motor area (SMA) once daily over 3 weeks ameliorates psychomotor slowing. In this trial the investigators use a shorter inhibitory protocol called cTBS and to be applied 3 times per day. This should lead to faster treatment response and less burden to patients.

The main question the investigators aim to answer are:

Can the treatment with cTBS 3 times per day ameliorate psychomotor slowing in schizophrenia over one week?

Participants will complete questionnaires on the first and last day of the study. Each day, participants will receive the TMS-treatment. Optionally, participants can receive a cerebral MRI before the study and/or come for an additional day 6 to repeat some of the questionnaires.

There is no comparison group. All participants will receive the same treatment.

Schizophrenia is a chronic disorder causing tremendous burden to the patients, families, and society. Besides prominent symptoms such as hallucinations, delusions, and thought disorder, the majority of patients also experiences motor abnormalities. Converging evidence links aberrant structure and function of the cerebral motor network to schizophrenia pathology, particularly to motor abnormalities. One of the most frequent motor abnormalities is psychomotor slowing (PS), which may impact both gross and fine motor behaviour. While PS causes significant distress and predicts poor outcome, researchers are just starting to understand its pathobiology. First evidence points to aberrant functional and structural connectivity within the cerebral motor network in schizophrenia patients with PS, particularly in connections between premotor/motor cortex and thalamus, as well as between motor cortex and cerebellum. In addition, severe motor inhibition was linked to increased neural activity in the premotor cortex. Repetitive transcranial magnetic stimulation (rTMS) may temporarily alter brain activity.

Data from OCoPS-P (BASEC 2018-02164, clinicaltrials.gov NCT03921450) double-blind RCT indicate that 15 sessions of inhibitory rTMS over three weeks on the supplementary motor area (SMA) alleviate PS.

However, three weeks of one daily rTMS session is rather inconvenient for patients and medical professionals. Therefore, this study will aim to optimize the treatment protocol with regard to efficiency and efficacy by using an accelerated rTMS protocol with continuous theta-burst stimulation (cTBS). Inhibitory cTBS will be applied 3 times per day over 5 days, which will increase the session frequency and shorten sessions and treatment duration.

Reducing the duration of the treatment phase might increase treatment adherence, shorten inpatient treatment, alleviate PS faster, and will facilitate implementation in clinical practice.

Eligibility Criteria:
Inclusion Criteria:

* 18-60 years.
* Ability and willingness to participate in the study
* Ability to provide written informed consent
* Informed Consent as documented by signature (Appendix Informed Consent Form)
* Schizophrenia spectrum disorders according to DSM-5 with psychomotor slowing (SRRS score ≥ 15).

Exclusion Criteria:

* Substance abuse or dependence other than nicotine.
* Past or current medical or neurological conditions associated with impaired or aberrant movement, such as brain tumors, stroke, M. Parkinson, M. Huntington, dystonia.
* Severe head trauma with subsequent loss of consciousness.
* Epilepsy or other convulsions.
* History of any hearing problems or ringing in the ears.
* Standard exclusion criteria for TMS (implanted electronic devices (e.g. pacemakers, implantable cardioverter-defibrillators, vagus nerve stimulators and wearable cardioverter-defibrillators, ocular implants, deep brain stimulators, implanted medication pumps, intracardiac lines even when removed) and/or conductive objects near the coil (e.g. cochlear implants, implanted electrodes/stimulators, aneurysm clips or coils, stents and bullet fragments)
* Women who are pregnant or breastfeeding.
* Any TMS treatment in the past 2 months.
* If applicable: standard exclusion criteria for MRI (study participation without MRI is possible)
* Intention to become pregnant during the course of the study
* Previous enrolment into the current study
* Enrolment of the investigator, his/her family members, employees, and other dependent persons