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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
Continuous Theta Burst Stimulation (cTBS) is an inhibitory stimulation protocol of the Transcranial Magnetic Stimulation (TMS) device that temporarily inhibits brain activation in a small targeted brain area. The investigators apply the cTBS protocol 3 times daily at 100% of the resting motor threshold (RMT) for 1500 pulses per session.
University Hospital of Psychiatry and Psychotherapy
Bern, Switzerland
Change in Salpetriere Retardation Rating Scale (SSRS) from baseline
Changes in psychomotor slowing as measured by the Salpêtrière retardation rating scale (SRRS) throughout the study. The SRRS is a 15-item rating scale that measures psychomotor slowing. Each item can be scored from 0 to 4, thus the total ranging from 0 to 60, with lower scores representing better outcome.
Time frame: At baseline, day 3, post at day 5, and follow-up 1 week later
Proportion of responders in SRRS
Proportion of responders (\>= 30% reduction from baseline SRRS) at day 3 and day 5. This will provide an additional categorical measure of who benefits from the intervention in terms of the main target (psychomotor slowing).
Time frame: At baseline, day 3, post at day 5, and follow-up 1 week later
Change in psychosis severity from baseline
Change in the Positive And Negative Symptom Scale (PANSS) from baseline, PANSS total score assesses the severity of positive, negative and general symptoms, ranging from 30-210 with higher scores indicating increased symptom severity, i.e. poorer outcome
Time frame: At baseline, post at day 5, and follow-up 1 week later
Change in negative symptoms from baseline
Change in the Brief Negative Symptom Scale (BNSS) from baseline, total score is used, ranging from 0-78 with higher values indicating poorer outcome, i.e. more negative symptom severity
Time frame: At baseline, post at day 5, and follow-up 1 week later
Change in catatonia severity from baseline
Observer based rating of catatonia severity with the Bush Francis Catatonia Rating Scale (BFCRS), total score of the BFCRS ranging 0-69, with higher scores indicating poorer outcome Observer based rating of catatonia severity with the Northoff Catatonia Rating Scale (NCRS), total score ranging 0-80, with higher scores indicating poorer outcome
Time frame: At baseline, day 3, post at day 5, and follow-up 1 week later
Change in parkinsonism severity from baseline
Observer based rating of parkinsonism severity with the Unified Parkinson Disease Rating Scale Part III (UPDRS), total score of the UPDRS ranging 0-104, with higher scores indicating poorer outcome
Time frame: At baseline, day 3, post at day 5, and follow-up 1 week later
Changes in neurological soft signs from baseline
Observer based rating of neurological soft signs with the Neurological Evaluation Scale (NES), total score ranging 0-82, with higher scores indicating poorer outcome
Time frame: At baseline, post at day 5, and follow-up 1 week later
Changes in dyskinesia from baseline
Observer based rating of dyskinesia with the Abnormal Involuntary Movement Scale (AIMS), 7-item scale with the total ranging fro 0-28, with higher scores indicating poorer outcome
Time frame: At baseline, post at day 5
Changes in self-reported negative symptoms from baseline
Self-reported negative symptoms with the Self-evaluation of Negative Symptoms (SNS), total score ranging 0-40, with higher scores indicating poorer outcome
Time frame: At baseline, post at day 5
Changes in self-reported catatonia symptoms from baseline
Self-reported catatonia symptoms with the Northoff Scale for Subjective Experience in Catatonia (NSSC), total score ranging 0-48, with higher scores indicating poorer outcome
Time frame: At baseline, post at day 5
Changes in self-reported activity from baseline
Change in the International Physical Activity Questionnaire (IPAQ), the total score is used ranging from 0-70000 metabolic equivalent (MET)
Time frame: At baseline, post at day 5
Change in objectively measured physical activity from baseline
Change in the activity levels using wrist actigraphy from baseline. Actigraphy is measured continuously from baseline to post and a sleep diary is collected to separate wake from sleep hours
Time frame: Continuously from baseline to post at day 5
Change in dexterity from baseline
Change in the coin rotation task from baseline
Time frame: At baseline, post at day 5
Change in grip strength from baseline
Change in grip strength measured with a grip force task
Time frame: At baseline, post at day 5
Change in cortical excitability of the motor cortex from baseline
Changes in motor cortex excitability from beginning of day 1, end of day 1, end of day 3, and end of day 5 using a TMS paradigm of short interval intracortical inhibition (SICI), intracortical facilitation (ICF) and 1 mV motor evoked potentials (MEP).
Time frame: Baseline before the first 3 TMS, baseline after the first 3 TMS, day 3 (after 9 TMS), post at day 5 (after 15 TMS)
Change in social and community functioning
Change in Social and Occupational Functional Assesment Scale (SOFAS) from baseline, the score ranges from 0-100 with higher scores indicating better functioning, i.e. better outcome
Time frame: Baseline, post at day 5
Change in global functioning
Change in Global Assessment of Functioning (GAF) from baseline, total score ranging 0-100 with higher scores indicating better functioning/outcome
Time frame: Baseline, post at day 5
Change in functional capacity
Change in the Score of the brief version of the University of California, San Diego, Performance-Based Skills Assessment (UPSA-brief) assessment from baseline, higher scores indicating better function, the total score is used ranging 0-100
Time frame: Baseline, post at day 5
Change in DSM 5 Severity Scale of Dimensions
Change in expert rated DMS 5 Severity Scale of Dimensions from baseline. Eight symptom dimensions are rated from 0 to 4 (total 0-32), with higher scores indicating worse outcomes
Time frame: Baseline, post at day 5
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.