Transcranial Magnetic Stimulation (TMS) for Motor Symptoms in Psychiatric Disorders

Study Overview
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Brief Summary
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Psychomotor slowing may occur in major psychiatric disorders, such as major depressive disorders or schizophrenia spectrum disorders. It refers to slowing of fine motor skills, motor planning and gross motor behavior. In major depression and schizophrenia, psychomotor slowing is associated with alterations of premotor cortex, dorsolateral prefrontal cortex and basal ganglia. This randomized, sham-controlled, prospective trial will test, whether 15 sessions of repetitive transcranial magnetic stimulation (rTMS) may ameliorate psychomotor slowing in schizophrenia or major depression.

Detailed Description
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Psychomotor slowing may occur in major psychiatric disorders, such as major depressive disorders or schizophrenia spectrum disorders. It refers to slowing of fine motor skills, motor planning and gross motor behavior. In major depression and schizophrenia, psychomotor slowing is associated with alterations of premotor cortex, dorsolateral prefrontal cortex and basal ganglia. This randomized, sham-controlled, prospective trial will test, whether 15 sessions of rTMS in 3 weeks may ameliorate psychomotor slowing in schizophrenia or major depression. Eligible participants will be randomized to one of four arms:

Official Title
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Effects of Transcranial Magnetic Stimulation on Motor Symptoms of Patients With Psychiatric Disorders

Conditions
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Psychomotor Retardation, Psychomotor Slowing, Schizophrenia and Related Disorders, Major Depressive Disorder

Intervention / Treatment
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* Other: DLPFC facilitatory
* Other: SMA inhibitory
* Other: SMA facilitatory
* Other: sham TMS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: suffering from major depressive disorder or schizophrenia spectrum disorder according to DSM-5 criteria right handedness normal or corrected-to-normal vision and hearing Exclusion Criteria: epilepsy history of severe head trauma current abuse of drugs or alcohol; past addiction to drugs or alcohol pregnancy incompatibility to cerebral MRI

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: DLPFC facilitatory<br>repetitive transcranial magnetic stimulation (rTMS) of 15 Hz over left DLPFC usually effective in depression treatment, probably no specific effect on psychomotor slowing | Other: DLPFC facilitatory<br>* 15 Hz stimulation of left dorsolateral prefrontal cortex (DLPFC)(15 sessions/3weeks, 1500 stimuli per session, stimulation intensity 100% of the individual active motor threshold; in total 22500 stimuli<br>* Other names: rTMS facilitatory DLPFC;|
| Experimental: preSMA/SMA inhibitory<br>repetitive transcranial magnetic stimulation (rTMS) of 1 Hz over preSMA/SMA should inhibit overactive premotor cortices | Other: SMA inhibitory<br>* 1 Hz stimulation of preSMA/SMA (15 sessions/3weeks, 1500 stimuli per session, stimulation intensity 100% of the individual active motor threshold; in total 22500 stimuli<br>* Other names: rTMS inhibitory SMA;|
| Experimental: preSMA/SMA facilitatory<br>intermittend theta burst stimulation (iTBS) over preSMA/SMA should facilitate neural activity within premotor cortices | Other: SMA facilitatory<br>* Three pulses of stimulation at 50 Hz of preSMA/SMA, repeated every 200 ms. 2 s trains are repeated every 10 s for a total of 190 s (600 pulses, 200 seconds). intensity 80% of individual active motor threshold; in total 9000 stimuli<br>* Other names: iTBS facilitatory SMA;|
| Sham Comparator: sham TMS<br>sham rTMS with a placebo coil over occipital cortex should have no effect at all (no transcranial magnetic stimulation, only sound) | Other: sham TMS<br>* Determination of active motor threshold and subsequent stimulation with the placebo coil, with the same sounds but without effects. 15 sessions in three weeks, duration of 20 mins per session<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Responders at Week 3 | Number of participants with >30% reduction from baseline in the Salpetriere Retardation Rating Scale, last observation carried forward method applied | week 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Salpetriere Retardation Rating Scale Total Score From Baseline to Week 3 | observer based rating scale of the severity of psychomotor slowing, assessment blind to intervention Scores may range from 0 - 60, higher scores indicate worse outcome | week 3 | 
| Change in Activity Level From Baseline to Week 3 | actigraphically (wrist of the non-dominant arm) assessed motor activity during the wake periods of one day, given in counts/h | week 3 | 
| Change in Catatonia Severity From Baseline to Week 3 | observer based rating of catatonia severity with the Bush Francis Catatonia Rating Scale, assessment blind to intervention | week 3 | 
| Change in Fingertapping Score From Baseline to Week 3 | Fingertapping test with the dominant and nondominant index finger for 10 sec, video-taped and blind assessment | week 3 | 
| Change in Coin Rotation From Baseline to Week 3 | test of manual dexterity in both hands, rotation of a specified coin for 10 seconds, video-taped and blinded evaluation | week 3 | 
| Change in Hand Gesture Performance From Baseline to Week 3 | videotaped performance of hand gestures according to the Test of Upper Limb Apraxia (TULIA), blind evaluation and rating | week 3 | 
| Change in SANS Total Score From Baseline to Week 3 | scale for the assessment of negative symptoms, applies to schizophrenia spectrum disorder patients, assessment blind to intervention | week 3 | 
| Change From HAMD Total Score From Baseline to Week 3 | Hamilton Rating Scale for Depression, 21-item version, applies to depression patients, assessment blind to intervention | week 3 | 
| Change in CAINS Total Score From Baseline to Week 3 | the clinical assessment interview for negative symptoms, assessment blind to intervention | week 3 | 
| Change in PANSS Total and Subscores From Baseline to Week 3 | the positive and negative syndrome scale, interview to assess severity of schizophrenia symptoms, applies to schizophrenia spectrum disorder patients, assessment blind to intervention | week 3 |