Major Depressive Disorder, Psychomotor Retardation, Psychomotor Slowing, Schizophrenia and Related Disorders
Conditions
Brief summary
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
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:
Interventions
OTHERDLPFC facilitatory
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
OTHERSMA inhibitory
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
OTHERSMA facilitatory
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
OTHERsham TMS
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
Sponsors
University of Bern
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Responders at Week 3 | week 3 | Number of participants with \>30% reduction from baseline in the Salpetriere Retardation Rating Scale, last observation carried forward method applied |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Activity Level From Baseline to Week 3 | week 3 | actigraphically (wrist of the non-dominant arm) assessed motor activity during the wake periods of one day, given in counts/h |
| Change in Catatonia Severity From Baseline to Week 3 | week 3 | observer based rating of catatonia severity with the Bush Francis Catatonia Rating Scale, assessment blind to intervention |
| Change in Fingertapping Score From Baseline to Week 3 | week 3 | Fingertapping test with the dominant and nondominant index finger for 10 sec, video-taped and blind assessment |
| Change in Coin Rotation From Baseline to Week 3 | week 3 | test of manual dexterity in both hands, rotation of a specified coin for 10 seconds, video-taped and blinded evaluation |
| Change in Salpetriere Retardation Rating Scale Total Score From Baseline to Week 3 | 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 |
| Change in SANS Total Score From Baseline to Week 3 | week 3 | scale for the assessment of negative symptoms, applies to schizophrenia spectrum disorder patients, assessment blind to intervention |
| Change From HAMD Total Score From Baseline to Week 3 | week 3 | Hamilton Rating Scale for Depression, 21-item version, applies to depression patients, assessment blind to intervention |
| Change in CAINS Total Score From Baseline to Week 3 | week 3 | the clinical assessment interview for negative symptoms, assessment blind to intervention |
| Change in PANSS Total and Subscores From Baseline to Week 3 | 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 |
| Change in Hand Gesture Performance From Baseline to Week 3 | week 3 | videotaped performance of hand gestures according to the Test of Upper Limb Apraxia (TULIA), blind evaluation and rating |
Countries
Switzerland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DLPFC Facilitatory repetitive transcranial magnetic stimulation (rTMS) of 15 Hz over left DLPFC
usually effective in depression treatment, probably no specific effect on psychomotor slowing
DLPFC facilitatory: 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 | 12 |
| preSMA/SMA Inhibitory repetitive transcranial magnetic stimulation (rTMS) of 1 Hz over preSMA/SMA
should inhibit overactive premotor cortices
SMA inhibitory: 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 | 11 |
| preSMA/SMA Facilitatory intermittend theta burst stimulation (iTBS) over preSMA/SMA
should facilitate neural activity within premotor cortices
SMA facilitatory: 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 | 11 |
| Sham TMS sham rTMS with a placebo coil over occipital cortex
should have no effect at all (no transcranial magnetic stimulation, only sound)
sham TMS: 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 | 10 |
| Total | 44 |
Baseline characteristics
| Characteristic | Sham TMS | Total | DLPFC Facilitatory | preSMA/SMA Inhibitory | preSMA/SMA Facilitatory |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 44 Participants | 12 Participants | 11 Participants | 11 Participants |
| Age, Continuous | 41.2 years STANDARD_DEVIATION 15.3 | 39.5 years STANDARD_DEVIATION 15 | 45.3 years STANDARD_DEVIATION 15.2 | 38.0 years STANDARD_DEVIATION 15.6 | 34.2 years STANDARD_DEVIATION 14 |
| Diagnosis major depression | 4 participants | 19 participants | 5 participants | 5 participants | 5 participants |
| Diagnosis schizophrenia | 6 participants | 25 participants | 7 participants | 6 participants | 6 participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — | — | — |
| Region of Enrollment Switzerland | 10 participants | 44 participants | 12 participants | 11 participants | 11 participants |
| Sex: Female, Male Female | 3 Participants | 13 Participants | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 7 Participants | 31 Participants | 10 Participants | 8 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 11 | 0 / 11 | 0 / 10 |
| other Total, other adverse events | 1 / 12 | 1 / 11 | 0 / 11 | 1 / 10 |
| serious Total, serious adverse events | 0 / 12 | 0 / 11 | 1 / 11 | 0 / 10 |
Outcome results
Primary
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
Time frame: week 3
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DLPFC Facilitatory | Number of Responders at Week 3 | 4 responders |
| preSMA/SMA Inhibitory | Number of Responders at Week 3 | 9 responders |
| preSMA/SMA Facilitatory | Number of Responders at Week 3 | 0 responders |
| Sham TMS | Number of Responders at Week 3 | 3 responders |
Secondary
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
Time frame: week 3
Secondary
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
Time frame: week 3
Secondary
Change in CAINS Total Score From Baseline to Week 3
the clinical assessment interview for negative symptoms, assessment blind to intervention
Time frame: week 3
Secondary
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
Time frame: week 3
Secondary
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
Time frame: week 3
Secondary
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
Time frame: week 3
Secondary
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
Time frame: week 3
Secondary
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
Time frame: week 3
Secondary
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
Time frame: week 3
Secondary
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
Time frame: week 3