Schizophrenia
Conditions
Keywords
Transcranial Magnetic Stimulation, Schizophrenia, Negative Symptoms
Brief summary
There is pilot data to suggest the therapeutic value of rTMS applied to the left prefrontal cortex in the treatment of negative symptoms. Neuroimaging studies demonstrate abnormal activity in this region in patients experiencing negative symptoms. Finally rTMS applied at high frequency shows the capacity to up-regulate cortical activity in a way that would provide an explanation for a therapeutic response. The study involves participants receiving 15 sessions of high frequency rTMS treatment applied bilaterally to the prefrontal cortex over a 3 week period or sham rTMS. Following this double blind phase, participants randomised to placebo treatment will be offered 15 sessions of active treatment. In addition, ppTMS (paired pulse TMS) will be conducted prior to the onset of treatment and after completion of the course, as a means of measuring cortical inhibition and facilitation. NIRS (Near Infra red spectroscopy) will also be conducted prior to, during and after the first and last treatment sessions to allow monitoring of oxygenated and deoxygenated haemoglobin.
Detailed description
The main outcome measure used is the SANS (Scale for the Assessment of Negative Symptoms. This is a semi strucutured interview which provides scores from 0-70. This is administered at baseline, week 2, 3, 5 and 6. Other outcome measures administered are (frequency mentioned above): PANSS (Positive and Negative Syndrome Scale) and the Calgery Depression Scale for Schizophrenia, A cognitive battery is also administered. Inclusion Criteria: * Diagnostic and Statistical Manual-IV diagnosis of schizophrenia or schizoaffective disorder, age over 18 * Persistent negative symptoms of moderate to severe intensity * Failure to respond to a minimum of two antipsychotic medications * No increase or initiation of new antipsychotic therapy in the four weeks prior to entering the trial Exclusion Criteria * Prominent positive symptoms * Have an unstable medical condition, neurological disorder or any history of seizure disorder or are currently pregnant or lactating * Previous brain injury or surgery, any metal clips, plates or other metal items in the head, cardiac pacemaker * Subjects at high risk of violence or suicide as determined by the investigator and treating clinicians * Substance dependence
Interventions
DEVICETranscranial Magnetic Stimulation
Participants were sequentially randomly assigned to either 15 active bilateral treatments or 15 sham bilateral treatments that were administered on a daily basis, five days per week.
DEVICEsham TMS
Sponsors
The Alfred
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* DSM-IV diagnosis of schizophrenia or schizoaffective disorder, age over 18 * Persistent negative symptoms of moderate to severe intensity * Failure to respond to a minimum of two antipsychotic medications * No increase or initiation of new antipsychotic therapy in the four weeks prior to entering the trial
Exclusion criteria
* Prominent positive symptoms * Have an unstable medical condition, neurological disorder or any history of seizure disorder or are currently pregnant or lactating * Previous brain injury or surgery, any metal clips, plates or other metal items in the head, cardiac pacemaker * Subjects at high risk of violence or suicide as determined by the investigator and treating clinicians * Substance dependence
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Scale for the Asessment of Negative Symptoms (SANS) | 3 weeks | Scale for Assessment of Negative Symptoms \[SANS\]. This is a semi structured interview. Assessments are conducted on a six-point scale (0=not at all to 5=severe)with a total score range of 0-70. A score of \>50 is considered to be a moderate-severe intensity. |
Countries
Australia
Participant flow
Recruitment details
A total of 20 patients were randomly assigned. Patients were recruited from the outpatient department of two public area mental health services and by referral from a number of private psychiatrists between January 2003 and July 2007.
Participants by arm
| Arm | Count |
|---|---|
| Active Treatment Bilateral high frequency (10Hz) rTMS | 12 |
| Sham Treatment Sham bilateral rTMS treatment | 10 |
| Total | 22 |
Baseline characteristics
| Characteristic | Active Treatment | Sham Treatment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 10 Participants | 22 Participants |
| Region of Enrollment Australia | 12 participants | 10 participants | 22 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 10 Participants | 8 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 0 / 10 |
| serious Total, serious adverse events | 0 / 12 | 0 / 10 |
Outcome results
Primary
Scale for the Asessment of Negative Symptoms (SANS)
Scale for Assessment of Negative Symptoms \[SANS\]. This is a semi structured interview. Assessments are conducted on a six-point scale (0=not at all to 5=severe)with a total score range of 0-70. A score of \>50 is considered to be a moderate-severe intensity.
Time frame: 3 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Treatment | Scale for the Asessment of Negative Symptoms (SANS) | 38.8 Scores on a scale | Standard Deviation 11 |
| Sham Treatment | Scale for the Asessment of Negative Symptoms (SANS) | 53.7 Scores on a scale | Standard Deviation 8.3 |