A Double-Blind Placebo Controlled Trial of Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Negative Symptoms in Schizophrenia

Not Applicable

Completed

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

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Sham rTMS	sham TMS	Bilateral Sham rTMS
Active Treatment	Transcranial Magnetic Stimulation	Bilateral high frequency (10 Hertz) rTMS

Primary Outcome Measures

Name	Time	Method
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.

Secondary Outcome Measures