Deep Brain Stimulation for Treatment-Resistant Schizophrenia

Inclusion criteria

• Males and females who are at least 22 years of age.
• Subject has a diagnosis of schizophrenia or schizoaffective disorder as determined by a review of medical records, discussion with referring psychiatrist as well as the Structured Clinical Interview for DSM-V (SCID-V).
• Subject determined to be treatment-resistant for at least one year prior to the Screening Visit as demonstrated by clinical evidence (determined by review of medical records and discussion with referring psychiatrist) of persistent auditory hallucinations and/or delusions that have not responded to treatment with three adequate regimens of antipsychotic medication including one failed trial of clozapine as defined as follows:

• Adequate trials of two different antipsychotic drugs (not including clozapine) belonging to different classes of at least 12 weeks equivalent to at least 500 mg/day of chlorpromazine within the previous 5 years.
• A trial of clozapine of at least12 weeks at a dose of at least 400 mg (or a clozapine level of at least 350 ng/mL). Subjects who were unable to tolerate clozapine at this dose or for this duration because of intolerable side effects are also eligible.
• Subject has at least a score of 6 (severe) on 2 of the 4 Brief Psychiatric Rating Scale (BPRS) positive symptoms (conceptual disorganization, grandiosity, hallucinatory behavior and unusual thought content) at all three Baseline Visits prior to undergoing surgery. One of the 2 must be hallucinatory behavior.
• Subject must be ambulatory.
• Females who are postmenopausal, physically incapable of childbearing, or practicing an acceptable method of birth control. Acceptable methods of birth control include surgical sterilization, hormonal contraceptives, or double-barrier methods (condom or diaphragm with a spermicidal agent or intrauterine device (IUD). If practicing an acceptable method of birth control, a negative urine pregnancy test result has been obtained at baseline Visits 1 and 3.
• Subject is determined by independent psychiatrist with expertise in capacity assessments to have decision-making capacity to provide informed consent.
• Subject is able to read English, understand and cooperate with study procedures, and has signed a written informed consent form prior to any study procedures.

Exclusion criteria

• Subject has a positive urine drug screen at any of the three Baseline Visits.
• Subject had major surgery within three months prior to Baseline Visit 1 or has other surgery planned during the proposed study period.
• Subject is determined by medical consultant to have medical contraindications to undergoing surgery.
• Subject is pregnant or breast-feeding.
• Subject has a history of alcohol or drug abuse within the past 6 months and dependence within the past year.
• Subject has a medical illness/condition, co-morbid psychiatric illness, and/or abnormal diagnostic finding that would interfere with the completion of the study, confound the results of the study, or pose risk to the patient.
• Subject has participated in another investigational drug trial or therapeutic trial within 30 days of Baseline Visit 1.
• Subject has a diagnosis of mental retardation.
• Subject has a neurological condition, or a history of traumatic brain injury associated with loss of consciousness of > 1 hour and/or intracranial/epidural/subdural bleeding.
• Subject has defibrillator or pacemaker or other implants that will interfere with MRI and functioning of the device.
• Unstable psycho-social condition including housing and poor support.