Efficacy of Pimozide Augmentation for Clozapine Partial Response
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: Pimozide; placebo
Intervention description: half of the subjects are randomized to the active drug group; half of the subjects are randomized to placebo group
Intervention MeSH terms: Pimozide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: schizophrenia; pimozide; clozapine

Summary:

      This is a 12 week outpatient study for patients with schizophrenia who are on Clozapine, but
      continue to experience symptoms. The purpose of this project is to find out if small doses of
      pimozide (an antipsychotic medication, taken by mouth) will be helpful in reducing symptoms
      (such as hearing voices, having trouble in organizing your thoughts, lack of interest in life
      events and social activities), compared to placebo (an inactive substance, "sugar pill"),
      when added to clozapine in patients with schizophrenia.

      The participant will be asked to come in once a week to meet with the research staff and
      study doctor. The participant will continue to see your regular clinician during this study
      for all normal appointments. The participant will remain on your current medications
      throughout the study. During the study you will be randomly selected to be put on a small
      dose of Pimozide or placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of schizophrenia or schizoaffective disorder.

          -  A minimum Brief Psychiatric Rating Scale (BPRS) score of 35 and a BPRS psychotic
             symptom cluster score of at least 8.

          -  Currently taking clozapine with a blood level between 350-1000 ng/ml and on a stable
             dose of clozapine for the past 2 weeks.

          -  Able to give informed consent.

        Exclusion Criteria:

          -  A history of significant medical/neurological disease such as thyroid, renal, hepatic
             abnormality, seizure disorder.

          -  History of Neuroleptic Malignant Syndrome.

          -  Current substance abuse determined by urine toxicology.

          -  Cardiac arrhythmia, sinus bradycardia (heart rate less than 60/min), sinus tachycardia
             (heart rate greater than 110/min), supraventricular tachycardia, ventricular
             tachycardia, Wolff-Parkinson-White Syndrome, first, second, third degree
             atrioventricular (AV) block, atrial fibrillation, atrial flutter and junctional
             complexes. in baseline electrocardiogram (EKG). Study doctors will examine the EKGs
             and consult with an internist/cardiologist as needed.

          -  on EKG: QTc > 450 ms.

          -  Current use of macrolide antibiotics (e.g., erythromycin, clarithromycin), azole
             antifungal agents (e.g., ketoconazole, itraconazole), protease inhibitors (e.g.,
             ritonavir, indinavir), nefazodone, and other medications that are associated with
             prolonged QTc.

          -  Current use of antipsychotics other than clozapine.

          -  Current use of sertraline.

          -  IQ level below 70.

          -  At high risk for suicidal/homicidal behavior.

          -  Pregnancy, lack of birth control for females of childbearing age (female patients must
             report use of effective method for birth control such as birth control pills, condoms,
             barrier methods, abstinence or have written statement from their doctors that they are
             medically sterile).

          -  Non-English speaking.