Rasagiline in the Treatment of Persistent Negative Symptoms of Schizophrenia

• Neuropsychological Tests, Including RBANS, Probabilistic Learning Task, and N-Back Task [ Time Frame: Beginning of treatment phase (week 0) and end of treatment phase (week 12) ] [ Designated as safety issue: No ]
• Simpson Angus Scale [ Time Frame: Every 4 weeks ] [ Designated as safety issue: Yes ]
• Side Effect Checklist and Vital Signs [ Time Frame: Weekly ] [ Designated as safety issue: Yes ]

This is a study of a new medication for the treatment of cognitive impairments (thinking difficulties) and negative symptoms in people with schizophrenia. The new medication is rasagiline. Rasagiline is a drug which has been approved by the Food and Drug Administration for the treatment of Parkinson's disease. It is used to treat cognitive problems.

The study will consist of two phases: a 4-week continued stability phase (lead-in phase) and a 12-week double-blind treatment phase. In the lead-in phase, subjects receiving antipsychotic medication, who manifest moderate to severe and persistent negative symptoms, will remain on their maintenance regimen for at least four weeks. The treatment phase will be a 12-week, parallel groups, double-blind, placebo-controlled trial of adjunctive rasagiline (1 mg/day), a selective MAO-B oxidase inhibitor.

• Drug: rasagiline (Pharmacodynamics)
  Rasagiline 1 mg/day for 12 weeks
• Drug: Placebo
  Placebo 1 tablet each day

• Active Comparator: Rasagiline
  Treatment with Rasagiline
  Intervention: Drug: rasagiline (Pharmacodynamics)
• Placebo Comparator: Inactive pill
  Treatment with Placebo
  Intervention: Drug: Placebo

Inclusion Criteria:

• Subjects will meet DSM-IV criteria for schizophrenia or schizoaffective disorder.
• Current treatment with one or more second generation antipsychotics, except ziprasidone
• On same second generation antipsychotic(s)for at least 56 days
• On same dose of second generation antipsychotic(s)for at least 30 days
• 22-item SANS: Total score (i.e.all items minus global items and poverty of content of speech)greater than 20 or global Rating of Affective Flattening greater than or equal to 3 or global Rating of alogia greater than or equal to 3
• BPRS: Sum of the four positive symptom items less than or equal to 16 (items 4,11,12,15)
• BPRS: Sum of the four Anxiety/Depression Factor items less than or equal to 14 (items 1,2,5,9)
• Simpson-Angus Scale: Total score less than or equal to 8

Exclusion Criteria:

• DSM-IV Major Depressive Disorder within last 6 months
• Current treatment with ziprasidone
• DSM-IV diagnosis of alcohol or substance dependence within the last 6 months
• DSM-IV criteria for alcohol or substance abuse within the last month
• evidence of illicit substance use, as identified with urine toxicology screen
• History of an organic brain disorder, mental retardation,epilepsy, or a medical condition, whose pathology or treatment could alter the presentation or treatment of schizophrenia or significantly increase the risk associated with the proposed treatment protocol. See those listed below
• Uncontrolled hypertension defined as BP exceeding 145/90 on 3 consecutive readings despite adequate treatment, pheochromocytoma, melanoma, hepatic insufficiency
• Pregnancy or lactation in females
• Pheochromocytoma
• Melanoma
• Hepatic insufficiency