Effects of Pravastatin on Cholesterol, Inflammation and Cognition in Schizophrenia

This study is a 12-week randomized, double-blind, placebo-controlled pilot study of
pravastatin 40mg a day, administered for 12 consecutive weeks to subjects with schizophrenia
to examine pravastatin's effects on lowering cholesterol levels and inflammatory markers,
and improving cognition. The study will be conducted at the Freedom Trail Clinic and will
use the Massachusetts General Hospital Clinical Research Center. The innovative approach of
using pravastatin to not only decrease cholesterol levels, but to decrease inflammation and
improve cognition in patients with schizophrenia is promising and may lead to a different
approach to treatment in this population.

Inclusion Criteria:

- Male or female

- Age 18-68 years

- Diagnosis of schizophrenia, any subtype, schizoaffective disorder, any subtype or
schizophreniform disorder

- Well established compliance with outpatient medications including their antipsychotic
medication

Exclusion Criteria:

- Inability to provide informed consent

- Current substance and alcohol abuse

- Significant medical illness, including congestive heart failure, severe
cardiovascular disease, renal disease (serum creatinine > 1.5), severe hepatic
impairment or active liver disease, anemia (hemoglobin <11.0 gm/dL), history of
severe head injury, and not treated muscle disease.

- Psychiatrically unstable

- Women of child bearing potential who are pregnant, breastfeeding, or who are
unwilling or unable to use an effective form of birth control during the entire study

- Subjects treated with anti-inflammatory drugs (including daily aspirin and
ibuprofen), thiazide diuretics; agents that induce weight loss, and St. John's Wort
will be excluded from the study

- Current history of untreated thyroid disease

- Current treatment with insulin

- Subjects being treated with drugs such as: colchicine, azole antifungals
(fluconazole, ketoconazole, itraconazole); macrolide antibiotics (clarithromycin,
erythromycin); HIV protease inhibitors (ritonavir, indinavir, saquinavir, nelfinavir)
that inhibit the CYP 450 3A liver enzyme

- Known hypersensitivity to pravastatin or any of its components