Effects of Low-dose Levetiracetam on Clinical Symptoms, Cognition and Hippocampal Hyperactivity in Schizophrenia

LEV is typically administered in twice-daily doses of 500-1500 mg for the treatment of
epilepsy; these doses are generally well tolerated (Patsalos, 2000). Most relevant to the
proposed study, LEV (125 mg twice-daily, two week administration) has been shown to reduce
hippocampal hyperactivity and improves cognition in patients with mild cognitive impairment
(MCI).

The proposed study will administer 125 mg of immediate release LEV twice-daily for two weeks.
This dose was chosen to potentially maximize efficacy while minimizing side effects. The
proposed dose is substantially lower than the most common dose used clinically for epilepsy
treatment of 3000 mg/day.

Inclusion Criteria:

- Diagnosis of schizophrenia or schizoaffective disorder

- Good general health

- Normal vital signs (blood pressure, pulse, cardiac, pulmonary, abdominal, neurological
exam)

- Normal renal function (as assessed by a metabolic panel at screening if results
current within three months are not already available)

Exclusion Criteria:

1. Substance abuse

2. Significant neurological disorders

3. Significant head trauma/injury

4. Left-handedness

5. Pregnancy

6. MRI-specific exclusion criteria (e.g., claustrophobia, weight > 450lbs, metal in the
body)