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

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

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

Levetiracetam (LEV: (S)-α-ethyl-2-oxo-pyrrolidine acetamide) is an anticonvulsant/antiepileptic drug. The specific aim of this study is to assess the efficacy of low-dose LEV in reducing hippocampal activity in schizophrenia. The investigators also hypothesize that LEV will improve neurocognition in participants with 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.

2 weeks of levetiracetam administration (125 mg pill, bid), followed by a 1-2 week washout, then 2 weeks of placebo pill administration (bid).

2 weeks of placebo pill administration (bid), followed by a 1-2 week washout, then 2 weeks of levetiracetam administration (125 mg pill, bid).

Neuronal response (measured via functional magnetic resonance imaging, fMRI) in the hippocampus during rest

Cognitive function as measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)

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: Substance abuse Significant neurological disorders Significant head trauma/injury Left-handedness Pregnancy MRI-specific exclusion criteria (e.g., claustrophobia, weight > 450lbs, metal in the body)