# Levetiracetamin in First Episode Psychosis

> **NIH NIH R33** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $759,078

## Abstract

Increased perfusion of the hippocampal CA1 subfield is a clinical biomarker for early psychosis that also
predicts hippocampal volume loss. Converging evidence suggests that CA1 hyperperfusion reflects excessive
glutamatergic transmission which drives psychosis and may produce excitotoxic hippocampal injury that is
associated with poor outcomes. Antipsychotics reduce hippocampal activity but may worsen hippocampal
injury via oxidative stress from increased dopamine release. We recently demonstrated hippocampal volume
loss at an annualized mean rate of 6.5% during the first 8 weeks of antipsychotic treatment. Levetiracetam, an
anticonvulsant, normalizes excessive glutamatergic and dopaminergic neurotransmission by targeting the
synaptic vesicle protein (SVP2A). Levetiracetam is neuroprotective in animal and human models of
hippocampal hyperactivity. We hypothesize that levetiracetam will protect against hippocampal volume loss
and improve clinical outcomes in early psychosis by reducing excessive glutamate and dopamine
transmission. Approach: We will establish target engagement and dose selection by measuring the effects of
levetiracetam 185 mg and 500 mg on hippocampal perfusion in a placebo-controlled trial in 24 medication-
naïve individuals with first episode psychosis. We will then study the optimal levetiracetam dose added to
antipsychotic in a 12-week placebo-controlled trial in 84 medication naïve individuals with first episode
psychosis. We will examine whether levetiracetam prevents hippocampal volume loss and improves clinical
symptoms and cognition and will explore potential mediators and modulators of effect. Significance: By
correcting a fundamental dysregulation of hippocampal neurotransmission, we believe levetiracetam will
improve initial treatment response in first episode psychosis and fundamentally change the course of illness.

## Key facts

- **NIH application ID:** 9795138
- **Project number:** 4R33MH112833-03
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** DONALD C. GOFF
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $759,078
- **Award type:** 4N
- **Project period:** 2017-05-24 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9795138

## Citation

> US National Institutes of Health, RePORTER application 9795138, Levetiracetamin in First Episode Psychosis (4R33MH112833-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9795138. Licensed CC0.

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