Levetiracetam in Tardive Dyskinesia Giuseppe Meco, MD,* Edito Fabrizio, MD,* Antonio Epifanio, MD,† Francesca Morgante, MD,† Marcella Valente, MD,* Nicola Vanacore, MD,‡ Antonio E. Di Rosa, MD,† and Letterio Morgante, MD † Abstract Objectives: The aim of this study was to evaluate the effect of levetiracetam on tardive dyskinesia (TD), which is known to be a major limitation of chronic anti- psychotic drug therapy, particularly with conven- tional antipsychotics. Methods: Sixteen patients suffering from chronic psychosis with TD were enrolled consecutively. Levetirace- tam was given in gradually increasing doses, starting with 125 twice a day until the best clinical benefit was achieved (mean dosage, 2290 mg; range, 1000Y3000 mg). Tardive dyskinesia was assessed using the Abnormal Involuntary Move- ment Scale at baseline and after 1 month and 3 months of treatment with levetiracetam. Results: Compared with baseline, there was a significant improvement in the Abnormal Involuntary Move- ment Scale score after 1 month still present after 3 months (P G 0.001). All patients well tolerated levetiracetam, except one who dropped out of the trial after the first 2 weeks owing to excessive drowsiness. Conclusions: The results of this open-label observational study suggest that levetiracetam is a well-tolerated drug and effectively controls TD. Key Words: levetiracetam, tardive dyskinesia, glutamate, NMDA receptor (Clin Neuropharmacol 2006;29:265Y268) T ardive dyskinesia (TD) is known to be a major limitation of chronic antipsychotic drug therapy, particularly conventional anti- psychotics, 1 having the atypical antipsy- chotics’ fewer extrapyramidal adverse effects. There is no known effective treatment for TD, and its pathophysiology is not clear. Levetiracetam is a novel antiepileptic drug used in the treatment of partial crises as an add-on to other antiepileptic drugs. 2 Although the underlying mechanism of action of levetiracetam is unknown, it might counteract the neuronal hypersynchroniza- tion of the firing patterns of neurons in the substantia nigra pars reticulate and globus pallidus pars interna 3 that are considered critical structures for the development of dyskinesia. 4 Levetiracetam at a dose of 60 mg/kg decreased levodopa-induced dyskinesias (LIDs) and potentiated the antidyskinetic action of amantadine 5 in animal models of Parkinson disease (PD) and in a small group of parkinsonian patients; 6 however, a recent open-label observational study showed that levetiracetam was a poorly tolerated drug and did not effectively control LIDs in 16 parkinsonian patients. 7 A positive response to levetiracetam in one patient suffering from TD has suggested a possible role of this drug in the treatment of TD. 8 The aim of this study was to evaluate the effect of levetiracetam on TD. MATERIALS AND METHODS Sixteen patients suffering from chronic psychosis with TD were enrolled consec- utively. All patients were fully informed about the aims of the study and all gave their written informed consent. The study was performed using an open-label observa- tional design. The neuroleptic treatment given to the patients was not changed at any time during the trial. Levetiracetam was given in gradually increasing doses, starting with 125 twice a day (in the morning and in the evening); this dose was raised by 125 mg DOI: 10.1097/01.WNF.0000228807.49044.7D 265 Original Article CLINICAL NEUROPHARMACOLOGY Volume 29, Number 5 September - October 2006 *Department of Neurological Sciences, BLa Sapienza^ University, Rome, Italy; †Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, Messina, Italy; and ‡National Institute of Health, Rome, Italy. Supported in part by grants from the Italian Ministry for University and Research (MIUR) to G. Meco. Address correspondence and reprint requests to Giuseppe Meco, MD, Department of Neurosciences, Viale dell`Universit(, 30, 00185 Rome, Italy. E-mail: giuseppe.meco@ uniroma1.it. Copyright Ó 2006 by Lippincott Williams & Wilkins Copyr ight © Lippincott Williams & Wilkins. Unauthor iz ed reproduction of this article is prohibited.