Effects of zonisamide on tardive dyskinesia: A preliminary open-label trial

Abstract 

Once developed, tardive dyskinesia (TD) is a challenging condition to treat. The recent evidence has indicated that zonisamide, an antiepileptic drug indicated for partial-onset seizures, may also have beneficial effects for ameliorating dyskinesia in Parkinson's disease. However, this finding has not systematically been tested in psychiatric patients with TD associated with antipsychotic treatment. The objective of this study was to examine the efficacy, tolerability, and safety of zonisamide against TD in these patients. In this 4-week open-label study, subjects who suffered TD were given 50–100mg/day of add-on zonisamide. Severity of TD was evaluated at the baseline and endpoint, using the Abnormal Involuntary Movement Scale (AIMS). Eleven subjects (6 females; mean±SD age, 75.5±4.7years; schizophrenia [N=6], bipolar affective disorder [N=2], schizoaffective disorder [N=1], mental retardation [N=1], mental retardation with epilepsy [N=1]; 6 were antipsychotic free at baseline) participated in this study. The AIMS total score (mean±SD) was significantly decreased from 24.1±5.5 to 19.5±5.9, with 36.4% of the subjects (N=4) demonstrating 20% or more decrease in the AIMS total score. Treatment with zonisamide was well-tolerated and no participants dropped out prematurely. In conclusion, zonisamide may be safe and effective for the treatment of TD associated with antipsychotic treatment. These preliminary findings need to be further explored by larger well-designed trials.

Abbreviations: AIMS, Abnormal Involuntary Movement Scale, CSF, cerebrospinal fluid, FGAs, first-generation antipsychotics, GABA, γ-aminobutric acid, SGAs, second-generation antipsychotics, TD, tardive dyskinesia, TBARS, thiobarbituric acid reactive substances

Keywords: Antiepileptic drug, Free radicals, Tardive dyskinesia, Zonisamide, Treatment, Parkinsonism