The new antiepileptic drug levetiracetam normalises chlordiazepoxide withdrawal-induced anxiety in mice

Abstract

Some antiepileptic drugs have been used with success to counteract withdrawal symptoms following chronic use of sedatives, hypnotics or alcohol. We evaluated the potential of levetiracetam (Keppra™), a new antiepileptic drug, to prevent benzodiazepine withdrawal in an animal model sensitive to the anxiogenic effect resulting from drug cessation. The effects of levetiracetam (17 and 54 mg/kg) given intraperitoneally (i.p.) were determined on anxiety induced in female NMRI mice by withdrawal from 21 days of chronic administration of chlordiazepoxide. Administration of chlordiazepoxide was i.p. twice daily, in increments of 2 mg/kg, from 10 up to 40 mg/kg. Anxiety was evaluated using an elevated plus-maze test 24-h after chlordiazepoxide withdrawal. Discontinuation of chronic chlordiazepoxide induced a significant anxiogenic profile in the plus-maze test mainly characterised by a decrease in open arm exploration. This effect was dose-dependently prevented by administration of levetiracetam during the withdrawal period. The highest dose tested (54 mg/kg) induced statistically significant effects on all variables recorded but had no effect upon plus-maze exploration in normal mice. This suggests that the observed effects are dependent upon the level of stress or anxiety of the animals. These results support potential efficacy of levetiracetam in the benzodiazepine withdrawal syndrome.