Clinical evaluation of a combination therapy of imepitoin with phenobarbital in dogs with refractory idiopathic epilepsy

Abstract

BackgroundImepitoin was tested as a combination treatment with phenobarbital in an open-label mono-centre cohort study in dogs with drug-resistant epilepsy. Diagnosis of idiopathic epilepsy was based on clinical findings, magnetic resonance imaging and cerebrospinal fluid analysis. Three cohorts were treated. In cohort A, dogs not responding to phenobarbital with or without established add-on treatment of potassium bromide or levetiracetam were treated add-on with imepitoin, starting at 10 mg/kg BID, with titration allowed to 30 mg/kg BID. In cohort B, the only difference to cohort A was that the starting dose of imepitoin was reduced to 5 mg/kg BID. In cohort C, animals not responding to imepitoin at >20 mg/kg BID were treated with phenobarbital add-on starting at 0.5 mg/kg BID.ResultsThe add-on treatment resulted in a reduction in monthly seizure frequency (MSF) in all three cohorts. A reduction of ≥50% was obtained in 36-42% of all animals, without significant difference between cohorts. The lower starting dose of 5 mg/kg BID imepitoin was better tolerated, and an up-titration to on average of 15 mg/kg BID was sufficient in cohort A and B. In cohort C, a mean add-on dose of 1.5 mg/kg BID phenobarbital was sufficient to achieve a clinically meaningful effect. Six dogs developed a clinically meaningful increase in MSF of ≥ 50%, mostly in cohort A. Neither imepitoin nor phenobarbital add-on treatment was capable of suppressing cluster seizure activity, making cluster seizure activity an important predictor for drug-resistance.ConclusionA combination treatment of imepitoin and phenobarbital is a useful treatment option for a subpopulation of dogs with drug-resistant epilepsy, a low starting dose with 5 mg/kg BID is recommended.

Investigating the potential of the anti-epileptic drug imepitoin as a treatment for co-morbid anxiety in dogs with idiopathic epilepsy

“…Ataxia, a common AED side effect [30] was mild or not present in the majority of cases, in line with recent objective evidence demonstrating reduced levels in IE patients treated with imepitoin compared to phenobarbitone [31]. A greater number of side effects were seen in dogs treated with imepitoin alongside other AEDs, which is in line with recent studies; for example, when imepitoin was used as an add-on therapy to phenobarbital, or vice versa, the number of side effects increased [32]. In addition, a recent study of imepitoin polytherapy found that 69% of dogs treated with imepitoin and KBr, and 79% of dogs treated with imepitoin and phenobarbital experienced side effects [33].…”

Behavioral Changes Under Levetiracetam Treatment in Dogs

“…In the current study, 11% of the dogs were aggressive and 5% hyperactive after LEV treatment. The incidence of these two behavioral factors is comparable with other AEDs used in veterinary medicine (20,(38)(39)(40)(41)(42)(43)(44). A study in human medicine performed by White et al (14) showed that 38 of the 553 patients were forced to LEV discontinuation due to behavioral side effects.…”

“…Reported side effects for phenobarbital are aggression, restlessness and hyperactivity (20,(38)(39)(40). Imepitoin may also cause behavioral changes such as hyperactivity and aggression (41)(42)(43)(44). Moreover, potassium bromide is also reported to cause these two behavioral changes (10).…”

Pregabalin Add-On vs. Dose Increase in Levetiracetam Add-On Treatment: A Real-Life Trial in Dogs With Drug-Resistant Epilepsy

“…Imepitoin is only licensed for the treatment of single seizures. Its efficacy for cluster seizures is a matter of ongoing debate (5)(6)(7)(8). Dog owners and veterinarians considered the development of new ASMs among the three most important research topics for the future (9).…”