We have a great study to look at today! This is a rare prospective, multicenter, randomized, single-blinded, placebo-controlled trial in 37 naive epileptic cats! Drs. Marios Charalambous, Andrea Tipold and others from Germany and Belgium published this study recently in the Frontiers of Veterinary Science (DOI: 10.3389/fvets.2026.1770972). First, let’s talk about the two medications in this study: imepitoin and phenobarbital. Imepitoin is a low-affinity partial agonist at GABA receptors causing increased inhibition. Phenobarbital, although similar, works to reduced excitability. It is approved in Europe for seizures and in the US for noise sensitivity in dogs. This means we may be able to use it off label for cats. I have not done so yet – have you?
Materials and Methods
Drug naïve cats with type I or type II level confidence for idiopathic epilepsy (IE) were randomized into imepitoin (30 mg/kg PO q12h) , phenobarbital (2.5 mg/kg PO q12h) or a placebo (bold!) group for 15 weeks. This was a 3 week titration period and a 12 week observation period.
Results
Phenobarbital
Responder rate: 90%
Seizure freedom: 80%
Significant reductions compared to pre-treatment time: Seizure frequency and seizure days
Imepitoin
Responder rate: 62%
Seizure freedom: 25%
Significant reduction: Seizure frequency only
When compared directly, there was no significant difference in seizure frequency reduction, but phenobarbital treatment resulted in a reduction in seizure days and a longer time to first seizure after starting treatment. As a result, this study suggests that phenobarbital was the most effective first-line anti-convulsant in cats with idiopathic epilepsy. Based on this study, imepitoin is less useful for cats but could be a suitable alternative when phenobarbital is ineffective.
Adverse effects
Both groups of cats demonstrated common adverse effects, but they were more common in the phenobarbital group (90% vs 88% of cats). Most side effects were mild and transient. About 25% of cats in the imepitoin group had a dose reduction but subsequently efficacy also was reduced. No cats in the imepitoin group had treatment discontinued. One cat in the phenobarbital group needed to stop treatment due to a severe blood dyscrasia.
What’s the bottom line? Should you start stocking imepitoin? Not so fast. I like this line: “Imepitoin is a reasonable alternative, not an equivalent [drug]” . For now, phenobarbital is still your number 1 drug for feline epilepsy for ANY etiology other than reactive seizures (i.e., seizures secondary to metabolic or toxic causes). If a client is resistant to therapeutic drug monitor for phenobarbital, or concerned about pre-existing liver disease, and levetiracetam is not working, consider imepitoin. Imepitoin is metabolized in the liver but does not appear to induce hepatic CP450 microsomal pathway. Some cats showed increases in ALP and AST in this study so it isn’t completely liver safe. A few cats receiving phenobarbital also showed an increase in ALT in this study. Overall, this was a well designed and executed study. Although we do not use a lot of imepitoin in the US (I know not all of the readers of TidBit Tuesdays are US veterinarians) I hope you will find this review full of useful fuel to continue prescribing phenobarbital for cats with seizures!
Thanks for reading! I hope you have a great week, and I look forward to working with you soon.