A study by Dr. Mojarradi et al, out of Sweden, was recently published in the Journal of Feline Medicine and Surgery reporting on once daily phenobarbital administration for cats with seizures. The reported half-life of phenobarbital in cats is 43-72 hours which could suggest once daily treatment is possible, however based on pharmacokinetic data twice daily dosing has been the standard of care. This retrospective study questioned if this was necessary.
This study was a retrospective review of 9 cats up to 3 years from enrollment. They tracked the number of seizures before starting phenobarbital (unfortunately for an unknown amount of time) and compared that to the number of seizures after starting phenobarbital. The cats were required to have 2 or more seizures, separated by at least 24 hours, prior to starting phenobarbital however the frequency and duration of the seizure disorder for each cat isn't known. They do comment that 6/9 cats had 1 or more per month prior to starting phenobarbital. Phenobarbital was started at a mean dose of 1.8 mg/kg PO q24h, the mean serum concentration of phenobarbital was 11 ug/ml (range 6-17) at about 1 month (range 19-54 days). All but 1 cat was seizure-free at that first follow-up. The second and third follow-up appointments, roughly 1 year apart, showed a few more seizures in the time range however overall 8/9 cats were considered to be in seizure remission (no seizures for more than 12 months) at the end of the study. Seizure remission, as defined in this study, was less than 1 seizure every 12 months. If they started at 1 seizure/month, and ended at 1 per year that is a pretty remarkable improvement! So remarkable, I wonder if the phenobarbital is responsible for that shift, or not.
My questions:
Could such a low serum phenobarbital concentration cause such a dramatic response?
Could this be the natural regression to the mean (shifts that are unrelated to intervention)?
Did the retrospective nature of the study include only cats that did well on once daily phenobarbital, otherwise they would have taken twice daily phenobarbital and therefore been excluded from the study? Was this group of cats bound to do well, in other words, and it wasn't due to medication?
Another study by Pakozdy (https://doi.org/10.1177/1098612X12464627) noted that over time, most cats have a natural reduction in seizures while on anticonvulsant drugs. They tracked seizures in cats over a 10 year period and noted that most improved, some were seizure-free and some stopped medication. About 16% of the cats that stopped medication needed to have it restarted due to a return of seizures.
The data reported in the study from Sweden suggests that we could administer phenobarbital once daily but the results are so remarkable (marked seizure improvement in a short period of time, low serum drug concentrations) that I feel compelled to repeat this study with a different, perhaps large, cohort of cats and make sure this is reliable. My advice: don't switch to once daily just yet!
Thanks for reading! I love managing seizures so please schedule a consult if you have a case that you'd like more assistance with seizure management. I'm happy to help!