“Resistance Is Futile”: A Pilot Study into Pseudoresistance in Canine Epilepsy

Abstract

Epilepsy is a common neurological disorder in veterinary practice, complicated by frequent occurrence of medication-resistant epilepsy. In human medicine, it has been noted that some patients with medication-resistant epilepsy have in fact other reasons for their apparent medication-resistance. The aim of this retrospective study was to describe the issue of pseudoresistance using as an example a population of dogs presented with presumed medication-resistant epilepsy and provide an in-depth review of what is known in human medicine about pseudoresistant epilepsy. One-hundred fifty-two cases were identified with medication-resistant epilepsy, of which 73% had true medication-resistant epilepsy and 27% patients had pseudoresistance. Low serum anti-seizure medication levels were the most common cause of pseudoresistance, present in almost half of the cases (42%), followed by inadequate choice of drugs or dosages (22%), misclassification (22%) or misdiagnosis (9%) of epilepsy and poor compliance (9%). All cases of pseudoresistance, except for one, responded to a modification of the initial therapy protocol. Pseudoresistance can bias clinical trials, misinform the clinical decision-making process, delay diagnosis and treatment, and misinform owners about their pets’ prognosis. A substantial proportion of these cases can have improvement of their seizure frequency or achieve seizure freedom upon modification of their therapeutic protocol.

Factors influencing serum concentrations of levetiracetam in dogs with epilepsy

“… 9 Moreover, the lack of reference interval for serum concentration to correct for individual variation in drug absorption may contribute to pseudo‐resistance in some dogs that could respond to higher dosages. 6 , 10 In dogs, pharmacokinetics studies suggested a dosage of 20 mg/kg q8h in monotherapy, although this dosage resulted in trough plasma levetiracetam concentrations <20 μg/mL. 11 Concurrent administration of phenobarbital resulted in lower plasma levetiracetam concentrations and faster clearance leading to recommendation of a higher dosage (30 mg/kg q8h) of levetiracetam when given concurrently with phenobarbital.…”