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Pharmacoresistance to anti-epileptic drugs (AEDs) can be a source of frustration for owners and veterinarians alike in the treatment of canine idiopathic epilepsy (IE), with ongoing seizures having a significant negative impact upon the quality of life of affected dogs and owners (Chang and others 2006, Wessmann and others 2014). Finding an effective AED that reduces seizure frequency to an acceptable level (generally classed as more than 50 per cent reduction in veterinary medicine), or results in remission (seizure-freedom) can be a long process, with several AEDs trialled before optimum treatment is reached (Packer and others 2014). With more AEDs becoming available to veterinary patients, knowing whether (and when) to include further therapies can be challenging for practitioners, when faced with the balance between seizure control and side effect profiles.
In human epilepsy, response rates to first-line and further AEDs have been studied in several populations, with the probability of seizure control diminishing progressively with successive AED treatments. Kwan and Brodie (2000) reported response rates (as a proportion of the population) of 47, 13 and 4 per cent for first-line, second-line and third-line drugs, respectively (Kwan and Brodie 2000). Similarly, Mohanraj and Brodie (2006) reported response rates of 50.4, 10.7 and 2.3 per cent, respectively, with just 0.8 per cent responding to any further drugs (Mohanraj and Brodie 2006).
If the initial AED fails to control seizures, the prognosis for seizure control may be poor. Failure to respond to the first AED has been demonstrated to predict becoming refractory at two-year follow-up in a study of children with temporal lobe epilepsy (Dlugos and others 2001). In a further study, of those patients unresponsive to the first AED, 76 per cent failed two or more AEDs and 38 per cent failed at least four (Perucca and others 2011). These …