What to do when the first monotherapy fails?
By Dr. Yotin Chinvarun M.D. Ph.D.
Long-term outcome studies and randomized trials suggested that less than 50% of patients will become seizure-free on first AED. Seizures persist despite a sufficient dose of first AED. An alternative drug to substitute is unavoidable when patient develops intolerable adverse events. If failure of first AED is caused by lack of efficacy, with seizures persisting after titration to highest tolerated dose, the first step is to exclude non-compliance, reassess the diagnosis and the appropriateness of the initial treatment. Up to 20–30% who resistant to initial AED achieve seizure freedom on alternative monotherapy. However, combination therapy could be tried earlier, particularly in severe epilepsies when the first AED is partially effective and well tolerated. Some patients might be benefit from judicious use of AED combinations, and evidence exists. Carefully individualized polytherapy is not necessarily increase the burden of adverse effects. When trying additional, AED should be consider the spectrum of efficacy, adverse effects, the pharmacokinetic and pharmacodynamic drug interactions. Role of combination therapy acceptable treatment strategy is undergoing re-evaluation. However, convincing evidence to guide clinicians on when and how to combine AEDs is still lacking. Well-designed studies the possibilities of AED combinations would address these practical questions. Mechanistic approach to pharmacological management of each epilepsy syndrome has potential to optimize chance of perfect seizure control.
It has long been recognized that seizures will be or will become refractory to opharmacotherapy >30% of patients. Certain structural abnormalities, particularly hippocampal sclerosis, cortical dysplasia are more likely to produce pharmacoresistant epilepsy. Possible negative predictive factors are younger age at onset, history of SE or high seizure number before treatment, neuropsychological deficits and abnormal imaging or neurological examination. It should prompt consideration of epilepsy surgery in a patient with a resectable brain abnormality. For the majority who are not suitable for surgery, AEDs should be combined to improve the outcome.