Reinvestigation and Reduction of Polytherapy in Children With Chronic Seizures

Abstract

From October 2001 to October 2003, the authors reviewed all patients with chronic seizures taking antiepileptic drugs for more than 2 years with follow-up at the pediatric neurological clinic. They identified 31 patients who were using 3 or more drugs. Twenty-nine patients agreed to undergo a drug reduction and readjustment. The authors spent a mean period of 14.1 months to either purely reduce the numbers of drugs or introduce a new drug (rational polytherapy) plus removal of some drugs to achieve the end goal of a maximum of 2 or 3 drugs (if necessary). Seizure control in 96.6% of patients (28 of 29 patients) did not worsen after the readjustment and reduction of the antiepileptic drugs. Instead, 65.5% (19 of 29 patients) got better, and 37.9% (11 of 29) were seizure free. The number of antiepileptic drugs before and after adjusting was 3.6 (range, 3-6) to 1.9 (4 monotherapy, 22 duotheray, and 2 triple drugs). The most common combined therapies were sodium valproate/lamotrigine (n = 10) and carbamazepine/ topiramate (n = 5). Although the results could be possibly attributed to the spontaneous remission of the seizures, it was still shown that those patients were overtreated. Serial addition to 3 or more antiepileptic drugs is less likely to lead to seizure freedom for patients with difficult-to-treat epilepsy. On the contrary, polytherapy and some antiepileptic drugs could aggravate seizures. Certain combinations of antiepileptic drugs (rational polytherapy) offer better efficacy to control seizures.

Truly “Rational” Polytherapy: Maximizing Efficacy and Minimizing Drug Interactions, Drug Load, and Adverse Effects

“…Over-treatment may be defined as an excessive number or amount of AED(s) given, that results in a suboptimal risk-to-benefit balance [20,67]. Tapering of one or more AEDs can be successfully accomplished in many patients receiving chronic polytherapy, without substantial loss of seizure control [2,8]. There are many reasons to consider reducing polytherapy, including reducing the risk of serious adverse effects, minimizing drug interactions [60], and decreasing costs [4].…”

“…Uncontrolled seizures and polytherapy have been linked to decreased quality of life [75]. Paradoxically, over-treatment with AEDs can occasionally result in an increase in seizure activity, and reduction in polytherapy has been shown to lead to improved seizure control in approximately two-thirds of patients [8,20]. …”

Does One More Medication Help? Effect of Adding Another Anticonvulsant in Childhood Epilepsy

“…In a recent study by Chen et al, the number of antiepileptic drugs was decreased in 29 patients from a mean of 3.6 to 1.9, which led to improvement in 65.5% of patients with no worsening in 96.6%. 15 Is it rational to add antiepileptic drugs serially? This question needs further investigation.…”