Pharmacokinetic interaction between modified Atkins diet and antiepileptic drugs in adults with drug-resistant epilepsy.

Abstract

The aim was to examine the influence of modified Atkins diet on serum concentration of antiepileptic drugs (AEDs). Prospective data from 63 adult patients with either focal or generalized drug-resistant epilepsy recruited to 12-week dietary treatment as add-on to AEDs are analyzed. AED serum concentrations, ketones, glucose, and hemoglobin A1c were measured before and after the dietary intervention. Paired t test was used and Spearman correlation coefficient, r, was estimated. Mean age was 37years (range 16-65years). Mean serum concentrations of carbamazepine, clobazam, and valproate were significantly reduced after 4 and 12weeks of the diet period (<.001≤P≤.02). Levels of lacosamide, lamotrigine, and topiramate were less reduced (.02≤P≤.08), whereas the serum concentrations of oxcarbazepine, zonisamide, and levetiracetam were unchanged (.06≤P≤.90). The largest reduction in serum concentration was found for clobazam: mean reduction after 12weeks was 1.5μmol/L (34%). Percent change in serum concentration after 4 and 12weeks of all drugs analyzed was -10.5% (95% confidence interval [CI] -14.1 to -6.8; n=60; P<.001) and -13.5% (95% CI -18.8 to -8.3; n=56; P<.001), respectively. Percent change in serum concentration of AEDs was not significantly correlated to percent change in seizure frequency after 12weeks of dietary treatment (r=.14, P=.33, n=53) but negatively correlated to urine ketosis (r=-.43; P=.003; n=46). A reduction in AED serum concentrations may counteract a seizure-reducing effect of the diet, and in patients without such an effect, it may cause seizure aggravation. Thus, we recommend that clinicians who are treating patients with ketogenic diets monitor serum concentrations of the concomitant AEDs.