Lamotrigine–valproic acid combination therapy for medically refractory epilepsy

Abstract

Summary Purpose: A retrospective study of lamotrigine (LTG)–valproic acid (VPA) combination therapy in medically refractory epilepsy. Methods: Patients were identified with an adult epilepsy clinic database and were included if they had been on LTG–VPA combination therapy for at least 6 months. Patient demographics and information about epilepsy type, severity, and degree of medical intractability were obtained by retrospective chart review. The primary outcome measure was change in baseline seizure frequency, and patients were stratified into three groups: (i) seizure‐free, (ii) improved (at least 50% reduction in baseline seizure frequency), and (iii) not improved. Results: Thirty‐five patients met all inclusion–exclusion criteria. Epilepsy type was generalized in 25 patients (71%) and partial in 10 patients (29%). Before LTG–VPA treatment, 27 of 35 (77%) experienced disabling seizures on a monthly basis, and 17 of 35 (49%) of patients had at least one disabling seizure per week. Patients had previously failed treatment with a median of five antiepileptic drugs (AEDs), alone or in combination. With LTG–VPA therapy, 18 (51.4%) remained completely seizure‐free, four (11.4%) were improved, and 13 (37.1%) were unimproved. Median follow‐up was 42 months. Of the 22 patients who improved, 11 had previously failed LTG and VPA monotherapy. There was no significant difference between improved and unimproved patients with respect to demographics, epilepsy type or severity, or number of previously failed AEDs. Discussion: The combination of LTG and VPA should be considered in patients with medically refractory epilepsy. The effectiveness of this combination appears to be independent of epilepsy type or patient demographics.

Population pharmacokinetic of antiepileptic drugs in different populations

“…The dose of lamotrigine should be carefully titrated and reduced in patients on therapy with valproate, resulting in avoiding problems with toxicity and many adverse events of lamotrigine. Several studies have shown that this drug combination have a potentially sinergistic effect on refractory epilepsy [54][55][56]. Furthermore, other authors reported a significant decrease in lamotrigine clearance caused by concomitant administration of valproate, as it was confirmed in our study [43][44][45].…”

Effect of lamotrigine on seizure development in a rat pentylenetetrazole kindling model

“…Lamotrigine is a novel broad‐spectrum AED widely used in the treatment of epilepsy such as partial, secondarily generalized, and tonic‐clonic seizures (Messenheimer, ; Moeller, Rahey, & Sadler, ; Warshavsky, Eilam, & Gilad, ). For electrical kindling, as far as we know there was a study to observe the antiepileptogenic activity of LTG with a dose of 20 mg/kg in rats, and it proved LTG can delay the development of kindling, but cannot further stop the kindling acquisition after a washout phase (Stratton, Large, Cox, Davies, & Hagan, ).…”

Factors influencing medication adherence after epilepsy surgery

“…Postoperative seizure freedom is associated not only with completeness of surgical resection but also with the postoperative medication regimen (Moeller et al, 2009). Medication is crucial after surgery, particularly the combination and doses of AEDs (Moeller et al, 2009). Adherence to AED therapy is critical for effective epilepsy management (Faught, 2012), and nonadherence may be the most important cause of poorly controlled epilepsy (Manjunath et al, 2009).…”