Lamotrigine Therapy for Partial Seizures: A Multicenter, Placebo‐Controlled, Double‐Blind, Cross‐Over Trial

Abstract

The efficacy and safety of lamotrigine (LTG), a new antiepileptic drug (AED), were evaluated in a multicenter, randomized, double-blind, placebo-controlled, cross-over study of 98 patients with refractory partial seizures. Each treatment period lasted 14 weeks. Most patients were titrated to a LTG maintenance dose of 400 mg/day. Seizure frequency with LTG decreased by > or = 50%, as compared with placebo, in one fifth of patients. Overall median seizure frequency decreased by 25% with LTG as compared with placebo (p < 0.001). With LTG, the number of seizure days decreased by 18% as compared with placebo (p < 0.01), and investigator global evaluation of overall patient clinical status favored LTG by 2:1 (p = 0.013). Plasma LTG concentrations appeared to be linearly related to dosage. LTG had no clinically important effects on the plasma concentrations of concomitant AEDs. Adverse experiences were generally minor and most frequently were CNS-related (e.g., ataxia, dizziness, diplopia, headache). Most were transient and resolved without discontinuing treatment. Five patients withdrew as a result of adverse experiences while receiving LTG, including 3 patients with rash. One placebo patient was also withdrawn because of rash. The addition of twice-daily LTG to an existing AED regimen was safe, effective, and well tolerated in these medically refractory partial seizure patients.

Efficacy and tolerability of the new antiepileptic drugs II: Treatment of refractory epilepsy [RETIRED]

“…Three studies with class I evidence were identified. [14][15][16] In two of these studies, lamotrigine or placebo were added to a drug regimen with only enzyme-inducing AED. 14,15 In the third study, patients on an enzyme-inducing AED and valproic acid were also included, although the maximal dose for patients on valproic acid was titrated to 50% of the dose taken by patients on enzyme inducing AEDs only.…”

“…[14][15][16] In two of these studies, lamotrigine or placebo were added to a drug regimen with only enzyme-inducing AED. 14,15 In the third study, patients on an enzyme-inducing AED and valproic acid were also included, although the maximal dose for patients on valproic acid was titrated to 50% of the dose taken by patients on enzyme inducing AEDs only. 16 One study 14 compared placebo to two doses of lamotrigine: 300 mg/day and 500 mg/day; the responder rate was 18%, 20%, and 34%, respectively, and the median seizure reduction was 8%, 20%, and 36%, respectively.…”

Effectiveness of lamotrigine in clinical practice: Results of a retrospective population-based study

“…In the first year of treatment, LTG therapy was effective in 40% of the patients with refractory epilepsy. In the initial regulatory trials, with a maximum follow-up of 24 weeks, the percentage of patients experiencing a ≥50% reduction was lower (Matsuo et al, 1993;Messenheimer et al, 1994). This difference in efficacy may be due to a broader study population in our sample, i.e.…”

“…One of these new antiepileptic drugs, lamotrigine, has been evaluated in clinical trials in a variety of patient groups, including patients with newly diagnosed epilepsy (Brodie et al, 1995;Matsuo et al, 1993;Messenheimer et al, 1994;Motte et al, 1997;Nieto-Barrera et al, 2001). In addition, the effectiveness of LTG in clinical practice was evaluated in a number of observational studies, with retention time as the end point (Collins et al, 2000;Datta and Crawford, 2000;Lhatoo et al, 2000;Walker et al, 1996;Wong et al, 1999).…”

Clinical Development of Antiepileptic Drugs in Adults

“…However, under certain circumstances, well planned crossover designs may be useful within the context of early clinical exploratory work. 6 One classic mistake, frequently observed in AED development in the past few decades, is the underestimation of the value of a solid phase-II program. This has led to inaccurate dosing and titration regimens when entering the later pivotal studies, which then yield an unfavorable effectiveness pattern in the late stages of development-a major problem.…”