Lamotrigine monotherapy compared with carbamazepine, phenytoin, or valproate monotherapy in patients with epilepsy☆
Introduction
Choice of antiepileptic drug therapy is guided by the goals of maximizing seizure control and minimizing side effects. Provided that seizure control is maintained, monotherapy is preferred to polytherapy because polytherapy heightens the risk of side effects and drug interactions, increases the cost of therapy, and reduces patient compliance. Physicians may treat patients with several monotherapy alternatives in an attempt to identify the treatment providing the optimum ratio of efficacy to tolerability.
The broad spectrum of efficacy and documented tolerability of the antiepileptic drug lamotrigine [1], introduced in the United States in 1994, render it a good candidate for monotherapy for patients inadequately controlled or experiencing unacceptable side effects with other antiepileptic drugs. In patients with newly diagnosed epilepsy, lamotrigine monotherapy is as effective against partial and generalized tonic–clonic seizures as carbamazepine [2] or phenytoin monotherapy [3]. Moreover, while it controls seizures as well as these conventional agents, lamotrigine is better tolerated [1], [2], [3], and it improves patients’ health-related quality of life [4]. Compared with carbamazepine and phenytoin, lamotrigine is associated with a lower incidence of neurologic adverse events such as asthenia, dizziness, and somnolence; and it does not negatively impact cognitive function [2], [3], [5], [6]. Unlike valproate, lamotrigine does not cause weight gain [7]. This randomized, open-label study compared the efficacy and tolerability of lamotrigine monotherapy with those of monotherapy with the conventional antiepileptic drugs carbamazepine, phenytoin, or valproate in patients who required a change in therapy because of inadequate seizure control or unacceptable side effects.
Section snippets
Patients
Patients ⩾16 years of age diagnosed with epilepsy and experiencing any seizure type classifiable by the International Classification of Seizures [8] were eligible for the study. Females were eligible only if they had a negative urine or serum pregnancy test at screening and agreed to use acceptable contraceptive methods during the study or were incapable of bearing children. Eligible patients were currently being treated with one of the conventional antiepileptic drugs carbamazepine, phenytoin,
Patients
One hundred twenty-two (122) patients were enrolled in the study, and 115 were randomized (Fig. 2). Fifty-seven (57) patients were randomized to receive lamotrigine, and 58 patients were randomized to receive a conventional antiepileptic drug. The numbers of patients completing the study were 37 in the lamotrigine group and 33 in the conventional therapy group. The most common reason for discontinuation from either the Escalation/Taper Phase or the Maintenance Phase in both groups was adverse
Discussion
These data suggest that when monotherapy with a conventional antiepileptic drug is unsuccessful because of inadequate seizure control or poor tolerability, converting to monotherapy with lamotrigine may be more beneficial than converting to an alternative conventional antiepileptic drug. In this study, conversion from unsuccessful monotherapy with carbamazepine, phenytoin, or valproate to lamotrigine monotherapy was associated with a higher incidence of treatment success (primary endpoint,
Acknowledgements
The authors thank Jane Saiers, Ph.D., for assistance with writing the manuscript. The following investigators participated in this study: George Adam (Minneapolis, MN); Ricardo Ayala (Tallahassee, FL); Andrew Bragdon (Syracuse, NY); D Combs Cantrell (Irving, TX); Walter Carlini (Medford, OR); Jose E. Cavazos (Denver, CO); Joan Christine Dean (Winston-Salem, NC); James DeMatteis (Erie, PA); Maroun Dick (Memphis, TN); Lewis Eberly (Alexandria, VA); Michael Englert (South Bend, IN); Irl Extein
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GlaxoSmithKline, the maker of lamotrigine, sponsored the research described in this article.