Elsevier

Epilepsy & Behavior

Volume 5, Issue 2, April 2004, Pages 224-230
Epilepsy & Behavior

Quality of life improvement with conversion to lamotrigine monotherapy

https://doi.org/10.1016/j.yebeh.2003.11.031Get rights and content

Abstract

This report describes the effect on patient-reported quality of life (QOL) after reduction from two drugs to monotherapy with lamotrigine. Patients taking lamotrigine (LTG) with an enzyme-inducing drug were converted to LTG monotherapy for a 12-week follow-up. Changes in QOLIE-31 between baseline and follow-up were compared with physicians' global change ratings and patient-reported health status. Total QOLIE-31 scores increased 10.7 points for patients rated by physicians as having mild improvement, and 17 points for those reported as having moderate to marked improvement. Subscale scores also increased by minimum important change (MIC) amounts (⩾11.76), with the largest change in Cognition, Energy, Medication Effects, and Seizure Worry subscales. The data also support ⩾11 MIC as a clinically important change in total score for the QOLIE-31. Exploratory analyses also provide information about MIC for individual subscales (8–18 for physician rated global change, 10–26 for patient-rated global health status change). This study demonstrates the value of reduction to monotherapy from the patients' and physicians' perspectives.

Introduction

Cessation of partial-onset seizures is achieved with an initial antiepileptic drug (AED) by approximately two-thirds of patients [1], [2], [3]. Success with an alternative monotherapy may be achieved with a direct crossover between AEDs, or a transitional crossover with a stable period on two drugs to evaluate the additive usefulness of the second AED. If the patient and physician determine that the second drug improved seizure control, they often decide to attempt a reduction to monotherapy with the second AED. This method has been tested in several clinical trials [4], [5]. A double-blind, controlled study of lamotrigine (LTG) included patients taking an enzyme-inducing AED (phenytoin or carbamazepine) who added LTG or low-dose valproate (VPA) as an active control. When the enzyme-inducing AED was withdrawn, seizures were controlled for a significantly larger proportion of patients receiving LTG than those receiving low-dose VPA [4]. A similar study of levetiracetam (LEV) showed that patients whose seizures were well-controlled during an add-on study could discontinue their original AED to remain on LEV monotherapy [5]. To date, LTG is the only AED indicated for conversion to monotherapy in adults with partial seizures who are receiving treatment with a single enzyme-inducing AED, in addition to use as adjunctive therapy for adults and children age 2 and older with partial seizures.

The method of conversion to monotherapy often is used in clinical practice (when a patient has good seizure control) to reduce the burden of adverse effects. Previous studies have not evaluated the impact of this practice on patient reports of health-related quality of life (HRQOL) domains. A recent LTG study examined seizure control and HRQOL, as well as physician's clinical global impression of change and patient satisfaction with LTG monotherapy [6]. The question remains as to how much of a change in HRQOL represents a clinically important improvement [7]. This report addresses the relationships among these measures of treatment outcome and the amount of change in HRQOL.

Section snippets

Clinical trial design

A clinical trial enrolled 547 patients (⩾16 years) across the United States who required a change in AED because of inadequate seizure control of partial-onset seizures and/or unacceptable adverse effects with their current AED regimen [8], [9]. LTG was added to the one or two baseline AEDs for 16 weeks of combined therapy. Those patients who were taking a single enzyme-inducing AED (e.g., carbamazepine, phenytoin) at the end of the adjunctive phase were eligible for conversion to LTG

Results

Characteristics of the monotherapy cohort are described in Table 1. Of the 178 patients initiating the monotherapy phase, 35 discontinued before the conclusion of the 12-week follow-up on LTG monotherapy. Primary reasons included lack of efficacy (N=12), adverse effects related to LTG (N=8), and administrative reasons (N=12). Among patients for whom final data were available, seizure frequency decreased from baseline (3.9 ± 9.6 [median 2.0] seizures monthly) to final follow-up (1.8 ± 6.1 [median 0]

Discussion

This study demonstrates the value of reduction to monotherapy from the patients' and physicians' perspectives. Although both patients and physicians often are reluctant to make changes when conditions are stable, discontinuation of one AED can provide unexpected benefits. The scenario in this study was to remove carbamazepine or phenytoin while maintaining the patient on lamotrigine. Patients perceived large improvements in every HRQOL domain. The most dramatic improvements were seen in the

Acknowledgements

This study was supported by GlaxoSmithKline.

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