PITTSBURGH, PA -- June 14, 2001 -- New study data presented at the Fourth International Conference on Bipolar Disorder suggests that lamotrigine (Lamictal) may be effective in delaying mood episodes, particularly depressive episodes, in patients with bipolar disorder.
Bipolar disorder, also known as manic-depressive illness, is characterized by distressing and disruptive mood swings. Lamotrigine is currently under investigation in Phase III development for the treatment of bipolar disorder.
"This is one of the longest maintenance studies ever conducted in bipolar patients and the results are telling. Lamotrigine delayed subsequent mood episodes, particularly depressive episodes, in patients who were recently manic," commented Joseph R. Calabrese, M.D., Director of the Mood Disorders Center at the University Hospitals of Cleveland, Professor of Psychiatry at the Case Western Reserve University School of Medicine. "While lamotrigine is not FDA-approved for bipolar disorder, these data -- combined with previously published placebo-controlled data -- suggest the efficacy and safety of lamotrigine in the treatment of bipolar disorder."
Bipolar disorder affects one percent of the general population and is characterized by mood swings that range from mania (heightened euphoria, activity and creativity) to depression. There are two types of bipolar disorder. In bipolar I disorder, a person experiences episodes of mania, depression and mixed episodes; in bipolar II disorder, a person experiences hypomania (a milder form of mania that has similar, less severe symptoms) and depression.
If left untreated, bipolar disorder can lead to an increase in morbidity and mortality. More than 50 percent of individuals with bipolar disorder abuse alcohol or drugs during their illness. Without effective treatment, bipolar disorder can lead to suicide in nearly 20 percent of cases.
This international multicenter, double-blind, placebo-controlled, flexible-dose study was conducted in outpatients diagnosed with bipolar I disorder. A total of 349 patients were enrolled in a preliminary open-label phase in which lamotrigine (100-200 mg/day) was used as add-on or monotherapy for up to 16 weeks, followed by withdrawal to monotherapy with lamotrigine before randomization.
A total of 175 patients achieved stabilization and were then randomized to lamotrigine (100-400 mg/day), lithium (dosed to blood levels of 0.8-1.1 mEq/l) or placebo and followed for up to 18 months. The primary efficacy variable was Time (from randomization) to Intervention for a Mood Episode (TIME). Secondary measures of efficacy included Time to Intervention for a Depressive Episode (TID) and Time to Intervention for Manic Episode (TIM).
Patients receiving lamotrigine demonstrated evidence of long-term mood stabilization as indicated by differences from placebo on TIME and other indices of stability and illness relapse. Lamotrigine was also shown to be superior to placebo in overall survival in study and time to intervention for a depressive episode. Lamotrigine was generally well tolerated in the patient population studied in both the preliminary and randomized phases of the study. Due to administrative reasons, the study was terminated before the prospective sample size was reached.
Lamotrigine is indicated as adjunctive therapy in adults with partial seizures and as adjunctive therapy in the generalized seizures of Lennox-Gastaut syndrome in pediatric and adult patients. Lamotrigine is indicated for conversion to monotherapy in adults with partial seizures who are receiving treatment with an enzyme-inducing antiepileptic drug (AED).
Safety and effectiveness of lamotrigine have not been established as initial monotherapy; for conversion to monotherapy from non-enzyme-inducing AEDs (e.g., valproate); or for simultaneous conversion to monotherapy from two or more concomitant AEDs. Safety and effectiveness in patients below the age of 16 other than those with Lennox-Gastaut syndrome have not been established.
Serious rashes requiring hospitalization and discontinuation of treatment have been reported in association with the use of lamotrigine. The incidence of these rashes, which have included Stevens-Johnson Syndrome, is approximately one percent in pediatric patients less than 16 years old and 0.3 percent in adults. In worldwide post-marketing experience, rare cases of toxic epidermal necrolysis (TEN) and/or rash-related death have been reported, but their numbers are too few to permit a precise estimate of the rate. Lamotrigine ordinarily should be discontinued at the first sign of rash, unless the rash is clearly not drug-related.
The risk of nonserious rash is increased when the recommended initial dose and/or the rate of dose escalation of lamotrigine is exceeded. There are suggestions, yet to be proven, that the risk of severe, potentially life-threatening rash may be increased by: 1) co-administration of lamotrigine with valproic acid; 2) exceeding the recommended initial dose of lamotrigine; or 3) exceeding the recommended dose escalation for lamotrigine. However, cases have been reported in the absence of these factors. Therefore, it is important that the dosing recommendations be followed closely.
SOURCE: GlaxoSmithKline
