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| |  AAN: Lamictal (Lamotrigine) Appears Effective as Add-On Treatment for Primary Generalized Tonic-Clonic Seizures Associated With Epilepsy MIAMI BEACH, FL -- April 13, 2005 -- Results from a new study presented today indicate that the use of Lamictal® (lamotrigine) Tablets as adjunctive therapy may be effective for the treatment of Primary Generalized Tonic-Clonic (PGTC) Seizures in children, adolescents and adults with epilepsy. The results from the double-blind, placebo-controlled study was presented today at the 57th annual meeting of the American Academy of Neurology (AAN). Generalized tonic-clonic seizures are associated with wide-ranging physiologic and behavioral changes before, during and after seizure episodes with potentially life-threatening complications. In the study, Lamictal was given to patients inadequately controlled with one or two concurrent antiepileptic drugs (AEDs). Lamictal significantly reduced PGTC seizures during the initial dose escalation phase by 61 percent from baseline (2.4 seizures per month) as compared to 33 percent for placebo and during the maintenance phase of treatment by 82 percent as compared to 43 percent for placebo. The median percent decrease in PGTC seizures from baseline for the entire treatment period was 66 percent for Lamictal and 34 percent for the placebo group. In a sub-group analysis involving children and adolescents, Lamictal reduced the number of PGTC seizures from baseline by 77 percent during the entire treatment period as compared to 40 percent for placebo. Strong trends were noted during the escalation (72 percent reduction from baseline for Lamictal vs. 30 percent for placebo) and maintenance (83 percent reduction from baseline for Lamictal vs. 42 percent for placebo) phases. Although there was no significant difference between Lamictal and placebo, the study was not powered to evaluate this subset of patients. "The study shows that Lamictal may be effective as add-on therapy for treating PGTC seizures. Despite the fact that PGTC seizures are a more serious form of epilepsy, few studies have focused on these types of seizures exclusively," said Victor Biton, M.D., Director of the Arkansas Epilepsy Program, Little Rock, AR, and lead investigator of one of the studies. "These data offer promising news in our effort to understand how to best control these types of seizures where there are few therapies approved." PGTC seizures also referred to as "grand mal" seizures, usually occur without warning. People who experience PGTC seizures become stiff, lose consciousness and have no memory of the seizure. During a tonic-clonic seizure, patients may bite their tongue, salivate or become incontinent. The seizure will typically last for a few minutes and then be followed by a period of drowsiness, confusion, headache and sleep. For some people who are affected by this type of seizure, it can take many hours to fully recover. PGTC seizures are the most common form of generalized seizure type-occurring in approximately 25 percent of epilepsy patients. "People who experience PGTC seizures can be injured during their seizures, which is why effective control of these seizures is especially critical in the vulnerable child and adolescent populations. In addition, uncontrolled PGTC seizures increase the risk of sudden unexplained death and increase the risk of status epilepticus," noted Edwin Trevathan, M.D., M.P.H., Director of the Division of Pediatric and Developmental Neurology at Washington University School of Medicine and Neurologist-in-Chief, St. Louis Children's Hospital, St. Louis, MO, and lead investigator of the children and adolescent study. "It is important for patients to work with their physicians to find therapies that control seizures while offering a favorable tolerability profile." About The Study In the study, led by Dr. Biton, entitled "Effects of Lamotrigine in Primary Generalized Tonic-Clonic Seizures (PGTCS): A Randomized, Placebo-Controlled Study, patients naive to Lamictal, 2 years of age or older with inadequately controlled PGTC seizures, taking a stable regimen of 1 or 2 AEDs and an electroencephalogram (EEG) with evidence of generalized epileptiform discharges or no evidence of interictal expression of partial seizures, were enrolled in a randomized, double-blind, placebo-controlled, parallel-group trial. Patients having 3 or more PGTC seizures over an 8-week Baseline were randomized to receive either Lamictal or placebo added to their current AEDs regimen. The treatment period consisted of an Escalation phase (12 weeks for patients 2-12 years, 7 weeks for patients older than 12) and a Maintenance phase (12 weeks). Of 184 patients enrolled, 117 were randomized. The median PGTC seizure count per month was 2.4 and 2.9 during Baseline for Lamictal and placebo, respectively, 1.0 and 2.3 during Escalation, and 0.4 and 1.6 during Maintenance, and 0.8 and 2.0 during the entire treatment phase. The most common (greater than or equal to 5 percent) drug-related adverse events for Lamictal and placebo, respectively, were dizziness, 5 and 2 percent; somnolence, 5 and 2 percent; and nausea, 5 and 3 percent. The non-serious rash rate was 3 percent for both Lamictal and placebo. No serious rash was reported. In a sub-group analysis of the study, presented by Dr. Trevathan, entitled "Double-Blind, Placebo-Controlled Evaluation of Lamotrigine Adjunctive Therapy in Children and Adolescents with Primary Generalized Tonic-Clonic Seizures," the efficacy of Lamictal was reported in children (2 years of age or older) and adolescents (up to 20 years of age). A total of 45 pediatric and adolescent patients were randomized (21 Lamictal, 24 placebo). The median PGTC seizure count per month was 0.7 and 3.6 during Escalation for Lamictal and placebo, respectively, 0.3 and 2.0 during Maintenance, and 0.4 and 2.5 during the entire treatment period. The most common treatment-emergent adverse events for Lamictal and placebo, respectively, were headache (10 percent for Lamictal vs. 25 percent for placebo, respectively), nasopharyngitis (14 percent vs. 4 percent), and convulsion (10 percent vs. 13 percent). One patient from each treatment group discontinued from the study due to an adverse event (disorientation in the group receiving Lamictal and convulsions with apnea in the placebo group). About Epilepsy Epilepsy, defined by recurrent unprovoked seizures, is a change in sensation, awareness, or behavior brought about by an electrical disturbance in the brain. The kind of seizure a person has depends on which part and how much of the brain is affected by the electrical disturbance that produces seizures. Generalized seizures are seizures that involve the entire brain from the outset. In 75 percent of cases, the cause of epilepsy is unknown. According to the Epilepsy Foundation, epilepsy affects 2.5 million Americans of all ages. About Lamictal Lamictal is indicated as adjunctive therapy for partial seizures and for the generalized seizures of Lennox-Gastaut syndrome in adult and pediatric patients (greater than or equal to 2 years of age). Lamictal is also indicated for conversion to monotherapy in adults with partial seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single AEDs. Safety and effectiveness of Lamictal have not been established as initial monotherapy, for conversion to monotherapy from AEDs other than carbamazepine, phenytoin, phenobarbital, primidone, or 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 partial seizures and the generalized seizures of Lennox-Gastaut syndrome have not been established. Lamictal is also approved for maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in patients treated for acute mood episodes with standard therapy. The effectiveness of Lamictal in the acute treatment of mood episodes has not been established (see Indications section in Prescribing Information). Serious rashes requiring hospitalization and discontinuation of treatment have been reported in association with the use of Lamictal. The incidence of these rashes, which have included Stevens-Johnson syndrome, is approximately 0.8 percent (8 per 1000) in pediatric patients under the age of 16 years receiving Lamictal as adjunctive therapy for epilepsy, and 0.3 percent (3 per 1000) in adults on adjunctive therapy for epilepsy. In clinical trials of bipolar and other mood disorders, the rate of serious rash was 0.08 percent of adult patients who received Lamictal as initial monotherapy and 0.13 percent of adult patients who received Lamictal as adjunctive therapy. In a prospectively followed cohort of 1,983 pediatric patients taking adjunctive Lamictal, there was one rash-related death. In worldwide postmarketing experience, rare cases of toxic epidermal necrolysis (TEN) and/or rash-related death have been reported in adult and pediatric patients, but their numbers are too few to permit a precise estimate of the rate. Because the rate of serious rash is greater in pediatric patients than in adults, it bears emphasis that Lamictal is approved only for use in pediatric patients below the age of 16 years who have partial seizures or seizures associated with the Lennox-Gastaut syndrome (see Indications section in Prescribing Information). Other than age, there are as yet no factors identified that are known to predict the risk of occurrence or the severity of rash associated with Lamictal. There are suggestions, yet to be proven, that the risk of rash may also be increased by co-administration of Lamictal with valproic acid (includes valproic acid and divalproex sodium), exceeding the recommended initial dose of Lamictal, or exceeding the recommended dose escalation for Lamictal. However, cases have been reported in the absence of these factors. Lamictal should ordinarily be discontinued at the first sign of rash, unless the rash is clearly not drug related.
SOURCE: GlaxoSmithKline
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