Uses
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Seizure Disorders
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Partial Seizures
Lamotrigine (given as immediate-release formulations) is used in combination with other anticonvulsant agents in the management of partial seizures, with or without secondary generalization, in adults and children 2 years of age or older. Lamotrigine (given as immediate-release formulations) also is used as monotherapy in patients converting from monotherapy with a hepatic enzyme-inducing anticonvulsant agent (e.g., phenytoin, carbamazepine, phenobarbital, primidone) or valproic acid in the management of partial seizures in patients 16 years of age or older. Extended-release lamotrigine is used in combination with other anticonvulsant agents in the management of partial seizures, with or without secondary generalization, in adults and children 13 years of age or older.
In 3 multicenter, double-blind, placebo-controlled clinical studies, adjunctive therapy with immediate-release lamotrigine was effective in reducing seizure frequency in adults with simple and/or complex partial seizures refractory to therapy with one or more conventional anticonvulsant drugs (e.g., phenytoin, carbamazepine, phenobarbital, valproic acid); the median reduction in seizure frequency was 20-36%. In a multicenter, double-blind, placebo-controlled clinical study in children 2-16 years of age with partial seizures, the median reduction in frequency of all partial seizures was 36 or 7% in patients receiving immediate-release lamotrigine or placebo, respectively, in addition to their current therapy (up to 2 conventional anticonvulsant drugs). In a multicenter, double-blind, placebo-controlled clinical study in adults and children 13 years of age or older with partial seizures and receiving 1 or 2 anticonvulsants, adjunctive treatment with extended-release lamotrigine substantially reduced the median weekly seizure frequency compared with placebo (by 47 versus 25%, respectively).
The effectiveness of lamotrigine monotherapy (given as immediate-release formulations) in adults with partial seizures who are converting from monotherapy with a hepatic enzyme-inducing anticonvulsant drug (e.g., phenytoin, carbamazepine, phenobarbital, primidone) was established in a controlled clinical study of patients who experienced at least 4 simple or complex partial seizures, with or without secondary generalization, during each of 2 consecutive 4-week baseline periods; during the baseline periods, patients were receiving either phenytoin or carbamazepine monotherapy. Patients were randomized either to lamotrigine (target dosage: 500 mg daily) or valproic acid (1000 mg daily) therapy, which was added to their baseline regimen over a 4-week period. Patients were then converted to either lamotrigine or valproic acid monotherapy over another 4-week period and monotherapy continued for another 12-week period. Study end points were either successful completion of the 12-week monotherapy period or meeting a study ''escape'' criterion, relative to baseline. Escape criteria were defined as doubling of the mean monthly seizure count; doubling of the highest consecutive 2-day seizure frequency; emergence of a new seizure type (defined as a seizure that did not occur during the 8-week baseline period) that was more severe than the other seizure types occurring during the study period; or clinically important prolongation of generalized tonic-clonic seizures. The proportion of lamotrigine- or valproic acid-treated patients meeting escape criteria was 42 or 69%, respectively; no differences in efficacy were detected based on age, race, or gender. It was noted that the patients in the valproic acid control arm were treated intentionally with a relatively low valproic acid dosage because the intent of the study was to establish the effectiveness of lamotrigine monotherapy, and that the study results cannot be interpreted to imply the superiority of lamotrigine therapy to adequate valproic acid therapy. In addition, the manufacturers state that the use of lamotrigine therapy for the management of partial seizures has not been established as initial monotherapy; for conversion from monotherapy from anticonvulsant drugs other than hepatic enzyme-inducing anticonvulsant drugs or valproate; or for simultaneous conversion to monotherapy from 2 or more concomitant anticonvulsant drugs.
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Primary Generalized Tonic-Clonic Seizures
Lamotrigine (given as immediate-release formulations) is used in combination with other anticonvulsant agents in the management of primary generalized tonic-clonic seizures in adults and children 2 years of age and older. Efficacy of the drug as adjunctive therapy was established in a placebo-controlled trial in adult and pediatric patients at least 2 years of age who had experienced at least 3 primary generalized tonic-clonic seizures during an 8-week baseline phase. Patients were randomized to receive either placebo or immediate-release lamotrigine in a fixed-dose regimen (target dosages of 200-400 mg daily in adults and 3-12 mg/kg daily in children) for 19-24 weeks, which was added to their current anticonvulsant regimen of up to 2 anticonvulsant drugs. Patients receiving lamotrigine experienced a substantially greater median reduction in seizure frequency compared with baseline than did patients receiving placebo (66 and 34%, respectively).
Extended-release lamotrigine is used in combination with other anticonvulsants in the management of primary generalized tonic-clonic seizures in adults and adolescents 13 years of age and older. Efficacy of the extended-release formulation of the drug as adjunctive therapy was established in a multicenter, double-blind, placebo-controlled trial in adult and pediatric patients at least 13 years of age who had experienced at least 3 primary generalized tonic-clonic seizures during an 8-week baseline phase. Patients were randomized to receive either placebo or extended-release lamotrigine in a fixed-dose regimen (target dosages of 200-500 mg daily based on concomitant anticonvulsant therapy) for 19 weeks, which was added to their current anticonvulsant regimen of up to 2 anticonvulsant drugs. Patients receiving extended-release lamotrigine experienced a substantially greater median reduction in seizure frequency compared with baseline than did patients receiving placebo (75 and 32%, respectively).
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Seizures Associated with Lennox-Gastaut Syndrome
Lamotrigine (given as immediate-release formulations) is used in combination with other anticonvulsant agents in the management of generalized seizures associated with Lennox-Gastaut syndrome in pediatric patients and adults. In a controlled clinical trial in patients with Lennox-Gastaut syndrome, adjunctive therapy with immediate-release lamotrigine resulted in a 32, 34, and 36% decrease in major motor seizures, drop attacks, and tonic-clonic seizures, respectively.
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Bipolar Disorder
Lamotrigine (given as immediate-release formulations) is used in the maintenance therapy of bipolar 1 disorder to prevent or attenuate recurrences of bipolar episodes in adult patients who remain at high risk of relapse following treatment of an acute depressive or manic episode. The American Psychiatric Association (APA) currently recommends use of lamotrigine as an alternative to first-line maintenance therapies (e.g., lithium, valproic acid, or divalproex). The APA also states that both lamotrigine and lithium are effective in the maintenance treatment of bipolar 1 disorder; however, the results of two randomized, double-blind, placebo-controlled studies of 18 months' duration indicate that lamotrigine may be more effective in preventing depressive episodes while lithium may be more effective in preventing manic episodes.
Although efficacy of the drug in the acute treatment of mood episodes has yet to be fully established, lamotrigine is considered a first-line agent by the APA for the management of acute depressive episodes in patients with bipolar disorder. The APA also recommends the use of lamotrigine as an alternative to lithium, valproic acid, or divalproex in the management of patients with rapid cycling bipolar disorder, particularly in those with the bipolar 2 form of rapid cycling.
For further information on the management of bipolar disorder,