Lamotrigine (marketed as Lamictal by GlaxoSmithKline) is an anticonvulsant drug used in the treatment of epilepsy and bipolar disorder. For epilepsy it is used to treat partial seizures, primary and secondary tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome. Lamotrigine also acts as a mood stabilizer. It is the only anticonvulsant mood stabilizer that treats the depressive as well as the manic phases of bipolar disorders, and it is the first medication since Lithium granted FDA-approval for the maintenance treatment of bipolar I. Chemically unrelated to other anticonvulsants, lamotrigine has relatively few side-effects and does not require blood monitoring. It is a Na+ channel blocker, and is inactivated by hepatic glucuronidation.
GlaxoSmithKline's trademarked brand of Lamotrigine, Lamictal, is manufactured in scored tablets (25mg, 100mg, 150mg and 200mg) and chewable dispersible tablets (2mg, 5mg and 25mg). 5-week sample kits are also available; these include titration instructions and scored tablets (25mg for patients taking valproate, 25mg and 100mg for patients not taking valproate). Lamotrigine is also available in un-scored tablet form. Lamotrigine is also available in some jurisdictions in generic form .
Recommended initial dosing begins at less than 1mg for epilepsy and 25mg for bipolar disorder, and a therapeutic response may require weeks or months of subsequent dose escalations. This conservative titration minimizes the risk of inducing a potentially serious rash. Dosing should be reduced gradually as well. Abrupt discontinuation of any anticonvulsant increases the risk of seizures, even without a history of epilepsy. Dosing depends on the metabolic effects of concomitant medications such as valproate (reducing) and carbamazepine (enhancing).
Therapeutic plasma concentrations of lamotrigine are unknown, and according to the manufacturer, dosing should be based on therapeutic response. Generally, the therapeutic range for epilepsy is 300mg-500mg a day. Antidepressant effects may begin at 100mg a day, if not earlier, and mood stabilization takes place between 100mg to 200mg a day. Clinical studies show no effective difference for depression or bipolar disorder beyond 200mg, however antimanic effects may not begin until doses of 400mg a day. GlaxoSmithKline suggests maintenance doses up to 500mg for epilepsy, and 400mg for bipolar disorder. Blood monitoring is not required.
Common side effects include headaches, dizziness and insomnia. In very rare cases, Lamotrigine has been known to cause the development of a dangerous rash in some people called Stevens-Johnson syndrome. The rash is more common in children, so this medication is often reserved for adults. There is also an increased incidence of this rash in patients who are currently on, or recently discontinued a valproates anti-convulsant drug, as these medications interact in such a way that the clearance of both is decreased and the effective dose of lamotrigine is increased.
Other medications can increase or decrease the effectiveness of lamotrigine. The valproate AEDs (divalproex, Depakote; valproate sodium, Depakon; valproic acid, Depakene) inhibit the metabolism of lamotrigine, more than doubling its half-life. The dosage of lamotrigine must be reduced in the presence of these drugs. The enzyme-inducing AEDs (including carbamazepine USP, Tegretol; oxcarbazepine, Trileptal; and phenytoin, Dilantin) enhance the metabolism of lamotrigine, and its dosage must be increased when taken with these drugs; the same consideration is required when Lamictal is taken with oral contraceptives.
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