Lamotrigine

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. more...

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.

U.S. FDA approval history

• December 1994 - for use as adjunctive treatment for partial seizures with or without secondary generalization in adult patients (16 years of age and older).
• August 1998 - for use as adjunctive treatment of Lennox-Gastaut syndrome in pediatric and adult patients, new dosage form: chewable dispersible tablets.
• December 1998 - for use as monotherapy for treatment of partial seizures in adult patients when converting from a single enzyme-inducing anti-epileptic drug (EIAED).
• January 2003 - for use as adjunctive therapy for partial seizures in pediatric patients as young as 2 years of age.
• June 2003 - for the maintenance treatment of adults with 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. Additionally, the FDA has noted that findings for Lamictal maintenance treatment were more robust in bipolar depression.
• January 2004 - for use as monotherapy for treatment of partial seizures in adult patients when converting from the anti-epileptic drug valproate (including valproic acid (Depakene) and divalproex sodium (Depakote)).

Indications & Usage

The FDA approved lamotrigine (Lamictal) for the treatment of epilepsy in 1994, and bipolar I disorder in 2003 (

Lennox-Gastaut syndrome (LGS) is a severe form of epilepsy. Typically developing before 4 years of age, LGS is associated with developmental delays. There is no cure, treatment is often complicated, and complete recovery is rare. Symptoms include the atonic seizure (also known as a "drop attack"), during which brief loss of muscle tone and consciousness cause abrupt falls. Lamotrigine significantly reduces the frequency of LGS seizures, and is one of two medications known to decrease the severity of drop attacks (French et al., 2004). Combination with valproate is common, but this increases the risk of lamotrigine-induced rash, and necessitates reduced dosing due to the interaction of these drugs (Pellock, 1999).

Lamotrigine (Lamictal) is the first FDA-approved therapy since Lithium for maintenance treatment of bipolar I disorder (GlaxoSmithKline, 2003). These are the only true "mood stabilizers" in that they possess antidepressant as well as antimanic properties, and research has shown that of the two, lamotrigine is the more effective treatment for bipolar depression. Traditional anticonvulsant drugs are primarily antimanics. Lamotrigine treats depression without triggering mania, hypomania, mixed states, or rapid-cycling, and the 2002 American Psychiatric Association guidelines recommended lamotrigine as a first-line treatment for acute depression in bipolar disorder as well as a maintenance therapy, however lamotrigine is not indicated "on label" for treatment of acute symptoms.

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