Lamictal

Also Known As: Lamictal, Lamotrigine

Lamotrigine, marketed in the US and most of Europe as Lamictal by GlaxoSmithKline, is an anticonvulsant drug used in the treatment of epilepsy and bipolar disorder. It is also used as an adjunct in treating depression, though this is considered off-label usage. For epilepsy, it is used to treat partial seizures, primary and secondary tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome. Like many other anticonvulsant medications, Lamotrigine also seems to act as an effective mood stabilizer, and in fact has been the only U.S. Food and Drug Administration (FDA)-approved drug for this purpose since lithium, a drug approved almost 30 years earlier. It is approved for the maintenance treatment of bipolar type I. Chemically unrelated to other anticonvulsants (due to lamotrigine's being a phenyltriazine), lamotrigine has many possible side-effects. Lamotrigine is generally accepted to be a member of the sodium channel blocking class of antiepileptic drugs, but it could have additional actions inasmuch as it has a broader spectrum of action than other sodium channel antiepileptic drugs such as phenytoin and carbamazepine and is effective in the treatment of the depressed phase of bipolar disorder, whereas other sodium channel blocking antiepileptic drugs are not. In addition, lamotrigine shares few side-effects with other, unrelated anticonvulsants known to inhibit sodium channels, which further emphasizes its unique properties. Lamotrigine is inactivated by hepatic glucuronidation.

Epilepsy and seizures

Lamotrigine is approved in the US for the treatment of partial seizures.[3] Lamotrigine is one of a small number of FDA-approved therapies for seizures associated with Lennox-Gastaut syndrome, a severe form of epilepsy. Typically developing before four 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.[4] 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.[5]

Bipolar disorder

Lamotrigine is approved in the US for maintenance treatment of Bipolar I disorder.[6] While traditional anticonvulsant drugs are predominantly antimanics, lamotrigine is most effective for preventing the recurrent depressive episodes of bipolar disorder. The drug seems ineffective in the maintenance of rapid-cycling bipolar disorder;[7] however, according to studies in 2007, lamotrigine may treat bipolar depression without triggering mania, hypomania, mixed states, or rapid-cycling.[8]

There is less evidence of therapeutic benefit when lamotrigine is used to treat a preexisting mood episode. It has not demonstrated effectiveness in treating acute mania,[9] and there is controversy regarding the drug’s effectiveness in treating acute bipolar depression. While the 2002 American Psychiatric Association (APA) guidelines recommend lamotrigine as a first-line treatment for acute depression in Bipolar II disorder,[10] the APA’s website notes that the guidelines, being more than five years old, “can no longer be assumed to be current."[11] A paper written in 2008 by Nasser et al. reviewed evidence from trials that were unpublished and not referenced in the 2002 APA guidelines, and it concludes that lamotrigine has "very limited, if any, efficacy in the treatment of acute bipolar depression."[7] A 2008 paper by Calabrese et al. examined much of the same data, and found that in five placebo controlled studies, lamotrigine did not significantly differ from placebo in the treatment of bipolar depression.[12] However, in a meta-analysis of these studies conducted in 2008, Calabrese found that lamotrigine was effective in individuals with bipolar depression, with a number needed to treat (NNT) of 11, or 7 in severe depression.[13]

Other uses

Off-label uses include the treatment of peripheral neuropathy, trigeminal neuralgia, cluster headaches, migraines, and reducing neuropathic pain. [14][15][16] Off-label psychiatric usage includes the treatment of depersonalization disorder, bipolar II disorder and other bipolar disorders, schizoaffective disorder, borderline personality disorder and post-traumatic stress disorder.[citation needed] Lamotrigine has been studied as an adjunctive therapy for treatment of refractory unipolar depression, attaining efficacy on the secondary metric for treatment outcomes (Clinical Global Impressions), but not the primary metrics (Montgomery-Åsberg Depression Rating Scale and Hamilton Rating Scale for Depression).[17]

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