Lamotrigine, sold under the brand name Lamictal among others, is a medication used to treat epilepsy and stabilize mood in bipolar disorder. For epilepsy, this includes focal seizures, tonic-clonic seizures, and seizures in Lennox-Gastaut syndrome. In bipolar disorder, lamotrigine has not been shown to reliably treat acute depression; but for patients with bipolar disorder who are not currently symptomatic, it appears to be effective in reducing the risk of future episodes of depression.
Common side effects include nausea, sleepiness, headache, vomiting, trouble with coordination, and rash. Serious side effects include excessive breakdown of red blood cells, increased risk of suicide, severe skin reaction (Stevens–Johnson syndrome), and allergic reactions, which can be fatal. Lamotrigine is a phenyltriazine, making it chemically different from other anticonvulsants. Its mechanism of action is not clear, but it appears to inhibit release of excitatory neurotransmitters via voltage-sensitive sodium channels and voltage-gated calcium channels in neurons.
Lamotrigine was first marketed in Ireland in 1991, and approved for use in the United States in 1994. It is on the World Health Organization's List of Essential Medicines. In 2020, it was the 62nd most commonly prescribed medication in the United States, with more than 10million prescriptions.
Medical uses
Epilepsy
Lamotrigine is considered a first-line drug for primary generalized tonic-clonic seizures (includes simple partial, complex partial, and secondarily generalized seizures such as focal-onset tonic-clonic seizures). It is also used as an alternative or adjuvant medication for partial seizures, such as absence seizure, myoclonic seizure, and atonic seizures. A 2020 review on the use of lamotrigine as an add-on therapy for drug resistant generalized tonic-clonic seizures was unable to come to conclusions to inform clinical practice. Although low-certainty evidence suggest that it reduces generalized tonic-clonic seizures by 50% the level of uncertainty indicates that the actual findings could be significantly different. Another 2020 Cochrane review examining the use of lamotrigine as an add-on therapy for drug-resistant focal epilepsy found it to be effective for reducing seizure frequency and was well tolerated.
Lennox–Gastaut syndrome
Lamotrigine is one of a small number of FDA-approved therapies for the form of epilepsy known as Lennox–Gastaut syndrome. It reduces the frequency of LGS seizures, and is one of two medications known to decrease the severity of drop attacks. Combination with valproate is common, but this increases the risk of lamotrigine-induced severe skin reaction Stevens–Johnson syndrome, and necessitates reduced dosing due to the interaction of these drugs.
Bipolar disorder
Lamotrigine is approved in the US for maintenance treatment of bipolar I disorder and bipolar II disorder. While the anticonvulsants carbamazepine and valproate are predominantly antimanics, lamotrigine has demonstrated efficacy only in preventing or reducing the risk of recurrent depressive episodes of bipolar disorder. The drug seems ineffective in the treatment of current rapid-cycling, acute mania, or acute depression in bipolar disorder. Lamotrigine has been shown to be as effective as lithium, the standard treatment for bipolar disorder.
Lamotrigine has not demonstrated clear efficacy in treating acute mood episodes, either mania or depression. It has not demonstrated effectiveness in treating acute mania, and there is controversy regarding the drug's effectiveness in treating acute bipolar depression. A paper written in 2008 by Nassir 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". 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. However, in a meta-analysis of these studies conducted in 2008, Geddes, Calabrese and Goodwin found that lamotrigine was effective in individuals with bipolar depression, with a number needed to treat (NNT) of 11, or 7 in severe depression.
A 2013 review concluded that lamotrigine is recommended in bipolar maintenance when depression is prominent and that more research is needed in regard to its role in the treatment of acute bipolar depression and unipolar depression. No information to recommend its use in other psychiatric disorders was found.