Lamotrigine is a synthetic phenyltriazine that works as an anticonvulsant and a mood stabilizer. Though not fully understood, its effects are believed to be mediated through multiple mechanisms. The drug inhibits voltage-gated sodium ion channels by selectively binding to the inactive form, which prevents the release of glutamate, an excitatory neurotransmitter.1 Lamotrigine also increases the activity of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter that has relaxant and depressive effects because it blocks nerve transmission in the brain. In addition, lamotrigine may block calcium ion channels, which contributes to its antiepileptic effects. It may also prevent serotonin reuptake, increasing its efficacy as an antidepressant.2
Common side effects of lamotrigine include:
Patients should contact a doctor immediately if they experience worsening depression, suicidal thoughts, or serious side effects, which may include fainting, unusual bruising, extreme fatigue, muscle pain or weakness, jaundice, abdominal pain, dark urine, persistent vomiting, or a change in the amount of urine. Patients should also seek medical attention in the event of a serious allergic reaction, which may be characterized by rash, extreme dizziness, difficulty breathing, or swelling of the face, tongue, or throat.7
Some drugs can change the rate at which lamotrigine is metabolized, so doctors may need to adjust the dosage for patients who take the following medications: estrogen replacement drugs, seizure medications (such as carbamazepine, phenobarbital, phenytoin, primidone, and valproic acid), HIV protease inhibitors, and rifampin. Lamotrigine can decrease the effectiveness of hormonal birth control products, including pills, patches, and rings. Patients are more likely to experience drowsiness as a side effect when lamotrigine is taken in conjunction with other drugs that cause drowsiness, such as alcohol, antihistamines, sleep aids, muscle relaxants, and narcotic pain relievers.8
Lamotrigine was developed in the early 1990’s after scientists observed the strong anticonvulsant effects of phenyltriazine compounds in animal models. The FDA approved lamotrigine for the treatment of partial seizures in December 1994.9 In 2003, lamotrigine became the first drug since lithium to be approved for the treatment of patients with Bipolar I Disorder.10 Originally marketed as Lamictal, the drug has since gone to generic.
Recent research continues to probe the chemical interactions that mediate the drug’s clinical effects. Because lamotrigine affects so many different signaling pathways,these mechanisms remain unclear. There is also a longstanding debate within the research community about the efficacy of using lamotrigine to for the treatment of chronic and acute pain.11 Many studies have focused particularly on the drug’s ability to relieve neuropathic pain and pain from fibromyalgia, but evidence remains inconclusive.12
Many studies have also explored the safety of lamotrigine. In particular, scientists have asked whether the use of lamotrigine by pregnant women poses risks for the developing fetus13 and whether taking lamotrigine while breastfeeding can harm an infant, but findings are mixed. There are also studies on the safety and efficacy of using lamotrigine to treat children with epilepsy. The results suggest that taking the drug is relatively safe, but children are more likely to experience side effects.14