Lamotrigine is a widely used treatment for epilepsy and bipolar disorder. Certain HLA variants, such as HLA-B*15:02, have been studied for their possible association with increased susceptibility to serious skin reactions associated with treatment.
Lamotrigine (Adverse effects)
Lamotrigine is an antiepileptic drug widely used for the treatment of various forms of epilepsy and for the prevention of depressive episodes in patients with bipolar disorder. Its efficacy, broad spectrum of action, and good general tolerability have favored its use in both adults and pediatric populations.
Although most patients tolerate the treatment adequately, lamotrigine can be associated with skin reactions of varying severity. In rare cases, severe cutaneous adverse reactions (SCAR) may occur, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and DRESS syndrome.
Mechanism of action
Lamotrigine acts primarily by blocking voltage-dependent sodium channels, stabilizing neuronal membranes and reducing the release of excitatory neurotransmitters, especially glutamate and aspartate. This mechanism contributes to reducing neuronal excitability and preventing the onset of epileptic seizures.
Contraindications
Lamotrigine is contraindicated in patients with known hypersensitivity to the active substance or to any of its excipients. It should be administered according to the recommended dose escalation guidelines, as rapid titration or concomitant use of valproate increases the risk of serious skin reactions.
Adverse reactions
The most frequent adverse effects include headache, dizziness, somnolence, diplopia, blurred vision, nausea, vomiting, and balance disorders. Skin reactions are relatively frequent during the first weeks of treatment and usually present as mild rashes. However, in rare cases, severe cutaneous adverse reactions (SCAR) may occur, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and DRESS syndrome, which require immediate discontinuation of treatment.
Trade names
- Lamictal®
- Lamictal XR®
Genes analyzed
Bibliography
An DM, Wu XT, Hu FY, et al.Association study of lamotrigine-induced cutaneous adverse reactions and HLA-B*1502 in a Han Chinese population. Epilepsy Res. 2010 Dec;92(2-3):226-30.
Manson LEN, Nijenhuis M, Soree B, et al.Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of CYP2C9, HLA-A and HLA-B with anti-epileptic drugs. Eur J Hum Genet. 2024 Aug;32(8):903-911. doi: 10.1038/s41431-024-01572-4.
Sabourirad S, Mortezaee R, Mojarad M, et al.Investigating the association of Lamotrigine and Phenytoin-induced Stevens-Johnson syndrome/Toxic Epidermal Necrolysis with HLA-B*1502 in Iranian population. Exp Dermatol. 2021 Feb;30(2):284-287.
