Lamotrigine

By Marcello Cherchi, MD PhD

For patients

Lamotrigine is an oral medication that was originally developed to treat certain kinds of epilepsy. Less commonly, it is used to treat some psychiatric disorders, and some diseases causing dizziness or hearing abnormalities. Some patients stop the drug because of a rash. In rare cases this drug can cause a very severe skin problem called Stevens-Johnson syndrome.

For clinicians

Practical summary

Lamotrigine was originally developed as an anti-epileptic medication, though it found off-label applications in the management of certain psychiatric disorders. Its half-life can be substantially affected by enzyme-inducing and enzyme-inhibiting drugs. The main applications in otoneurology include visual snow syndrome; less common applications include vestibular paroxysmia, migraine and musical hallucinations. Skin rash is the most common reason for discontinuing the drug. The most feared complication is Stevens-Johnson syndrome, for which there may be a genetic predisposition.

Introduction

Lamotrigine is a phenyltriazine compound that was devised at Wellcome Laboratories in the 1980s. Lamotrigine blocks voltage-sensitive sodium channels, thereby inhibiting the release of glutamate. The drug was initially approved in Ireland for treatment of epilepsy in 1990. In 1994 it received FDA approval in the United States as an adjunctive therapy for epilepsy (Weisler et al. 2008). It has come to be used for a variety of off-label purposes, including in the management of various psychiatric disorders. The main applications in otoneurology include visual snow syndrome; less common applications include vestibular paroxysmia, migraine and musical hallucinations. Though generally well-tolerated, the most common cause for discontinuing the medication is a rash. The most feared adverse effect is Stevens-Johnson syndrome, for which there may be a genetic predisposition.

Pharmacology

Lamotrigine blocks voltage-sensitive sodium channels, leading to inhibition of neuronal release of the excitatory neurotransmitter glutamate (Fitton and Goa 1995; Steiner et al. 1997).

Lamotrigine is rapidly and fairly completely absorbed, it has a high bioavailability (Rambeck and Wolf 1993), it exhibits first-order enzyme kinetics, and is eliminated in the urine (Peck 1991). The mean half-life of lamotrigine is 24.1 – 35 hours; it does not exhibit significant autoinduction, but its half-life can substantially vary when co-administered with drugs (Garnett 1997) that are enzyme-inducing (such as phenytoin, phenobarbital or carbamazepine) or enzyme-inhibiting (such as valproate) (Rambeck and Wolf 1993).

Adverse effects

Skin rash is the most common adverse effect of lamotrigine, as well as the most common reason for discontinuing this drug (Fitton and Goa 1995). The risk of skin rash diminishes if the drug is slowly uptitrated.

The most feared complication of lamotrigine is Stevens-Johnson syndrome, which is severe mucocutaneous epidermal necrolysis and detachment of the epidermis (Edinoff et al. 2021), and to which there may be some genetic predisposition (Das et al. 2023).

Several ocular motor abnormalities have been documented in association with lamotrigine toxicity, including:

• Spontaneous down beat nystagmus (Alkawi et al. 2005; Oh et al. 2006).
• Spontaneous torsional nystagmus (O’Donnell and Bateman 2000).
• Pathological gaze-evoked nystagmus (GEN) (Jung et al. 2020).

Other neurological adverse effects reported in association with lamotrigine include worsening of cerebellar symptoms in a patient with spinocerebellar ataxia (Hayashi et al. 2025).

Other reported adverse effects of lamotrigine include QRS prolongation (Herold 2006).

Cautions and contraindications

Valproate significantly inhibits the catabolism of lamotrigine (Peck 1991), thus when these drugs are co-administered (such as in the treatment for epilepsy), serum levels should be monitored closely to detect potentially toxic levels of lamotrigine (Sang et al. 2025).

Pregnancy and lactation

A meta-analysis of 21 studies concluded that there was no association between lamotrigine monotherapy during pregnancy and increased rates of birth defects (Pariente et al. 2017).  A more recent Cochrane review concluded that the risk of major congenital malformations from prenatal lamotrigine exposure was 1% (Bromley et al. 2023).  A systematic review reported no adverse developmental outcomes from breastfeeding while on lamotrigine (Tomson et al. 2022).

Relevance in otoneurology

Lamotrigine has several applications in otoneurology, such as:

• Visual snow syndrome (VSS) (Barrachina-Esteve et al. 2021; Bou Ghannam and Pelak 2017; Eren and Schankin 2020; Mehta et al. 2021; Traber et al. 2020; Unal-Cevik and Yildiz 2015; van Dongen et al. 2019).
• Migraine, including migraine associated vertigo (MAV) (Bisdorff 2004; Buch and Chabriat 2019; Steiner et al. 1997).
• Vestibular paroxysmia (VP) (Brandt et al. 2016).
• Musical hallucinations (Huntley et al. 2011).

References

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Bisdorff AR (2004) Treatment of migraine related vertigo with lamotrigine an observational study. Bull Soc Sci Med Grand Duche Luxemb: 103-8.

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Hayashi K, Izumi R, Suzuki A, Nakaya Y, Sato M, Miura T, Hayashi K, Kobayashi Y (2025) Exacerbation of Cerebellar Symptoms in Spinocerebellar Ataxia Induced by Lamotrigine: A Case Report. Cureus 17: e77448. doi: 10.7759/cureus.77448

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