Late side-effects of valproate and lamotrigine

Abstract

Lamotrigine (LTG) is a generally well-tolerated antiepileptic drug with broad-spectrum efficacy in several forms of partial and generalized epilepsy. Adverse effects of lamotrigine are usually associated with introduction and titration. This risk increases in children and in the co-medication with valproate. Herein, we report four patients with late adverse-effects, under the co-medication valproate and LTG, not related to drug introduction or titration. This study demonstrates that late side-effects without apparent etiology in children, adolescents and adults in chronic use of LTG, especially when associated to VPA, led to a diagnostic investigation, sometimes invasive. It must be emphasized that, due to the excellent seizure control, the authors opted for drug decrease instead of drug withdrawal, as previously done. Studies on late adverse effects are scarce, but physicians must be aware of these risks.Key words: lamotrigine, side-effects, epilepsy, anti-epileptic drugs. RESUMOEfeitos adversos tardios no uso de valproate e lamotrigina Lamotrigina (LTG) é uma droga antiepiléptica bem tolerada com eficácia em diferentes formas de epilepsia, parcial e generalizada. Os efeitos adversos da lamotrigina estão freqüentemente associados com a sua introdução e a sua titulação. Este risco encontra-se aumentado em crianças e quando a LTG é usada em associação com o valproato. Nós relatamos quatro pacientes que apresentaram efeitos adversos tardios com a co-administração de LTG e valproato, não relacionados à introdução ou o escalonamento das drogas antiepilépticas. Este estudo demonstra que efeitos adversos tardios sem etiologia aparente nas crianças, adolescentes e adultos em uso crônico de LTG, especialmente quando associados ao valproato, levou à investigação diagnóstica, por vezes invasiva. Os autores enfatizam que, devido ao bom controle de crises, os autores optaram pela redução da dose ao invés da suspensão da medicação, como previamente realizado. Embora os estudos sobre efeitos adversos tardios das drogas antiepilépticas sejam escassos, os clínicos devem estar cientes deste risco.Unitermos: lamotrigine, efeitos adversos, epilepsia, drogas antiepilépticas.

Development of an incipient Stevens–Johnson reaction while on a stable dose of lamotrigine

“…Lamotrigine-induced rashes are usually divided into ‘benign’ and ‘serious’, with representative data provided by Calabrese et al 1 quantifying rates of 8.3% and 0% respectively in one sample and 13.1% and 0.1% in another. While there have been case reports 2 of late onset of side-effects, they have more been in the nature of neurological symptoms rather than rashes. I am not aware of any previous journal report of such a late-onset serious side-effect, although there are anecdotal reports on the internet.…”

Lamotrigine Induces Tremor among Epilepsy Patients Probably via Cerebellar Pathways

“…A recent report showed that in patients with bipolar disorder after 12-week of lamotrigine monotherapy the volume of the cerebellum decreased (Bauer et al 2018). Cerebellar signs and symptoms, like ataxia, nystagmus, vertigo, as LTG side-effects were also noted in epilepsy patients (Moreira et al 2007;Thome-Souza et al 2012). These findings raise the possibility that lamotrigine-induced tremor might be a result of cerebellar dysfunction.…”

“…Various cerebellar symptoms, like nystagmus, ataxia, vertigo and tremor were reported as side effects of chronic co-medication of VPA and LTG at stable doses. Although serum levels were not provided, it might be hypothesized that these cerebellar signs were related to toxicity which ceased after 25-50 mg dose reduction of LTG (Moreira et al 2007). It was demonstrated that glutamate is necessary for oligodendrocyte proliferation and differentiation in the developing cerebellum (Yuan et al 1998).…”