Recognising Acute Lamotrigine Induced Tourette’s Syndrome in Adults

After six years of remission on carbamazepine, a 33-yearold woman with focal epilepsy of unknown cause had a seizure three weeks post-partum. Within 48 hours of starting lamotrigine (25mg twice daily), she developed severe complex motor tics and coprolalia. There was no personal or family history of tics or obsessionality. Tourette’s resolved within 72 hours of stopping lamotrigine. She declined re-challenge. There is no recurrence over nine years. Previous reports of Tourette’s in patients treated with lamotrigine for epilepsy, bipolar disorders or refractory depression demonstrated a dose-dependent effect (Table). Our patient’s symptoms occurred and resolved within 48 hours (compared to a mean 5 months and 72 hours respectively in all reports, see Table), more rapidly than previously reported. The severity of lamotrigine-induced Tourette’s varies from mild to severe. In most patients, lamotrigine was withdrawn, but in 5/16 dose reduction resolved symptoms (Table). Several cases recurred on re-challenge, and 7/16 occurred in adults (see Table) in contrast to primary Tourette’s syndrome (commencing at mean 7 years), occurring in 0.5% of the population [1].

Carbamazepine, phenobarbital and phenytoin [2] as well as lamotrigine, are rare secondary causes of Tourette’s. Only one previously reported patient had a prior tic disorder and 2/16 had pre-existing obsessional traits (Table). No predisposing or genetic factors have been identified, in contrast to primary Tourette’s syndrome [1].

Tourettes syndrome is postulated to be due to basal ganglia and frontal dysfunction [3], along with genetic factors [1]. The mechanism of the reaction to lamotrigine is uncertain. Inhibition of voltage-gated sodium channels and subsequent attenuation of pre-synaptic glutamate release modulates basal ganglia circuitry and is postulated as the cause [3]. Lamotrigine-mediated nicotinic receptor agonism, mediating basal ganglia dopamine release, has also been suggested [3]. Neither hypothesis explains susceptibility in such a small percentage of patients.

Table 1:Reported lamotrigine-induced Tourette’s syndrome.

In our secondary care cohort, lamotrigine induced Tourettes occurred in 0.3% of adults with epilepsy, and a previous report estimated 1.3% in children [4]. The reaction can be delayed up to 10 months after commencing Lamotrigine. A careful drug history is important in Tourette’s syndrome, especially if atypical features, such as adulthood onset, or absent family history. Clinicians should be aware of this reversible cause of Tourette’s syndrome.

Our thanks to the patient who gave informed consent for this publication.

None.

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