Anticonvulsants-induced chorea: a role for pharmacodynamic drug interaction?

Abstract

Chorea is a rare side effect of anticonvulsants. We describe three patients who developed chorea secondary to anticonvulsant combination use. A mechanism to explain this finding is proposed. After identification of an index case with anticonvulsant-induced chorea, we reviewed the electronic data base records for all patients with seizures followed in the epilepsy clinics at our university-based hospital for cases of dyskinesia associated with anticonvulsants. Two additional patients, one adult and one pediatric patient were identified. Three patients developed chorea while receiving combination anticonvulsants. Two patients had transient chorea that resolved with withdrawal of one of the drugs. All three patients were using phenytoin and lamotrigine in combination when the chorea started, chorea improved with tapering one of the medications. Polytherapy with certain anticonvulsants may predispose patients to drug-induced chorea. A particular increased risk was seen with combinations that have phenytoin and lamotrigine. This could be due to an additive or a synergistic effect on central dopaminergic pathways.

Evidence for Efficacy of Combination of Antiepileptic Drugs in Treatment of Epilepsy

“…Notably, in one paper, three patients experienced an onset of chorea upon being treated with a combination of lamotrigine and PHT. Interestingly, the chorea was resolved in all patients with the tapering of the dosage of one AED [72]. Another example is the studies that demonstrated that the combination of CBZ and vigabatrin led to increase in the adverse effects such as ataxia and weight gain [73].…”

Chorea

“…Phenytoin may also induce involuntary movements including orofacial chorea, particularly when other antiepileptic drugs are administered (Harrison, Lyons and Landow, 1993). There are occasional reports of chorea induced by other anti-epileptic drugs, such as carbamazepine (Bimpong-Buta and Froescher, 1982) and, more recently, lamotrigine (Zaatreh et al, 2001). Chronic exposure to amphetamines and other stimulants may induce orofacial dyskinesias and choreic movements of the trunk and extremities (Stork and Cantor, 1997;Morgan, Winter and Wooten, 2004).…”

Dyskinetische Bewegungsstörung unter antikonvulsiver Behandlung

“…Die vorgestellte Kasuistik weist entscheidende Parallelen zu drei Fällen auf, die vor wenigen Jahren von Zaatreh und Mitarbeitern [4] publiziert worden waren: Unwillkürliche, Chorea-bzw. Choreoathetoseähnliche Bewegungsstörungen traten unter Kombinationsbehandlung mit LTG und PHT auf, wobei beide Medikamente in Monotherapie oder in Kombination mit anderen Substanzen vorausgehend gut vertragen worden waren und das Absetzen von PHT jeweils zu einem Sistieren der Bewegungsstörungen führte.…”

“…Wenn Dyskinesien unter der Kombination von LTG mit PHT auftreten, ist dies auch unter relativ niedrigen Serumspiegeln dieser Antikonvulsiva mög-lich, wie der Fall unseres Patienten und auch die in der Literatur berichteten Fälle belegen [4].…”

“…Athetosen auszulösen. Dies ist für Carbamazepin (CBZ), Gabapentin (GBP), Felbamat (FBM), Valproat (VPA) und Tiagabin (TGB), auch für Lamotrigin (LTG) und insbesondere für Phenytoin (PHT) beschrieben [1,3,4]. Insgesamt sind solche Phäno-mene selten.…”