Levetiracetam is an effective and generally well-tolerated antiepileptic drug, but may provoke psychiatric adverse effects such as aggression and irritability in some patients. Clinical data suggest that patients with pre-existing impulsive and aggressive tendencies might be at risk for adverse events after Levetiracetam administration.

The authors of this study found that genetic variants in aggression-related genes regulating dopaminergic, but not noradrenergic or serotonergic neuronal pathways, were associated with the adverse psychiatric profile of Levetiracetam. Specifically, genetic variants associated with decreased dopaminergic activity were involved. These were: rs1611115 (dopamine-β-hydroxylase, DBH), rs4680 (catechol-O-methyltransferase, COMT), and rs1800497 (dopamine receptor D2-associated ANKK1 TAQ-1A). The authors recommend further studies to confirm these initial correlative findings. This pharmacogenetic approach may provide a useful future tool for predicting adverse side effects of antiepileptic drugs.

Helmstaedter C, Mihov Y, Toliat MR, Thiele H, Nuernberg P, Schoch S, Surges R, Elger CE, Kunz WS, Hurlemann R: Genetic variation in dopaminergic activity is associated with the risk for psychiatric side effects of levetiracetam. Epilepsia [Epub ahead of print, August 6, 2012] doi: 10.1111/j.1528-1167.2012.03603.x


See commentary in:

Nature Reviews Neurology 8(10): 532 (2012).                http://www.ncbi.nlm.nih.gov/pubmed/22945543

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