Drug induced encephalopathy in six epileptic patients: topiramate? valproate? or both?

Six severe epileptic patients developed stuporous encephalopathy with marked cognitive impairment when topiramate (TPM) and sodium valproate (VPA) were coprescribed for five patients, and when monotherapy with TPM was introduced for one patient. In four patients, ammonaemia increased and then returned to normal after TPM or VPA withdrawal. This severe potential side effect must be recognized. Moreover two distinct mechanisms might explain this toxicity: (1). a pharmacokinetic interaction between VPA and TPM, leading to hyperammonaemia, (2). a pharmacodynamic mechanism due to a direct toxicity of TPM in at-risk epileptic patients.