Metabolic encephalopathy is a rare but serious complication of
valproic acid (VPA)
therapy that usually presents with impaired consciousness or increased seizure frequency. Although it has been suggested that
topiramate (TPM) increases the risk of VPA-induced
encephalopathy, the additional risk in patients receiving TPM
therapy has not been evaluated. We reviewed all adult patients who took VPA between January 2005 and February 2009 at the Seoul National University Hospital and identified patients with VPA-induced
encephalopathy based on clinical and electroencephalography (EEG) data. Information on sex, age, serum
ammonia level, serum VPA level, liver function test, and EEG was collected from patient registry and medical data. We enrolled 8,372 patients who received VPA
therapy and 1,236 patients who received VPA/TPM combination
therapy. We identified 11 patients with VPA-induced
encephalopathy (0.13%), 7 of whom received a combination
therapy of VPA and TPM. The odds ratio of VPA-induced
encephalopathy with TPM over that without TPM was 10.16. There were no significant differences in sex distribution, number of
antiepileptic agents,
ammonia level, VPA serum level, underlying diseases, dosage of VPA, duration of VPA treatment, treatment of
encephalopathy, and outcomes between the two groups. Our study showed that the prevalence of VPA-induced
encephalopathy is approximately 0.1% among patients treated with VPA and that the risk of this condition, although still low, can increase by approximately 10 times in the presence of TPM
therapy. Based on these results, we suggest that TPM should be carefully used in patients receiving VPA treatment.