Interactions between antiepileptic drugs and herbal medicines

As a therapeutic class, antiepileptic drugs (AEDs) have a high propensity to interact and many interactions with concomitant medications have been described. Increasingly, herbal medicines are often used by patients with epilepsy and the risk that these may interact with their AED medication is now being realised. The purpose of this review is to highlight the interactions that have been reported between AEDs and herbal medicines. Overall, the published data are sparse and comprise of both pharmacodynamic (preclinical only) and pharmacokinetic (preclinical and clinical) interactions. Pharmacodynamic interactions between diazepam and the Chinese herb Saiboku-to and with Ginkgo biloba, and between phenytoin, valproate and gabapentin and Centella asiatica have been described. Pre-clinical studies suggest that the Japanese herbs Sho-seiryu-to and Sho-saiko-to, the herbal infusion preparation from Cassia auriculata, the traditional Chinese herbal medicine Paeoniae Radix and the herb Mental can affect the pharmacokinetics of carbamazepine by various mechanisms. Pharmacokinetic interactions have also been reported with phenytoin (Paenoniae Radix, Ayurvedic syrup shankhapushpi), phenobarbital (Ginkgo biloba) and diazepam (the Chinese herbs Angelica dahurica and Salvia miltiorrhiza Bge). Clinical studies have reported a reduction in serum carbamazepine concentrations when co-administered with the traditional Chinese herb Free and Easy Wanderer Plus and also a reduction in serum midazolam concentrations by Echinacea and by St John's Wort. The mechanism of these interactions is considered to be induction of hepatic metabolism. In contrast, piperine elevates serum phenytoin concentrations, possibly be enhancing the gastrointestinal absorption of phenytoin. More research and information are required in order to clarify the propensity of AEDs and herbal medicine to interact and therefore potentially compromise the therapeutics of AEDs.