Pharmacokinetics of new anticonvulsants in psychiatry
Harold H. Morris, MDAddress reprint requests to H.H.M., Department of Neurology, M52, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195.
Since bromide was used for catamenial seizures and hysteria by Locock in the mid-1800s, antiepileptic drugs (AEDs) have been utilized in the treatment of various psychiatric disorders.1 Today, valproate and carbamazepine are important therapies for treatment of mania and bipolar disorder. Now, a number of newer anticonvulsant agents—including gabapentin, lamotrigine, topiramate, and tiagabine—with improved pharmacokinetic profiles are being investigated for psychiatric indications as well. In addition, the range of their psychiatric utility has been expanded, and the effect of AEDs is currently being considered not only in bipolar disorder but in panic and social phobia and in the treatment of neuropathic pain and detoxification.
The mechanisms by which these agents influence mental status and pain perception is unclear, but a review of their pharmacologic properties may reveal some potential mechanisms of action. In addition, an outline of their metabolism, drug interactions, and adverse effects will help to establish their most appropriate administration guidelines and most effective application in the psychiatric arena.
IMPROVING THE PHARMACOLOGIC PROFILE
Several pharmacologic features of the older AEDs have complicated their use. A short half-life necessitating multiple daily doses can undermine patient compliance with several of the agents.2 High protein binding associated with some of the drugs may also result in drug interactions.3 In addition, active metabolites of carbamazepine, valproic acid, and primidone alter the safety profile of several compounds; hepatic metabolism and clearance complicate the use of most older AEDs. All of the older AEDs are known to interact with other drugs.
The. . .