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Interactions between Antiepileptic and Antipsychotic Drugs

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Abstract

Antiepileptic and antipsychotic drugs are often prescribed together. Interactions between the drugs may affect both efficacy and toxicity. This is a review of human clinical data on the interactions between the antiepileptic drugs carbamazepine, valproic acid (sodium valproate), vigabatrin, lamotrigine, gabapentin, topiramate, tiagabine, oxcarbazepine, levetiracetam, pregabalin, felbamate, zonisamide, phenobarbital and phenytoin with the antipsychotic drugs risperidone, olanzapine, quetiapine, clozapine, amisulpride, sulpiride, ziprasidone, aripiprazole, haloperidol and chlorpromazine; the limited information on interactions between antiepileptic drugs and zuclopenthixol, periciazine, fluphenazine, flupenthixol and pimozide is also presented. Many of the interactions depend on the induction or inhibition of the cytochrome P450 isoenzymes, but other important mechanisms involve the uridine diphosphate glucuronosyltransferase isoenzymes and protein binding.

There is some evidence for the following effects. Carbamazepine decreases the plasma concentrations of both risperidone and its active metabolite. It also decreases concentrations of olanzapine, clozapine, ziprasidone, haloperidol, zuclopenthixol, flupenthixol and probably chlorpromazine and fluphenazine. Quetiapine increases the ratio of carbamazepine epoxide to carbamazepine and this may lead to toxicity. The data on valproic acid are conflicting; it may either increase or decrease clozapine concentrations, and it appears to decrease aripiprazole concentrations. Chlorpromazine possibly increases valproic acid concentrations. Lamotrigine possibly increases clozapine concentrations. Phenobarbital decreases clozapine, haloperidol and chlorpromazine concentrations. Phenytoin decreases quetiapine, clozapine, haloperidol and possibly chlorpromazine concentrations. There are major gaps in the data. In many cases there are no published clinical data on interactions that would be predicted on theoretical grounds.

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Acknowledgements

The authors would like to thank the many pharmaceutical companies that provided information on the interactions, which supplemented the literature search. The authors are not aware of any conflicts of interest. The preparation of this paper was not supported by funding from any pharmaceutical company. The authors have attended conferences and given lectures sponsored by a number of different pharmaceutical companies over the years. They have also had past research funding from Fisons, GlaxoSmithKline and Roche.

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  1. Bedfordshire and Luton Partnership NHS Trust, Luton University and Institute of Epileptology, London, UK

    Frank M.C. Besag

  2. Toxicology Unit, Guys and St Thomas’s Hospitals, London, UK

    David Berry

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  1. Frank M.C. Besag
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  2. David Berry
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Correspondence to Frank M.C. Besag.

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Besag, F.M., Berry, D. Interactions between Antiepileptic and Antipsychotic Drugs. Drug-Safety 29, 95–118 (2006). https://doi.org/10.2165/00002018-200629020-00001

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