Drug-drug interactions between antiseizure medications and antipsychotic medications: a narrative review and expert opinion

ABSTRACT

Introduction

Antiseizure medications (ASMs) and antipsychotic drugs are frequently coadministered with the potential for drug-drug interactions. Interactions may either be pharmacokinetic or pharmacodynamic, resulting in a decrease or increase in efficacy and/or an increase or decrease in adverse effects.

Areas covered

The clinical evidence for pharmacokinetic and pharmacodynamic interactions between ASMs and antipsychotics is reviewed based on the results of a literature search in MEDLINE conducted in April 2023.

Expert opinion

There is now extensive published evidence for the clinical importance of interactions between ASMs and antipsychotics. Enzyme-inducing ASMs can decrease blood concentrations of many of the antipsychotics. There is also evidence that enzyme-inhibiting ASMs can increase antipsychotic blood concentrations. Similarly, there is limited evidence showing that antipsychotic drugs may affect the blood concentrations of ASMs through pharmacokinetic interactions. There is less available evidence for pharmacodynamic interactions, but these can also be important, as can displacement from protein binding. The lack of published evidence for an interaction should not be interpreted as meaning that the given interaction does not occur; the evidence is building continually. There is no substitute for careful patient monitoring and sound clinical judgment.

KEYWORDS:

• Antiseizure medication
• antipsychotic
• pharmacokinetic
• pharmacodynamic
• metabolism
• CYP450
• uridine diphosphate glucuronosyltransferase (UGT)
• efficacy

Article highlights

• Enzyme-inducing ASMs, such as carbamazepine, phenytoin and phenobarbital decrease the blood concentrations of several antipsychotic medications.

• Enzyme-inhibiting ASMs can increase the blood concentrations of antipsychotic medications, although the clinical evidence is somewhat limited.

• Pharmacodynamic interactions between ASMs and antipsychotic medications can also be important, although the published evidence for these remains very limited.

• Adding a medication that is extensively (typically >90%) protein bound can potentially increase free blood concentrations; however, these will clear faster causing little change in efficacy or adverse effects from the initial medication.

• Careful patient monitoring, taking into account both clinical and theoretical interactions, remains important, with the constant aim of achieving the therapeutic goals while maintaining patient safety.

Declarations of interest

P Patsalos is an associate editor of Epilepsia and Therapeutic Drug Monitoring. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17425255.2023.2278676

Additional information

Funding

This paper was not funded.