Clinical significance of pharmacokinetic interactions between antiepileptic and psychotropic drugs

Edoardo Spina, Emilio Perucca

Research output: Contribution to journalArticle

Abstract

As antiepileptic drugs (AEDs) and psychotropic agents are increasingly used in combination, the possibility of pharmacokinetic interactions between these compounds is relatively common. Most pharmacokinetic interactions between AEDs and psychoactive drugs occur at a metabolic level, and usually involve changes in the activity of the cytochrome P450 mixed-function oxidases (CYP) involved in their biotransformation. As a consequence of CYP inhibition or induction, plasma concentrations of a given drug may reach toxic or subtherapeutic levels, and dosage adjustments may be required to avoid adverse effects or clinical failure. Enzyme-inducing AEDs, such as carbamazepine (CBZ), phenytoin (PHT), and barbiturates, stimulate the oxidative biotransformation of many concurrently prescribed psychotropics. In particular, these AEDs may decrease the plasma concentrations of tricyclic antidepressants, many antipsychotics, including traditional compounds, i.e., haloperidol and chlorpromazine, and newer agents, i.e., clozapine, risperidone, olanzapine, quetiapine, and ziprasidone, and some benzodiazepines. Conversely, new AEDs appear to have a lower potential for interactions with all psychotropic drugs. While antipsychotics and anxiolytics do not significantly influence the pharmacokinetics of most AEDs, some newer antidepressants, such as viloxazine, fluoxetine, and fluvoxamine, may lead to higher serum levels of some AEDs, namely CBZ and PHT, through inhibition of CYP enzymes. No significant pharmacokinetic interactions have been documented between AEDs and lithium. Information about CYP enzymes responsible for the biotransformation of individual agents and about the effects of these compounds on the activity of specific CYP enzymes may help in predicting and avoiding clinically significant interactions. Apart from careful clinical observation, serum level monitoring of AEDs and psychotropic drugs can be useful in determining the need for dosage adjustments, especially if there is any change in seizure control, or possible toxicity.

Original languageEnglish
Pages (from-to)37-44
Number of pages8
JournalEpilepsia
Volume43
Issue numberSUPPL. 2
Publication statusPublished - 2002

Fingerprint

Psychotropic Drugs
Anticonvulsants
Pharmacokinetics
Biotransformation
Carbamazepine
Phenytoin
Enzymes
olanzapine
Antipsychotic Agents
Viloxazine
Fluvoxamine
Barbiturates
Risperidone
Clozapine
Tricyclic Antidepressive Agents
Fluoxetine
Poisons
Anti-Anxiety Agents
Chlorpromazine
Haloperidol

Keywords

  • Antidepressants
  • Antiepileptics
  • Antipsychotics
  • Anxiolytics
  • Cytochrome P450
  • Lithium
  • Pharmacokinetic interactions

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Clinical significance of pharmacokinetic interactions between antiepileptic and psychotropic drugs. / Spina, Edoardo; Perucca, Emilio.

In: Epilepsia, Vol. 43, No. SUPPL. 2, 2002, p. 37-44.

Research output: Contribution to journalArticle

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