Clinically significant pharmacokinetic drug interactions with psychoactive drugs: Antidepressants and antipsychotics and the cytochrome P450 system

Abstract

Psychotherapeutic drugs (antipsychotics and antidepressants) are widely used for treating anxiety. Many psychotherapeutic drugs are metabolized mainly by cytochrome P450 (CYP)2C19 and CYP2D6, and are often administered with other drugs. Therefore, it is necessary to be careful when coadministering psychotherapeutic drugs whose metabolism might be inhibited by other drugs. In particular, selective serotonin reuptake inhibitors (SSRIs) inhibit the metabolism of psychotherapeutic drugs mediated by CYP2C19 and CYP2D6. It is useful to phenotype CYP2C19 and CYP2D6 (extensive metabolizers or poor metabolizers) before giving such medication. Knowledge of substrates, inhibitors and inducers of CYP isoenzymes may help clinicians to anticipate and avoid psychotherapeutic drug interactions and improve rational prescribing practices. In addition, genotyping for these drugs may be also useful in preventing side-effects.