Drug-Drug Interactions (DDIs) in Psychiatric Practice, Part 9: Interactions Mediated by Drug-metabolizing Cytochrome P450 Enzymes

Abstract

This column is the ninth in a series exploring drug-drug interactions (DDIs) with a special emphasis on psychiatric medications. The first 3 columns in this DDI series discussed why patients being treated with psychiatric medications are at increased risk for taking multiple medications and thus experiencing DDIs, how to recognize such DDIs, strategies for avoiding and/or minimizing adverse outcomes from such DDIs, and pharmacokinetic considerations concerning DDIs in psychiatric practice. The fourth and fifth columns in this series presented a pair of parallel tables, one of which outlined the primary, known mechanism(s) of action of all commonly used psychiatric medications and one of which summarized major types of pharmaco-dynamic DDIs based on mechanism of action. Clinicians can use these 2 tables together to predict pharmacodynamically mediated DDIs. The sixth column discussed key pharmacodynamic interactions involving ethanol, opioids, and monoamine oxidase inhibitors. The seventh and eighth columns presented the concept of relative receptor binding and included tables summarizing the relative receptor binding affinity of currently available antipsychotics and antidepressants, respectively. This ninth and final column in this series discusses pharmacokinetic DDIs with a focus on psychiatric medications and contains 3 tables. The first table is an abbreviated version of a table available online showing which drugs are substrates for which cytochrome P450 (CYP) enzymes and which drugs are inhibitors or inducers of specific CYP enzymes. The abbreviated version of the table presented in this column focuses on psychiatric medications. This table and the larger website version can allow prescribers to anticipate which drug combinations may pose the risk of a CYP enzyme-mediated DDI. The second table summarizes which antidepressants inhibit specific CYP enzymes and which antidepressants do not or are unlikely to inhibit specific CYP enzymes. The third table presents psychiatric medications whose clearance is not principally dependent on CYP enzyme-mediated oxidative metabolism as a necessary step in their clearance from the body. The latter 2 tables inform prescribers as to which drugs they may prefer to use to avoid CYP enzyme-mediated DDIs. The overall goal of this series of columns is to present a simple way of conceptualizing neuropsychiatric medications in terms of their pharmacodynamics and pharmacokinetics to allow prescribers to take these facts into consideration when they need to use ≥2 drugs in combination to optimally treat a patient.