Metabolism of Psychotropic Drugs

Abstract

In this chapter, the metabolism of psychotropic drugs is explained. The most important enzymes are the polymorphic cytochrome P450 enzymes CYP2D6, CYP2C19, and CYP2C9. The functional impact of other drug‐metabolizing enzymes including CYP1A2, CYP2A6, CYP2B6, CYP3A4, CYP3A5, and CYP3A7 or phase II enzymes in psychopharmacology is less, but some agents are cleared predominantly by the latter pathways. The clinical importance of drug metabolism is mainly determined by alteration of the individual activity of a relevant drug‐metabolizing enzyme. This is frequently the case in drug–drug interactions leading to enzyme inhibition or enzyme induction. Alternatively, individual patient factors such as pharmacogenetic polymorphisms may contribute to variability in CYP isozyme activity. In this chapter, specific metabolism of antidepressant and antipsychotic drugs is presented for the main CYP enzymes CYP2D6, CYP2C19, CYP2C9, and CYP1A2 and the impact of genetic polymorphisms in these enzymes is pointed out. As many psychotropic drugs are metabolized to equally active metabolites, more than one CYP isoform may be important in metabolism and exposure data of both metabolite and parent drug have to be taken into account. For many antidepressants or antipsychotic drugs, therapeutic drug monitoring is practiced regularly.

The Influence of CYP2D6 and CYP2C19 Genetic Variation on Diabetes Mellitus Risk in People Taking Antidepressants and Antipsychotics

“…Tricyclic antidepressants that are known substrates for CYP2D6 include amitriptyline, clomipramine, duloxetine, and doxepin. SSRIs that are known substrates for CYP2D6 are fluoxetine, fluvoxamine, paroxetine, sertraline, as well as the SNRIs mirtazapine and venlafaxine [10,50]. Several drugs are metabolized through both CYP2C19 and CYP2D6 (e.g., tricyclic antidepressants).…”