Clinically significant drug interactions with newer antidepressants

After the introduction of selective serotonin reuptake inhibitors (SSRIs),other newer antidepressants with different mechanisms of action have beenintroduced in clinical practice. Because antidepressants are commonlyprescribed in combination with other medications used to treat co-morbidpsychiatric or somatic disorders, they are likely to be involved in clinicallysignificant drug interactions. This review examines the drug interaction profilesof the following newer antidepressants: escitalopram, venlafaxine, desvenlafaxine,duloxetine, milnacipran, mirtazapine, reboxetine, bupropion,agomelatine and vilazodone.In general, by virtue of a more selective mechanism of action and receptorprofile, newer antidepressants carry a relatively low risk for pharmacodynamicdrug interactions, at least as compared with first-generation antidepressants,i.e. monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressantsREVIEWARTICLE CNS Drugs 2012; 26 (1): 39-671172-7047/12/0001-0039/$49.95/0ª 2012 Adis Data Information BV. All rights reserved.(TCAs). On the other hand, they are susceptible to pharmacokinetic druginteractions. All new antidepressants are extensively metabolized in the liverby cytochrome P450 (CYP) isoenzymes, and therefore may be the target ofmetabolically based drug interactions. Concomitant administration of inhibitorsor inducers of the CYP isoenzymes involved in the biotransformationof specific antidepressants may cause changes in their plasma concentrations.However, due to their relatively wide margin of safety, the consequences ofsuch kinetic modifications are usually not clinically relevant. Conversely, somenewer antidepressants may cause pharmacokinetic interactions through theirability to inhibit specific CYPs.With regard to this, duloxetine and bupropionare moderate inhibitors of CYP2D6. Therefore, potentially harmful drug interactionsmay occur when they are coadministered with substrates of theseisoforms, especially compounds with a narrow therapeutic index. The othernew antidepressants are only weak inhibitors or are not inhibitors of CYPisoforms at usual therapeutic concentrations and are not expected to affect thedisposition of concomitantly administered medications.Although drug interactions with newer antidepressants are potentially, butrarely, clinically significant, the use of antidepressants with a more favourabledrug interaction profile is advisable. Knowledge of the interaction potential ofindividual antidepressants is essential for safe prescribing and may help cliniciansto predict and eventually avoid certain drug combinations.