Clinically relevant interactions between newer antidepressants and second-generation antipsychotics

Abstract

More PK DI studies are needed to better establish dose correction factors after adding fluoxetine and paroxetine to aripiprazole, iloperidone and risperidone. Further PK DI studies and case reports are also needed to better establish the need for dose correction factors after adding i) fluoxetine to clozapine, lurasidone, quetiapine and olanzapine; ii) paroxetine to olanzapine; iii) fluvoxamine to asenapine, aripiprazole, iloperidone, lurasidone, olanzapine, quetiapine and risperidone; iv) high sertraline doses to aripiprazole, clozapine, iloperidone and risperidone: v) bupropion and duloxetine to aripiprazole, clozapine, iloperidone and risperidone; and vi) asenapine to paroxetine and venlafaxine. Possible beneficial PD DI effects occur after adding SGAs to newer antidepressants for treatment-resistant major depressive and obsessive-compulsive disorders. The lack of studies combining newer antidepressants and SGAs in psychotic depression is worrisome. PD DIs between newer antidepressants and SGAs may be more likely for mirtazapine and bupropion. Adding selective serotonin reuptake inhibitors and SGAs may increase QTc interval and may very rarely contribute to torsades de pointes.

Investigation of a Potential Pharmacokinetic Interaction Between Nebivolol and Fluvoxamine in Healthy Volunteers

“…This characteristic is linked to their potency for inhibition of cytochrome P450 isoenzymes involved in the hepatic metabolism of most of the drugs (17,24). Alongside fluoxetine and paroxetine, fluvoxamine is considered one of the SSRIs with the highest risk of interaction as it influences the activity of various isoenzymes and perturbs the pharmacokinetics of numerous drugs, like warfarin, diazepam, alprazolam, amitryptiline, clomipramine, clozapine, imipramine, mexiletine or thioridazine (18,25,26). and heart rate (HR-c) measured at rest, following oral administration of single-dose 5 mg nebivolol (NEB), before (□) and after fluvoxamine (FLV) pretreatment (▲) for 6 days (50-100 mg/day), in 18 healthy volunteers (extensive metabolizersEMs).…”

“…As mentioned previously, in view of the fact that depression can often coexist with cardiovascular disease and its associated risk factors, including hypertension (27), the present study aimed to investigate whether fluvoxamine, a weak inhibitor of CYP2D6 (18), has an impact upon the pharmacokinetics of nebivolol, a cardiovascular drug that is a substrate of the same metabolic pathway. The potential pharmacokinetic drug interaction between nebivolol and fluvoxamine was investigated in volunteers considered to be EMs.…”

“…With a nonlinear pharmacokinetics, fluvoxamine undergoes hepatic biotransformation through oxidative demethylation and oxidative deamination resulting in inactive metabolites (17). Most importantly, a great concern lies in the potential interactions of fluvoxamine, as it is known to be a potent inhibitor of CYP1A2 and CYP2C19, a moderate inhibitor of CYP2C9 and CYP3A4, and a weak inhibitor of CYP2D6 (18).…”

Lurasidone drug-drug interaction studies: a comprehensive review

“…It has been estimated that this enzyme metabolizes 50% of marketed drugs [15], including many psychotropic medications such as antidepressants and antipsychotic agents [16,17]. Circulating plasma/serum concentrations of such drugs may be influenced by coadministration of drugs that inhibit or induce CYP3A4 [18].…”

Efectos de los inductores antiepilépticos en la neuropsicofarmacología: una cuestión ignorada. Parte II: cuestiones farmacológicas y comprensión adicional

“…Para confundir aún más la historia de CYP3A5, la relevancia de su polimorfismo puede variar de un fármaco a otro, no habiéndose establecido de manera definitiva 34 . dosificación de los ATC, basadas en la genotipificación del CYP2D6 y el CYP2C19 7 . Con los antipsicóticos y los antidepresivos de segunda generación, la genotipificación de los CYP es menos útil, ya que poseen rutas metabólicas muy diferentes 9,13,39 . Se ha recomendado realizar correcciones de dosificación, conforme a la genotipificación del CYP2D6 para venlafaxina, aripiprazol, risperidona, zuclopentixol y atomoxetina 29 .…”