Comparative CYP3A4 Inhibitory Effects of Venlafaxine, Fluoxetine, Sertraline, and Nefazodone in Healthy Volunteers

  title={Comparative CYP3A4 Inhibitory Effects of Venlafaxine, Fluoxetine, Sertraline, and Nefazodone in Healthy Volunteers},
  author={C. Lindsay DeVane and Jennifer L. Donovan and Heidi L. Liston and John Seth Markowitz and Kenneth T. Cheng and Samuel Craig Risch and L. Willard},
  journal={Journal of Clinical Psychopharmacology},
Abstract: An antidepressant for use in the patient receiving concomitant drug treatment, over-the-counter medications, or herbal products should lack cytochrome P-450 (CYP) 3A4 inductive or inhibitory activity to provide the least likelihood of a drug-drug interaction. This study addresses the potential of 4 diverse antidepressants (venlafaxine, nefazodone, sertraline, and fluoxetine) to inhibit or induce CYP3A4. In a 4-way crossover design, 16 subjects received clinically relevant doses of… 
An Evaluation of the Potential of Cytochrome P450 3A4-Mediated Drug-Drug Interactions with Desvenlafaxine Use
Desvenlafaxine is minimally metabolized by CYP3A4 and does not appear to inhibit CYP1A4, and the effect of CYP2A4 inhibition on desvenl Lafaxine metabolism is not known.
Letter: depression and the use of anti‐depressants in patients with chronic liver disease or liver transplantation – authors’ reply
The evidence-based Drug Information System: MICROMEDEX SOLUTIONS Truven Health Analytics Inc. 2015.
"In-vivo" phenotyping of CYP3A using midazolam as probe drug : development of novel approaches based on highly sensitive LC-MS/MS methods
A sensitive LC-MS/MS method was developed and validated allowing for the first time the simultaneous determination of MDZ and two of its metabolites in human OF, and appears to be useful for assessing the CYP3A activity in OF.
New-generation, non-SSRI antidepressants: Drug-drug interactions and therapeutic drug monitoring. Part 2: NaSSAs, NRIs, SNDRIs, MASSAs, NDRIs, and others.
After the development of "classical" tricyclic antidepressants and monoamine oxidase inhibitors, numerous other classes of antidepressant drugs have been introduced onto the market, usually identified by their mechanism of activity.
Selective serotonin reuptake inhibitor drug interactions in patients receiving statins.
  • C. Andrade
  • Medicine, Biology
    The Journal of clinical psychiatry
  • 2014
Elderly patients commonly receive statin drugs for the primary or secondary prevention of cardiovascular and cerebrovascular events and SSRIs for the treatment of depression, anxiety, or other conditions, and a detailed literature review of statin metabolism and of SSRI effects on CYP enzymes suggests that escitalopram, citaloprams, and paroxetine are almost certain to be safe with all statins.
Drugs as CYP3A Probes, Inducers, and Inhibitors
This review systematically summarized the frequently used CYP3A probe drugs, inducers and inhibitors, and evaluated their current status in drug development and research.
In Vitro Inhibition and Induction of Human Liver Cytochrome P450 Enzymes by Milnacipran
Milnacipran is not expected to cause clinically significant P450 inhibition or induction and is distinguished by a nearly 3-fold greater potency in inhibiting norepinephrine reuptake in vitro compared with serotonin.
In vivo Effect of I'm-Yunity™ on Hepatic Cytochrome P450 3A4
Short-term administration of I'm-Yunity™ with medications primarily metabolized by CYP3A4 is safe and not expected to be associated with significant herb-drug interactions, however, it is still unknown whether interactions exist between I's-Y unity™ and other medications metabolizing by other CYP450 isozymes or enzyme/transporter systems.


CYP2D6 Inhibition by Fluoxetine, Paroxetine, Sertraline, and Venlafaxine in a Crossover Study: Intraindividual Variability and Plasma Concentration Correlations
The results demonstrate the potent, but variable, CYP2D6 inhibition of fluxetine and paroxetine compared to sertraline and venlafaxine and may be related, in part, to dose, plasma concentration, and baseline isoenzyme activity.
Venlafaxine: in vitro inhibition of CYP2D6 dependent imipramine and desipramine metabolism; comparative studies with selected SSRIs, and effects on human hepatic CYP3A4, CYP2C9 and CYP1A2.
It is concluded that venlafaxine has a low potential to inhibit the metabolism of substrates for CYP2D6 such as imipramine and desipramines compared with several of the most widely used SSRIs, as well as the metabolism for several ofThe other major human hepatic P450s.
Coadministration of nefazodone and benzodiazepines: III. A pharmacokinetic interaction study with alprazolam.
Because alprazolam concentrations in plasma are increased in the presence of nefazodone, a reduction in alpazolam dosage is recommended when the two agents are coadministered.
Absence of a sertraline-mediated effect on the pharmacokinetics and pharmacodynamics of carbamazepine.
Findings indicate that sertraline does not affect the pharmacokinetics of carbamazepine or its principal metabolite and does not potentiate the cognitive effects of carbazepine.
Dose-response evaluation of the interaction between sertraline and alprazolam in vivo.
It is suggested that sertraline (50-150 mg/day) does not alter the single-dose kinetics or dynamics of alprazolam; therefore, the combination may be prescribed without an increased risk ofAlprazoam toxicity.
Effect of venlafaxine on the pharmacokinetics of alprazolam.
Overall, venlafaxine did not inhibit the CYP3A4-mediated metabolism of alprazolam in vivo, which corroborates other in vitro and in vivo data showing a lack of CYP 3A4 inhibition with venl Lafaxine.
A pharmacokinetic drug-drug interaction study of venlafaxine and indinavir.
As the plasma concentration of protease inhibitors is a critical factor in maintaining efficacy and minimizing the potential for viral resistance, the decrease in both AUC and Cmax of indinavir from coadministration of venlafaxine is of concern.
Venlafaxine and metabolites are very weak inhibitors of human cytochrome P450-3A isoforms
Pharmacokinetic pharmacodynamic evaluation of the combined administration of alprazolam and fluoxetine
Increased patient monitoring and patient education is recommended when alprazolam and fluoxetine are prescribed concurrently, as when any two psychoactive drugs are administered together.
Coadministration of nefazodone and benzodiazepines: IV. A pharmacokinetic interaction study with lorazepam.
Overall, no change in LOR or NEF dosage is necessary when the two drugs are coadministered, and the absence of an interaction appears to be attributable to LOR's metabolic clearance being dependant on conjugation rather than hydroxylation.