CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine

@article{Shams2006CYP2D6PA,
  title={CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine},
  author={Mohamed E. E. Shams and Borros M Arneth and Christoph Hiemke and Aleksandra Dragi{\vc}evi{\'c} and M. J. M{\"u}ller and R. Kaiser and K. Lackner and Sebastian H{\"a}rtter},
  journal={Journal of Clinical Pharmacy and Therapeutics},
  year={2006},
  volume={31}
}
Background:  Venlafaxine (V) is a mixed serotonin and noradrenaline reuptake inhibitor used as a first‐line treatment of depressive disorders. It is metabolized primarily by the highly polymorphic cytochrome P450 (CYP) enzyme CYP2D6 to yield a pharmacologically active metabolite, O‐desmethylvenlafaxine (ODV), and to a lesser extent by CYP3A4, to yield N‐desmethylvenlafaxine (NDV). 
Severe tremor after cotrimoxazole-induced elevation of venlafaxine serum concentrations in a patient with major depressive disorder.
TLDR
The observed overall pharmacokinetic effect was most probably the result of decreased N-demethylation of venlafaxine by (1) reduced expression of CYP2C19 due to a genetic deficit and (2) inhibition of CYp2C9 by cotrimoxazole.
The role of the poor metabolizer genotype CYP2D6 and CYP1A2 phenotype in the pharmacokinetics of duloxetine and venlafaxine—A case report
TLDR
The polymorphism of the enzyme results in poor, intermediate, extensive or ultrarapid metabolizers of CYP2D6 drugs.
Chapter 5 Depressive effect of an antidepressant : therapeutic failure of venlafaxine in a case lacking CYP 2 D 6 activity
TLDR
This case highlights the potential benefit of both clinical and genetic risk stratification (pharmacogenetics) prior to treatment, either for setting the individual dose or for making a decision about using a particular drug.
PharmGKB summary: venlafaxine pathway
TLDR
Venlafaxine is a serotonin–norepinephrine reuptake inhibitor marketed for the treatment of depression disorders and consists of a racemic mixture of R(+) and S(−) enantiomer, which has been shown to show greater serotonin reuptakes inhibition property.
Depressive effect of an antidepressant: therapeutic failure of venlafaxine in a case lacking CYP2D6 activity
TLDR
Results indicated that the patient was a poor metabolizer for CYP2D6, the most important phase I enzyme to metabolize venlafaxine, corroborates that polymorphisms in the CYP450 gene influence the metabolic activity of the corresponding enzymes, thus affecting the subsequent serum drug levels and their metabolites.
Antidepressant Treatment and Altered CYP2D6 Activity: Are Pharmacokinetic Variations Clinically Relevant?
TLDR
This literature review describes the clinical and empirical evidence indicating that alterations in CYP2D6 activity can negatively affect treatment outcomes in patients receiving antidepressant pharmacotherapies that are CYP 2D6 substrates and proposes a strategy to allow for stratification of treatment outcomes by CYP1D6 metabolizer status.
Palpitations and Asthenia Associated with Venlafaxine in a CYP2D6 Poor Metabolizer and CYP2C19 Intermediate Metabolizer
TLDR
It is proposed that the palpitations and asthenia are related to sustained VEN exposure due to reduced metabolism, and the patient takes VEN extended release 150 mg twice daily.
Influence of CYP2D6 and CYP2C19 gene variants on antidepressant response in obsessive-compulsive disorder
TLDR
This study is the first to indicate that CYP genes may have a role in antidepressant response in OCD and more research is required for a future clinical application of genetic testing, which could lead to improved treatment outcomes.
Polymorphism of Human Cytochrome P450 2D6 and Its Clinical Significance
TLDR
There is a considerable variability in the CYP2D6 allele distribution among different ethnic groups, resulting in variable percentages of PMs, IMs, EMs and UMs in a given population and the number of alleles is still growing.
Desvenlafaxine : Frequently Asked Questions
TLDR
Since February 2008 when desvenlafaxine first came to market, clinicians have wondered about the differences between this new antidepressant and venlafAXine extended release (ER).
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TLDR
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TLDR
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TLDR
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TLDR
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