Ther Drug Monit ;—8. Wellington K, Perry CM. Venlafaxine extended-release: a review of its use in the management of major depression. Establishing bioequivalence of racemic venlafaxine formulations using stereoselective assay method: is it necessary? Chirality ; Differential physiological effects of a low dose and high doses of venlafaxine in major depression.
Int J Neuropsychopharmacol ;— Severe tremor after cotrimoxazole-induced elevation of venlafaxine serum concentrations in a patient with major depressive disorder. Int Clin Psychopharmacol ;—6. Pharmacogenetics of antidepressants. Front Pharmacol ; Horstmann S, Binder EB. Pharmacogenomics of antidepressant drugs. Pharmacol Ther ;— Pharmacologic approaches to treatment resistant depression: a re-examination for the modern era.
Expert Opin Pharmacother ;— Depressive effect of an antidepressant: therapeutic failure of venlafaxine in a case lacking CYP2D6 activity. Ann Clin Biochem ;— Antidepressant treatment and altered CYP2D6 activity: are pharmacokinetic variations clinically relevant?
J Psychiatry Pract ;—9. Masand PS. Tolerability and adherence issues in antidepressant therapy. Clin Ther ;— The cost of depression — a cost analysis from a large database.
J Affect Disord ;— Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Mol Psychiatry ;— Differentiating antidepressants of the future: efficacy and safety. Pharmacol Ther ; — Pharmacogenetic testing and therapeutic drug monitoring are complementary tools for optimal individualization of drug therapy.
Eur J Clin Pharmacol ;— European Medicines Agency. Summary of product characteristics — Efexor. Available from: www. Accessed on 26 May, Caccia S. Metabolism of the newer antidepressants. An overview of the pharmacological and pharmacokinetic implications.
Clin Pharmacokinet ;— Eur J Clin Pharmacol ;—7. Pharmacokinetics and effect of food on the bioavailability of orally administered venlafaxine. J Clin Pharmacol ;— Optimization and in vivo pharmacokinetic study of a novel controlled release venlafaxine hydrochloride three-layer tablet.
Effects of venlafaxine extended release formulation on the clinical management of patients. Actas Esp Psiquiatr ;— DeVane CL. Immediate-release versus controlled-release formulations: pharmacokinetics of newer antidepressants in relation to nausea. J Clin Psychiatry ;— Distribution and excretion of venlafaxine and O-desmethylvenlafaxine in human milk.
Br J Clin Pharmacol ;— Gentile S. The safety of newer antidepressants in pregnancy and breastfeeding. Drug Saf ;— Pharmacopsychiatry ;— Induction of drug efflux protein expression by venlafaxine but not desvenlafaxine. Biopharm Drug Dispos ;— Wikinski S.
Pharmacokinetic mechanisms underlying resistance in psychopharmacological treatment. The role of P-glycoprotein. Vertex ;— Thuerauf N, Fromm MF. The role of the transporter P-glycoprotein for disposition and effects of centrally acting drugs and for the pathogenesis of CNS diseases. Eur Arch Psychiatry Clin Neurosci ;—6.
Interactions between antidepressants and P-glycoprotein at the blood-brain barrier: clinical significance of in vitro and in vivo findings. Br J Pharmacol ;— Effects on enantiomeric drug disposition and open-field behavior after chronic treatment with venlafaxine in the P-glycoprotein knockout mice model. Psychopharmacology ;— Inhibition of P-glycoprotein by newer antidepressants. J Pharmacol Exp Ther ;— Venlafaxine induces P-glycoprotein in human Caco-2 cells.
Hum Psychopharmacol ;— Genetic polymorphisms of cytochrome P enzymes and antidepressant metabolism. Expert Opin Drug Metab Toxicol ;— Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors.
DOI: Search ADS. Desvenlafaxine succinate: A new serotonin and norepinephrine reuptake inhibitor. Cytochrome P 2D6 phenotype predicts antidepressant efficacy of venlafaxine: a secondary analysis of 4 studies in major depressive disorder.
CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine. Pharmacokinetics of venlafaxine extended release 75 mg and desvenlafaxine 50 mg in healthy CYP2D6 extensive and poor metabolizers: a randomized, open-label, two-period, parallel-group, crossover study. CYP2D6 genotype: impact on adverse effects and nonresponse during treatment with antidepressants-a pilot study.
Comparison of the pharmacokinetics of venlafaxine extended release and desvenlafaxine in extensive and poor cytochrome P 2D6 metabolizers. Pristiq desvenlafaxine extended release tablets [internet]. Cytochrome P 2D6: overview and update on pharmacology, genetics, biochemistry. McKesson Connect [Internet]. Subscription required to view. Drug development and drug interactions: table of substrates, inhibitors and inducers [internet].
Metabolism of the newer antidepressants. An overview of the pharmacological and pharmacokinetic implications. A double-blind, placebo-controlled study of the efficacy and safety of desvenlafaxine succinate in the treatment of major depressive disorder. A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in the treatment of major depressive disorder. Efficacy and tolerability of once-daily venlafaxine extended release XR in outpatients with major depression.
Once-daily venlafaxine extended release XR and venlafaxine immediate release IR in outpatients with major depression. Venlafaxine XR Study Group. Despite the recession's effects on incomes and jobs, the share of people with high medical costs was mostly unchanged [abstract].
Send Email Recipient s will receive an email with a link to 'Key differences between Venlafaxine XR and Desvenlafaxine: An analysis of pharmacokinetic and clinical data' and will not need an account to access the content.
Recipient Optional Message: Optional message may have a maximum of characters. View Metrics. Citing articles via Google Scholar. Latest Most Read Clinical pearls for the monitoring and treatment of antipsychotic induced metabolic syndrome Beth M. Pharmacotherapy treatment of stimulant use disorder Mei T.
Long-term use of antidepressants, mood stabilizers, and antipsychotics in pediatric patients with a focus on appropriate deprescribing Danielle L. Latest Issue Alert. Close Modal.
This site uses cookies. He has no history of diabetes, dyslipidemia, or hypertension. Electrocardiogram holter examination revealed symptoms of skipped beats and heart racing which were associated with sinus rhythm and occasional premature atrial beats. He was in sinus tachycardia at beats per minute with normal intervals and normal axis. There were no other abnormalities.
He has no associated syncope or presyncope. He also underwent a dobutamine stress test. His hemoglobin A1C was borderline elevated at 5. Blood urea nitrogen, creatinine, and urinary profile were all within normal limits. Antinuclear antibodies and other immunology blood testing were unremarkable. Also serum calcium level was slightly elevated at Vitamin D levels were not available; however a pelvic X-ray suggested normal bone mineral density. Genomic testing was performed from a buccal swab sample using a commercial laboratory.
Briefly, genomic DNA was isolated from a buccal swab and the relevant genomic regions were amplified by polymerase chain reaction. Due to reports of cardiotoxicity in VEN overdose and in poor metabolizer patients [ 12 , 13 ], our recommendations included switching the patient to alternative agents.
Antidepressants with alternative metabolic pathways were considered. Desvenlafaxine was recommended since metabolism does not involve catalysis by CYP2D6 [ 16 ]. Other alternatives considered were sertraline or citalopram based on recommendations published by Swen et al.
Additional suggestions were given to gradually tapper down the patient from VEN based on recommendations published by Shelton [ 18 ]. It has been suggested that cardiotoxicity can be expected in patients on VEN and with poor metabolism in the CYP2D6 enzyme [ 12 , 13 ]. ODV is an active metabolite with similar pharmacological activity as the parent drug VEN and a half-life of about 10 hours [ 15 , 21 ]. NDV, a minor metabolite, has been associated with weak norepinephrine and serotonin reuptake inhibition [ 21 ].
Elimination entails biotransformation to ODV. The patient is taking a high dose of the extended release formulation. We posit that the impaired metabolism of VEN and the high dose of medication that the patient is receiving can place the patient at increased risk of experiencing side effects. Multiple reports of cardiotoxicity have been documented in the literature with the use of VEN palpitations, shortness of breath, proarrhythmias, and QT interval prolongation [ 5 , 12 , 26 ].
In a study comparing VEN overdose to overdoses caused by other antidepressants, VEN was significantly associated with higher heart rate [ 27 ].
Also of concern, the patient reported a previous history of QT interval prolongation resolved. A similar pattern was observed in a previous electrocardiogram holter performed over 12 years ago in this patient. The possibility that adalimumab might have a role in the mild tachycardia the patient is experiencing cannot be discarded. However, we propose that the elevated heart rate is associated with high levels of VEN due to the impaired metabolism. Neither lamotrigine nor adalimumab are metabolized by the CYP enzymes.
Lamotrigine is mainly metabolized via glucuronic acid conjugation [ 30 ] and adalimumab seems to be removed by opsonization via the reticuloendothelial system [ 31 ]. Therefore additional impact on VEN metabolism due to drug interactions is not anticipated. The patient also is experiencing severe asthenia. Even though our patient has a significant past medical history of weakness and fatigue, the patient reported worsening of his symptoms after VEN initiation.
Several reports of asthenia in patients on VEN have been published [ 4 , 32 — 35 ]. Asthenia has also been reported in low frequency in patients taking lamotrigine [ 30 ]. It is more likely that the patient is experiencing worsening of asthenia and cardiovascular symptoms as a result of accumulation of VEN.
The authors attributed the unintended death of the subject to VEN high concentration as a result of the reduced metabolic capacity. Based on this forensic case and previous reports in CYP2D6 poor metabolizers, it is tempting to state that our patient is experiencing severe asthenia and palpitations as a result of high plasma levels of VEN due to impaired metabolism.
Unfortunately, these levels were not available and this remains a limitation of this study. In summary, we present a case of severe asthenia and palpitations. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Article of the Year Award: Outstanding research contributions of , as selected by our Chief Editors. Read the winning articles. Journal overview. Academic Editor: Balraj Mittal. Received 14 Apr Revised 25 Aug Accepted 20 Sep Published 16 Oct Abstract Cardiotoxicity has been extensively reported in venlafaxine VEN overdoses. Case Presentation The patient is a year-old Caucasian male with a history of depression and complex posttraumatic stress disorder PTSD that presented for a medical therapy management MTM consult.
Pharmacogenomic Analysis Genomic testing was performed from a buccal swab sample using a commercial laboratory. Conflicts of Interest The authors have no conflicts of interest to report. References J. Hardy, S. Argyropoulos, and D. View at: Google Scholar J. Davidson, D. Baldwin, D.
0コメント