The Influence of Combined CYP2D6 and CYP2C19 Genotypes on Venlafaxine and O-Desmethylvenlafaxine Concentrations in a Large Patient Cohort.

Abstract:

PURPOSE:The antidepressant venlafaxine is largely O-desmethylated by CYP2D6, whereas CYP2C19 mediates an alternative metabolic route of venlafaxine through N-desmethylation. The aim of this study was to investigate the combined effect of genotype-predicted CYP2D6 and CYP2C19 phenotypes on serum concentrations of venlafaxine and metabolites in a large patient population. METHODS:Patients were retrospectively included from a therapeutic drug monitoring service at Diakonhjemmet Hospital in Oslo (Norway) between January 01, 2007, and December 31, 2017. The study population was divided into different phenotype subgroups according to the combinations of CYP2D6/CYP2C19 phenotypes; intermediate metabolizers (IMs), poor metabolizers (PMs) and ultrarapid metabolizers, and compared using combined normal metabolizers (NMs) as reference. FINDINGS:The dose-adjusted serum concentration of venlafaxine was 4- and 13-fold increased in combined CYP2D6 IM/CYP2C19 PMs and combined PMs, respectively, compared with combined NMs (P < 0.001). The sum concentration of venlafaxine + ODV (pharmacological active moiety) was increased 1.9 and 3.6-fold, respectively, in the same phenotype groups. Furthermore, the dose-adjusted active moiety exposure was similar in combined IMs as combined CYP2D6 PM/CYP2C19 NMs. CYP2D6 and CYP2C19 phenotypes explained 46% of the interindividual variability in dose-adjusted venlafaxine serum concentrations, whereas CYP2D6 alone explained 24%. CONCLUSIONS:The combined CYP2D6/CYP2C19 phenotype has a significant impact on serum concentrations of venlafaxine and also on the active moiety of venlafaxine + ODV, than CYP2D6 alone. In clinical practice, it is therefore important to take into account phenotype variabilities of both enzymes when assessing the risk of dose-dependent adverse effects during venlafaxine treatment.

journal_name

J Clin Psychopharmacol

authors

Kringen MK,Bråten LS,Haslemo T,Molden E

doi

10.1097/JCP.0000000000001174

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

137-144

issue

2

eissn

0271-0749

issn

1533-712X

pii

00004714-202003000-00006

journal_volume

40

pub_type

杂志文章
  • Effects of acute doses of prosocial drugs methamphetamine and alcohol on plasma oxytocin levels.

    abstract::Many drugs, including alcohol and stimulants, demonstrably increase sociability and verbal interaction and are recreationally consumed in social settings. One drug, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), seems to produce its prosocial effects by increasing plasma oxytocin levels, and the oxytocin system ha...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1097/JCP.0000000000000314

    authors: Bershad AK,Kirkpatrick MG,Seiden JA,de Wit H

    更新日期:2015-06-01 00:00:00

  • Lack of pharmacologic interaction between paroxetine and alprazolam at steady state in healthy volunteers.

    abstract::This investigation aimed to provide evidence on the lack of pharmacokinetic interaction of paroxetine (20 mg/d) and alprazolam (1 mg/d) in combined therapy. In addition, the central effects of both drugs when administered alone and in combination were assessed to rule out any relevant synergistic depressant central ef...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/01.jcp.0000125689.05091.c6

    authors: Calvo G,García-Gea C,Luque A,Morte A,Dal-Ré R,Barbanoj M

    更新日期:2004-06-01 00:00:00

  • A Pilot Study of a Topical Intervention for Treatment of Female Sexual Dysfunction.

    abstract:PURPOSE/BACKGROUND:Many investigators reported that pharmacological treatment of female sexual dysfunction (FSD) has been a promising field yet to be explored. The purpose of this pilot study was to investigate the efficacy and safety of a topical cream containing small concentrations of three vasodilators with differe...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1097/JCP.0000000000000811

    authors: Gomaa AA,Abdel Aziz NM,Thabet RH,Fouly HA,Altellawy SH,Gomaa GA

    更新日期:2018-02-01 00:00:00

  • Clonidine improves hyperarousal in borderline personality disorder with or without comorbid posttraumatic stress disorder: a randomized, double-blind, placebo-controlled trial.

    abstract::The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition borderline personality disorder (BPD) seems to constitute a very heterogeneous category. Therefore, pharmacological therapy is symptom-oriented or targets comorbid conditions. A high comorbidity exists between BPD and posttraumatic stress disord...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1097/JCP.0b013e31819a4bae

    authors: Ziegenhorn AA,Roepke S,Schommer NC,Merkl A,Danker-Hopfe H,Perschel FH,Heuser I,Anghelescu IG,Lammers CH

    更新日期:2009-04-01 00:00:00

  • Optimizing early prediction for antipsychotic response in schizophrenia.

    abstract:OBJECTIVE:Researchers, by studying first-generation antipsychotics, have established an early prediction model, which had a favorable specificity but a low sensitivity. This study aims to optimize early prediction of treatment response for schizophrenia using a novel statistic method that can be done even under the Mic...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1097/01.jcp.0000246211.95905.8c

    authors: Chang YC,Lane HY,Yang KH,Huang CL

    更新日期:2006-12-01 00:00:00

  • Clozapine and global cognition in schizophrenia.

    abstract:OBJECTIVE:Clozapine (CLZ) has been shown to have a beneficial effect on cognition in schizophrenia in some studies and a detrimental effect in others. The relative effect and exposure to CLZ and its major metabolite-N-desmethylclozapine (NDMC)-could explain these discrepancies. METHODS:Using a validated measure of glo...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 杂志文章

    doi:10.1097/JCP.0b013e3181e69060

    authors: Rajji TK,Uchida H,Ismail Z,Ng W,Mamo DC,Remington G,Pollock BG,Mulsant BH

    更新日期:2010-08-01 00:00:00

  • Evaluation of the Relationship Between Pharmacokinetics and the Safety of Aripiprazole and Its Cardiovascular Effects in Healthy Volunteers.

    abstract:AIMS:The aim of this study was the evaluation of the possible relationship between pharmacokinetics and the safety of aripiprazole as well as its influence on blood pressure (BP), heart rate (HR), and corrected QT (QTc) interval. METHODS:The study population comprised 157 healthy volunteers from 6 bioequivalence clini...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 杂志文章

    doi:10.1097/JCP.0000000000000577

    authors: Belmonte C,Ochoa D,Román M,Cabaleiro T,Talegón M,Sánchez-Rojas SD,Abad-Santos F

    更新日期:2016-12-01 00:00:00

  • Comparison of the Metabolic Characteristics of Newer Second Generation Antipsychotics: Brexpiprazole, Lurasidone, Asenapine, Cariprazine, and Iloperidone With Olanzapine as a Comparator.

    abstract:PURPOSE/BACKGROUND:Extensive research has been conducted comparing the metabolic characteristics of older second-generation antipsychotics (SGAs); minimal data exist comparing the long-term metabolic effects of SGAs approved in the last 10 years. METHODS/PROCEDURES:A retrospective chart review of patients treated with...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 杂志文章

    doi:10.1097/JCP.0000000000001318

    authors: Greger J,Aladeen T,Lewandowski E,Wojcik R,Westphal E,Rainka M,Capote H

    更新日期:2021-01-01 00:00:00

  • Effects of Intranasal Oxytocin Administration on Sexual Functions in Healthy Women: A Laboratory Paradigm.

    abstract:PURPOSE:The neuropeptide oxytocin (OXT) has a variety of physiological functions in maternal behavior and attachment including sexual behavior. Based on animal research and our previous human studies, we set out to investigate intranasal administration of OXT and hypothesized that OXT should be able to modulate sexual ...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1097/JCP.0000000000000863

    authors: Kruger THC,Deiter F,Zhang Y,Jung S,Schippert C,Kahl KG,Heinrichs M,Schedlowski M,Hartmann U

    更新日期:2018-06-01 00:00:00

  • Lithium poisoning: pharmacokinetics and clearance during different therapeutic measures.

    abstract::The clinical features and pharmacokinetics of 22 lithium overdoses are described. Effectiveness of different treatment regimens regarding elimination of lithium is discussed. Origin of overdose was due to deliberate poisoning or precipitated by concomitant diseases, coadministration of drugs, or combination of both. T...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 杂志文章

    doi:10.1097/01.jcp.0000218405.02738.b3

    authors: Eyer F,Pfab R,Felgenhauer N,Lutz J,Heemann U,Steimer W,Zondler S,Fichtl B,Zilker T

    更新日期:2006-06-01 00:00:00

  • Nifedipine in the treatment of tardive dyskinesia.

    abstract::There have been several case reports of improvement in tardive dyskinesia (TD) after treatment with calcium-blocking agents. We have conducted prior single-blind (rater-blind) studies of verapamil and diltiazem and found a statistically significant improvement in TD with verapamil, and a small improvement that did not...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1097/00004714-199010060-00006

    authors: Duncan E,Adler L,Angrist B,Rotrosen J

    更新日期:1990-12-01 00:00:00

  • Insulin Resistance-Related Proteins Are Overexpressed in Patients and Rats Treated With Olanzapine and Are Reverted by Pueraria in the Rat Model.

    abstract:BACKGROUND:Olanzapine, a commonly used second-generation antipsychotic, causes severe metabolic adverse effects, such as elevated blood glucose and insulin resistance (IR). Previous studies have proposed that overexpression of CD36, GGPPS, PTP-1B, GRK2, and adipose triglyceride lipase may contribute to the development ...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 杂志文章

    doi:10.1097/JCP.0000000000001028

    authors: Yang N,Li S,Liu S,Lv Y,Yu L,Deng Y,Li H,Fang M,Huo Y,Li W,Peng S

    更新日期:2019-05-01 00:00:00

  • Interrater reliability of the modified Monitoring of Side Effects Scale for assessment of adverse effects of psychiatric medication in clinical and research settings.

    abstract::The assessment of adverse effects of psychiatric medications is important in clinical and research settings because they are often associated with medication discontinuation, symptom exacerbation, and reduced quality of life. Currently available assessment tools are either limited with regard to the number and variety...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 杂志文章

    doi:10.1097/JCP.0000000000000311

    authors: Nugent KL,Spahr E,Toroney J,Mojtabai R,Nettles C,Turner LW,Fenton A,Spivak A,Cullen BA,Everett A,Eaton WW

    更新日期:2015-06-01 00:00:00

  • Trends in the adoption of medications for alcohol dependence.

    abstract::Increasing attention is being paid to the development and dissemination of effective pharmacotherapies for the treatment of alcohol and other drug dependence. However, numerous structural and philosophical barriers impede the widespread adoption of these treatment approaches in everyday clinical practice. Research is ...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 杂志文章,meta分析,评审

    doi:10.1097/01.jcp.0000246209.18777.14

    authors: Ducharme LJ,Knudsen HK,Roman PM

    更新日期:2006-12-01 00:00:00

  • Comparative abuse liability of intravenously administered remifentanil and fentanyl.

    abstract::Remifentanil is a short-acting, esterase-metabolized opioid analgesic. This study compared the abuse liability of remifentanil with that of fentanyl and placebo in a randomized, double-blind, crossover study. Twelve recreational users of opioids received increasing doses of remifentanil (0.6, 1.2, 1.8, 2.4, and 3.0 mi...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00004714-200012000-00002

    authors: Baylon GJ,Kaplan HL,Somer G,Busto UE,Sellers EM

    更新日期:2000-12-01 00:00:00

  • Comparison of physician-rating and self-rating scales for patients with major depressive disorder.

    abstract::Physician-rating scales remain the standard in antidepressant clinical trials. The current study aimed to examine the discrepancies between physician-rating scales and self-rating scales for symptoms and functioning, before and after treatment, in newly hospitalized patients. A total of 131 acutely ill inpatients with...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1097/JCP.0000000000000229

    authors: Lin CH,Lu MJ,Wong J,Chen CC

    更新日期:2014-12-01 00:00:00

  • Exploring Nitrous Oxide as Treatment of Mood Disorders: Basic Concepts.

    abstract::Nitrous oxide (laughing gas) has shown early promise as a rapidly acting antidepressant in patients with treatment-resistant major depression and is currently investigated in several clinical trials. Because nitrous oxide is rarely administered outside operating rooms or dental practices, most psychiatrists are not fa...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 杂志文章,评审

    doi:10.1097/JCP.0000000000000837

    authors: Nagele P,Zorumski CF,Conway C

    更新日期:2018-04-01 00:00:00

  • Pharmacokinetics of benzodiazepines and psychostimulants in children.

    abstract::The pharmacokinetics of benzodiazepines and psychostimulants are reviewed and an overview of the kinetic principles relevant to the utilization of these drugs in infancy and childhood is provided. Newborns and premature infants can metabolize and eliminate diazepam, although the parent drug has a longer half-life and ...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 杂志文章

    doi:

    authors: Coffey B,Shader RI,Greenblatt DJ

    更新日期:1983-08-01 00:00:00

  • Cholinergic challenges in affective illness: behavioral and neuroendocrine correlates.

    abstract::The cholinergic-adrenergic balance hypothesis of affective disorders suggests that, in the areas of the brain that regulate mood, depression may represent a relative predominance of central cholinergic tone over adrenergic tone and that mania may represent the converse. Currently, converging lines of investigation fro...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1097/00004714-198107000-00003

    authors: Risch SC,Kalin NH,Janowsky DS

    更新日期:1981-07-01 00:00:00

  • Methamphetamine self-administration in humans during D-amphetamine maintenance.

    abstract::Agonist replacement may be a viable treatment approach for managing stimulant use disorders. This study sought to determine the effects of D-amphetamine maintenance on methamphetamine self-administration in stimulant using human participants. We predicted that D-amphetamine maintenance would reduce methamphetamine sel...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 杂志文章

    doi:10.1097/JCP.0000000000000207

    authors: Pike E,Stoops WW,Hays LR,Glaser PE,Rush CR

    更新日期:2014-12-01 00:00:00

  • Dose-ranging kinetics and behavioral pharmacology of naltrexone and acamprosate, both alone and combined, in alcohol-dependent subjects.

    abstract::We examined kinetic and dynamic factors to determine the pharmacological and behavioral safety and tolerability of low versus high doses of an opiate antagonist, naltrexone (50 mg/day vs. 100 mg/day), and acamprosate (2 g/day vs. 3 g/day), a functional N-methyl-D-aspartate receptor antagonist, both independently and c...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/01.jcp.0000084029.22282.bb

    authors: Johnson BA,O'Malley SS,Ciraulo DA,Roache JD,Chambers RA,Sarid-Segal O,Couper D

    更新日期:2003-06-01 00:00:00

  • Blood pressure and heart rate response of panic disorder patients receiving imipramine in a dose-response treatment paradigm.

    abstract::This article reports the effects of imipramine on heart rate and blood pressure in panic disorder patients who participated in an 8-week double-blind dosage response treatment protocol. At the end of a placebo baseline, patients were randomly assigned to placebo or one of three weight-adjusted imipramine dosages: low ...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:

    authors: de Groot CM,Mavissakalian MR

    更新日期:1994-04-01 00:00:00

  • The Utility of Low-Dose Aripiprazole for the Treatment of Bipolar II and Bipolar NOS Depression.

    abstract:BACKGROUND:Despite initial reports of efficacy in bipolar depression, multicenter trials did not show aripiprazole to be better than placebo, possibly because the doses used were too high, leading to lower efficacy and high dropout rates. This study evaluated the effects of low-dose aripiprazole. Extensive clinical exp...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 杂志文章

    doi:10.1097/JCP.0000000000000636

    authors: Kelly T,Lieberman DZ

    更新日期:2017-02-01 00:00:00

  • Venlafaxine extended release in posttraumatic stress disorder: a sertraline- and placebo-controlled study.

    abstract::This 12-week, double-blind, multicenter trial evaluated the efficacy of venlafaxine extended release (ER), sertraline, and placebo in adult outpatients (N = 538) with a primary diagnosis of posttraumatic stress disorder (PTSD), as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, sy...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1097/01.jcp.0000222514.71390.c1

    authors: Davidson J,Rothbaum BO,Tucker P,Asnis G,Benattia I,Musgnung JJ

    更新日期:2006-06-01 00:00:00

  • Duloxetine in the treatment of depression: a double-blind placebo-controlled comparison with paroxetine.

    abstract:CONTEXT:Major depressive disorder causes significant morbidity and mortality. Current therapies fail to fully treat both emotional and physical symptoms of major depressive disorder. OBJECTIVE:To evaluate duloxetine, a dual reuptake inhibitor of serotonin and norepinephrine, on improvement of emotional and painful phy...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.1097/01.jcp.0000132448.65972.d9

    authors: Goldstein DJ,Lu Y,Detke MJ,Wiltse C,Mallinckrodt C,Demitrack MA

    更新日期:2004-08-01 00:00:00

  • Malpractice and tardive dyskinesia: a conceptual dilemma.

    abstract::This discussion focuses on three basic areas relevant to tardive dyskinesia (TD). The first area includes an overview of some specific acts of negligence that have been the basis for successful malpractice cases involving TD. Some of these acts of negligence include inappropriate assessment of the patient, failure to ...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 杂志文章,评审

    doi:10.1097/00004714-198808001-00014

    authors: Tancredi LR

    更新日期:1988-08-01 00:00:00

  • Paliperidone Palmitate Once-Monthly Injectable Treatment for Acute Exacerbations of Schizoaffective Disorder.

    abstract::The optimal treatment for schizoaffective disorder (SCA) is not well established. In this initial 6-month open-label treatment period of a large, multiphase, relapse-prevention study, the efficacy and safety of paliperidone palmitate once-monthly (PP1M) injectable were evaluated in subjects with symptomatic SCA. Subje...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 杂志文章

    doi:10.1097/JCP.0000000000000535

    authors: Fu DJ,Turkoz I,Simonson RB,Walling D,Schooler N,Lindenmayer JP,Canuso C,Alphs L

    更新日期:2016-08-01 00:00:00

  • Effects of aripiprazole on insight and subjective experience in individuals with an at-risk mental state.

    abstract:INTRODUCTION:Although medication with antipsychotic for the psychosis prodrome has often caused some ethical issues, recent studies have shown that some novel antipsychotics are safer and more tolerable for young people. This study aimed to investigate whether the administration of aripiprazole would not only relieve t...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1097/JCP.0b013e3181b2fe22

    authors: Kobayashi H,Morita K,Takeshi K,Koshikawa H,Yamazawa R,Kashima H,Mizuno M

    更新日期:2009-10-01 00:00:00

  • Coadministration of fluvoxamine increases serum concentrations of haloperidol.

    abstract::Four patients with chronic schizophrenia were treated with a combination of fluvoxamine, haloperidol, and benztropine. The combination significantly impaired performance on tests of delayed recall memory and attentional function. Haloperidol concentrations in serum were monitored in three patients and were robustly el...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:

    authors: Daniel DG,Randolph C,Jaskiw G,Handel S,Williams T,Abi-Dargham A,Shoaf S,Egan M,Elkashef A,Liboff S

    更新日期:1994-10-01 00:00:00

  • Olanzapine plasma concentrations and clinical response in acutely ill schizophrenic patients.

    abstract::Olanzapine is an atypical antipsychotic effective in the treatment of schizophrenic patients. After a 2- to 9-day placebo lead-in, 79 inpatients with schizophrenia according to DSM-III-R criteria were placed on an olanzapine dosage of 10 mg/day or 1 mg/day for up to 6 weeks. Blood samples were obtained weekly during t...

    journal_title:Journal of clinical psychopharmacology

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1097/00004714-199712000-00006

    authors: Perry PJ,Sanger T,Beasley C

    更新日期:1997-12-01 00:00:00