Evidence map›Paper›PMID 23486447›Full record

GuidelineClinical pharmacology and therapeutics2013

Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants.

J K Hicks, J J Swen, C F Thorn, K Sangkuhl, E D Kharasch, V L Ellingrod, T C Skaar, D J Müller, A Gaedigk, J C Stingl and 1 more

Open access · bronzeAbstract readPractice Guideline
PubMed Full text at PMC Publisher
In one paragraph

Guideline in Clinical pharmacology and therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 180 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
180citing papers in PubMed, 8 pooled it
82.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

180 citing papers in PubMed, 8 syntheses or guidelines pooled it, 452 citations in OpenAlex.

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  13. CYP2D6 Genotype Phenotype Discordance Due to Drug-Drug Interaction.Clinical pharmacology and therapeutics · 2018
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120 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 9 institutions in 4 countries.

J K HicksDepartment of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
J J Swen
C F Thorn
K Sangkuhl
E D Kharasch
V L Ellingrod
T C Skaar
D J Müller
A Gaedigk
J C Stingl
Clinical Pharmacogenetics Implementation Consortium
Stanford University · USCentre for Addiction and Mental Health · CAChildren's Mercy Hospital · USFederal Institute for Drugs and Medical Devices · DEIndiana University – Purdue University Indianapolis · USLeiden University Medical Center · NLSt. Jude Children's Research Hospital · USUniversity of Michigan–Ann Arbor · USWashington University in St. Louis · US

Funding

PharmGKB: pharmacogenomics knowledge for precision medicineR24GM061374 · NIGMS · STANFORD UNIVERSITY · PI ALTMAN, RUSS BIAGIO, KLEIN, TERI ELLEN · 2010 to 2018
$25.2M
Pharmacogenomics of Anti-platlet Intervention-2 (PAPI-2) StudyU01HL105198 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI SHULDINER, ALAN R. · 2010 to 2014
$13.6M
PAARK4Kids-Pharmacogenomics of Anticancer Agents Research in ChildrenU01GM092666 · NIGMS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI RELLING, MARY V · 2010 to 2014
$8.9M
Indiana PROSPECTR01HS019818 · AHRQ · INDIANA UNIVERSITY INDIANAPOLIS · PI DEXTER, PAUL · 2010 to 2010
$8.4M
METHADONE AND HIV DRUG INTERACTIONSR01DA014211 · NIDA · WASHINGTON UNIVERSITY · PI KHARASCH, EVAN D. · 2001 to 2012
$4.8M
Folate Pharmacogenomics and Risk of Atypical Antipsychtoic Metabolic Side EffectsR01MH082784 · NIMH · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ELLINGROD, VICKI L · 2008 to 2017
$4.0M
Regulation of drug metabolizing enzymes by miRNAsR01GM088076 · NIGMS · INDIANA UNIVERSITY INDIANAPOLIS · PI SKAAR, TODD C. · 2009 to 2017
$3.8M
Novel noninvasive assessment of cytochrome P450 activityR01GM063674 · NIGMS · WASHINGTON UNIVERSITY · PI KHARASCH, EVAN D. · 2001 to 2009
$1.8M
AHRQ HHS R01 HS019818AHRQ HHS R01 HS19818-01CIHRNHLBI NIH HHS U01 HL105198NIDA NIH HHS R01 DA014211NIDA NIH HHS R01 DA14211NIGMS NIH HHS R01 GM063674NIGMS NIH HHS R01 GM088076NIGMS NIH HHS R01 GM63674NIGMS NIH HHS R24 GM061374NIGMS NIH HHS R24 GM61374NIGMS NIH HHS U01 GM092666NIGMS NIH HHS U01 GM92666NIMH NIH HHS R01 MH082784
6 · The paper itself

Abstract

Polymorphisms in CYP2D6 and CYP2C19 affect the efficacy and safety of tricyclics, with some drugs being affected by CYP2D6 only, and others by both polymorphic enzymes. Amitriptyline, clomipramine, doxepin, imipramine, and trimipramine are demethylated by CYP2C19 to pharmacologically active metabolites. These drugs and their metabolites, along with desipramine and nortriptyline, undergo hydroxylation by CYP2D6 to less active metabolites. Evidence from published literature is presented for CYP2D6 and CYP2C19 genotype-directed dosing of tricyclic antidepressants.

Indexed as

Antidepressive Agents, TricyclicAryl Hydrocarbon HydroxylasesCytochrome P-450 CYP2C19Cytochrome P-450 CYP2D6Dose-Response Relationship, DrugGenotypeHumansMental DisordersPharmacogeneticsPolymorphism, GeneticAntidepressive Agents, TricyclicAryl Hydrocarbon HydroxylasesCYP2C19 protein, humanCytochrome P-450 CYP2C19Cytochrome P-450 CYP2D6

Identifiers

PMID23486447
PMCPMC3689226
OpenAlexW2021635654

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.