Evidence map›Paper›PMID 41496526›Full record

Observational studyJournal of clinical psychopharmacology

CYP2D6 Phenotype as a Predictor of Adverse Drug Reactions in Patients Treated With Trazodone: An Explorative Pharmacogenetic Study.

Florine M Wiss, Christian D Krieg, Markus L Lampert, Henriette E Meyer Zu Schwabedissen, Céline K Stäuble, Thorsten Mikoteit, Christian Imboden, Samuel S Allemann

Abstract readObservational Study
In one paragraph

Observational study in Journal of clinical psychopharmacology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Florine M WissPharmaceutical Care, Department of Pharmaceutical Sciences, University of Basel, Basel.ORCID 0009-0001-3618-4679
Christian D KriegPharmaceutical Care, Department of Pharmaceutical Sciences, University of Basel, Basel.
Markus L LampertPharmaceutical Care, Department of Pharmaceutical Sciences, University of Basel, Basel.ORCID 0000-0001-7037-2799
Henriette E Meyer Zu SchwabedissenBiopharmacy, Department of Pharmaceutical Sciences, University of Basel, Basel.ORCID 0000-0003-0458-4579
Céline K StäublePharmaceutical Care, Department of Pharmaceutical Sciences, University of Basel, Basel.ORCID 0000-0002-2437-4803
Thorsten MikoteitPsychiatric Services Solothurn, Solothurner Spitäler, Solothurn.ORCID 0000-0003-2166-6330
Christian ImbodenPsychiatric Services Solothurn, Solothurner Spitäler, Solothurn.ORCID 0000-0001-9912-0413
Samuel S AllemannPharmaceutical Care, Department of Pharmaceutical Sciences, University of Basel, Basel.ORCID 0000-0003-4067-9401

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeTrazodone is metabolized by CYP3A4 to the active metabolite meta-chlorophenylpiperazine (mCPP), which is associated with various adverse drug reactions (ADRs). mCPP is further inactivated by CYP2D6. Despite the knowledge of trazodone metabolism, the evidence regarding the impact of pharmacogenetics remains limited. This study aimed to examine the association between pharmacogenetic variants in genes involved in the metabolism of trazodone and the occurrence of ADRs during trazodone treatment.

methodsWe performed an explorative observational study using available data and serum samples from 2 ongoing pharmacogenetic studies. For patients treated with trazodone, we analyzed information on trazodone tolerability, genetic variants in CYP2D6, CYP3A5, and ABCB1 , as well as co-medications to assess potential drug-drug-gene interactions (phenoconversion). Serum levels of mCPP and trazodone were measured in a subset of patients.

resultsData from 98 patients were analyzed. Reduced CYP2D6 activity was associated with an increased risk of ADRs during trazodone therapy. After accounting for phenoconversion and adjusting for sex, trazodone dose, and CYP3A5 phenotype, CYP2D6 poor metabolizers were found to be more likely to develop ADRs compared with normal metabolizers (OR: 8.96; 95% CI=1.67-48.08). No association with ADRs was found for genetic variants in CYP3A5 and ABCB1 . Subgroup analysis revealed that reduced CYP2D6 activity was associated with a higher mCPP-to-trazodone ratio and a greater tendency for ADRs.

conclusionsOur findings suggest that mCPP could contribute to trazodone-related ADRs, especially in individuals with reduced CYP2D6 metabolism. Larger clinical studies are needed to confirm that CYP2D6 genotyping could contribute to preventing ADRs in clinical practice.

Indexed as

Cytochrome P-450 CYP2D6Drug-Related Side Effects and Adverse ReactionsTrazodoneAdultAgedATP Binding Cassette Transporter, Subfamily BFemaleGenotypeHumansMaleMiddle AgedPharmacogeneticsPhenotypePiperazines1-(3-chlorophenyl)piperazineATP Binding Cassette Transporter, Subfamily BCytochrome P-450 CYP2D6PiperazinesTrazodoneadverse drug reactionCYP2D6mCPPpharmacogenetictrazodone

Identifiers

PMID41496526
PMCPMC12931868

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Registered trials

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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.