Evidence map›Paper›PMID 36333412›Full record

ArticleThe pharmacogenomics journal2023

Effect of CYP2C19 polymorphisms on antidepressant prescription patterns and treatment emergent mania in bipolar disorder.

Erik Joas, Lina Jonsson, Alexander Viktorin, Erik Smedler, Erik Pålsson, Guy M Goodwin, Mikael Landén

Open access · hybridAbstract read
In one paragraph

Article in The pharmacogenomics journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

7 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. The Swedish bipolar collection (SWEBIC).International journal of bipolar disorders · 2025
    Article
  3. Pharmaceuticals (Basel, Switzerland) · 2024
    Review
  4. Article
  5. Review
  6. From genes to drugs:Frontiers in pharmacology · 2024
    Review
  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Erik JoasInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. erik.joas@gu.se.ORCID 0000-0001-9546-2192
Lina JonssonInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Alexander ViktorinDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0003-2141-2816
Erik SmedlerInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.ORCID 0000-0003-4609-3620
Erik PålssonInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Guy M GoodwinDepartment of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.ORCID 0000-0002-1426-2816
Mikael LandénInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.ORCID 0000-0002-4496-6451
University of Gothenburg · SEKarolinska Institutet · SEWarneford Hospital · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antidepressant medication is used extensively to treat bipolar depression despite uncertain efficacy. The cytochrome P450 (CYP) 2C19 enzyme metabolize several antidepressants, and polymorphisms in the corresponding gene CYP2C19 influence plasma concentration and hence treatment outcomes in major depressive disorder. Here, we investigate if CYP2C19 polymorphisms are associated with antidepressant treatment patterns and the risk of mania when antidepressants are used in bipolar disorder. Two single nucleotide polymorphisms (rs4244285 and rs12248560) were used to classify 5019 bipolar disorder patients into CYP2C19 metabolic phenotypes ranging from poor to ultra-rapid metabolizers. We used Swedish national registry data 2005-2017 on dispensed medications and inpatient care to estimate risks for early-treatment persistence, treatment discontinuation, switching to a new antidepressant medication, and mania within 3 months of treatment initiation in patients treated with citalopram, escitalopram, sertraline, amitriptyline, and clomipramine. Metabolic phenotypes of CYP2C19 were not robustly associated with the investigated treatment outcomes based on dispense patterns. Slower metabolism was associated with an increased risk of treatment emergent mania for sertraline (hazard ratio [HR] = 1.3, 95% CI = 1.04-1.62, p = 0.02) and the tricyclic antidepressants amitriptyline and clomipramine (HR = 1.46, 95% CI = 1.05-2.02, p = 0.024). In a large study of the impact of CYP2C19 metabolic phenotypes on antidepressant treatment of bipolar depression, we found an association between slower CYP2C19 metabolism and higher risk of treatment emergent mania, which is a step towards personalized risk assessments. There were, however, no clear associations with early treatment persistence, treatment discontinuation, and switching to a new antidepressant.

Indexed as

Bipolar DisorderCytochrome P-450 Enzyme SystemMajor Depressive DisorderAmitriptylineAntidepressive AgentsClomipramineCytochrome P-450 CYP2C19HumansManiaPolymorphism, Single NucleotideSertralineAmitriptylineAntidepressive AgentsClomipramineCYP2C19 protein, humanCytochrome P-450 CYP2C19Cytochrome P-450 Enzyme SystemSertraline

Identifiers

PMID36333412
PMCPMC9925376
OpenAlexW4308253294

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.