Effect of CYP2C19 polymorphisms on antidepressant prescription patterns and treatment emergent mania in bipolar disorder
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 dep...
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| creator | Joas, Erik Jonsson, Lina Viktorin, Alexander Smedler, Erik Pålsson, Erik Goodwin, Guy M. Landén, Mikael |
| description | 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. |
| doi_str_mv | 10.1038/s41397-022-00294-4 |
| format | Article |
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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.</description><identifier>ISSN: 1470-269X</identifier><identifier>ISSN: 1473-1150</identifier><identifier>EISSN: 1473-1150</identifier><identifier>DOI: 10.1038/s41397-022-00294-4</identifier><identifier>PMID: 36333412</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45/23 ; 692/308/2056 ; 692/308/409 ; Affective disorders ; Amitriptyline ; Amitriptyline - therapeutic use ; Antidepressants ; Antidepressive Agents - adverse effects ; Biomedical and Life Sciences ; Biomedicine ; Bipolar disorder ; Bipolar Disorder - drug therapy ; Bipolar Disorder - genetics ; Citalopram ; Clinical outcomes ; Clomipramine ; Clomipramine - therapeutic use ; Cytochrome P-450 CYP2C19 - genetics ; Cytochrome P-450 Enzyme System - genetics ; Cytochrome P450 ; Depressive Disorder, Major - drug therapy ; Gene Expression ; Human Genetics ; Humans ; Mania - chemically induced ; Mania - drug therapy ; Medical Genetics ; Medicinsk genetik ; Mental depression ; Metabolism ; Oncology ; Pharmacotherapy ; Phenotypes ; Polymorphism, Single Nucleotide - genetics ; Psychiatry ; Psychopharmacology ; Psykiatri ; Sertraline ; Single-nucleotide polymorphism ; Tricyclic antidepressants</subject><ispartof>The pharmacogenomics journal, 2023-01, Vol.23 (1), p.28-35</ispartof><rights>The Author(s) 2022</rights><rights>2022. The Author(s).</rights><rights>The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c550t-2e4fc80cbbfcd3c373b349da352d9b78f778ff545f0e3b34e5f3e3f912d00e743</citedby><cites>FETCH-LOGICAL-c550t-2e4fc80cbbfcd3c373b349da352d9b78f778ff545f0e3b34e5f3e3f912d00e743</cites><orcidid>0000-0003-4609-3620 ; 0000-0002-1426-2816 ; 0000-0001-9546-2192 ; 0000-0002-4496-6451 ; 0000-0003-2141-2816</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,552,780,784,885,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36333412$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://gup.ub.gu.se/publication/319748$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:151119677$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Joas, Erik</creatorcontrib><creatorcontrib>Jonsson, Lina</creatorcontrib><creatorcontrib>Viktorin, Alexander</creatorcontrib><creatorcontrib>Smedler, Erik</creatorcontrib><creatorcontrib>Pålsson, Erik</creatorcontrib><creatorcontrib>Goodwin, Guy M.</creatorcontrib><creatorcontrib>Landén, Mikael</creatorcontrib><title>Effect of CYP2C19 polymorphisms on antidepressant prescription patterns and treatment emergent mania in bipolar disorder</title><title>The pharmacogenomics journal</title><addtitle>Pharmacogenomics J</addtitle><addtitle>Pharmacogenomics J</addtitle><description>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.</description><subject>45/23</subject><subject>692/308/2056</subject><subject>692/308/409</subject><subject>Affective disorders</subject><subject>Amitriptyline</subject><subject>Amitriptyline - therapeutic use</subject><subject>Antidepressants</subject><subject>Antidepressive Agents - adverse effects</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Bipolar disorder</subject><subject>Bipolar Disorder - drug therapy</subject><subject>Bipolar Disorder - genetics</subject><subject>Citalopram</subject><subject>Clinical outcomes</subject><subject>Clomipramine</subject><subject>Clomipramine - therapeutic use</subject><subject>Cytochrome P-450 CYP2C19 - genetics</subject><subject>Cytochrome P-450 Enzyme System - genetics</subject><subject>Cytochrome P450</subject><subject>Depressive Disorder, Major - drug therapy</subject><subject>Gene Expression</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Mania - chemically induced</subject><subject>Mania - drug therapy</subject><subject>Medical Genetics</subject><subject>Medicinsk genetik</subject><subject>Mental depression</subject><subject>Metabolism</subject><subject>Oncology</subject><subject>Pharmacotherapy</subject><subject>Phenotypes</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Psychiatry</subject><subject>Psychopharmacology</subject><subject>Psykiatri</subject><subject>Sertraline</subject><subject>Single-nucleotide polymorphism</subject><subject>Tricyclic antidepressants</subject><issn>1470-269X</issn><issn>1473-1150</issn><issn>1473-1150</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>D8T</sourceid><recordid>eNp9kkFv1DAQhSMEoqXwBzggS1y4BGyPvY4vSGhVClIlOIAEJ8tJxqlLEgc7KfTf19ldCuXQg-UnzzfPHusVxXNGXzMK1ZskGGhVUs5LSrkWpXhQHDOhoGRM0oc7TUu-0d-OiicpXVLKNkxVj4sj2ACAYPy4-H3qHDYzCY5sv3_mW6bJFPrrIcTpwqchkTASO86-xSliSlmSVTTRT7PPtcnOM8YxZaglc0Q7D5gZHDB2qxjs6C3xI6l99rWRtD6F2GJ8Wjxytk_47LCfFF_fn37ZfijPP5193L47Lxsp6VxyFK6paFPXrmmhAQU1CN1akLzVtaqcystJIR3FtYTSAYLTjLeUohJwUpR73_QLp6U2U_SDjdcmWG8ORz-yQiOEVpW-l--WyeSjbll5YFqJKvNv93yGB2ybPHS0_Z22u5XRX5guXBmtuQS1yQavDgYx_FwwzWbwqcG-tyOGJRmuIINSaJ7Rl_-hl2GJY_6-TClZKaC7ifmeamJIKaK7fQyjZg2O2QfH5OCYXXDM2vTi3zFuW_4kJQNw-JdcGjuMf---x_YG3iXSuQ</recordid><startdate>20230101</startdate><enddate>20230101</enddate><creator>Joas, Erik</creator><creator>Jonsson, Lina</creator><creator>Viktorin, Alexander</creator><creator>Smedler, Erik</creator><creator>Pålsson, Erik</creator><creator>Goodwin, Guy M.</creator><creator>Landén, Mikael</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>F1U</scope><scope>D8T</scope><scope>ZZAVC</scope><orcidid>https://orcid.org/0000-0003-4609-3620</orcidid><orcidid>https://orcid.org/0000-0002-1426-2816</orcidid><orcidid>https://orcid.org/0000-0001-9546-2192</orcidid><orcidid>https://orcid.org/0000-0002-4496-6451</orcidid><orcidid>https://orcid.org/0000-0003-2141-2816</orcidid></search><sort><creationdate>20230101</creationdate><title>Effect of CYP2C19 polymorphisms on antidepressant prescription patterns and treatment emergent mania in bipolar disorder</title><author>Joas, Erik ; Jonsson, Lina ; Viktorin, Alexander ; Smedler, Erik ; Pålsson, Erik ; Goodwin, Guy M. ; Landén, Mikael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c550t-2e4fc80cbbfcd3c373b349da352d9b78f778ff545f0e3b34e5f3e3f912d00e743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>45/23</topic><topic>692/308/2056</topic><topic>692/308/409</topic><topic>Affective disorders</topic><topic>Amitriptyline</topic><topic>Amitriptyline - therapeutic use</topic><topic>Antidepressants</topic><topic>Antidepressive Agents - adverse effects</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Bipolar disorder</topic><topic>Bipolar Disorder - drug therapy</topic><topic>Bipolar Disorder - genetics</topic><topic>Citalopram</topic><topic>Clinical outcomes</topic><topic>Clomipramine</topic><topic>Clomipramine - therapeutic use</topic><topic>Cytochrome P-450 CYP2C19 - genetics</topic><topic>Cytochrome P-450 Enzyme System - genetics</topic><topic>Cytochrome P450</topic><topic>Depressive Disorder, Major - drug therapy</topic><topic>Gene Expression</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Mania - chemically induced</topic><topic>Mania - drug therapy</topic><topic>Medical Genetics</topic><topic>Medicinsk genetik</topic><topic>Mental depression</topic><topic>Metabolism</topic><topic>Oncology</topic><topic>Pharmacotherapy</topic><topic>Phenotypes</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Psychiatry</topic><topic>Psychopharmacology</topic><topic>Psykiatri</topic><topic>Sertraline</topic><topic>Single-nucleotide polymorphism</topic><topic>Tricyclic antidepressants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Joas, Erik</creatorcontrib><creatorcontrib>Jonsson, Lina</creatorcontrib><creatorcontrib>Viktorin, Alexander</creatorcontrib><creatorcontrib>Smedler, Erik</creatorcontrib><creatorcontrib>Pålsson, Erik</creatorcontrib><creatorcontrib>Goodwin, Guy M.</creatorcontrib><creatorcontrib>Landén, Mikael</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Göteborgs universitet</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>The pharmacogenomics journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Joas, Erik</au><au>Jonsson, Lina</au><au>Viktorin, Alexander</au><au>Smedler, Erik</au><au>Pålsson, Erik</au><au>Goodwin, Guy M.</au><au>Landén, Mikael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of CYP2C19 polymorphisms on antidepressant prescription patterns and treatment emergent mania in bipolar disorder</atitle><jtitle>The pharmacogenomics journal</jtitle><stitle>Pharmacogenomics J</stitle><addtitle>Pharmacogenomics J</addtitle><date>2023-01-01</date><risdate>2023</risdate><volume>23</volume><issue>1</issue><spage>28</spage><epage>35</epage><pages>28-35</pages><issn>1470-269X</issn><issn>1473-1150</issn><eissn>1473-1150</eissn><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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>36333412</pmid><doi>10.1038/s41397-022-00294-4</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-4609-3620</orcidid><orcidid>https://orcid.org/0000-0002-1426-2816</orcidid><orcidid>https://orcid.org/0000-0001-9546-2192</orcidid><orcidid>https://orcid.org/0000-0002-4496-6451</orcidid><orcidid>https://orcid.org/0000-0003-2141-2816</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; SWEPUB Freely available online; Alma/SFX Local Collection |
| subjects | 45/23 692/308/2056 692/308/409 Affective disorders Amitriptyline Amitriptyline - therapeutic use Antidepressants Antidepressive Agents - adverse effects Biomedical and Life Sciences Biomedicine Bipolar disorder Bipolar Disorder - drug therapy Bipolar Disorder - genetics Citalopram Clinical outcomes Clomipramine Clomipramine - therapeutic use Cytochrome P-450 CYP2C19 - genetics Cytochrome P-450 Enzyme System - genetics Cytochrome P450 Depressive Disorder, Major - drug therapy Gene Expression Human Genetics Humans Mania - chemically induced Mania - drug therapy Medical Genetics Medicinsk genetik Mental depression Metabolism Oncology Pharmacotherapy Phenotypes Polymorphism, Single Nucleotide - genetics Psychiatry Psychopharmacology Psykiatri Sertraline Single-nucleotide polymorphism Tricyclic antidepressants |
| title | Effect of CYP2C19 polymorphisms on antidepressant prescription patterns and treatment emergent mania in bipolar disorder |
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