Adverse Renal, Endocrine, Hepatic, and Metabolic Events during Maintenance Mood Stabilizer Treatment for Bipolar Disorder: A Population-Based Cohort Study
There is limited, poorly characterized information about adverse events occurring during maintenance treatment of bipolar disorder. We aimed to determine adverse event rates during treatment with lithium, valproate, olanzapine, and quetiapine. We conducted a propensity score adjusted cohort study us...
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| description | There is limited, poorly characterized information about adverse events occurring during maintenance treatment of bipolar disorder. We aimed to determine adverse event rates during treatment with lithium, valproate, olanzapine, and quetiapine.
We conducted a propensity score adjusted cohort study using nationally representative United Kingdom electronic health records from January 1, 1995, until December 31, 2013. We included patients who had a diagnosis of bipolar disorder and were prescribed lithium (n = 2148), valproate (n = 1670), olanzapine (n = 1477), or quetiapine (n = 1376) as maintenance mood stabilizer treatment. Adverse outcomes were chronic kidney disease, thyroid disease, hypercalcemia, weight gain, hypertension, type 2 diabetes mellitus, cardiovascular disease, and hepatotoxicity. The propensity score included important demographic, physical health, and mental health predictors of drug treatment allocation. The median duration of drug treatment was 1.48 y (interquartile range 0.64-3.43). Compared to patients prescribed lithium, those taking valproate, olanzapine, and quetiapine had reduced rates of chronic kidney disease stage 3 or more severe, following adjustment for propensity score, age, and calendar year, and accounting for clustering by primary care practice (valproate hazard ratio [HR] 0.56; 95% confidence interval [CI] 0.45-0.69; p < 0.001, olanzapine HR 0.57; 95% CI 0.45-0.71; p < 0.001, quetiapine HR 0.62; 95% CI 0.47-0.80; p < 0.001). Hypothyroidism was reduced in those taking valproate (HR 0.60; 95% CI 0.40-0.89; p = 0.012) and olanzapine (HR 0.48; 95% CI 0.29-0.77; p = 0.003), compared to those taking lithium. Rates of new onset hyperthyroidism (valproate HR 0.24; 95% CI 0.09-0.61; p = 0.003, olanzapine HR 0.31; 95% CI 0.13-0.73; p = 0.007) and hypercalcemia (valproate HR 0.25; 95% CI 0.10-0.60; p = 0.002, olanzapine HR 0.32; 95% CI 0.14-0.76; p = 0.008, quetiapine HR 0.23; 95% CI 0.07-0.73; p = 0.013) were also reduced relative to lithium. However, rates of greater than 15% weight gain on valproate, olanzapine, and quetiapine were higher (valproate HR 1.62; 95% CI 1.31-2.01; p < 0.001, olanzapine HR 1.84; 95% CI 1.47-2.30; p < 0.001, quetiapine HR 1.67; 95% CI 1.24-2.20; p < 0.001) than in individuals prescribed lithium, as were rates of hypertension in the olanzapine treated group (HR 1.41, 95% CI 1.06-1.87; p = 0.017). We found no significant difference in rates of chronic kidney disease stage 4 or more severe, type 2 diabetes |
| doi_str_mv | 10.1371/journal.pmed.1002058 |
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We conducted a propensity score adjusted cohort study using nationally representative United Kingdom electronic health records from January 1, 1995, until December 31, 2013. We included patients who had a diagnosis of bipolar disorder and were prescribed lithium (n = 2148), valproate (n = 1670), olanzapine (n = 1477), or quetiapine (n = 1376) as maintenance mood stabilizer treatment. Adverse outcomes were chronic kidney disease, thyroid disease, hypercalcemia, weight gain, hypertension, type 2 diabetes mellitus, cardiovascular disease, and hepatotoxicity. The propensity score included important demographic, physical health, and mental health predictors of drug treatment allocation. The median duration of drug treatment was 1.48 y (interquartile range 0.64-3.43). Compared to patients prescribed lithium, those taking valproate, olanzapine, and quetiapine had reduced rates of chronic kidney disease stage 3 or more severe, following adjustment for propensity score, age, and calendar year, and accounting for clustering by primary care practice (valproate hazard ratio [HR] 0.56; 95% confidence interval [CI] 0.45-0.69; p < 0.001, olanzapine HR 0.57; 95% CI 0.45-0.71; p < 0.001, quetiapine HR 0.62; 95% CI 0.47-0.80; p < 0.001). Hypothyroidism was reduced in those taking valproate (HR 0.60; 95% CI 0.40-0.89; p = 0.012) and olanzapine (HR 0.48; 95% CI 0.29-0.77; p = 0.003), compared to those taking lithium. Rates of new onset hyperthyroidism (valproate HR 0.24; 95% CI 0.09-0.61; p = 0.003, olanzapine HR 0.31; 95% CI 0.13-0.73; p = 0.007) and hypercalcemia (valproate HR 0.25; 95% CI 0.10-0.60; p = 0.002, olanzapine HR 0.32; 95% CI 0.14-0.76; p = 0.008, quetiapine HR 0.23; 95% CI 0.07-0.73; p = 0.013) were also reduced relative to lithium. However, rates of greater than 15% weight gain on valproate, olanzapine, and quetiapine were higher (valproate HR 1.62; 95% CI 1.31-2.01; p < 0.001, olanzapine HR 1.84; 95% CI 1.47-2.30; p < 0.001, quetiapine HR 1.67; 95% CI 1.24-2.20; p < 0.001) than in individuals prescribed lithium, as were rates of hypertension in the olanzapine treated group (HR 1.41, 95% CI 1.06-1.87; p = 0.017). We found no significant difference in rates of chronic kidney disease stage 4 or more severe, type 2 diabetes mellitus, cardiovascular disease, or hepatotoxicity. Despite estimates being robust following sensitivity analyses, limitations include the potential for residual confounding and ascertainment bias and an inability to examine dosage effects.
Lithium use is associated with more renal and endocrine adverse events but less weight gain than commonly used alternative mood stabilizers. Risks need to be offset with the effectiveness and anti-suicidal benefits of lithium and the potential metabolic side effects of alternative treatment options.]]></description><identifier>ISSN: 1549-1676</identifier><identifier>ISSN: 1549-1277</identifier><identifier>EISSN: 1549-1676</identifier><identifier>DOI: 10.1371/journal.pmed.1002058</identifier><identifier>PMID: 27483368</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Analysis ; Antidepressants ; Antipsychotic Agents - adverse effects ; Antipsychotic Agents - therapeutic use ; Benzodiazepines - adverse effects ; Benzodiazepines - therapeutic use ; Biology and Life Sciences ; Bipolar disorder ; Bipolar Disorder - drug therapy ; Cardiovascular disease ; Cardiovascular Diseases - chemically induced ; Chemical and Drug Induced Liver Injury - etiology ; Chronic kidney failure ; Cohort Studies ; Collaboration ; Complications and side effects ; Confidence intervals ; Diabetes ; Diabetes Mellitus, Type 2 - chemically induced ; Dosage and administration ; Drug therapy ; Family medicine ; Female ; Humans ; Hypercalcemia - chemically induced ; Hypertension ; Hypertension - chemically induced ; Kidney diseases ; Lithium Compounds - adverse effects ; Lithium Compounds - therapeutic use ; Longitudinal Studies ; Male ; Management ; Medicine and Health Sciences ; Metabolism ; Middle Aged ; Olanzapine ; Patients ; Physical Sciences ; Physiology ; Primary care ; Primary health care ; Propensity Score ; Quetiapine Fumarate - adverse effects ; Quetiapine Fumarate - therapeutic use ; Renal Insufficiency - chemically induced ; Research and Analysis Methods ; Studies ; Substance abuse treatment ; Thyroid diseases ; Thyroid Diseases - chemically induced ; Type 2 diabetes ; Valproic Acid - adverse effects ; Valproic Acid - therapeutic use</subject><ispartof>PLoS medicine, 2016-08, Vol.13 (8), p.e1002058</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Hayes JF, Marston L, Walters K, Geddes JR, King M, Osborn DPJ (2016) Adverse Renal, Endocrine, Hepatic, and Metabolic Events during Maintenance Mood Stabilizer Treatment for Bipolar Disorder: A Population-Based Cohort Study. PLoS Med 13(8): e1002058. doi:10.1371/journal.pmed.1002058</rights><rights>2016 Hayes et al 2016 Hayes et al</rights><rights>2016 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Hayes JF, Marston L, Walters K, Geddes JR, King M, Osborn DPJ (2016) Adverse Renal, Endocrine, Hepatic, and Metabolic Events during Maintenance Mood Stabilizer Treatment for Bipolar Disorder: A Population-Based Cohort Study. PLoS Med 13(8): e1002058. doi:10.1371/journal.pmed.1002058</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c830t-d794014eae3411cb5af620761933cee38bb9180af348dc6442f97ea2954031523</citedby><cites>FETCH-LOGICAL-c830t-d794014eae3411cb5af620761933cee38bb9180af348dc6442f97ea2954031523</cites><orcidid>0000-0003-2286-3862</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970809/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970809/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23871,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27483368$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Tsai, Alexander C.</contributor><creatorcontrib>Hayes, Joseph F</creatorcontrib><creatorcontrib>Marston, Louise</creatorcontrib><creatorcontrib>Walters, Kate</creatorcontrib><creatorcontrib>Geddes, John R</creatorcontrib><creatorcontrib>King, Michael</creatorcontrib><creatorcontrib>Osborn, David P J</creatorcontrib><title>Adverse Renal, Endocrine, Hepatic, and Metabolic Events during Maintenance Mood Stabilizer Treatment for Bipolar Disorder: A Population-Based Cohort Study</title><title>PLoS medicine</title><addtitle>PLoS Med</addtitle><description><![CDATA[There is limited, poorly characterized information about adverse events occurring during maintenance treatment of bipolar disorder. We aimed to determine adverse event rates during treatment with lithium, valproate, olanzapine, and quetiapine.
We conducted a propensity score adjusted cohort study using nationally representative United Kingdom electronic health records from January 1, 1995, until December 31, 2013. We included patients who had a diagnosis of bipolar disorder and were prescribed lithium (n = 2148), valproate (n = 1670), olanzapine (n = 1477), or quetiapine (n = 1376) as maintenance mood stabilizer treatment. Adverse outcomes were chronic kidney disease, thyroid disease, hypercalcemia, weight gain, hypertension, type 2 diabetes mellitus, cardiovascular disease, and hepatotoxicity. The propensity score included important demographic, physical health, and mental health predictors of drug treatment allocation. The median duration of drug treatment was 1.48 y (interquartile range 0.64-3.43). Compared to patients prescribed lithium, those taking valproate, olanzapine, and quetiapine had reduced rates of chronic kidney disease stage 3 or more severe, following adjustment for propensity score, age, and calendar year, and accounting for clustering by primary care practice (valproate hazard ratio [HR] 0.56; 95% confidence interval [CI] 0.45-0.69; p < 0.001, olanzapine HR 0.57; 95% CI 0.45-0.71; p < 0.001, quetiapine HR 0.62; 95% CI 0.47-0.80; p < 0.001). Hypothyroidism was reduced in those taking valproate (HR 0.60; 95% CI 0.40-0.89; p = 0.012) and olanzapine (HR 0.48; 95% CI 0.29-0.77; p = 0.003), compared to those taking lithium. Rates of new onset hyperthyroidism (valproate HR 0.24; 95% CI 0.09-0.61; p = 0.003, olanzapine HR 0.31; 95% CI 0.13-0.73; p = 0.007) and hypercalcemia (valproate HR 0.25; 95% CI 0.10-0.60; p = 0.002, olanzapine HR 0.32; 95% CI 0.14-0.76; p = 0.008, quetiapine HR 0.23; 95% CI 0.07-0.73; p = 0.013) were also reduced relative to lithium. However, rates of greater than 15% weight gain on valproate, olanzapine, and quetiapine were higher (valproate HR 1.62; 95% CI 1.31-2.01; p < 0.001, olanzapine HR 1.84; 95% CI 1.47-2.30; p < 0.001, quetiapine HR 1.67; 95% CI 1.24-2.20; p < 0.001) than in individuals prescribed lithium, as were rates of hypertension in the olanzapine treated group (HR 1.41, 95% CI 1.06-1.87; p = 0.017). We found no significant difference in rates of chronic kidney disease stage 4 or more severe, type 2 diabetes mellitus, cardiovascular disease, or hepatotoxicity. Despite estimates being robust following sensitivity analyses, limitations include the potential for residual confounding and ascertainment bias and an inability to examine dosage effects.
Lithium use is associated with more renal and endocrine adverse events but less weight gain than commonly used alternative mood stabilizers. Risks need to be offset with the effectiveness and anti-suicidal benefits of lithium and the potential metabolic side effects of alternative treatment options.]]></description><subject>Adult</subject><subject>Analysis</subject><subject>Antidepressants</subject><subject>Antipsychotic Agents - adverse effects</subject><subject>Antipsychotic Agents - therapeutic use</subject><subject>Benzodiazepines - adverse effects</subject><subject>Benzodiazepines - therapeutic use</subject><subject>Biology and Life Sciences</subject><subject>Bipolar disorder</subject><subject>Bipolar Disorder - drug therapy</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular Diseases - chemically induced</subject><subject>Chemical and Drug Induced Liver Injury - etiology</subject><subject>Chronic kidney failure</subject><subject>Cohort Studies</subject><subject>Collaboration</subject><subject>Complications and side effects</subject><subject>Confidence intervals</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 2 - chemically induced</subject><subject>Dosage and administration</subject><subject>Drug therapy</subject><subject>Family medicine</subject><subject>Female</subject><subject>Humans</subject><subject>Hypercalcemia - chemically induced</subject><subject>Hypertension</subject><subject>Hypertension - chemically induced</subject><subject>Kidney diseases</subject><subject>Lithium Compounds - adverse effects</subject><subject>Lithium Compounds - therapeutic use</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Management</subject><subject>Medicine and Health Sciences</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>Olanzapine</subject><subject>Patients</subject><subject>Physical Sciences</subject><subject>Physiology</subject><subject>Primary care</subject><subject>Primary health care</subject><subject>Propensity Score</subject><subject>Quetiapine Fumarate - adverse effects</subject><subject>Quetiapine Fumarate - therapeutic use</subject><subject>Renal Insufficiency - chemically induced</subject><subject>Research and Analysis Methods</subject><subject>Studies</subject><subject>Substance abuse treatment</subject><subject>Thyroid diseases</subject><subject>Thyroid Diseases - chemically induced</subject><subject>Type 2 diabetes</subject><subject>Valproic Acid - adverse effects</subject><subject>Valproic Acid - therapeutic use</subject><issn>1549-1676</issn><issn>1549-1277</issn><issn>1549-1676</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>DOA</sourceid><recordid>eNqVk99u0zAUxiMEYmPwBggsISEhtcWOnT_mAqkrhVVaGdoGt5Zrn7Su0jjYScV4FJ4Wl2ZTIw0JlItE9u_7jv2dnCh6TvCI0Iy8XdvWVbIc1RvQI4JxjJP8QXRMEsaHJM3ShwffR9ET79eB4Zjjx9FRnLGc0jQ_jn6N9RacB3QJwWyAppW2ypkKBugMatkYNUCy0mgOjVzY0ig03ULVeKTbQC3RXJqqCdJKAZpbq9FV4ExpfoJD1w5kswk0KqxDp6a2pXTog_HWaXDv0Bh9sXVbhiK2Gp5KDxpN7Mq6Jpi0-uZp9KiQpYdn3fsk-vpxej05G55ffJpNxudDlVPcDHXGGSYMJFBGiFokskhjnKWEU6oAaL5YcJJjWVCWa5UyFhc8AxnzhGFKkpieRC_3vnVpvehi9YLkMY7zFPMkELM9oa1ci9qZjXQ3wkoj_ixYtxTShahKEIRqFjyzUDVhyYJKrXQmeaZ4nuQ85cHrfVetXYTOqRCPk2XPtL9TmZVY2q1gPMM53hm86gyc_d6Cb_5y5I5aynAqUxU2mKmN8UqMWUiMUE52Vx_eQy2hglDZVlCYsNzjR_fw4dGwMepewZueIDAN_GiWsvVezK4u_4P9_O_sxbc--_qAXYEsm5W3Zbv77XwfZHtQOeu9g-KuKwSL3czdJi12Mye6mQuyF4cdvRPdDhn9DbvPJY8</recordid><startdate>20160802</startdate><enddate>20160802</enddate><creator>Hayes, Joseph F</creator><creator>Marston, Louise</creator><creator>Walters, Kate</creator><creator>Geddes, John R</creator><creator>King, Michael</creator><creator>Osborn, David P J</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISN</scope><scope>ISR</scope><scope>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope><scope>DOA</scope><scope>CZK</scope><orcidid>https://orcid.org/0000-0003-2286-3862</orcidid></search><sort><creationdate>20160802</creationdate><title>Adverse Renal, Endocrine, Hepatic, and Metabolic Events during Maintenance Mood Stabilizer Treatment for Bipolar Disorder: A Population-Based Cohort Study</title><author>Hayes, Joseph F ; Marston, Louise ; Walters, Kate ; Geddes, John R ; King, Michael ; Osborn, David P J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c830t-d794014eae3411cb5af620761933cee38bb9180af348dc6442f97ea2954031523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Analysis</topic><topic>Antidepressants</topic><topic>Antipsychotic Agents - adverse effects</topic><topic>Antipsychotic Agents - therapeutic use</topic><topic>Benzodiazepines - adverse effects</topic><topic>Benzodiazepines - therapeutic use</topic><topic>Biology and Life Sciences</topic><topic>Bipolar disorder</topic><topic>Bipolar Disorder - drug therapy</topic><topic>Cardiovascular disease</topic><topic>Cardiovascular Diseases - chemically induced</topic><topic>Chemical and Drug Induced Liver Injury - etiology</topic><topic>Chronic kidney failure</topic><topic>Cohort Studies</topic><topic>Collaboration</topic><topic>Complications and side effects</topic><topic>Confidence intervals</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 2 - chemically induced</topic><topic>Dosage and administration</topic><topic>Drug therapy</topic><topic>Family medicine</topic><topic>Female</topic><topic>Humans</topic><topic>Hypercalcemia - chemically induced</topic><topic>Hypertension</topic><topic>Hypertension - chemically induced</topic><topic>Kidney diseases</topic><topic>Lithium Compounds - adverse effects</topic><topic>Lithium Compounds - therapeutic use</topic><topic>Longitudinal Studies</topic><topic>Male</topic><topic>Management</topic><topic>Medicine and Health Sciences</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>Olanzapine</topic><topic>Patients</topic><topic>Physical Sciences</topic><topic>Physiology</topic><topic>Primary care</topic><topic>Primary health care</topic><topic>Propensity Score</topic><topic>Quetiapine Fumarate - adverse effects</topic><topic>Quetiapine Fumarate - therapeutic use</topic><topic>Renal Insufficiency - chemically induced</topic><topic>Research and Analysis Methods</topic><topic>Studies</topic><topic>Substance abuse treatment</topic><topic>Thyroid diseases</topic><topic>Thyroid Diseases - chemically induced</topic><topic>Type 2 diabetes</topic><topic>Valproic Acid - adverse effects</topic><topic>Valproic Acid - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hayes, Joseph F</creatorcontrib><creatorcontrib>Marston, Louise</creatorcontrib><creatorcontrib>Walters, Kate</creatorcontrib><creatorcontrib>Geddes, John R</creatorcontrib><creatorcontrib>King, Michael</creatorcontrib><creatorcontrib>Osborn, David P J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</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>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>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Publicly Available Content Database</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>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><collection>PLoS Medicine</collection><jtitle>PLoS medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hayes, Joseph F</au><au>Marston, Louise</au><au>Walters, Kate</au><au>Geddes, John R</au><au>King, Michael</au><au>Osborn, David P J</au><au>Tsai, Alexander C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adverse Renal, Endocrine, Hepatic, and Metabolic Events during Maintenance Mood Stabilizer Treatment for Bipolar Disorder: A Population-Based Cohort Study</atitle><jtitle>PLoS medicine</jtitle><addtitle>PLoS Med</addtitle><date>2016-08-02</date><risdate>2016</risdate><volume>13</volume><issue>8</issue><spage>e1002058</spage><pages>e1002058-</pages><issn>1549-1676</issn><issn>1549-1277</issn><eissn>1549-1676</eissn><abstract><![CDATA[There is limited, poorly characterized information about adverse events occurring during maintenance treatment of bipolar disorder. We aimed to determine adverse event rates during treatment with lithium, valproate, olanzapine, and quetiapine.
We conducted a propensity score adjusted cohort study using nationally representative United Kingdom electronic health records from January 1, 1995, until December 31, 2013. We included patients who had a diagnosis of bipolar disorder and were prescribed lithium (n = 2148), valproate (n = 1670), olanzapine (n = 1477), or quetiapine (n = 1376) as maintenance mood stabilizer treatment. Adverse outcomes were chronic kidney disease, thyroid disease, hypercalcemia, weight gain, hypertension, type 2 diabetes mellitus, cardiovascular disease, and hepatotoxicity. The propensity score included important demographic, physical health, and mental health predictors of drug treatment allocation. The median duration of drug treatment was 1.48 y (interquartile range 0.64-3.43). Compared to patients prescribed lithium, those taking valproate, olanzapine, and quetiapine had reduced rates of chronic kidney disease stage 3 or more severe, following adjustment for propensity score, age, and calendar year, and accounting for clustering by primary care practice (valproate hazard ratio [HR] 0.56; 95% confidence interval [CI] 0.45-0.69; p < 0.001, olanzapine HR 0.57; 95% CI 0.45-0.71; p < 0.001, quetiapine HR 0.62; 95% CI 0.47-0.80; p < 0.001). Hypothyroidism was reduced in those taking valproate (HR 0.60; 95% CI 0.40-0.89; p = 0.012) and olanzapine (HR 0.48; 95% CI 0.29-0.77; p = 0.003), compared to those taking lithium. Rates of new onset hyperthyroidism (valproate HR 0.24; 95% CI 0.09-0.61; p = 0.003, olanzapine HR 0.31; 95% CI 0.13-0.73; p = 0.007) and hypercalcemia (valproate HR 0.25; 95% CI 0.10-0.60; p = 0.002, olanzapine HR 0.32; 95% CI 0.14-0.76; p = 0.008, quetiapine HR 0.23; 95% CI 0.07-0.73; p = 0.013) were also reduced relative to lithium. However, rates of greater than 15% weight gain on valproate, olanzapine, and quetiapine were higher (valproate HR 1.62; 95% CI 1.31-2.01; p < 0.001, olanzapine HR 1.84; 95% CI 1.47-2.30; p < 0.001, quetiapine HR 1.67; 95% CI 1.24-2.20; p < 0.001) than in individuals prescribed lithium, as were rates of hypertension in the olanzapine treated group (HR 1.41, 95% CI 1.06-1.87; p = 0.017). We found no significant difference in rates of chronic kidney disease stage 4 or more severe, type 2 diabetes mellitus, cardiovascular disease, or hepatotoxicity. Despite estimates being robust following sensitivity analyses, limitations include the potential for residual confounding and ascertainment bias and an inability to examine dosage effects.
Lithium use is associated with more renal and endocrine adverse events but less weight gain than commonly used alternative mood stabilizers. Risks need to be offset with the effectiveness and anti-suicidal benefits of lithium and the potential metabolic side effects of alternative treatment options.]]></abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27483368</pmid><doi>10.1371/journal.pmed.1002058</doi><orcidid>https://orcid.org/0000-0003-2286-3862</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1549-1676 |
| ispartof | PLoS medicine, 2016-08, Vol.13 (8), p.e1002058 |
| issn | 1549-1676 1549-1277 1549-1676 |
| language | eng |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central |
| subjects | Adult Analysis Antidepressants Antipsychotic Agents - adverse effects Antipsychotic Agents - therapeutic use Benzodiazepines - adverse effects Benzodiazepines - therapeutic use Biology and Life Sciences Bipolar disorder Bipolar Disorder - drug therapy Cardiovascular disease Cardiovascular Diseases - chemically induced Chemical and Drug Induced Liver Injury - etiology Chronic kidney failure Cohort Studies Collaboration Complications and side effects Confidence intervals Diabetes Diabetes Mellitus, Type 2 - chemically induced Dosage and administration Drug therapy Family medicine Female Humans Hypercalcemia - chemically induced Hypertension Hypertension - chemically induced Kidney diseases Lithium Compounds - adverse effects Lithium Compounds - therapeutic use Longitudinal Studies Male Management Medicine and Health Sciences Metabolism Middle Aged Olanzapine Patients Physical Sciences Physiology Primary care Primary health care Propensity Score Quetiapine Fumarate - adverse effects Quetiapine Fumarate - therapeutic use Renal Insufficiency - chemically induced Research and Analysis Methods Studies Substance abuse treatment Thyroid diseases Thyroid Diseases - chemically induced Type 2 diabetes Valproic Acid - adverse effects Valproic Acid - therapeutic use |
| title | Adverse Renal, Endocrine, Hepatic, and Metabolic Events during Maintenance Mood Stabilizer Treatment for Bipolar Disorder: A Population-Based Cohort Study |
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