{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:02:12Z","timestamp":1792627332305,"version":"4.5.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T00:00:00Z","timestamp":1727827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008487","name":"Sosiaali- ja Terveysministeri\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008487","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Psychiatr Scand"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Finding effective treatment regimens for bipolar disorder is challenging, as many patients suffer from significant symptoms despite treatment. This study investigated the risk of relapse (psychiatric hospitalization) and treatment safety (non\u2010psychiatric hospitalization) associated with different doses of antipsychotics and mood stabilizers in persons with bipolar disorder.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Individuals aged 15\u201365 with bipolar disorder were identified from Finnish national health registers in 1996\u20132018. Studied antipsychotics included olanzapine, risperidone, quetiapine, aripiprazole; mood stabilizers lithium, valproic acid, lamotrigine, and carbamazepine. Medication use was divided into three time\u2010varying dose categories: low, standard, and high. The studied outcomes were risk of psychiatric hospitalization (relapse) and the risk of non\u2010psychiatric hospitalization (treatment safety). Stratified Cox regression in within\u2010individual design was used.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The cohort included 60,045 individuals (mean age 41.7\u2009years, SD 15.8; 56.4% female). Mean follow\u2010up was 8.3\u2009years (SD 5.8). Of antipsychotics, olanzapine and aripiprazole were associated with a decreased risk of relapse in low and standard doses, and risperidone in low dose. The lowest adjusted hazard ratio (aHR) was observed for standard dose aripiprazole (aHR 0.68, 95% CI 0.57\u20130.82). Quetiapine was not associated with a decreased risk of relapse at any dose. Mood stabilizers were associated with a decreased risk of relapse in low and standard doses; lowest aHR was observed for standard dose lithium (aHR 0.61, 95% CI 0.56\u20130.65). Apart from lithium, high doses of antipsychotics and mood stabilizers were associated with an increased risk of non\u2010psychiatric hospitalization. Lithium was associated with a decreased risk of non\u2010psychiatric hospitalization in low (aHR 0.88, 95% CI 0.84\u20130.93) and standard doses (aHR 0.81, 95% CI 0.74\u20130.88).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Standard doses of lithium and aripiprazole were associated with the lowest risk of relapse, and standard dose of lithium with the lowest risk of non\u2010psychiatric hospitalization. Quetiapine was not associated with decreased risk of relapse at any dose.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acps.13762","type":"journal-article","created":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T08:57:23Z","timestamp":1727859443000},"page":"81-91","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Dosing levels of antipsychotics and mood stabilizers in bipolar disorder: A Nationwide cohort study on relapse risk and treatment safety"],"prefix":"10.1111","volume":"151","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5627-2388","authenticated-orcid":false,"given":"Jonne","family":"Lintunen","sequence":"first","affiliation":[{"name":"Department of Forensic Psychiatry University of Eastern Finland, Niuvanniemi Hospital  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2417-4059","authenticated-orcid":false,"given":"Aleksi","family":"Hamina","sequence":"additional","affiliation":[{"name":"Department of Forensic Psychiatry University of Eastern Finland, Niuvanniemi Hospital  Kuopio Finland"},{"name":"Norwegian Centre for Addiction Research (SERAF) Institute of Clinical Medicine, University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markku","family":"L\u00e4hteenvuo","sequence":"additional","affiliation":[{"name":"Department of Forensic Psychiatry University of Eastern Finland, Niuvanniemi Hospital  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tapio","family":"Palj\u00e4rvi","sequence":"additional","affiliation":[{"name":"Department of Forensic Psychiatry University of Eastern Finland, Niuvanniemi Hospital  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti","family":"Tanskanen","sequence":"additional","affiliation":[{"name":"Department of Forensic Psychiatry University of Eastern Finland, Niuvanniemi Hospital  Kuopio Finland"},{"name":"Department of Clinical Neuroscience Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jari","family":"Tiihonen","sequence":"additional","affiliation":[{"name":"Department of Forensic Psychiatry University of Eastern Finland, Niuvanniemi Hospital  Kuopio Finland"},{"name":"Department of Clinical Neuroscience Karolinska Institutet  Stockholm Sweden"},{"name":"Neuroscience Center University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3281-934X","authenticated-orcid":false,"given":"Heidi","family":"Taipale","sequence":"additional","affiliation":[{"name":"Department of Forensic Psychiatry University of Eastern Finland, Niuvanniemi Hospital  Kuopio Finland"},{"name":"Department of Clinical Neuroscience Karolinska Institutet  Stockholm Sweden"},{"name":"School of Pharmacy University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.18588"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2011.12"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.59.6.530"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145703003341"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40345\u2010023\u201000302\u2010x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1017\/S2045796019000593"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(15)00241\u2010X"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1906193"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/acps.13509"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12911\u2010015\u20100140\u2010z"},{"key":"e_1_2_10_12_1","volume-title":"Defined Daily Dose (DDD) \u2013 Definition and general considerations","author":"World Health Organization","year":"2024"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165\u20100327(11)70005\u20102"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/jcp.0b013e3181618eb4"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3109\/13651501.2011.632680"},{"key":"e_1_2_10_16_1","unstructured":"NICE.Bipolar disorder: assessment and management [NICE Guideline No. 185].2014."},{"key":"e_1_2_10_17_1","unstructured":"The Working group set up by the Finnish Medical Society Finnish Psychiatric Association and Finnish Adolescent Psychiatry Association. 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