{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:46:08Z","timestamp":1790747168307,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T00:00:00Z","timestamp":1673913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007132","name":"Otsuka Pharmaceutical","doi-asserted-by":"publisher","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/501100007132","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropsychopharm Rep"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Selective serotonin reuptake inhibitors (SSRIs) are used to treat major depressive disorder (MDD) and other psychiatric disorders (e.g., obsessive compulsive disorder, social anxiety disorder, and panic disorder). In MDD treatment, SSRIs do not show remission in approximately 30% of patients, indicating a need for a better treatment option. Forced swimming test (FST) is a behavioral assay to evaluate depression\u2010like behavior and antidepressant efficacy in rodents. In the present study, we evaluated the combination effect of brexpiprazole with SSRIs on FST in mice, in order to investigate their synergistic effect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Brexpiprazole (0.003\u2009mg\/kg) was intraperitoneally injected to mice 15\u00a0min before testing. Escitalopram (10\u00a0mg\/kg), fluoxetine (75\u2009mg\/kg), paroxetine (10\u00a0mg\/kg), or sertraline (15\u2009mg\/kg) were orally administered to mice 60\u00a0min before testing. Then, the mice were placed in water and immobility time was measured. Data from animals treated with escitalopram, fluoxetine, paroxetine, and sertraline were pooled as SSRI\u2010treated group data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Combination treatment of brexpiprazole with SSRIs reduced immobility time in FST more than vehicle or each single treatment. A significant interaction effect was confirmed in the combination of brexpiprazole and SSRIs (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.0411).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Efficacy of adjunctive brexpiprazole has already been demonstrated in clinical trials in MDD patients not adequately responding to antidepressants including escitalopram, fluoxetine, paroxetine, and sertraline. The synergistic antidepressant\u2010like effect of brexpiprazole with SSRIs found in this study supports the already known clinical findings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/npr2.12316","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T22:59:42Z","timestamp":1673996382000},"page":"132-136","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Synergistic anti\u2010depressive effect of combination treatment of Brexpiprazole and selective serotonin reuptake inhibitors on forced swimming test in mice"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9625-6240","authenticated-orcid":false,"given":"Naoki","family":"Amada","sequence":"first","affiliation":[{"name":"Department of CNS Research Otsuka Pharmaceutical Co., Ltd.  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Hirose","sequence":"additional","affiliation":[{"name":"Department of CNS Research Otsuka Pharmaceutical Co., Ltd.  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikio","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of CNS Research Otsuka Pharmaceutical Co., Ltd.  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Kakumoto","sequence":"additional","affiliation":[{"name":"Department of Lead Discovery Research Otsuka Pharmaceutical Co., Ltd.  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Futamura","sequence":"additional","affiliation":[{"name":"Department of CNS Research Otsuka Pharmaceutical Co., Ltd.  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Lead Discovery Research Otsuka Pharmaceutical Co., Ltd.  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3902-7302","authenticated-orcid":false,"given":"Tetsuro","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Pharmaceutical Division Otsuka Pharmaceutical Co., Ltd.  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