{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T02:59:41Z","timestamp":1789095581270,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,5,17]],"date-time":"2018-05-17T00:00:00Z","timestamp":1526515200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 103\u20102622\u2010B\u2010006\u2010006\u2010CC2"],"award-info":[{"award-number":["MOST 103\u20102622\u2010B\u2010006\u2010006\u2010CC2"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 104\u20102622\u2010B\u2010006\u2010006\u2010CC2"],"award-info":[{"award-number":["MOST 104\u20102622\u2010B\u2010006\u2010006\u2010CC2"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 103\u20102314\u2010B\u2010075B\u2010006"],"award-info":[{"award-number":["MOST 103\u20102314\u2010B\u2010075B\u2010006"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000276","name":"Department of Health","doi-asserted-by":"publisher","award":["DOH95\u2010TD\u2010M\u2010113\u2010055"],"award-info":[{"award-number":["DOH95\u2010TD\u2010M\u2010113\u2010055"]}],"id":[{"id":"10.13039\/501100000276","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["NHRI\u2010EX\u201097\u20109738NI"],"award-info":[{"award-number":["NHRI\u2010EX\u201097\u20109738NI"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Bipolar disorder (BD), especially BD\u2010II, is frequently comorbid with alcohol dependence. Because BD\u2010II and alcohol dependence are neurodegenerative disorders, agents with anti\u2010inflammatory and neurotrophic effects might provide effective therapy. We investigated whether add\u2010on memantine to regular valproic acid treatment ameliorated clinical symptoms, reduced alcohol use, and cytokine levels, and increased plasma brain\u2010derived neurotrophic factor (BDNF) in BD\u2010II patients with comorbid alcohol dependence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a single\u2010arm 12\u2010week clinical trial, BD\u2010II patients with comorbid alcohol dependence (<jats:italic>n<\/jats:italic>\u00a0=\u00a045) undergoing regular valproic acid treatments were given add\u2010on memantine (5\u00a0mg\/d). Symptom severity, alcohol use, cytokine (plasma tumor necrosis factor\u2010\u03b1 and C\u2010reactive protein [CRP], transforming growth factor\u2010\u03b21 [TGF\u2010\u03b21], interleukin\u20108 [IL\u20108], IL\u201010), and plasma BDNF levels were regularly assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mean within\u2010group decreases in Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) scores, alcohol use, CRP, BDNF, and IL\u20108 levels were significantly different from baseline after 12\u00a0weeks of treatment. We found no significant correlation between alcohol use levels and changes in HDRS or YMRS scores. The correlation between reduced alcohol use and reduced TGF\u2010\u03b21 level was significant (<jats:italic>B<\/jats:italic>\u00a0=\u00a00.003, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.019).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>BD\u2010II comorbid with alcohol dependence might benefit from add\u2010on memantine treatment, which significantly reduced clinical severity, alcohol use, and plasma cytokine levels, and increased BDNF levels.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.13640","type":"journal-article","created":{"date-parts":[[2018,4,15]],"date-time":"2018-04-15T21:50:02Z","timestamp":1523829002000},"page":"1044-1050","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Add\u2010On Memantine Treatment for Bipolar II Disorder Comorbid with Alcohol Dependence: A 12\u2010Week Follow\u2010Up Study"],"prefix":"10.1111","volume":"42","author":[{"given":"Sheng\u2010Yu","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Psychiatry  Kaohsiung Veterans General Hospital Kaohsiung Taiwan"},{"name":"Department of Psychiatry  School of Medicine Graduate Institute of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan"},{"name":"Department of Psychiatry  College of Medicine National Yang\u2010Ming University Taipei Taiwan"},{"name":"Department of Psychiatry  College of Medicine and Hospital National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu\u2010Yun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry  College of Medicine and Hospital National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiou\u2010Lan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology  School of Medicine Kaohsiung Medical University Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun\u2010Hsuan","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Psychology  College of Medical and Health Science Asia University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po\u2010See","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry  College of Medicine and Hospital National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"San\u2010Yuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry  Tri\u2010Service General Hospital National Defense Medical Center Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nian\u2010Sheng","family":"Tzeng","sequence":"additional","affiliation":[{"name":"Department of Psychiatry  Tri\u2010Service General Hospital National Defense Medical Center Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang\u2010Jen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry  Kaohsiung Chang Gung Memorial Hospital Chang Gung University College of Medicine Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. Hui","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Psychiatry  College of Medicine and Hospital National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kao Ching","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry  College of Medicine and Hospital National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen Kuang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry  College of Medicine and Hospital National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jau\u2010Shyong","family":"Hong","sequence":"additional","affiliation":[{"name":"Laboratory of Toxicology and Pharmacology  NIH\/NIEHS Research Triangle Park North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6411-3547","authenticated-orcid":false,"given":"Ru\u2010Band","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry  College of Medicine and Hospital National Cheng Kung University Tainan Taiwan"},{"name":"Addiction Research Center  National Cheng Kung University Tainan Taiwan"},{"name":"Beijing YiNing Hospital  Beijing China"},{"name":"Center for Neuropsychiatric Research  National Health Research Institutes Miaoli Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,5,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12177"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcn.12089"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3109\/08039488.2014.990919"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2010.09071011"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.1992.tb01921.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0327(99)00038-5"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0327(02)00327-0"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2004.04.006"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-003-1617-5"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2008.01.006"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-011-9337-9"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2882604"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2017.04.033"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eurpsy.2013.07.004"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1978.01770310043002"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2007.00360.x"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2006.00370.x"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0010-440X(00)90043-9"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ALC.0000117832.62901.61"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0327(02)00324-5"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2009.24.5.941"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2008.00627.x"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep10140"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0000000000000109"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2013.09.013"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0379-0738(88)90225-3"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2015-0257"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2005.11.015"},{"key":"e_1_2_9_30_1","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1176\/ajp.156.7.1094","article-title":"Awareness of illness and subjective experience of cognitive complaints in patients with bipolar I and bipolar II disorder","volume":"156","author":"Pallanti S","year":"1999","journal-title":"Am J Psychiatry"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(98)00141-5"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(98)00086-6"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-160860"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(99)00019-2"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60989-7"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1177\/0004867413499077"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0193-953X(05)70101-5"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-001-0479-6"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2010.10.004"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/neup.12191"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1177\/0004867415585855"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2015.07.027"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1503\/jpn.100080"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/YCO.0b013e32835aa4b4"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyw012"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2009.64"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2012.02880.x"}],"container-title":["Alcoholism: Clinical and Experimental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Facer.13640","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acer.13640","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T20:13:38Z","timestamp":1695500018000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acer.13640"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,17]]},"references-count":46,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1111\/acer.13640"],"URL":"https:\/\/doi.org\/10.1111\/acer.13640","archive":["Portico"],"relation":{},"ISSN":["0145-6008","1530-0277"],"issn-type":[{"value":"0145-6008","type":"print"},{"value":"1530-0277","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,17]]},"assertion":[{"value":"2017-10-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}