{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T08:17:15Z","timestamp":1777537035842,"version":"3.51.4"},"reference-count":19,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,3,15]],"date-time":"2012-03-15T00:00:00Z","timestamp":1331769600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bipolar Disorders"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:p>Fan A, Berg A, Bresee C, Glassman LH, Rapaport MH. Allopurinol augmentation in the outpatient treatment of bipolar mania: a pilot study. Bipolar Disord 2012: 14: 206\u2013210. \u00a9 2012 The Authors. Journal compilation \u00a9 2012 John Wiley &amp; Sons A\/S.<\/jats:p><jats:p><jats:bold>Background:\u2002<\/jats:bold> Allopurinol promotes the salvage of purines, possibly increasing endogenous adenosine levels. Recent studies suggest that adenosine has neuroprotective and inhibitory effects. Two previous inpatient trials demonstrated that allopurinol has anti\u2010manic activity. Our objective was to test allopurinol as an adjunct to standard medications in bipolar disorder manic outpatients.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> In this double\u2010blind, placebo\u2010controlled trial, 27 subjects who met DSM\u2010IV criteria for bipolar disorder and scored \u2265 14 on the Young Mania Rating Scale (YMRS) were randomized to augmentation with allopurinol or placebo for six weeks. The primary efficacy measure was the YMRS. The primary safety measure was the Treatment Emergent Symptom Scale.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> The effect of allopurinol augmentation in decreasing mean YMRS scores was modest, with an overall effect size of \u22120.25 (Cohen\u2019s <jats:italic>d<\/jats:italic>). Allopurinol\u2010treated individuals who abstained from caffeine (n\u2003=\u20034) had a greater decrease in YMRS scores (\u221215.3\u2003\u00b1\u20031.8) than subjects using caffeine (n\u2003=\u20035) (\u22129.6\u2003\u00b1\u20033.4, p\u2003=\u20030.219), with an effect size of \u22120.86.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> In this small outpatient pilot study, allopurinol augmentation did not show a statistically significant improvement over placebo in attenuating manic symptoms. Subjects with restricted caffeine use showed a greater effect size compared to caffeine users. This finding may be interpreted as corroborating the hypothesized mechanism of action of allopurinol\u2019s anti\u2010manic effect in previous studies.<\/jats:p>","DOI":"10.1111\/j.1399-5618.2012.01001.x","type":"journal-article","created":{"date-parts":[[2012,3,15]],"date-time":"2012-03-15T13:52:20Z","timestamp":1331819540000},"page":"206-210","source":"Crossref","is-referenced-by-count":23,"title":["Allopurinol augmentation in the outpatient treatment of bipolar mania: a pilot study"],"prefix":"10.1111","volume":"14","author":[{"given":"Alexander","family":"Fan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Berg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Bresee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa Hayley","family":"Glassman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark Hyman","family":"Rapaport","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,3,15]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001793"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1517\/14656560903064170"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2010.109"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-89615-9_17"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-5949.2009.00126.x"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2010.06.005"},{"key":"e_1_2_6_8_2","first-page":"466","article-title":"Recent progress in the discovery of adenosine A(2A) receptor antagonists for the treatment of Parkinson\u2019s disease","volume":"13","author":"Shah U","year":"2010","journal-title":"Curr Opin Drug Discov Devel"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.11.061"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.16.7238"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2004.11.008"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcmed.2006.10.010"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2006.00363.x"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v69n0806"},{"issue":"20","key":"e_1_2_6_15_2","first-page":"22","article-title":"The Mini\u2010International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM\u2010IV and ICD\u201010","volume":"59","author":"Sheehan DV","year":"1998","journal-title":"J Clin Psychiatry"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2044-8341.1959.tb00467.x"},{"key":"e_1_2_6_17_2","volume-title":"ECDEU Assessment Manual for Psychopharmacology","author":"Guy W","year":"1976"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1053\/comp.2003.50024"},{"key":"e_1_2_6_19_2","first-page":"321","article-title":"Quality of Life Enjoyment and Satisfaction Questionnaire: a new measure","volume":"29","author":"Endicott J","year":"1993","journal-title":"Psychopharmacol Bull"},{"key":"e_1_2_6_20_2","volume-title":"Statistical Power Analysis for the Behavioral Sciences","author":"Cohen J","year":"1988"}],"container-title":["Bipolar Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1399-5618.2012.01001.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1399-5618.2012.01001.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T05:49:36Z","timestamp":1698731376000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1399-5618.2012.01001.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,3]]},"references-count":19,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2012,3]]}},"alternative-id":["10.1111\/j.1399-5618.2012.01001.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1399-5618.2012.01001.x","archive":["Portico"],"relation":{},"ISSN":["1398-5647","1399-5618"],"issn-type":[{"value":"1398-5647","type":"print"},{"value":"1399-5618","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,3]]}}}