{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T03:04:05Z","timestamp":1785380645954,"version":"3.55.0"},"reference-count":20,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,4,8]],"date-time":"2014-04-08T00:00:00Z","timestamp":1396915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bipolar Disorders"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>An emerging body of evidence supports a role for dysfunctional purinergic neurotransmission in mood disorders. Adenosine agonists have been shown to have properties similar to those of dopamine antagonists; there is a well\u2010characterized interaction between adenosine and dopamine receptors in the ventral striatum, and increasing adenosinergic transmission has been demonstrated to reduce the affinity of dopamine agonists for dopamine receptors. Allopurinol increases adenosine levels in the brain, and hence is hypothesized to reduce the symptoms of mania. Two randomized, placebo\u2010controlled trials administering add\u2010on allopurinol to manic patients showed significantly greater improvements in Young Mania Rating Scale (<jats:styled-content style=\"fixed-case\">YMRS<\/jats:styled-content>) scores for drug compared to placebo, while a more recent, relatively small, add\u2010on study showed negative results. Based on these data, our objective was to examine the efficacy of allopurinol as add\u2010on treatment to mood stabilizers and\/or antipsychotic agents in manic patients with bipolar disorder.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a large, well\u2010powered, multicenter, six\u2010week, randomized, placebo\u2010controlled trial of allopurinol added to mood stabilizers and\/or antipsychotic agents in 180 patients with bipolar disorder in an acute manic episode.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both groups showed improvement on the <jats:styled-content style=\"fixed-case\">YMRS<\/jats:styled-content> (effect size of 1.5 for placebo and 1.6 for allopurinol), with no difference observed between groups on <jats:styled-content style=\"fixed-case\">YMRS<\/jats:styled-content> scores (<jats:italic>t\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.28, p\u00a0=\u00a00.78). There was no difference in the proportion of patients who responded to treatment (defined as showing at least 50% improvement in <jats:styled-content style=\"fixed-case\">YMRS<\/jats:styled-content> score) between the two groups (p\u00a0=\u00a00.92), or in dropout rates (p\u00a0=\u00a00.84).<\/jats:p><\/jats:sec><jats:sec><jats:title>Limitations<\/jats:title><jats:p>None of our patients received lithium. However, the side effects of lithium and its narrow therapeutic index made the use of lithium less common and, therefore, our study results reflect common current clinical practice. In the present study, we used a variety of antipsychotic and\/or mood stabilizing treatments, to which we added allopurinol; one might hypothesize that add\u2010on allopurinol has a different effect in combination with different antipsychotic agents or mood stabilizers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The findings of this large, well\u2010powered study do not support add\u2010on allopurinol as a treatment for acute mania. This study did not test the efficacy of allopurinol as monotherapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bdi.12202","type":"journal-article","created":{"date-parts":[[2014,4,8]],"date-time":"2014-04-08T19:18:09Z","timestamp":1396984689000},"page":"441-447","source":"Crossref","is-referenced-by-count":30,"title":["Allopurinol for mania: a randomized trial of allopurinol versus placebo as add\u2010on treatment to mood stabilizers and\/or antipsychotic agents in manic patients with bipolar disorder"],"prefix":"10.1111","volume":"16","author":[{"given":"Mark","family":"Weiser","sequence":"first","affiliation":[{"name":"Division of Psychiatry Chaim Sheba Medical Center Tel\u2010Hashomer Israel"},{"name":"Sackler School of Medicine Tel Aviv University Ramat Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimon","family":"Burshtein","sequence":"additional","affiliation":[{"name":"Division of Psychiatry Chaim Sheba Medical Center Tel\u2010Hashomer Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari A","family":"Gershon","sequence":"additional","affiliation":[{"name":"Division of Psychiatry Chaim Sheba Medical Center Tel\u2010Hashomer Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Marian","sequence":"additional","affiliation":[{"name":"Spitalul Clinic de Psihiatrie Obregia Bucuresti Romania"},{"name":"TGD\u2010Tangent Data Bucharest Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolae","family":"Vlad","sequence":"additional","affiliation":[{"name":"TGD\u2010Tangent Data Bucharest Romania"},{"name":"Spitalul de Psihiatrie Botosani I.C.Bratianu Botosani Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iosif G","family":"Grecu","sequence":"additional","affiliation":[{"name":"TGD\u2010Tangent Data Bucharest Romania"},{"name":"Spitalul Clinic Judetean Mures\u2010Sectia Clinica Psihiatrie I. Gh Marinescu  Craiova Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Tocari","sequence":"additional","affiliation":[{"name":"TGD\u2010Tangent Data Bucharest Romania"},{"name":"Spitalul Judetean Vrancea Sectia Psihiatrie Focsani Comisia Centrala Craiova Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandru","family":"Tiugan","sequence":"additional","affiliation":[{"name":"TGD\u2010Tangent Data Bucharest Romania"},{"name":"Sp. Clinic de Urgenta Militar \u201cDr. Stefan Odoblegea\u201d Craiova Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihail","family":"Hotineanu","sequence":"additional","affiliation":[{"name":"TGD\u2010Tangent Data Bucharest Romania"},{"name":"Spitalul Clinic de Psihiatrie Chisinau Chisinau Republica Moldova"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Illinois Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,4,8]]},"reference":[{"issue":"13","key":"e_1_2_7_2_1","first-page":"38","article-title":"The economic burden of bipolar disease","volume":"61","author":"Woods SW","year":"2000","journal-title":"J Clin Psychiatry"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001793"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.16.7238"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-5949.2009.00126.x"},{"key":"e_1_2_7_6_1","first-page":"466","article-title":"Recent progress in the discovery of adenosine A(2A) receptor antagonists for the treatment of Parkinson's disease","volume":"13","author":"Shah U","year":"2010","journal-title":"Curr Opin Drug Discov Devel"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2006.02.002"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.11.061"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002130050380"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(95)00668-0"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2010.109"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-89615-9_17"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2006.00363.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v69n0806"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2012.01001.x"},{"key":"e_1_2_7_16_1","volume-title":"Structured Clinical Interview for DSM\u2010IV Axis I Disorders (SCID)","author":"First MB","year":"1997"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.133.5.429"},{"key":"e_1_2_7_18_1","first-page":"217","volume-title":"ECDEU Assessment Manual for Psychopharmacology","author":"Guy W","year":"1976"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/13.2.261"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2007.06081358"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.11m07031"}],"container-title":["Bipolar Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbdi.12202","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bdi.12202","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T10:03:52Z","timestamp":1695549832000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bdi.12202"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,4,8]]},"references-count":20,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,6]]}},"alternative-id":["10.1111\/bdi.12202"],"URL":"https:\/\/doi.org\/10.1111\/bdi.12202","archive":["Portico"],"relation":{},"ISSN":["1398-5647","1399-5618"],"issn-type":[{"value":"1398-5647","type":"print"},{"value":"1399-5618","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,4,8]]}}}