{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T14:35:25Z","timestamp":1775054125393,"version":"3.50.1"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,1,12]],"date-time":"2006-01-12T00:00:00Z","timestamp":1137024000000},"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":[[2006,2]]},"abstract":"<jats:p>\n                    <jats:bold>Introduction:\u2002<\/jats:bold>\n                    Because there is a high rate of partial response to standard thymoleptic medication, novel augmentation strategies for treatment\u2010resistant bipolar disorder are needed. In an open trial, donepezil augmentation was associated with improvement in manic symptoms in 9 of 11 subjects.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Method:\u2002<\/jats:bold>\n                    We conducted a 6\u2010week, double\u2010blind, placebo\u2010controlled trial of donepezil for treatment\u2010resistant bipolar mania. Eligible subjects had a Young Mania Rating Scale (YMRS) score of at least 15 despite two or more weeks of proven therapeutic levels of lithium or valproate. Subjects who completed the trial were eligible for an 8\u2010week open trial of donepezil. Subjects were started on donepezil 5\u2003mg\/day and were eligible for dose increase to 10\u2003mg\/day after 4\u2003weeks.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:\u2002<\/jats:bold>\n                    Twelve subjects were enrolled. Eleven subjects received at least 1\u2003week of study medication and were included in the analysis. No subjects in the donepezil group (0\/6) and 60% (3\/5) in the placebo group met response criteria of &gt;30% reduction in YMRS score (Fisher's Exact p\u2003=\u20030.061). YMRS scores were higher at trial endpoint in the donepezil group 20.17 (3.66) compared with the placebo group [11.20 (4.60), Z\u2003=\u2003\u22122.476, p\u2003=\u20030.01]. There were no differences at trial endpoint in Hamilton Rating Scale for Depression (HAM\u2010D) or Brief Psychiatric Rating Scale (BPRS) scores in either the intent\u2010to\u2010treat or the completer analyses.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:\u2002<\/jats:bold>\n                    Donepezil does not appear to be an effective adjunctive treatment for refractory manic symptoms. The strength of the conclusion of this trial is limited by the possibility of a false\u2010negative result due to the small sample.\n                  <\/jats:p>","DOI":"10.1111\/j.1399-5618.2006.00243.x","type":"journal-article","created":{"date-parts":[[2006,1,12]],"date-time":"2006-01-12T08:25:50Z","timestamp":1137054350000},"page":"75-80","source":"Crossref","is-referenced-by-count":36,"title":["A double\u2010blind, placebo\u2010controlled trial of adjunctive donepezil in treatment\u2010resistant mania"],"prefix":"10.1111","volume":"8","author":[{"given":"Evins","family":"A E","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Demopulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Nierenberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa A.","family":"Culhane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lori","family":"Eisner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Sachs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,1,12]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291700001975"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.147.4.431"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.149.1.108"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1991.01810250064008"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1997.01830130041008"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1991.01810340047006"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.152.11.1635"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1994.03510360044034"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(72)90956-7"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001019"},{"key":"e_1_2_6_12_2","first-page":"23","article-title":"Pharmacological 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donepezil","volume":"44","author":"Benazzi F","year":"1999","journal-title":"Can J Psychiatry"},{"key":"e_1_2_6_22_2","first-page":"468","article-title":"Mania associated with donepezil","volume":"24","author":"Benazzi F","year":"1999","journal-title":"J Psychiatry Neurosci"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(98)00320-5"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.133.5.429"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.2466\/pr0.1962.10.3.799"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2044-8341.1959.tb00467.x"},{"key":"e_1_2_6_27_2","first-page":"343","article-title":"SAFTEE: a technique for the systematic assessment of side effects in clinical trials","volume":"22","author":"Levine J","year":"1986","journal-title":"Psychopharmacol Bull"}],"container-title":["Bipolar 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