{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:29:52Z","timestamp":1787066992593,"version":"build-2736575974"},"reference-count":66,"publisher":"Wiley","issue":"5-6","license":[{"start":{"date-parts":[[2011,10,21]],"date-time":"2011-10-21T00:00:00Z","timestamp":1319155200000},"content-version":"vor","delay-in-days":81,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bipolar Disorders"],"published-print":{"date-parts":[[2011,8]]},"abstract":"<jats:p>Sarris J, Mischoulon D, Schweitzer I. Adjunctive nutraceuticals with standard pharmacotherapies in bipolar disorder: a systematic review of clinical trials.\u2028Bipolar Disord 2011: 13: 454\u2013465. \u00a9 2011 The Authors. Journal compilation \u00a9 2011 John Wiley &amp; Sons A\/S.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Objective:\u2002<\/jats:bold>\n                    Studies using augmentation of pharmacotherapies with nutraceuticals in bipolar disorder (BD) have been conducted and preliminary evidence in many cases appears positive. To date, however, no specialized systematic review of this area has been conducted. We present the first systematic review of clinical trials using nutrient\u2010based nutraceuticals in combination with standard pharmacotherapies to treat BD. A subsequent aim of this report was to discuss posited underlying mechanisms of action.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:\u2002<\/jats:bold>\n                    PubMed, CINAHL, Web of Science, and Cochrane Library databases, and grey literature were searched during mid\u20102010 for human clinical trials in English using nutraceuticals such as omega\u20103, N\u2010acetyl cysteine (NAC), inositol, and vitamins and minerals, in combination with pharmacotherapies to treat bipolar mania and bipolar depression. A review of the results including an effect size analysis (Cohen\u2019s\n                    <jats:italic>d<\/jats:italic>\n                    ) was subsequently conducted.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:\u2002<\/jats:bold>\n                    In treating bipolar depression, positive evidence with large effect sizes were found for NAC (\n                    <jats:italic>d\u2003<\/jats:italic>\n                    =\n                    <jats:italic>\u2003<\/jats:italic>\n                    1.04) and a chelated mineral and vitamin formula (\n                    <jats:italic>d\u2003<\/jats:italic>\n                    =\n                    <jats:italic>\u2003<\/jats:italic>\n                    1.70). On the outcome of bipolar mania, several nutraceuticals reduced mania with strong clinical effects: a chelated mineral formula (\n                    <jats:italic>d\u2003<\/jats:italic>\n                    =\n                    <jats:italic>\u2003<\/jats:italic>\n                    0.83), L\u2010tryptophan (\n                    <jats:italic>d\u2003<\/jats:italic>\n                    =\n                    <jats:italic>\u2003<\/jats:italic>\n                    1.47), magnesium (\n                    <jats:italic>d\u2003<\/jats:italic>\n                    =\n                    <jats:italic>\u2003<\/jats:italic>\n                    1.44), folic acid (\n                    <jats:italic>d\u2003<\/jats:italic>\n                    =\n                    <jats:italic>\u2003<\/jats:italic>\n                    0.40), and branched\u2010chain amino acids (\n                    <jats:italic>d\u2003<\/jats:italic>\n                    =\n                    <jats:italic>\u2003<\/jats:italic>\n                    1.60). Mixed, but mainly positive, evidence was found for omega\u20103 for bipolar depression, while no evidentiary support was found for use in mania. No significant effect on BD outcome scales was found for inositol (possibly due to small samples).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:\u2002<\/jats:bold>\n                    BD treatment outcomes may potentially be improved by additional use of certain nutraceuticals with conventional pharmacotherapies. However, caution should be extended in interpreting the large effects of several isolated studies, as they have not yet been replicated in larger trials.\n                  <\/jats:p>","DOI":"10.1111\/j.1399-5618.2011.00945.x","type":"journal-article","created":{"date-parts":[[2011,10,21]],"date-time":"2011-10-21T10:50:32Z","timestamp":1319194232000},"page":"454-465","source":"Crossref","is-referenced-by-count":68,"title":["Adjunctive nutraceuticals with standard pharmacotherapies in bipolar disorder: a systematic review of clinical trials"],"prefix":"10.1111","volume":"13","author":[{"given":"Jerome","family":"Sarris","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Mischoulon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Schweitzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,10,21]]},"reference":[{"issue":"5","key":"e_1_2_7_2_2","first-page":"11","article-title":"Challenges in the management of bipolar depression","volume":"66","author":"Suppes T","year":"2005","journal-title":"J Clin Psychiatry"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/jclp.20333"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.clinpsy.2.022305.095332"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1159\/000091771"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1208\/ps050325"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ogc.2009.10.005"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.2009.00180.x"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v62n1204"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1037\/0033-2909.133.5.747"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v62n1203"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.182.3.210"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00406-007-0711-9"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2008.06.003"},{"issue":"1","key":"e_1_2_7_15_2","first-page":"220","article-title":"The role of eicosanoids in the brain","volume":"17","author":"Tassoni D","year":"2008","journal-title":"Asia Pac J Clin Nutr"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2006.07.009"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.2174\/1874467210902020207"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0278-5846(90)90099-3"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1517\/14728220802517901"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2009.04.001"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2009.12.005"},{"key":"e_1_2_7_22_2","volume-title":"Statistical Power Analyses for the Behavioral Sciences","author":"Cohen J","year":"1988"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2008.04.022"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v66n1219b"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/ejcn.2008.81"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v66n0608"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2010.00799.x"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2044-8341.1959.tb00467.x"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.56.5.407"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.188.1.46"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.133.5.429"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1177\/0269881106067787"},{"key":"e_1_2_7_33_2","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1176\/ajp.161.10.1922","article-title":"Omega\u20103 fatty acid treatment and T(2) whole brain relaxation times in bipolar disorder","volume":"161","author":"Hirashima F","year":"2004","journal-title":"Am J Psychiatry"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.03.056"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0b013e328336b615"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001887"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2006.07.005"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.134.4.382"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300659"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-3223(85)90026-5"},{"key":"e_1_2_7_41_2","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1080\/j.1440-1614.2005.01628.x","article-title":"Acute tryptophan depletion. Part II: clinical effects and implications","volume":"39","author":"Bell CJ","year":"2005","journal-title":"Aust N Z J Psychiatry"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2010.04.001"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-5618.2000.020107.x"},{"key":"e_1_2_7_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2006.00303.x"},{"key":"e_1_2_7_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-1781(99)00116-X"},{"key":"e_1_2_7_46_2","first-page":"483","article-title":"Benzodiazepine\/GABA(A) receptors are involved in magnesium\u2010induced anxiolytic\u2010like behavior in mice","volume":"60","author":"Poleszak E","year":"2008","journal-title":"Pharmacol Rep"},{"key":"e_1_2_7_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2006.01.047"},{"key":"e_1_2_7_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0327(86)90043-1"},{"key":"e_1_2_7_49_2","volume-title":"The Beck Depression Inventory","author":"Beck A","year":"1987"},{"key":"e_1_2_7_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.2009.01368.x"},{"key":"e_1_2_7_51_2","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.2007.164.6.861"},{"key":"e_1_2_7_52_2","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.2009.28313"},{"key":"e_1_2_7_53_2","doi-asserted-by":"publisher","DOI":"10.1080\/07315724.2009.10719785"},{"key":"e_1_2_7_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2006.07.003"},{"key":"e_1_2_7_55_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2007.00386.x"},{"key":"e_1_2_7_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2010.09.004"},{"key":"e_1_2_7_57_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/75.3.492"},{"key":"e_1_2_7_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(02)00123-9"},{"key":"e_1_2_7_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.03.039"},{"key":"e_1_2_7_60_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2009.09060881"},{"key":"e_1_2_7_61_2","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2009.192"},{"key":"e_1_2_7_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2006.11.006"},{"key":"e_1_2_7_63_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.160.5.996"},{"key":"e_1_2_7_64_2","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v64n0317d"},{"key":"e_1_2_7_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-3223(95)00423-8"},{"key":"e_1_2_7_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-1781(99)00107-9"},{"key":"e_1_2_7_67_2","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.139.9.1162"}],"container-title":["Bipolar Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1399-5618.2011.00945.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1399-5618.2011.00945.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T08:09:24Z","timestamp":1693382964000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1399-5618.2011.00945.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,8]]},"references-count":66,"journal-issue":{"issue":"5-6","published-print":{"date-parts":[[2011,8]]}},"alternative-id":["10.1111\/j.1399-5618.2011.00945.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1399-5618.2011.00945.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":[[2011,8]]}}}