{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T08:12:42Z","timestamp":1794557562389,"version":"4.9.1"},"reference-count":56,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:p>Depression is the predominant pole of disability in bipolar disorder and compared with mania\/hypomania, has less systematic research guiding the development of treatment especially in its acute phase (acute bipolar depression). The deficiency in the management of the acute bipolar depression largely reflects the natural divergence of opinion resulting from significant knowledge gaps. At present, there are only 3 approved drug treatments for acute bipolar depression: olanzapine\/fluoxetine combination, quetiapine (immediate or extended release), and lurasidone (monotherapy or adjunctive to lithium or valproate). Nonapproved agents and nonpharmacologic treatment such as lamotrigine, antidepressants, modafinil, pramipexole, ketamine, and electroconvulsive therapy are often prescribed to treat acute bipolar depression. This article discusses the challenges of diagnosing bipolar depression, and reviews above treatment options for acute bipolar depression.<\/jats:p>","DOI":"10.4103\/tcmj.tcmj_71_18","type":"journal-article","created":{"date-parts":[[2018,5,29]],"date-time":"2018-05-29T02:11:17Z","timestamp":1527559877000},"page":"141-147","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":8,"title":["Treatment of acute bipolar depression"],"prefix":"10.4103","volume":"30","author":[{"given":"Yu-Chih","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Buddhist Tzu Chi General Hospital, Hualien, Taiwan"},{"name":"School of Medicine, Tzu Chi University, Hualien, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-20250518","doi-asserted-by":"crossref","first-page":"e8508","DOI":"10.1136\/bmj.e8508","article-title":"Bipolar disorder","volume":"345","author":"Anderson","year":"2012","journal-title":"BMJ"},{"key":"R2-20250518","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1001\/archpsyc.60.3.261","article-title":"A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder","volume":"60","author":"Judd","year":"2003","journal-title":"Arch Gen Psychiatry"},{"key":"R3-20250518","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1001\/archpsyc.59.6.530","article-title":"The long-term natural history of the weekly symptomatic status of bipolar I disorder","volume":"59","author":"Judd","year":"2002","journal-title":"Arch Gen Psychiatry"},{"key":"R4-20250518","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1001\/archpsyc.62.12.1322","article-title":"Psychosocial disability in the course of bipolar I and II disorders: A prospective, comparative, longitudinal study","volume":"62","author":"Judd","year":"2005","journal-title":"Arch Gen Psychiatry"},{"key":"R5-20250518","doi-asserted-by":"crossref","first-page":"161","DOI":"10.4088\/JCP.v64n0209","article-title":"Perceptions and impact of bipolar disorder: How far have we really come?. Results of the national depressive and manic-depressive association 2000 survey of individuals with bipolar disorder","volume":"64","author":"Hirschfeld","year":"2003","journal-title":"J Clin Psychiatry"},{"key":"R6-20250518","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.jad.2015.03.027","article-title":"Causes of decreased life expectancy over the life span in bipolar disorder","volume":"180","author":"Kessing","year":"2015","journal-title":"J Affect Disord"},{"key":"R7-20250518","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1001\/jamapsychiatry.2013.1394","article-title":"Comorbidities and mortality in bipolar disorder: A Swedish national cohort study","volume":"70","author":"Crump","year":"2013","journal-title":"JAMA Psychiatry"},{"key":"R8-20250518","doi-asserted-by":"crossref","first-page":"e19590","DOI":"10.1371\/journal.pone.0019590","article-title":"Life expectancy at birth for people with serious mental illness and other major disorders from a secondary mental health care case register in London","volume":"6","author":"Chang","year":"2011","journal-title":"PLoS One"},{"key":"R9-20250518","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1590\/S1516-44462009005000003","article-title":"Suicidal ideation and suicide attempts in bipolar disorder type I: An update for the clinician","volume":"31","author":"Abreu","year":"2009","journal-title":"Rev Bras Psiquiatr"},{"key":"R10-20250518","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1111\/bdi.12087","article-title":"Epidemiology of suicide in bipolar disorders: A systematic review of the literature","volume":"15","author":"Pompili","year":"2013","journal-title":"Bipolar Disord"},{"key":"R11-20250518","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1001\/archgenpsychiatry.2011.113","article-title":"Absolute risk of suicide after first hospital contact in mental disorder","volume":"68","author":"Nordentoft","year":"2011","journal-title":"Arch Gen Psychiatry"},{"key":"R12-20250518","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/bdi.12271","article-title":"International Society for Bipolar Disorders Task Force on Suicide: Meta-analyses and meta-regression of correlates of suicide attempts and suicide deaths in bipolar disorder","volume":"17","author":"Schaffer","year":"2015","journal-title":"Bipolar Disord"},{"key":"R13-20250518","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1001\/jamapsychiatry.2013.3579","article-title":"Accuracy of reports of lifetime mental and physical disorders: Results from the Baltimore Epidemiological Catchment Area Study","volume":"71","author":"Takayanagi","year":"2014","journal-title":"JAMA Psychiatry"},{"key":"R14-20250518","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1176\/appi.ps.52.1.51","article-title":"Strategies to reduce misdiagnosis of bipolar depression","volume":"52","author":"Bowden","year":"2001","journal-title":"Psychiatr Serv"},{"key":"R15-20250518","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.jad.2010.02.118","article-title":"A population-based analysis of distinguishers of bipolar disorder from major depressive disorder","volume":"125","author":"Schaffer","year":"2010","journal-title":"J Affect Disord"},{"key":"R16-20250518","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1192\/bjp.bp.110.086983","article-title":"Association between antidepressant resistance in unipolar depression and subsequent bipolar disorder: Cohort study","volume":"200","author":"Li","year":"2012","journal-title":"Br J Psychiatry"},{"key":"R17-20250518","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3109\/15622970903555881","article-title":"The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders: Update 2010 on the treatment of acute bipolar depression","volume":"11","author":"Grunze","year":"2010","journal-title":"World J Biol Psychiatry"},{"key":"R18-20250518","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/j.1399-5618.2007.00559.x","article-title":"Diagnostic guidelines for bipolar depression: A probabilistic approach","volume":"10","author":"Mitchell","year":"2008","journal-title":"Bipolar Disord"},{"key":"R19-20250518","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1001\/archpsyc.60.11.1079","article-title":"Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression","volume":"60","author":"Tohen","year":"2003","journal-title":"Arch Gen Psychiatry"},{"key":"R20-20250518","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1192\/bjp.bp.112.108357","article-title":"Randomised, double-blind, placebo-controlled study of olanzapine in patients with bipolar I depression","volume":"201","author":"Tohen","year":"2012","journal-title":"Br J Psychiatry"},{"key":"R21-20250518","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1176\/appi.ajp.162.7.1351","article-title":"A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression","volume":"162","author":"Calabrese","year":"2005","journal-title":"Am J Psychiatry"},{"key":"R22-20250518","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1097\/01.jcp.0000248603.76231.b7","article-title":"Efficacy of quetiapine monotherapy in bipolar I and II depression: A double-blind, placebo-controlled study (the BOLDER II study)","volume":"26","author":"Thase","year":"2006","journal-title":"J Clin Psychopharmacol"},{"key":"R23-20250518","doi-asserted-by":"crossref","first-page":"163","DOI":"10.4088\/JCP.08m04942gre","article-title":"A double-blind, placebo-controlled study of quetiapine and paroxetine as monotherapy in adults with bipolar depression (EMBOLDEN II)","volume":"71","author":"McElroy","year":"2010","journal-title":"J Clin Psychiatry"},{"key":"R24-20250518","doi-asserted-by":"crossref","first-page":"150","DOI":"10.4088\/JCP.08m04995gre","article-title":"A double-blind, placebo-controlled study of quetiapine and lithium monotherapy in adults in the acute phase of bipolar depression (EMBOLDEN I)","volume":"71","author":"Young","year":"2010","journal-title":"J Clin Psychiatry"},{"key":"R25-20250518","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jad.2009.10.007","article-title":"Effectiveness of the extended release formulation of quetiapine as monotherapy for the treatment of acute bipolar depression","volume":"121","author":"Suppes","year":"2010","journal-title":"J Affect Disord"},{"key":"R26-20250518","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1176\/appi.ajp.2013.13070985","article-title":"Lurasidone as adjunctive therapy with lithium or valproate for the treatment of bipolar I depression: A randomized, double-blind, placebo-controlled study","volume":"171","author":"Loebel","year":"2014","journal-title":"Am J Psychiatry"},{"key":"R27-20250518","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1176\/appi.ajp.2013.13070984","article-title":"Lurasidone monotherapy in the treatment of bipolar I depression: A randomized, double-blind, placebo-controlled study","volume":"171","author":"Loebel","year":"2014","journal-title":"Am J Psychiatry"},{"key":"R28-20250518","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/ijcp.12142","article-title":"When does a difference make a difference?. Interpretation of number needed to treat, number needed to harm, and likelihood to be helped or harmed","volume":"67","author":"Citrome","year":"2013","journal-title":"Int J Clin Pract"},{"key":"R29-20250518","doi-asserted-by":"crossref","first-page":"2751","DOI":"10.1517\/14656566.2011.632368","article-title":"Olanzapine-fluoxetine combination for the treatment of bipolar depression","volume":"12","author":"Citrome","year":"2011","journal-title":"Expert Opin Pharmacother"},{"key":"R30-20250518","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.jad.2013.10.040","article-title":"Clinical assessment of lurasidone benefit and risk in the treatment of bipolar I depression using number needed to treat, number needed to harm, and likelihood to be helped or harmed","volume":"155","author":"Citrome","year":"2014","journal-title":"J Affect Disord"},{"key":"R31-20250518","doi-asserted-by":"crossref","first-page":"79","DOI":"10.4088\/JCP.v60n0203","article-title":"A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal 602 Study Group","volume":"60","author":"Calabrese","year":"1999","journal-title":"J Clin Psychiatry"},{"key":"R32-20250518","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1192\/bjp.bp.107.048504","article-title":"Lamotrigine for treatment of bipolar depression: Independent meta-analysis and meta-regression of individual patient data from five randomised trials","volume":"194","author":"Geddes","year":"2009","journal-title":"Br J Psychiatry"},{"key":"R33-20250518","doi-asserted-by":"crossref","first-page":"223","DOI":"10.4088\/JCP.08m04152","article-title":"Efficacy and safety of lamotrigine as add-on treatment to lithium in bipolar depression: A multicenter, double-blind, placebo-controlled trial","volume":"70","author":"van der Loos","year":"2009","journal-title":"J Clin Psychiatry"},{"key":"R34-20250518","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/j.1399-5618.2007.00500.x","article-title":"Lamotrigine in the acute treatment of bipolar depression: Results of five double-blind, placebo-controlled clinical trials","volume":"10","author":"Calabrese","year":"2008","journal-title":"Bipolar Disord"},{"key":"R35-20250518","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1176\/appi.ajp.158.6.906","article-title":"Double-blind, placebo-controlled comparison of imipramine and paroxetine in the treatment of bipolar depression","volume":"158","author":"Nemeroff","year":"2001","journal-title":"Am J Psychiatry"},{"key":"R36-20250518","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1056\/NEJMoa064135","article-title":"Effectiveness of adjunctive antidepressant treatment for bipolar depression","volume":"356","author":"Sachs","year":"2007","journal-title":"N Engl J Med"},{"key":"R37-20250518","doi-asserted-by":"crossref","first-page":"156","DOI":"10.4088\/JCP.09r05385gre","article-title":"Antidepressants for the acute treatment of bipolar depression: A systematic review and meta-analysis","volume":"72","author":"Sidor","year":"2011","journal-title":"J Clin Psychiatry"},{"key":"R38-20250518","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.4088\/JCP.13m08951","article-title":"Armodafinil Treatment Trial Study Network. Efficacy and safety of adjunctive armodafinil in adults with major depressive episodes associated with bipolar I disorder: A randomized, double-blind, placebo-controlled, multicenter trial","volume":"75","author":"Calabrese","year":"2014","journal-title":"J Clin Psychiatry"},{"key":"R39-20250518","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.4088\/JCP.09m05900gry","article-title":"Adjunctive armodafinil for major depressive episodes associated with bipolar I disorder: A randomized, multicenter, double-blind, placebo-controlled, proof-of-concept study","volume":"71","author":"Calabrese","year":"2010","journal-title":"J Clin Psychiatry"},{"key":"R40-20250518","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1176\/appi.ajp.2007.06060981","article-title":"A placebo-controlled evaluation of adjunctive modafinil in the treatment of bipolar depression","volume":"164","author":"Frye","year":"2007","journal-title":"Am J Psychiatry"},{"key":"R41-20250518","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1176\/appi.ajp.161.3.564","article-title":"Preliminary randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment-resistant bipolar depression","volume":"161","author":"Goldberg","year":"2004","journal-title":"Am J Psychiatry"},{"key":"R42-20250518","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.biopsych.2004.03.013","article-title":"Pramipexole for bipolar II depression: A placebo-controlled proof of concept study","volume":"56","author":"Zarate","year":"2004","journal-title":"Biol Psychiatry"},{"key":"R43-20250518","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1001\/archgenpsychiatry.2010.90","article-title":"A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression","volume":"67","author":"Diazgranados","year":"2010","journal-title":"Arch Gen Psychiatry"},{"key":"R44-20250518","doi-asserted-by":"crossref","first-page":"e469","DOI":"10.1038\/tp.2014.105","article-title":"Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression","volume":"4","author":"Lally","year":"2014","journal-title":"Transl Psychiatry"},{"key":"R45-20250518","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.biopsych.2011.12.010","article-title":"Replication of ketamine\u2019s antidepressant efficacy in bipolar depression: A randomized controlled add-on trial","volume":"71","author":"Zarate","year":"2012","journal-title":"Biol Psychiatry"},{"key":"R46-20250518","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1097\/PRA.0000000000000106","article-title":"Efficacy of ketamine in bipolar depression: Systematic review and meta-analysis","volume":"21","author":"Parsaik","year":"2015","journal-title":"J Psychiatr Pract"},{"key":"R47-20250518","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1097\/00124509-200203000-00015","article-title":"The practice of electroconvulsive therapy: Recommendations for treatment, training, and privileging (second edition)","volume":"18","author":"Rasmussen","year":"2002","journal-title":"J ECT"},{"key":"R48-20250518","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1176\/appi.ajp.2014.13111517","article-title":"Treatment-resistant bipolar depression: A randomized controlled trial of electroconvulsive therapy versus algorithm-based pharmacological treatment","volume":"172","author":"Schoeyen","year":"2015","journal-title":"Am J Psychiatry"},{"key":"R49-20250518","first-page":"123","article-title":"ECT in bipolar disorder: Incidence of switch from depression to hypomania or mania","volume":"1","author":"Bost-Baxter","year":"2012","journal-title":"J Depress Anxiety"},{"key":"R50-20250518","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1097\/YCT.0000000000000117","article-title":"Autobiographical memory and electroconvulsive therapy: Do not throw out the baby","volume":"30","author":"Sackeim","year":"2014","journal-title":"J ECT"},{"key":"R51-20250518","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1038\/sj.npp.1301180","article-title":"The cognitive effects of electroconvulsive therapy in community settings","volume":"32","author":"Sackeim","year":"2007","journal-title":"Neuropsychopharmacology"},{"key":"R52-20250518","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.brs.2008.03.001","article-title":"Effects of pulse width and electrode placement on the efficacy and cognitive effects of electroconvulsive therapy","volume":"1","author":"Sackeim","year":"2008","journal-title":"Brain Stimul"},{"key":"R53-20250518","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1038\/npp.2013.149","article-title":"Relapse following successful electroconvulsive therapy for major depression: A meta-analysis","volume":"38","author":"Jelovac","year":"2013","journal-title":"Neuropsychopharmacology"},{"key":"R54-20250518","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1001\/archpsyc.63.12.1337","article-title":"Continuation electroconvulsive therapy vs. pharmacotherapy for relapse prevention in major depression: A multisite study from the Consortium for Research in Electroconvulsive Therapy (CORE)","volume":"63","author":"Kellner","year":"2006","journal-title":"Arch Gen Psychiatry"},{"key":"R55-20250518","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1176\/ajp.2007.164.2.201","article-title":"STAR*D: What have we learned?","volume":"164","author":"Rush","year":"2007","journal-title":"Am J Psychiatry"},{"key":"R56-20250518","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.euroneuro.2011.09.008","article-title":"Polarity index of pharmacological agents used for maintenance treatment of bipolar disorder","volume":"22","author":"Popovic","year":"2012","journal-title":"Eur Neuropsychopharmacol"}],"container-title":["Tzu Chi Medical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/00127828-201830030-00003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T16:29:23Z","timestamp":1786724963000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/00127828-201830030-00003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7]]},"references-count":56,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018]]}},"URL":"https:\/\/doi.org\/10.4103\/tcmj.tcmj_71_18","relation":{},"ISSN":["1016-3190","2223-8956"],"issn-type":[{"value":"1016-3190","type":"print"},{"value":"2223-8956","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7]]},"assertion":[{"value":"2018-03-22","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-09","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}