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Pharmacological Treatment of Acute Bipolar Depression

  • Gary S. SachsEmail author
Chapter
Part of the Milestones in Drug Therapy book series (MDT)

Abstract

Controversy regarding management of the acute phase of bipolar depression largely reflects the natural divergence of opinions arising from large gaps in knowledge and the fact that no medication is particularly effective in this population. While there remains a great need for more and better evidence from high-quality studies to close the gaps, the past decade has seen the publication of a substantial number of fully powered placebo-controlled trials for bipolar depression, including several new agents. This chapter addresses the challenges of treating bipolar depression by describing a general schema consisting of principles for iterative personalized care that can be applied to an evolving knowledge base. This chapter also reviews the state of the evidence supporting various pharmacological treatments for bipolar depression, including quetiapine, lurasidone, lamotrigine, olanzapine, olanzapine plus fluoxetine (OFC), modafinil, armodafinil, lithium, valproate, carbamazepine, ketamine, N-acetyl cysteine (NAC), inositol, pramipexole, riluzole, and standard antidepressants, among others. Currently, five medications are supported by Category A criteria. In order of the strength of support evidence, these are quetiapine, lurasidone, olanzapine, OFC, and lamotrigine. Regardless of whether patients accept these treatments or begin with alternatives, a measurement-based approach to treatment provides a systematic means of working toward an optimized individual treatment plan.

Keywords

Bipolar disorder Bipolar depression Treatment Mood stabilizer Antidepressant 

References

  1. Altshuler L, Suppes T, Black D, Nolen WA, Keck PE Jr, Frye MA, McElroy S, Kupka R, Grunze H, Walden J, Leverich G, Denicoff K, Luckenbaugh D, Post R (2003) Impact of antidepressant discontinuation after acute bipolar depression remission on rates of depressive relapse at 1-year follow-up. Am J Psychiatry 160(7):1252–1262CrossRefPubMedGoogle Scholar
  2. Altshuler LL, Post RM, Hellemann G, Leverich GS, Nolen WA, Frye MA, Keck PE Jr, Kupka RW, Grunze H, McElroy SL, Sugar CA, Suppes T (2009) Impact of antidepressant continuation after acute positive or partial treatment response for bipolar depression: a blinded, randomized study. J Clin Psychiatry 70(4):450–457CrossRefPubMedGoogle Scholar
  3. Amsterdam JD, Shults J (2010) Efficacy and Safety of Long-Term Fluoxetine Versus Lithium Monotherapy of Bipolar II Disorder: A Randomized, Double-Blind, Placebo-Substitution Study. Am J Psychiatry 167:792–800CrossRefPubMedPubMedCentralGoogle Scholar
  4. Amsterdam JD, Garcia-Espana F, Fawcett J, Quitkin FM, Reimherr FW, Rosenbaum JF, Schweizer E, Beasley C (1998) Efficacy and safety of fluoxetine in treating bipolar II major depressive episode. J Clin Psychopharmacol 18(6):435–440CrossRefPubMedGoogle Scholar
  5. Amsterdam JD, Shults J, Brunswick DJ, Hundert M (2004) Short-term fluoxetine monotherapy for bipolar type II or bipolar NOS major depression – low manic switch rate. Bipolar Disord 6(1):75–81CrossRefPubMedGoogle Scholar
  6. Benedetti F, Barbini B, Campori E, Fulgosi MC, Pontiggia A, Colombo C (2001) Sleep phase advance and lithium to sustain the antidepressant effect of total sleep deprivation in bipolar depression: new findings supporting the internal coincidence model? J Psychiatr Res 35(6):323–329CrossRefPubMedGoogle Scholar
  7. Berk M, Copolov DL, Dean O, Lu K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Bush AI (2008) N-acetyl cysteine for depressive symptoms in bipolar disorder – a double-blind randomized placebo-controlled trial. Biol Psychiatry 64(6):468–475CrossRefPubMedGoogle Scholar
  8. Bond DJ, Lam RW, Yatham LN (2010) Divalproex sodium versus placebo in the treatment of acute bipolar depression: A systematic review and meta-analysis. J Affect Disord 124(3):228–34CrossRefPubMedGoogle Scholar
  9. Bowden CL (2001) Strategies to reduce misdiagnosis of bipolar depression. Psychiatr Serv 52(1):51–55CrossRefPubMedGoogle Scholar
  10. Brown EB, McElroy SL, Keck PE Jr, Deldar A, Adams DH, Tohen M, Williamson DJ (2006) A 7-week, randomized, double-blind trial of olanzapine/fluoxetine combination versus lamotrigine in the treatment of bipolar I depression. J Clin Psychiatry 67(7):1025–1033CrossRefPubMedGoogle Scholar
  11. Calabrese JR, Bowden CL, Sachs GS, Ascher JA, Monaghan E, Rudd GD (1999) A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal 602 Study Group. J Clin Psychiatry 60(2):79–88CrossRefPubMedGoogle Scholar
  12. Calabrese JR, Keck PE Jr, Macfadden W, Minkwitz M, Ketter TA, Weisler RH, Cutler AJ, McCoy R, Wilson E, Mullen J (2005) A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry 162(7):1351–1360CrossRefPubMedGoogle Scholar
  13. Calabrese JR, Kemp DE, Ganocy SJ, Brecher M, Carlson BX, Edwards S, Eudicone J, Evoniuk G, Jansen WT, McQuade R, Millen B, Minkwitz M, Owen R, Pikalov A, Szegedi A, Tohen M, Vester-Blokland E, Willigenburg AP (2010a) Knowing when a drug is not going to work in bipolar depression: absence of early improvement as a predictor of later non-response in 3,369 patients from 10 placebo-controlled acute trials. Paper presented at the International Society for Clinical Trial Methodology, Washington, DCGoogle Scholar
  14. Calabrese JR, Ketter TA, Youakim JM, Tiller JM, Yang R, Frye MA (2010b) Adjunctive armodafinil for major depressive episodes associated with bipolar I disorder: a randomized, multicenter, double-blind, placebo-controlled, proof-of-concept study. J Clin Psychiatry 71:1363–1370Google Scholar
  15. Calabrese JR, Frye MA, Yang R, Ketter TA, Armodafinil Treatment Trial Study N (2014) 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. J Clin Psychiatry 75(10):1054–1061Google Scholar
  16. Chengappa KN, Levine J, Gershon S, Mallinger AG, Hardan A, Vagnucci A, Pollock B, Luther J, Buttenfield J, Verfaille S, Kupfer DJ (2000) Inositol as an add-on treatment for bipolar depression. Bipolar Disord 2(1):47–55CrossRefPubMedGoogle Scholar
  17. Coryell W, Solomon DA, Fiedorowicz JG, Endicott J, Schettler PJ, Judd LL (2009) Anxiety and outcome in bipolar disorder. Am J Psychiatry 166(11):1238–1243CrossRefPubMedPubMedCentralGoogle Scholar
  18. Davis LL, Bartolucci A, Petty F (2005) Divalproex in the treatment of bipolar depression: a placebo-controlled study. J Affect Disord 85(3):259–266CrossRefPubMedGoogle Scholar
  19. Diazgranados N, Ibrahim L, Brutsche NE, Newberg A, Kronstein P, Khalife S, Kammerer WA, Quezado Z, Luckenbaugh DA, Salvadore G, Machado-Vieira R, Manji HK, Zarate CA Jr (2010) A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression. Arch Gen Psychiatry 67(8):793–802CrossRefPubMedPubMedCentralGoogle Scholar
  20. Eden Evins A, Demopulos C, Yovel I, Culhane M, Ogutha J, Grandin LD, Nierenberg AA, Sachs GS (2006) Inositol augmentation of lithium or valproate for bipolar depression. Bipolar Disord 8(2):168–174CrossRefPubMedGoogle Scholar
  21. El-Mallakh RS (2000) An open study of methylphenidate in bipolar depression. Bipolar Disord 2(1):56–59CrossRefPubMedGoogle Scholar
  22. Frye MA, Grunze H, Suppes T, McElroy SL, Keck PE Jr, Walden J, Leverich GS, Altshuler LL, Nakelsky S, Hwang S, Mintz J, Post RM (2007) A placebo-controlled evaluation of adjunctive modafinil in the treatment of bipolar depression. Am J Psychiatry 164(8):1242–1249CrossRefPubMedGoogle Scholar
  23. Gao K, Wu R, Kemp DE, Chen J, Karberg E, Conroy C, Chan P, Ren M, Serrano MB, Ganocy SJ, Calabrese JR (2014) Efficacy and safety of quetiapine-XR as monotherapy or adjunctive therapy to a mood stabilizer in acute bipolar depression with generalized anxiety disorder and other comorbidities: a randomized, placebo-controlled trial. J Clin Psychiatry 75(10):1062–1068CrossRefPubMedGoogle Scholar
  24. Geddes JR, Calabrese JR, Goodwin GM (2009) Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials. Br J Psychiatry 194(1):4–9CrossRefPubMedGoogle Scholar
  25. Gijsman HJ, Geddes JR, Rendell JM, Nolen WA, Goodwin GM (2004) Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry 161(9):1537–1547CrossRefPubMedGoogle Scholar
  26. Goldberg JF, Burdick KE, Endick CJ (2004) Preliminary randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment-resistant bipolar depression. Am J Psychiatry 161(3):564–566CrossRefPubMedGoogle Scholar
  27. Himmelhoch JM, Thase ME, Mallinger AG, Houck P (1991) Tranylcypromine versus imipramine in anergic bipolar depression. Am J Psychiatry 148(7):910–916CrossRefPubMedGoogle Scholar
  28. Ionescu DF, Luckenbaugh DA, Niciu MJ, Richards EM, Zarate CA Jr (2015) A single infusion of ketamine improves depression scores in patients with anxious bipolar depression. Bipolar Disord 17(4):438–443CrossRefPubMedGoogle Scholar
  29. Joffe RT, MacQueen GM, Marriott M, Trevor Young L (2004) A prospective, longitudinal study of percentage of time spent ill in patients with bipolar I or bipolar II disorders. Bipolar Disord 6(1):62–66CrossRefPubMedGoogle Scholar
  30. Johnson SL, Brickman AL (2006) Diagnostic inconsistency: a marker of service utilization in bipolar disorder. Manag Care Interface 19(4):41–45PubMedGoogle Scholar
  31. Judd LL, Schettler PJ, Akiskal HS, Maser J, Coryell W, Solomon D, Endicott J, Keller M (2003) Long-term symptomatic status of bipolar I vs. bipolar II disorders. Int J Neuropsychopharmacol 6(2):127–137CrossRefPubMedGoogle Scholar
  32. Keck PE Jr, Mintz J, McElroy SL, Freeman MP, Suppes T, Frye MA, Altshuler LL, Kupka R, Nolen WA, Leverich GS, Denicoff KD, Grunze H, Duan N, Post RM (2006) Double-blind, randomized, placebo-controlled trials of ethyl-eicosapentanoate in the treatment of bipolar depression and rapid cycling bipolar disorder. Biol Psychiatry 60(9):1020–1022CrossRefPubMedGoogle Scholar
  33. Keller MB, Hanks DL, Klein DN (1996) Summary of the DSM-IV mood disorders field trial and issue overview. Psychiatr Clin North Am 19(1):1–28CrossRefPubMedGoogle Scholar
  34. Kelly TF, Lieberman DZ (2014) The utility of the combination of dextromethorphan and quinidine in the treatment of bipolar II and bipolar NOS. J Affect Disord 167:333–335CrossRefPubMedGoogle Scholar
  35. Kemp DE, Ganocy SJ, Brecher M, Carlson BX, Edwards S, Eudicone JM, Evoniuk G, Jansen W, Leon AC, Minkwitz M, Pikalov A, Stassen HH, Szegedi A, Tohen M, Van Willigenburg AP, Calabrese JR (2011a) Clinical value of early partial symptomatic improvement in the prediction of response and remission during short-term treatment trials in 3369 subjects with bipolar I or II depression. J Affect Disord 130(1–2):171–179CrossRefPubMedGoogle Scholar
  36. Kemp DE, Johnson E, Wang WV, Tohen M, Calabrese JR (2011b) Clinical utility of early improvement to predict response or remission in acute mania: focus on olanzapine and risperidone. J Clin Psychiatry 72:1236–1241CrossRefPubMedGoogle Scholar
  37. Klerman GL (1990) The psychiatric patient's right to effective treatment: implications of Osheroff v. Chestnut Lodge. Am J Psychiatry 147(4):409–418CrossRefPubMedGoogle Scholar
  38. Lambert PA, Carraz G, Borselli S (1966) Action neuropsychotrope d'un novel anti-epileptique: le Depamide [French]. Ann Med Psychol 1:707–710Google Scholar
  39. Lee EE, Della Selva MP, Liu A, Himelhoch S (2015) Ketamine as a novel treatment for major depressive disorder and bipolar depression: a systematic review and quantitative meta-analysis. Gen Hosp Psychiatry 37(2):178–184CrossRefPubMedGoogle Scholar
  40. Leverich GS, Altshuler LL, Frye MA, Suppes T, McElroy SL, Keck PE Jr, Kupka RW, Denicoff KD, Nolen WA, Grunze H, Martinez MI, Post RM (2006) Risk of switch in mood polarity to hypomania or mania in patients with bipolar depression during acute and continuation trials of venlafaxine, sertraline, and bupropion as adjuncts to mood stabilizers. Am J Psychiatry 163(2):232–239CrossRefPubMedGoogle Scholar
  41. Levine J, Barak Y, Gonzalves M, Szor H, Elizur A, Kofman O, Belmaker RH (1995) Double-blind, controlled trial of inositol treatment of depression. Am J Psychiatry 152(5):792–794CrossRefPubMedGoogle Scholar
  42. Loebel A, Cucchiaro J, Silva R, Kroger H, Hsu J, Sarma K, Sachs G (2014a) Lurasidone monotherapy in the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study. Am J Psychiatry 171(2):160–168CrossRefPubMedGoogle Scholar
  43. Loebel A, Cucchiaro J, Silva R, Kroger H, Sarma K, Xu J, Calabrese JR (2014b) Lurasidone as adjunctive therapy with lithium or valproate for the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study. Am J Psychiatry 171(2):169–177CrossRefPubMedGoogle Scholar
  44. Loebel A, Cucchiaro J, Silva R, Hsu J, Sarma K (2015) Double blind placebo controlled trial of Lurasidone vs placebo for treatment of unipolar major depressive episode with mixed features. In: Annual meeting American Psychaitric Association, TorontoGoogle Scholar
  45. McElroy SL, Weisler RH, Chang W, Olausson B, Paulsson B, Brecher M, Agambaram V, Merideth C, Nordenhem A, Young AH (2010) A double-blind, placebo-controlled study of quetiapine and paroxetine as monotherapy in adults with bipolar depression (EMBOLDEN II). J Clin Psychiatry 71(2):163–174CrossRefPubMedGoogle Scholar
  46. Nemeroff CB, Evans DL, Gyulai L, Sachs GS, Bowden CL, Gergel IP, Oakes R, Pitts CD (2001) Double-blind, placebo-controlled comparison of imipramine and paroxetine in the treatment of bipolar depression. Am J Psychiatry 158(6):906–912CrossRefPubMedGoogle Scholar
  47. Nemets H, Nemets B, Apter A, Bracha Z, Belmaker RH (2006) Omega-3 treatment of childhood depression: a controlled, double-blind pilot study. Am J Psychiatry 163(6):1098–1100CrossRefPubMedGoogle Scholar
  48. Nierenberg AA, Farabaugh AH, Alpert JE, Gordon J, Worthington JJ, Rosenbaum JF, Fava M (2000) Timing of onset of antidepressant response with fluoxetine treatment. Am J Psychiatry 157(9):1423–1428CrossRefPubMedGoogle Scholar
  49. Nierenberg AA, Ostacher MJ, Calabrese JR, Ketter TA, Marangell LB, Miklowitz DJ, Miyahara S, Bauer MS, Thase ME, Wisniewski SR, Sachs GS (2006) Treatment-resistant bipolar depression: a STEP-BD equipoise randomized effectiveness trial of antidepressant augmentation with lamotrigine, inositol, or risperidone. Am J Psychiatry 163(2):210–216CrossRefPubMedGoogle Scholar
  50. Nolen WA, Kupka RW, Hellemann G, Frye MA, Altshuler LL, Leverich GS, Suppes T, Keck PE Jr, McElroy S, Grunze H, Mintz J, Post RM (2007) Tranylcypromine vs. lamotrigine in the treatment of refractory bipolar depression: a failed but clinically useful study. Acta Psychiatr Scand 115(5):360–365CrossRefPubMedGoogle Scholar
  51. Osher Y, Bersudsky Y, Belmaker RH (2005) Omega-3 eicosapentaenoic acid in bipolar depression: report of a small open-label study. J Clin Psychiatry 66(6):726–729CrossRefPubMedGoogle Scholar
  52. Ostacher MJ (2014) When positive isn’t positive: the hopes and disappointments of clinical trials. J Clin Psychiatry 75(10):e1186–e1187CrossRefPubMedGoogle Scholar
  53. Pacchiarotti I, Bond DJ, Baldessarini RJ, Nolen WA, Grunze H, Licht RW, Post RM, Berk M, Goodwin GM, Sachs GS, Tondo L, Findling RL, Youngstrom EA, Tohen M, Undurraga J, Gonzalez-Pinto A, Goldberg JF, Yildiz A, Altshuler LL, Calabrese JR, Mitchell PB, Thase ME, Koukopoulos A, Colom F, Frye MA, Malhi GS, Fountoulakis KN, Vazquez G, Perlis RH, Ketter TA, Cassidy F, Akiskal H, Azorin JM, Valenti M, Mazzei DH, Lafer B, Kato T, Mazzarini L, Martinez-Aran A, Parker G, Souery D, Ozerdem A, McElroy SL, Girardi P, Bauer M, Yatham LN, Zarate CA, Nierenberg AA, Birmaher B, Kanba S, El-Mallakh RS, Serretti A, Rihmer Z, Young AH, Kotzalidis GD, MacQueen GM, Bowden CL, Ghaemi SN, Lopez-Jaramillo C, Rybakowski J, Ha K, Perugi G, Kasper S, Amsterdam JD, Hirschfeld RM, Kapczinski F, Vieta E (2013) The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders. Am J Psychiatry 170(11):1249–1262CrossRefPubMedPubMedCentralGoogle Scholar
  54. Post RM, Uhde TW, Roy-Byrne PP, Joffe RT (1986) Antidepressant effects of carbamazepine. Am J Psychiatry 143(1):29–34CrossRefPubMedGoogle Scholar
  55. Post RM, Altshuler LL, Leverich GS, Frye MA, Nolen WA, Kupka RW, Suppes T, McElroy S, Keck PE, Denicoff KD, Grunze H, Walden J, Kitchen CM, Mintz J (2006) Mood switch in bipolar depression: comparison of adjunctive venlafaxine, bupropion and sertraline. Br J Psychiatry 189:124–131CrossRefPubMedGoogle Scholar
  56. Revicki DA, Hanlon J, Martin S, Gyulai L, Nassir Ghaemi S, Lynch F, Mannix S, Kleinman L (2005) Patient-based utilities for bipolar disorder-related health states. J Affect Disord 87(2–3):203–210CrossRefPubMedGoogle Scholar
  57. Riemann D, Voderholzer U, Berger M (2002) Sleep and sleep-wake manipulations in bipolar depression. Neuropsychobiology 45(Suppl 1):7–12CrossRefPubMedGoogle Scholar
  58. Rush AJ, Trivedi MH, Ibrahim HM, Carmody TJ, Arnow B, Klein DN, Markowitz JC, Ninan PT, Kornstein S, Manber R, Thase ME, Kocsis JH, Keller MB (2003) The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biol Psychiatry 54(5):573–583CrossRefPubMedGoogle Scholar
  59. Rush AJ, Kraemer HC, Sackeim HA, Fava M, Trivedi MH, Frank E, Ninan PT, Thase ME, Gelenberg AJ, Kupfer DJ, Regier DA, Rosenbaum JF, Ray O, Schatzberg AF (2006) Report by the ACNP Task Force on response and remission in major depressive disorder. Neuropsychopharmacology 31(9):1841–1853CrossRefPubMedGoogle Scholar
  60. Sachs GS (2004a) Effectiveness study design and preliminary finding from STEP-BD. In: 59th Annual Convention Society for Biological Psychiatry, New York, NYGoogle Scholar
  61. Sachs GS (2004b) Strategies for improving treatment of bipolar disorder: integration of measurement and management. Acta Psychiatr Scand Suppl (422):7–17Google Scholar
  62. Sachs GS (2007) Bipolar disorder clinical synthesis: Where does the evidence lead? Focus V(1):1–11Google Scholar
  63. Sachs GS, Lafer B, Stoll AL, Banov M, Thibault AB, Tohen M, Rosenbaum JF (1994) A double-blind trial of bupropion versus desipramine for bipolar depression. J Clin Psychiatry 55(9):391–393PubMedGoogle Scholar
  64. Sachs GA, Ketter L, Suppes T, Rasgon N, Frey M, Collins M (2002) Divalproex versus placebo for treatment of Bipolar depression. In: 155th Annual Meeting of the American Psychiatric Association, Philadelphia, PAGoogle Scholar
  65. Sidor MM, Macqueen GM (2011) Antidepressants for the acute treatment of bipolar depression: a systematic review and meta-analysis. J Clin Psychiatry 72(2):156–167CrossRefPubMedGoogle Scholar
  66. Silverstone T (2001) Moclobemide vs. imipramine in bipolar depression: a multicentre double-blind clinical trial. Acta Psychiatr Scand 104(2):104–109CrossRefPubMedGoogle Scholar
  67. Speer AM, Kimbrell TA, Wassermann EM, D Repella J, Willis MW, Herscovitch P, Post RM (2000) Opposite effects of high and low frequency rTMS on regional brain activity in depressed patients. Biol Psychiatry 48(12):1133–1141CrossRefPubMedGoogle Scholar
  68. Suppes T, Datto C, Minkwitz M, Nordenhem A, Walker C, Darko D (2010) Effectiveness of the extended release formulation of quetiapine as monotherapy for the treatment of acute bipolar depression. J Affect Disord 121(1–2):106–115CrossRefPubMedGoogle Scholar
  69. Szegedi A, Jansen WT, van Willigenburg AP, van der Meulen E, Stassen HH, Thase ME (2009) Early improvement in the first 2 weeks as a predictor of treatment outcome in patients with major depressive disorder: a meta-analysis including 6562 patients. J Clin Psychiatry 70(3):344–353CrossRefPubMedGoogle Scholar
  70. Takayanagi Y, Spira AP, Roth KB, Gallo JJ, Eaton WW, Mojtabai R (2014) Accuracy of reports of lifetime mental and physical disorders: results from the Baltimore Epidemiological Catchment Area study. JAMA Psychiatry 71(3):273–280CrossRefPubMedPubMedCentralGoogle Scholar
  71. Thase ME, Macfadden W, Weisler RH, Chang W, Paulsson B, Khan A, Calabrese JR, Group BIS (2006) Efficacy of quetiapine monotherapy in bipolar I and II depression: a double-blind, placebo-controlled study (the BOLDER II study). J Clin Psychopharmacol 26(6):600–609CrossRefPubMedGoogle Scholar
  72. Tohen M, Vieta E, Calabrese J, Ketter TA, Sachs G, Bowden C, Mitchell PB, Centorrino F, Risser R, Baker RW, Evans AR, Beymer K, Dube S, Tollefson GD, Breier A (2003) Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Arch Gen Psychiatry 60(11):1079–1088CrossRefPubMedGoogle Scholar
  73. Tohen M, Calabrese JR, Sachs GS, Banov MD, Detke HC, Risser R, Baker RW, Chou JC, Bowden CL (2006) Randomized, placebo-controlled trial of olanzapine as maintenance therapy in patients with bipolar I disorder responding to acute treatment with olanzapine. Am J Psychiatry 163(2):247–256CrossRefPubMedGoogle Scholar
  74. Tohen M, McDonnell DP, Case M, Kanba S, Ha K, Fang YR, Katagiri H, Gomez JC (2012) Randomised, double-blind, placebo-controlled study of olanzapine in patients with bipolar I depression. Br J Psychiatry 201(5):376–382CrossRefPubMedGoogle Scholar
  75. van der Loos ML, Mulder PG, Hartong EG, Blom MB, Vergouwen AC, de Keyzer HJ, Notten PJ, Luteijn ML, Timmermans MA, Vieta E, Nolen WA (2009) Efficacy and safety of lamotrigine as add-on treatment to lithium in bipolar depression: a multicenter, double-blind, placebo-controlled trial. J Clin Psychiatry 70(2):223–231CrossRefPubMedGoogle Scholar
  76. Vieta E, Martinez-Aran A, Goikolea JM, Torrent C, Colom F, Benabarre A, Reinares M (2002) A randomized trial comparing paroxetine and venlafaxine in the treatment of bipolar depressed patients taking mood stabilizers. J Clin Psychiatry 63(6):508–512CrossRefPubMedGoogle Scholar
  77. Young AH, McElroy SL, Bauer M, Philips N, Chang W, Olausson B, Paulsson B, Brecher M (2010) A double-blind, placebo-controlled study of quetiapine and lithium monotherapy in adults in the acute phase of bipolar depression (EMBOLDEN I). J Clin Psychiatry 71(2):150–162CrossRefPubMedGoogle Scholar
  78. Young AH, Calabrese JR, Gustafsson U, Berk M, McElroy SL, Thase ME, Suppes T, Earley W (2013) Quetiapine monotherapy in bipolar II depression: combined data from four large, randomized studies. Int J Bipolar Disord 1:10CrossRefPubMedPubMedCentralGoogle Scholar
  79. Zarate CA Jr, Payne JL, Singh J, Quiroz JA, Luckenbaugh DA, Denicoff KD, Charney DS, Manji HK (2004) Pramipexole for bipolar II depression: a placebo-controlled proof of concept study. Biol Psychiatry 56(1):54–60CrossRefPubMedGoogle Scholar
  80. Zarate CA Jr, Quiroz JA, Singh JB, Denicoff KD, De Jesus G, Luckenbaugh DA, Charney DS, Manji HK (2005) An open-label trial of the glutamate-modulating agent riluzole in combination with lithium for the treatment of bipolar depression. Biol Psychiatry 57(4):430–432CrossRefPubMedGoogle Scholar
  81. Zarate CA Jr, Brutsche NE, Ibrahim L, Franco-Chaves J, Diazgranados N, Cravchik A, Selter J, Marquardt CA, Liberty V, Luckenbaugh DA (2012) Replication of ketamine's antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biol Psychiatry 71(11):939–946CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer International Publishing Switzerland (outside the USA)  2016

Authors and Affiliations

  1. 1.Bipolar Clinic and Research Program, Massachusetts General HospitalBostonUSA

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