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Pharmacological Management of Bipolar Depression: Acute Treatment, Maintenance, and Prophylaxis

  • Therapy in Practice
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Abstract

Although the most distinctive clinical feature of bipolar disorder is the pathologically elevated mood, it does not usually constitute the prevalent mood state of bipolar illness. The majority of patients with bipolar disorder spend much more time in depressive episodes, including subsyndromal depressive symptoms, and bipolar depression accounts for the largest part of the morbidity and mortality of the illness. The pharmacological treatment of bipolar depression mostly consists of combinations of at least two drugs, including mood stabilizers (lithium and anticonvulsants), atypical antipsychotics, and antidepressants. Antidepressants are the most frequently prescribed drugs, but recommendations from evidence-based guidelines are not conclusive and do not overtly support their use. Among antidepressants, best evidence exists for fluoxetine, but in combination with olanzapine. Although some guidelines recommend the use of selective serotonin reuptake inhibitors or bupropion in combination with antimanic agents as first-choice treatment, others do not, based on the available evidence. Among anticonvulsants, the use of lamotrigine is overall recommended as a first-line choice, but acute monotherapy studies have failed. Valproate is generally mentioned as a second-line treatment. Lithium monotherapy is also suggested by most guidelines as a first-line treatment, but its efficacy in acute use is not totally clear. Amongst atypical antipsychotics, quetiapine, in monotherapy or as adjunctive treatment, is recommended by most guidelines as a first-line choice. Olanzapine monotherapy is also suggested by some guidelines and is approved in Japan. Armodafinil, pramipexole, ketamine, and lurasidone are recent proposals. Long-term treatment in bipolar disorder is strongly recommended, but guidelines do not recommend the use of antidepressants as a maintenance treatment. Lithium, lamotrigine, valproate, olanzapine, quetiapine, and aripiprazole are the recommended first-line maintenance options.

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References

  1. Judd LL, Schettler PJ, Akiskal HS. The prevalence, clinical relevance, and public health significance of subthreshold depressions. Psychiatr Clin North Am. 2002;25:685–98.

    Article  PubMed  Google Scholar 

  2. Judd LL, Akiskal HS, Schettler PJ, Coryell W, Endicott J, Maser JD, Solomon DA, Leon AC, Keller MB. A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Arch Gen Psychiatry. 2003;60:261–9.

    Article  PubMed  Google Scholar 

  3. Vieta E, Sánchez-Moreno J, Lahuerta J, Zaragoza S, EDHIPO Group (Hypomania Detection Study Group). Subsyndromal depressive symptoms in patients with bipolar and unipolar disorder during clinical remission. J Affect Disord. 2008;107:169–74.

    Article  PubMed  CAS  Google Scholar 

  4. Kupka RW, Altshuler LL, Nolen WA, Suppes T, Luckenbaugh DA, Leverich GS, Frye MA, Keck PE Jr, McElroy SL, Grunze H, Post RM. Three times more days depressed than manic or hypomanic in both bipolar I and bipolar II disorder. Bipolar Disord. 2007;9:531–5.

    Article  PubMed  Google Scholar 

  5. Judd LL, Schettler PJ, Akiskal HS, Coryell W, Leon AC, Maser JD, Solomon DA. Residual symptom recovery from major affective episodes in bipolar disorders and rapid episode relapse/recurrence. Arch Gen Psychiatry. 2008;65:386–94.

    Article  PubMed  Google Scholar 

  6. Kessler R, Tubinow D, Homes C, Abelson J, Zhao S. The epidemiology of DSM-III-R bipolar I disorder in a general population survey. Psychol Med. 1997;27:1079–89.

    Article  PubMed  CAS  Google Scholar 

  7. Dilsaver SC, Chen YW, Swann AC, Shoaib AM, Tsai-Dilsaver Y, Krajewski KJ. Suicidality, panic disorder and psychosis in bipolar depression, depressive-mania and pure-mania. Psychiatry Res. 1997;73:47–56.

    Article  PubMed  CAS  Google Scholar 

  8. Tondo L, Isacsson G, Baldessarini R. Suicidal behaviour in bipolar disorder: risk and prevention. CNS Drugs. 2003;17:491–511.

    Article  PubMed  CAS  Google Scholar 

  9. Gutiérrez-Rojas L, Gurpegui M, Ayuso-Mateos JL, Gutiérrez-Ariza JA, Ruiz-Veguilla M, Jurado D. Quality of life in bipolar disorder patients: a comparison with a general population sample. Bipolar Disord. 2008;10:625–34.

    Article  PubMed  Google Scholar 

  10. Altshuler LL, Gitlin MJ, Mintz J, Leight KL, Frye MA. Subsyndromal depression is associated with functional impairment in patients with bipolar disorder. J Clin Psychiatry. 2002;63:807–11.

    Article  PubMed  Google Scholar 

  11. Calabrese JR, Hirschfeld RM, Frye MA, Reed ML. Impact of depressive symptoms compared with manic symptoms in bipolar disorder: results of a US community-based sample. J Clin Psychiatry. 2004;65:1499–504.

    Article  PubMed  Google Scholar 

  12. Judd LL, Schettler PJ, Solomon DA, Maser JD, Coryell W, Endicott J, Akiskal HS. Psychosocial disability and work role function compared across the long-term course of bipolar I, bipolar II and unipolar major depressive disorders. J Affect Disord. 2008;108:49–58.

    Article  PubMed  Google Scholar 

  13. Rosa AR, Reinares M, Michalak EE, Bonnín CM, Solé B, Franco C, Comes M, Torrent C, Kapczinski F, Vieta E. Functional impairment and disability across mood states in bipolar disorder. Value Health. 2010;13:984–8.

    Article  PubMed  Google Scholar 

  14. Martino DJ, Marengo E, Igoa A, Scápola M, Ais ED, Perinot L, Strejilevich SA. Neurocognitive and symptomatic predictors of functional outcome in bipolar disorders: a prospective 1 year follow-up study. J Affect Disord. 2009;116(1–2):37–42.

    Article  PubMed  Google Scholar 

  15. Goldberg JF, Harrow M. A 15-year prospective follow-up of bipolar affective disorders: comparisons with unipolar nonpsychotic depression. Bipolar Disord. 2011;13:155–63.

    Article  PubMed  Google Scholar 

  16. Malhi GS, Adams D, Berk M. Medicating mood with maintenance in mind: bipolar depression pharmacotherapy. Bipolar Disord. 2009;11(Suppl. 2):55–76.

    Article  PubMed  CAS  Google Scholar 

  17. Malhi GS, Mitchell PB, Salim S. Bipolar depression: management options. CNS Drugs. 2003;17:9–25.

    Article  PubMed  CAS  Google Scholar 

  18. Berk M, Berk L, Moss K, Dodd S, Malhi GS. Diagnosing bipolar disorder: how can we do it better? Med J Aust. 2006;184:459–62.

    PubMed  Google Scholar 

  19. Ghaemi SN, Boiman EE, Goodwin FK. Diagnosing bipolar disorder and the effect of antidepressants: a naturalistic study. J Clin Psychiatry. 2000;61:804–8.

    Article  PubMed  CAS  Google Scholar 

  20. Altshuler LL, Post RM, Leverich GS, Mikalauskas K, Rosoff A, Ackerman L. Antidepressant-induced mania and cycle acceleration: a controversy revisited. Am J Psychiatry. 1995;152:1130–8.

    PubMed  CAS  Google Scholar 

  21. Baldessarini RJ, Leahy L, Arcona S, Gause D, Zhang W, Hennen J. Patterns of psychotropic drug prescription for U.S. patients with diagnoses of bipolar disorders. Psychiatr Serv. 2007;58:85–91.

    Article  PubMed  Google Scholar 

  22. Vieta E. Case for caution, case for action. Bipolar Disord. 2003;5:434–5.

    Article  PubMed  Google Scholar 

  23. Vieta E. The package of care for patients with bipolar depression. J Clin Psychiatry. 2005;66(Suppl 5):34–9.

    PubMed  Google Scholar 

  24. Vieta E. Antidepressants in bipolar depression. Acta Psychiatr Scand. 2008;118:335–6.

    Article  PubMed  Google Scholar 

  25. Licht RW, Gijsman H, Nolen WA, Angst J. Are antidepressants safe in the treatment of bipolar depression? A critical evaluation of their potencial risk to induce switch into mania or cycle acceleration. Acta Psychiatr Scand. 2008;118(5):337–46.

    Article  PubMed  CAS  Google Scholar 

  26. Grunze H. Switching, induction of rapid cycling and increased suicidality with antidepressants in bipolar patients: fact or overinterpretation? CNS Spectr. 2008;13:790–5.

    PubMed  Google Scholar 

  27. NICE Clinical Guidelines. Bipolar disorder. The management of bipolar disorder in adults, children and adolescents, in primary and secondary care. National Institute for Health and Clinical Excellence, 2009.

  28. Kasper S, Calabrese JR, Johnson G, Tajima O, Vieta E, Viguera A, Yatham LN, Young AH. International Consensus Group on the Evidence-based Pharmacological Treatment of Bipolar I and II Depression. J Clin Psychiatry. 2008;69:1632–46.

    Article  CAS  Google Scholar 

  29. Goodwin GM and Consensus Group of the British Association for Psychopharmacology. Evidence-based guidelines for treating bipolar disorder: revised second edition—recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2009;23:346–88.

    Article  Google Scholar 

  30. Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Beaulieu S, Alda M, O’Donovan C, Macqueen G, McIntyre RS, Sharma V, Ravindran A, Young LT, Milev R, Bond DJ, Frey BN, Goldstein BI, Lafer B, Birmaher B, Ha K, Nolen WA, Berk M. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013. Bipolar Disord. 2013;15(1):1–44.

    Article  PubMed  CAS  Google Scholar 

  31. Grunze H, Vieta E, Goodwin G, Bowden C, Licht RW, Moller HJ, Kasper S. The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders: update 2009 on the treatment of bipolar depression. World J Biol Psychiatry. 2010;11:81–109.

    Article  PubMed  Google Scholar 

  32. Nivoli AM, Colom F, Murru A, Pacchiarotti I, Castro-Loli P, González-Pinto A, Fountoulakis KN, Vieta E. New treatment guidelines for acute bipolar depression: a systematic review. J Affect Disord. 2011;129:14–26.

    Article  PubMed  Google Scholar 

  33. Vieta E, Murru A, Pueyo MJ. Guia sobre el maneig del tratorn bipolar a Catalunya. Barcelona: Agència d′Informació, Avaluació i Qualitat en Salut. Servei Català de la Salut. Departament de Salut. Generalitat de Catalunya, 2011.

  34. Ghaemi SN, Sachs GS, Chiou AM, Pandurangi AK, Goodwin FK. Is bipolar disorder still underdiagnosed? Are antidepressants overutilized? J Affect Disord. 1999;52:135–44.

    Article  PubMed  CAS  Google Scholar 

  35. Gijsman HJ, Geddes JR, Rendell JM, Nolen WA, Goodwin GM. Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry. 2004;161(9):1537–47.

    Article  PubMed  Google Scholar 

  36. Sidor MM, Macqueen GM. Antidepressants for the acute treatment of bipolar depression: a systematic review and meta-analysis. J Clin Psychiatry. 2011;72(2):156–67.

    Article  PubMed  CAS  Google Scholar 

  37. Cohn JB, Collins G, Ashbrook E, Wernicke JF. A comparison of fluoxetine, imipramine, and placebo in patients with bipolar depressive disorder. Int Clin Psychopharmacol. 1989;4(4):313–22.

    Article  PubMed  CAS  Google Scholar 

  38. Amsterdam JD, García-Espana F, Fawcett J, Quitkin FM, Reimherr FW, Rosenbaum JF, Schweizer E, Beasley C. Efficacy and safety of fluoxetine in treating bipolar II major depressive episode. J Clin Psychopharmacol. 1998;18(6):435–40.

    Article  PubMed  CAS  Google Scholar 

  39. Amsterdam JD, Shults J. Comparison of fluoxetine, olanzapine, and combined fluoxetine plus olanzapine initial therapy of bipolar type I and type II major depression—lack of manic induction. J Affect Disord. 2005;87(1):121–30.

    Article  PubMed  CAS  Google Scholar 

  40. Amsterdam JD, Shults J. Fluoxetine monotherapy of bipolar type II and bipolar NOS major depression: a double-blind, placebo-substitution, continuation study. Int Clin Psychopharmacol. 2005;20(5):257–64.

    Article  PubMed  Google Scholar 

  41. Young LT, Joffe RT, Robb JC, MacQueen GM, Marriott M, Patelis-Siotis I. Double-blind comparison of addition of a second mood stabilizer versus an antidepressant to an initial mood stabilizer for treatment of patients with bipolar depression. Am J Psychiatry. 2000;157(1):124–6.

    PubMed  CAS  Google Scholar 

  42. Schaffer A, Zuker P, Levitt A. Randomized, double blind pilot trial comparing lamotrigine versus citalopram for the treatment of bipolar depression. J Affect Disord. 2006;96(1–2):95–9.

    Article  PubMed  CAS  Google Scholar 

  43. Sachs GS, Nierenberg AA, Calabrese JR, Marangell LB, Wisniewski SR, Gyulai L, Friedman ES, Bowden CL, Fossey MD, Ostacher MJ, Ketter TA, Patel J, Hauser P, Rapport D, Martínez JM, Allen MH, Miklowitz DJ, Otto MW, Dennehy EB, Thase ME. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med. 2007;356(17):1711–22.

    Google Scholar 

  44. Nemeroff CB, Evans DL, Gyulai L, Sachs GS, Bowden CL, Gergel IP, Oakes R, Pitts CD. Double-blind, placebo-controlled comparison of imipramine and paroxetine in the treatment of bipolar depression. Am J Psychiatry. 2001;158(6):906–12.

    Article  PubMed  CAS  Google Scholar 

  45. Vieta E, Martínez-Arán A, Goikolea JM, Torrent C, Colom F, Benabarre A, Reinares M. A randomized trial comparing paroxetine and venlafaxine in the treatment of bipolar depressed patients taking mood stabilizers. J Clin Psychiatry. 2002;63(6):508–12.

    Article  PubMed  CAS  Google Scholar 

  46. 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. Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Arch Gen Psychiatry. 2003;60(11):1079–88.

    Article  PubMed  CAS  Google Scholar 

  47. Parker G, Tully L, Olley A, Hadzi-Pavlovic D. SSRIs as mood stabilizers for bipolar II disorder? A proof of concept study. J Affect Disord. 2006;92(2–3):205–14.

    Article  PubMed  CAS  Google Scholar 

  48. McElroy SL, Weisler Rh, Chang W, Olausson B, Paulsson B, Brecher M, Agambaram V, Merideth C, Nordenhem A, Young AH. EMBOLDEN II (Trial D1447C00134) Investigators. J Clin Psychiatry. 2010;71(2):163–74.

    Article  PubMed  CAS  Google Scholar 

  49. Tondo L, Vázquez G, Baldessarini RJ. Mania associated with antidepressant treatment: comprehensive meta-analytic review. Acta Psychiatr Scand. 2010;121(6):404–14.

    Article  PubMed  CAS  Google Scholar 

  50. Leverich GS, Altshuler LL, Frye MA, Suppes T, McElroy SL, Keck PE Jr, Kupka RW, Denicoff KD, Nolen WA, Grunze H, Martínez MI, Post RM. 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. J Psychiatry. 2006;163(2):232–9.

    Google Scholar 

  51. Post RM, Altshuler LL, Frye MA, Suppes T, Rush AJ, Keck PE Jr, McElroy SL, Denicoff KD, Leverich GS, Kupka R, Nolen WA. Rate of switch in bipolar patients prospectively treated with second-generation antidepressants as augmentation to mood stabilizers. Bipolar Disord. 2001;3(5):259–65.

    Article  PubMed  CAS  Google Scholar 

  52. 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. Mood switch in bipolar depression: comparison of adjunctive venlafaxine, bupropion and sertraline. Br J Psychiatry. 2006;189:124–31.

    Article  PubMed  CAS  Google Scholar 

  53. Valentí M, Pacchiarotti I, Bonnín CM, Rosa AR, Popovic D, Nivoli AM, Goikolea JM, Murru A, Undurraga J, Colom F, Vieta E. Risk factors for antidepressant-related switch to mania. J Clin Psychiatry. 2012;73(2):271–6.

    Article  Google Scholar 

  54. Valentí M, Pacchiarotti I, Rosa AR, Bonnín CM, Popovic D, Nivoli AM, Murru A, Grande I, Colom F, Vieta E. Bipolar mixed episodes and antidepressants: a cohort study of bipolar I disorder patients. Bipolar Disord. 2011;13(2):145–54.

    Article  PubMed  Google Scholar 

  55. Goodwin FK, Murphy DL, Dunner DL, Bunney WE Jr. Lithium response in unipolar versus bipolar depression. Am J Psychiatry. 1972;129(1):44–7.

    PubMed  CAS  Google Scholar 

  56. Mendels J. Lithium in the acute treatment of depressive states in Lithium research and therapy. Edited by Johnson FN. London: Academic Press; 1975.

    Google Scholar 

  57. El-Mallak R. Lithium: actions and mechanisms. Washington, DC: American Psychiatric Press; 1996.

    Google Scholar 

  58. Yatham LN, Calabrese JR, Kusumakar V. Bipolar depression: criteria for treatment selection, definition of refractoriness, and treatment options. Bipolar Disord. 2003;5(2):85–97.

    Article  PubMed  CAS  Google Scholar 

  59. Young AH, McElroy SL, Bauer M, Philips N, Chang W, Olausson B, Paulsson B, Brecher M, EMBOLDEN I (Trial 001) Investigators. 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. 2010;71(2):150–62.

    Article  PubMed  CAS  Google Scholar 

  60. Gelenberg AJ, Kane JM, Keller MB, Lavori P, Rosenbaum JF, Cole K, Lavelle J. Comparison of standard and low serum levels of lithium for maintenance treatment of bipolar disorder. N Engl J Med. 1989;321(22):1489–93.

    Article  PubMed  CAS  Google Scholar 

  61. Keller MB, Lavori PW, Kane JM, Gelenberg AJ, Rosenbaum JF, Walzer EA, Baker LA. Subsyndromal symptoms in bipolar disorder. A comparison of standard and low serum levels of lithium. Arch Gen Psychiatry. 1992;49(5):371–6.

    Article  PubMed  CAS  Google Scholar 

  62. Reinares M, Rosa AR, Franco C, Goikolea JM, Fountoulakis K, Siamouli M, Gonda X, Frangou S, Vieta E. A systematic review on the role of anticonvulsants in the treatment of acute bipolar depression. Int J Neuropsychopharmacol. 2013;16(2):485–96.

    Article  PubMed  CAS  Google Scholar 

  63. Smith LA, Cornelius VR, Azorin JM, Perugi G, Vieta E, Young AH, Bowden CL. Valproate for the treatment of acute bipolar depression: Systematic review and meta-analysis. J Affect Disord. 2010;122(1–2):1–9.

    Article  PubMed  CAS  Google Scholar 

  64. Geddes JR, Calabrese JR, Goodwin GM. Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials. Br J Psychiatry. 2009;194:4–9.

    Article  PubMed  Google Scholar 

  65. 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, LamLit Study Group. Efficacy and safety of lamotrigine as add-on treatment to lithium in bipolar depression: a multicenter, double-blind, placebo-controlled trial. J Clin Psychiatry. 2009;70(2):223–31.

    Article  PubMed  Google Scholar 

  66. Post RM, Ketter TA, Denicoff K, Pazzaglia PJ, Leverich GS, Marangell LB, Callahan AM, George MS, Frye MA. The place of anticonvulsant therapy in bipolar illness. Psychopharmacology (Berl). 1996;128(2):115–29.

    Article  CAS  Google Scholar 

  67. Cruz N, Sánchez-Moreno J, Torres F, Goikolea JM, Valentí M, Vieta E. Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis. Int J Neuropsychopharmacol. 2009;29:1–10.

    Google Scholar 

  68. Bech P. Meta-analysis of placebo-controlled trials with mirtazapine using the core items of the Hamilton Depression Scale as evidence of a pure antidepressive effect in the short-term treatment of major depression. Int J Neuropsychopharmacol. 2001;4(4):337–45.

    Article  PubMed  CAS  Google Scholar 

  69. Lecrubier Y, Bech P. The Ham D(6) is more homogenous and as sensitive as the Ham D(17). Eur Psychiatry. 2007;22(4):252–5.

    Article  PubMed  CAS  Google Scholar 

  70. Brown EB, McElroy SL, Keck PE Jr, Deldar A, Adams DH, Tohen M, Williamson DJ. A 7-week, randomized, double-blind trial of olanzapine/fluoxetine combination versus lamotrigine in the treatment of bipolar I depression. J Clin Psychiatry. 2006;67(7):1025–33.

    Article  PubMed  CAS  Google Scholar 

  71. Tohen M, Chengappa KN, Suppes T, Zarate CA Jr, Calabrese JR, Bowden CL, Sachs GS, Kupfer DJ, Baker RW, Risser RC, Keeter EL, Feldman PD, Tollefson GD, Breier A. Efficacy of olanzapine in combination with valproate or lithium in the treatment of mania in patients partially nonresponsive to valproate or lithium monotherapy. Arch Gen Psychiatry. 2002;59(1):62–9.

    Article  PubMed  CAS  Google Scholar 

  72. Tohen M, Chengappa KN, Suppes T, Baker RW, Zarate CA, Bowden CL, Sachs GS, Kupfer DJ, Ghaemi SN, Feldman PD, Risser RC, Evans AR, Calabrese JR. Relapse prevention in bipolar I disorder: 18-month comparison of olanzapine plus mood stabiliser v. mood stabiliser alone. Br J Psychiatry. 2004;184:337–45.

    Article  PubMed  Google Scholar 

  73. Houston JP, Ahl J, Meyers AL, Kaiser CJ, Tohen M, Baldessarini RJ. Reduced suicidal ideation in bipolar I disorder mixed-episode patients in a placebo-controlled trial of olanzapine combined with lithium or divalproex. J Clin Psychiatry. 2006;67(8):1246–52.

    Article  PubMed  CAS  Google Scholar 

  74. Calabrese JR, Keck PE Jr, Macfadden W, Minkwitz M, Ketter TA, Weisler RH, Cutler AJ, McCoy R, Wilson E, Mullen J. A randomized, doubleblind, placebo controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry. 2005;162(7):1351–60.

    Article  PubMed  Google Scholar 

  75. Thase ME, Macfadden W, Weisler RH, Chang W, Paulsson B, Khan A, Calabrese JR. Efficacy of quetiapine monotherapy in bipolar I and II depression: a double-blind, placebo-controlled study (the BOLDER II study). J Clin Psychopharmacol. 2006;26(6):600–9.

    Article  PubMed  CAS  Google Scholar 

  76. Suppes T, Datto C, Minkwitz M, Nordenhem A, Walker C, Darko D. Effectiveness of the extended release formulation of quetiapine as monotherapy for the treatment of acute bipolar depression. J Affect Disord. 2010;121:106–15.

    Article  PubMed  CAS  Google Scholar 

  77. Loebel A, Cucchiaro J, Silva R, et al. Lurasidone monotherapy for the treatment of bipolar I depression: Results of a 6-week, double-blind, placebo-controlled study. Philadelphia: American Psychiatric Association; 2012.

    Google Scholar 

  78. Loebel A, Cucchiaro J, Silva R, et al. Lurasidone adjunctive to lithium or valproate for the treatment of bipolar I depression: Results of a 6-week, double-blind, placebo-controlled. Philadelphia: American Psychiatric Association; 2012.

    Google Scholar 

  79. McElroy SL, Suppes T, Frye MA, Altshuler LL, Stanford K, Martens B, Leverich GS, Post RM, Keck PE Jr. Open-label aripiprazole in the treatment of acute bipolar depression: a prospective pilot trial. J Affect Disord. 2007;101(1–3):275–81.

    Article  PubMed  CAS  Google Scholar 

  80. Thase ME, Jonas A, Khan A, Bowden CL, Wu X, McQuade RD, Carson WH, Marcus RN, Owen R. Aripiprazole monotherapy in nonpsychotic bipolar I depression: results of 2 randomized, placebo-controlled studies. J Clin Psychopharmacol. 2008;28(1):13–20.

    Article  PubMed  CAS  Google Scholar 

  81. Fountoulakis KN, Vieta E, Schmidt F. Aripiprazole monotherapy in the treatment of bipolar disorder: a meta-analysis. J Affect Disord. 2011;133(3):361–70.

    Article  PubMed  CAS  Google Scholar 

  82. Lombardo I, Sachs G, Kolluri S, Kremer C, Yang R. Two 6-week, randomized, double-blind, placebo-controlled studies of ziprasidone in outpatients with bipolar I depression: did baseline characteristics impact trial outcome? J Clin Psychopharmacol. 2012;32(4):470–8.

    Article  PubMed  CAS  Google Scholar 

  83. Sachs GS, Ice KS, Chappell PB, et al. Efficacy and safety of adjunctive oral ziprasidone for acute treatment of depression in patients with bipolar I disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2001;72:1413–22.

    Article  CAS  Google Scholar 

  84. Sienaert P, Lambrichts L, Dols A, De Fruyt J. Evidence-based treatment strategies for treatment-resistant bipolar depression: a systematic review. Bipolar Disorders. 2013;15:61–9.

    Article  PubMed  CAS  Google Scholar 

  85. Goldberg JF, Frye MA, Dunn RT. Pramipexole in refractory bipolar depression. Am J Psychiatry. 1999;156:798.

    PubMed  CAS  Google Scholar 

  86. Sporn J, Ghaemi SN, Sambur MR, et al. Pramipexole augmentation in the treatment of unipolar and bipolar depression: a retrospective chart review. Ann Clin Psychiatry. 2000;12:137–40.

    Article  PubMed  CAS  Google Scholar 

  87. Lattanzi L, Dell Osso L, Cassano P, et al. Pramipexole in treatment-resistant depression: a 16-week naturalistic study. Bipolar Disord. 2002;4:307–14.

    Article  PubMed  CAS  Google Scholar 

  88. Zarate CA, Payne JL, Singh J, et al. Pramipexole for bipolar II depression: a placebo-controlled proof of concept study. Biol Psychiatry. 2004;56:54–60.

    Article  PubMed  CAS  Google Scholar 

  89. Frye MA, Grunze H, Suppes T, et al. A placebo-controlled evaluation of adjunctive modafinil in the treatment of bipolar depression. Am J Psychiatry. 2007;164:1242–9.

    Article  PubMed  Google Scholar 

  90. Menza MA, Kaufman KR, Castellanos A. Modafinil augmentation of antidepressant treatment in depression. J Clin Psychiatry. 2000;61:378–81.

    Article  PubMed  CAS  Google Scholar 

  91. Fernandes PP, Petty F. Modafinil for remitted bipolar depression with hypersomnia. Ann Pharmacother. 2003;37:1807–9.

    Article  PubMed  Google Scholar 

  92. Kumar R. Approved and investigational uses of modafinil: an evidence-based review. Drugs. 2008;68:1803–39.

    Article  PubMed  CAS  Google Scholar 

  93. Calabrese JR, Ketter TA, Youakim JM, Tiller JM, Yang R, Frye MA. 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. 2010;71(10):1363–70.

    Article  PubMed  CAS  Google Scholar 

  94. Nierenberg AA, Ostacher MJ, Calabrese JR, et al. Treatment-resistant bipolar depression: a STEP-BD equipoise randomized effectiveness trial of antidepressant augmentation with lamotrigine, inositol, or risperidone. Am J Psychiatry. 2006;163:210–6.

    Article  PubMed  Google Scholar 

  95. Chengappa KNR, Levine J, Gershon S, et al. Inositol as an add-on treatment for bipolar depression. Bipolar Disord. 2000;2:47–55.

    Article  PubMed  CAS  Google Scholar 

  96. Evins AE, Demopulos C, Yovel I, et al. Inositol augmentation of lithium or valproate for bipolar depression. Bipolar Disord. 2006;8:168–74.

    Article  CAS  Google Scholar 

  97. Diazgranados N, Ibrahim L, Brutsche NE, et al. A randomized add-on trial of an N-methyl-d-aspartate antagonist in treatment-resistant bipolar depression. Arch Gen Psychiatry. 2010;67:793–802.

    Article  PubMed  CAS  Google Scholar 

  98. Zarate CA Jr, Brutsche NE, Ibrahim L, et al. Replication of ketamine’s antidepressant efficacy in bipolar depression: A randomized controlled add-on trial. Biol Psychiatry. 2012;71:939–46.

    Article  PubMed  CAS  Google Scholar 

  99. Berk M, Malhi GS, Gray LJ, Dean OM. The promise of N-acetylcysteine in neuropsychiatry. Trends Pharmacol Sci. 2013;34(3):167–77.

    Article  PubMed  CAS  Google Scholar 

  100. Berk M, Copolov DL, Dean O, Lu K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Bush AI. N-Acetyl-cysteine for depressive symptoms in bipolar disorder: a double-blind randomized placebo-controlled trial. Biol Psychiatry. 2008;64(6):468–75.

    Article  PubMed  CAS  Google Scholar 

  101. Goodwin FK, Jamison K. Manic-depressive illness. In: Bipolar disorders and recurrent depression. 2nd ed. Cambridge: Oxford Press; 2007.

  102. Burgess S, Geddes J, Hawton K, Townsend E, Jamison K, Goodwin G. Lithium for maintenance treatment of mood disorders. Cochrane Database Syst Rev. 2001;(3):CD003013.

  103. Davis JM, Janicak PG, Hogan DM. Mood stabilizers in the prevention of recurrent affective disorders: a meta-analysis. Acta Psychiatr Scand. 1999;100(6):406–17.

    Article  PubMed  CAS  Google Scholar 

  104. Geddes JR, Burgess S, Hawton K, Jamison K, Goodwin GM. Long-term lithium therapy for bipolar disorder: systematic review and meta-analysis of randomized controlled trials. Am J Psychiatry. 2004;161(2):217–22.

    Article  PubMed  Google Scholar 

  105. Nolen WA, Weisler RH. The association of the effect of lithium in the maintenance treatment of bipolar disorder with lithium plasma levels: a post hoc analysis of a double-blind study comparing switching to lithium or placebo in patients who responded to quetiapine (Trial 144). Bipolar Disord. 2013;15(1):100–9.

    Article  PubMed  CAS  Google Scholar 

  106. Calabrese JR, Bowden CL, Sachs G, Yatham LN, Behnke K, Mehtonen OP, Montgomery P, Ascher J, Paska W, Earl N, DeVeaugh-Geiss J, Lamictal 605 Study Group. A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. J Clin Psychiatry. 2003;64(9):1013–24.

    Article  PubMed  CAS  Google Scholar 

  107. Bowden CL, Calabrese JR, Sachs G, Yatham LN, Asghar SA, Hompland M, Montgomery P, Earl N, Smoot TM, DeVeaugh-Geiss J. A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder. Arch Gen Psychiatry. 2003;60(4):392–400.

    Article  PubMed  CAS  Google Scholar 

  108. Baldessarini RJ, Tondo L, Davis P, Pompili M, Goodwin FK, Hennen J. Decreased risk of suicides and attempts during long-term lithium treatment: a meta-analytic review. Bipolar Disord. 2006;8(5 Pt 2):625–39.

    Article  PubMed  CAS  Google Scholar 

  109. Gonzalez-Pinto A, Mosquera F, Alonso M, López P, Ramírez F, Vieta E, Baldessarini RJ. Suicidal risk in bipolar I disorder patients and adherence to long-term lithium treatment. Bipolar Disord. 2006;8(5 Pt 2):618–24.

    Article  PubMed  CAS  Google Scholar 

  110. Goodwin RD, Beautrais AL, Fergusson DM. Familial transmission of suicidal ideation and suicide attempts: evidence from a general population sample. Psychiatry Res. 2004;126(2):159–65.

    Article  PubMed  Google Scholar 

  111. Frye MA, Yatham LN, Calabrese JR, Bowden CL, Ketter TA, Suppes T, Adams BE, Thompson TR. Incidence and time course of subsyndromal symptoms in patients with bipolar I disorder: an evaluation of 2 placebocontrolled maintenance trials. J Clin Psychiatry. 2006;67(11):1721–8.

    Article  PubMed  CAS  Google Scholar 

  112. Geller B, Cooper TB, Watts HE, Cosby CM, Fox LW. Early findings from a pharmacokinetically designed double-blind and placebo-controlled study of lithium for adolescents comorbid with bipolar and substance dependency disorders. Prog Neuropsychopharmacol Biol Psychiatry. 1992;16(3):281–99.

    Article  PubMed  CAS  Google Scholar 

  113. Geller B, Cooper TB, Sun K, Zimerman B, Frazier J, Williams M, Heath J. Double-blind and placebocontrolled study of lithium for adolescent bipolar disorders with secondary substance dependency. J Am Acad Child Adolesc Psychiatry. 1998;37:171–8.

    Article  PubMed  CAS  Google Scholar 

  114. Abou-Saleh MT, Coppen A. Who responds to prophylactic lithium? J Affect Disord. 1986;10(2):115–25.

    Article  PubMed  CAS  Google Scholar 

  115. Goodwin GM. Recurrence of mania after lithium withdrawal. Implications for the use of lithium in the treatment of bipolar affective disorder. Br J Psychiatry. 1994;164(2):149–52.

    Article  PubMed  CAS  Google Scholar 

  116. Kemp DE, Gao K, Ganocy SJ, Elhaj O, Bilali SR, Conroy C, Findling RL, Calabrese JR. A 6-month, double-blind, maintenance trial of lithium monotherapy versus the combination of lithium and divalproex for rapid-cycling bipolar disorder and co-occurring substance abuse or dependence. J Clin Psychiatry. 2009;70(1):113–21.

    Article  PubMed  CAS  Google Scholar 

  117. Calabrese JR, Shelton MD, Rapport DJ, Youngstrom EA, Jackson K, Bilali S, Ganocy SJ, Findling RL. A 20-month, double-blind, maintenance trial of lithium versus divalproex in rapid-cycling bipolar disorder. Am J Psychiatry. 2005;162(11):2152–61.

    Article  PubMed  Google Scholar 

  118. Findling RL, McNamara NK, Youngstrom EA, Stansbrey R, Gracious BL, Reed MD, Calabrese JR. Double-blind 18-month trial of lithium versus divalproex maintenance treatment in pediatric bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2005;44(5):409–17.

    Article  PubMed  Google Scholar 

  119. Bowden CL, Calabrese JR, McElroy SL, Gyulai L, Wassef A, Petty F, Pope HG Jr, Chou JC, Keck PE, Keck PE Jr, Rhodes LJ, Swann AC, Hirschfeld RM, Wozniak PJ. A randomized, placebo-controlled 12-month trial of divalproex and lithium in treatment of outpatients with bipolar I disorder. Divalproex Maintenance Study Group. Arch Gen Psychiatry. 2000;57(5):481–9.

    Article  PubMed  CAS  Google Scholar 

  120. Lambert PA, Venaud G. Use of valpromide in psychiatric therapeutics. Encephale. 1987;13(6):367–73.

    PubMed  CAS  Google Scholar 

  121. Gyulai L, Bowden CL, McElroy SL, Calabrese JR, Petty F, Swann AC, Chou JC, Wassef A, Risch CS, Hirschfeld RM, Nemeroff CB, Keck PE Jr, Evans DL, Wozniak PJ. Maintenance efficacy of divalproex in the prevention of bipolar depression. Neuropsychopharmacology. 2003;28(7):1374–82.

    Article  PubMed  CAS  Google Scholar 

  122. Okuma T, Inanaga K, Otsuki S, Sarai K, Takahashi R, Hazama H, Mori A, Watanabe S. A preliminary double blind study on the efficacy of carbamazepine in prophylaxis of manic-depressive illness. Psychopharmacology. 1981;73(1):95–6.

    Article  PubMed  CAS  Google Scholar 

  123. Coxhead N, Silverstone T, Cookson J. Carbamazepine versus lithium in the prophylaxis of bipolar affective disorder. Acta Psychiatr Scand. 1992;85(2):114–8.

    Article  PubMed  CAS  Google Scholar 

  124. Denicoff KD, Smith-Jackson EE, Disney ER, Ali SO, Leverich GS, Post RM. Comparative prophylactic efficacy of lithium, carbamazepine, and the combination in bipolar disorder. J Clin Psychiatry. 1997;58(11):470–8.

    Article  PubMed  CAS  Google Scholar 

  125. Greil W, Kleindienst N. The comparative prophylactic efficacy of lithium and carbamazepine in patients with bipolar I disorder. Int Clin Psychopharmacol. 1999;14(5):277–81.

    PubMed  CAS  Google Scholar 

  126. Greil W, Ludwig-Mayerhofer W, Erazo N, Schöchlin C, Schmidt S, Engel RR, Czernik A, Giedke H, Müller-Oerlinghausen B, Osterheider M, Rudolf GA, Sauer H, Tegeler J, Wetterling T. Lithium versus carbamazepine in the maintenance treatment of bipolar disorders—a randomised study. J Affect Disord. 1997;43(2):151–61.

    Article  PubMed  CAS  Google Scholar 

  127. Kleindienst N, Greil W. Inter-episodic morbidity and drop-out under carbamazepine and lithium in the maintenance treatment of bipolar disorder. Psychol Med. 2002;32(3):493–501.

    Article  PubMed  CAS  Google Scholar 

  128. Lusznat RM, Murphy DP, Nunn CM. Carbamazepine vs lithium in the treatment and prophylaxis of mania. Br J Psychiatry. 1988;153:198–204.

    Article  PubMed  CAS  Google Scholar 

  129. Placidi GF, Lenzi A, Lazzerini F, Cassano GB, Akiskal HS. The comparative efficacy and safety of carbamazepine versus lithium: a randomized, double-blind 3-year trial in 83 patients. J Clin Psychiatry. 1986;47(10):490–4.

    PubMed  CAS  Google Scholar 

  130. Simhandl C, Denk E, Thau K. The comparative efficacy of carbamazepine low and high serum level and lithium carbonate in the prophylaxis of affective disorders. J Affect Disord. 1993;28(4):221–31.

    Article  PubMed  CAS  Google Scholar 

  131. Small JG, Klapper MH, Milstein V, Kellams JJ, Miller MJ, Marhenke JD, Small IF. Carbamazepine compared with lithium in the treatment of mania. Arch Gen Psychiatry. 1991;48(10):915–21.

    Article  PubMed  CAS  Google Scholar 

  132. Stoll K, Goncalves N, Krober H, Demisch K, Bellaire W. Use of Carbamazepine in affective illness. In: Lerer G, Gershon S (eds) New directions in affective disorders. New York: Springer; 1989. p. 540–4.

  133. Watkins SE, Callender K, Thomas DR, Tidmarsh SF, Shaw DM. The effect of carbamazepine and lithium on remission from affective illness. Br J Psychiatry. 1987;150:180–2.

    Article  PubMed  CAS  Google Scholar 

  134. Goldsmith DR, Wagstaff AJ, Ibbotson T, Perry CM. Lamotrigine: a review of its use in bipolar disorder. Drugs. 2003;63(19):2029–50.

    Article  PubMed  CAS  Google Scholar 

  135. Vieta E. Maintenance therapy for bipolar disorder: current and future management options. Expert Rev Neurother. 2004;4(6 Suppl 2):S35–42.

    Article  PubMed  CAS  Google Scholar 

  136. Popova E, Leighton C, Bernabarre A, Bernardo M, Vieta E. Oxcarbazepine in the treatment of bipolar and schizoaffective disorders. Expert Rev Neurother. 2007;7(6):617–26.

    Article  PubMed  CAS  Google Scholar 

  137. Juruena MF, Ottoni GL, Machado-Vieira R, Carneiro RM, Weingarthner N, Marquardt AR, Fleig SS, Broilo L, Busnello EA. Bipolar I and II disorder residual symptoms: oxcarbazepine and carbamazepine as add-on treatment to lithium in a double-blind, randomized trial. Prog Neuropsychopharmacol Biol Psychiatry 2009;33(1):94–9.

    Google Scholar 

  138. Vieta E, Cruz N, García-Campayo J, De Arce R, Crespo J, Valles V, Perez-Blanco J, Roca E, Olivares J, Morinigo A. Fernández-Villamor R, Comes M. A double-blind, randomized, placebo controlled prophylaxis trial of oxcarbazepine as adjunctive treatment to lithium in the long-term treatment of bipolar I and II disorder. Int J Neuropsychopharmacol. 2008;11(4):445–52.

    Google Scholar 

  139. Sernyak MJ, Woods SW. Chronic neuroleptic use in manic-depressive illness. Psychopharmacol Bull. 1993;29(3):375–81.

    PubMed  CAS  Google Scholar 

  140. Kukopulos A, Reginaldi D, Laddomada P, Floris G, Serra G, Tondo L. Course of the manic-depressive cycle and changes caused by treatment. Pharmakopsychiatr Neuropsychopharmakol. 1980;13(4):156–67.

    PubMed  CAS  Google Scholar 

  141. Vieta E, Goikolea JM. Atypical antipsychotics: newer options for mania and maintenance therapy. Bipolar Disord. 2005;7(Suppl 4):21–33.

    Article  PubMed  CAS  Google Scholar 

  142. Keck PE Jr, Calabrese JR, McQuade RD, Carson WH, Carlson BX, Rollin LM, Marcus RN, Sánchez R, Aripiprazole Study Group. A randomized, double-blind, placebo-controlled 26-week trial of aripiprazole in recently manic patients with bipolar I disorder. J Clin Psychiatry. 2006;67(4):626–37.

    Article  PubMed  CAS  Google Scholar 

  143. Keck PE Jr, Calabrese JR, McIntyre RS, McQuade RD, Carson WH, Eudicone JM, Carlson BX, Marcus RN, Sánchez R, Aripiprazole Study Group. Aripiprazole monotherapy for maintenance therapy in bipolar I disorder: a 100-week, double-blind study versus placebo. J Clin Psychiatry. 2007;68(10):1480–91.

    Article  PubMed  CAS  Google Scholar 

  144. Cipriani A, Rendell J, Geddes JR. Olanzapine in long-term treatment of bipolar disorder: a systematic review and meta-analysis. J Psychopharmacol. 2010;24(12):1729–38.

    Article  PubMed  CAS  Google Scholar 

  145. Tohen M, Ketter TA, Zarate CA, Suppes T, Frye M, Altshuler L, Zajecka J, Schuh LM, Risser RC, Brown E, Baker RW. Olanzapine versus divalproex sodium for the treatment of acute mania and maintenance of remission: a 47- week study. Am J Psychiatry. 2003;160(7):1263–71.

    Article  PubMed  Google Scholar 

  146. Tohen M, Greil W, Calabrese JR, Sachs GS, Yatham LN, Oerlinghausen BM, Koukopoulos A, Cassano GB, Grunze H, Licht RW, Dell’Osso L, Evans AR, Risser R, Baker RW, Crane H, Dossenbach MR, Bowden CL. Olanzapine versus lithium in the maintenance treatment of bipolar disorder: a 12-month, randomized, double-blind, controlled clinical trial. Am J Psychiatry. 2005;162(7):1281–90.

    Article  PubMed  Google Scholar 

  147. Ketter TA, Houston JP, Adams DH, Risser RC, Meyers AL, Williamson DJ, Tohen M. Differential efficacy of olanzapine and lithium in preventing manic or mixed recurrence in patients with bipolar I disorder based on number of previous manic or mixed episodes. Clin Psychiatry. 2006;67(1):95–101.

    Article  CAS  Google Scholar 

  148. Rendell JM, Gijsman HJ, Keck P, Goodwin GM, Geddes JR. Olanzapine alone or in combination for acute mania. Cochrane Database Syst Rev. 2003;(3):CD004040.

  149. Colom F, Vieta E, Daban C, Pacchiarotti I, Sánchez-Moreno J. Clinical and therapeutic implications of predominant polarity in bipolar disorder. J Affect Disord. 2006;93(1–3):13–7.

    Article  PubMed  CAS  Google Scholar 

  150. Rosa AR, Andreazza AC, Kunz M, Gomes F, Santin A, Sánchez-Moreno J, Reinares M, Colom F, Vieta E, Kapczinski F. Predominant polarity in bipolar disorder: diagnostic implications. J Affect Disord. 2008;107:45–51.

    Article  PubMed  CAS  Google Scholar 

  151. Vieta E, Suppes T, Eggens I, Persson I, Paulsson B, Brecher M. Efficacy and safety of quetiapine in combination with lithium or divalproex for maintenance of patients with bipolar I disorder (international trial 126). J Affect Disord. 2008;109(3):251–63.

    Article  PubMed  CAS  Google Scholar 

  152. Suppes T, Vieta E, Liu S, Brecher M. Paulsson B; Trial 127 Investigators. Maintenance treatment for patients with bipolar I disorder: results from a north american study of quetiapine in combination with lithium or divalproex (trial 127). Am J Psychiatry. 2009;166(4):476–88.

    Article  PubMed  Google Scholar 

  153. Vieta E, Suppes T, Ekholm B, Udd M, Gustafsson U. Long-term efficacy of quetiapine in combination with lithium or divalproex on mixed symptoms in bipolar I disorder. J Affect Disord. 2012;142(1–3):36–44.

    Article  PubMed  CAS  Google Scholar 

  154. Weisler RH, Montgomery SA, Earley WR, Szamosi J, Lazarus A. Efficacy of extended release quetiapine fumarate monotherapy in patients with major depressive disorder: a pooled analysis of two 6-week, double-blind, placebo-controlled studies. Int Clin Psychopharmacol. 2012;27(1):27–39.

    Article  PubMed  Google Scholar 

  155. Vieta E, Calabrese JR, Goikolea JM, Raines S. MacfaddenW. Quetiapine monotherapy in the treatment of patients with bipolar I or II depression and a rapid-cycling disease course: a randomized, double-blind, placebo controlled study. Bipolar Disord. 2007;9(4):413–25.

    Article  PubMed  CAS  Google Scholar 

  156. Yatham LN, Binder C, Kusumakar V, Riccardelli R. Risperidone plus lithium versus risperidone plus valproate in acute and continuation treatment of mania. Int Clin Psychopharmacol. 2004;19(2):103–9.

    Article  PubMed  Google Scholar 

  157. Vieta E, Herraiz M, Fernández A, Gastó C, Benabarre A, Colom F, Martínez-Arán A, Reinares M. Efficacy and safety of risperidone in the treatment of schizoaffective disorder: initial results from a large, multicenter surveillance study. Group for the Study of Risperidone in Affective Disorders (GSRAD). J Clin Psychiatry. 2001;62(8):623–30.

    Article  PubMed  CAS  Google Scholar 

  158. Kujawa M, Turner N, Turkoz L, MacFadden W, Bossie C, Alphs L. Frequently relapsing bipolar disorder: evidence for an effective treatment. Schizophr Res. 2008;98(S-1):4.

    Google Scholar 

  159. Han C, Lee MS, Pae CU, Ko YH, Patkar AA, Jung IK. Usefulness of long-acting injectable risperidone during 12-month maintenance therapy of bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(6):1219–23.

    Google Scholar 

  160. Benabarre A, Castro P, Sánchez-Moreno J, Martínez-Arán A, Salamero M, Murru A, Franco C, Vieta E. Efficacy and safety of long-acting injectable risperidone in maintenance phase of bipolar and schizoaffective disorder. Actas Esp Psiquiatr. 2009;37(3):143–7.

    PubMed  CAS  Google Scholar 

  161. Vieta E, Nieto E, Autet A, Rosa AR, Goikolea JM, Cruz N, Bonet P. A long-term prospective study on the outcome of bipolar patients treated with long-acting injectable risperidone. World J Biol Psychiatry. 2008;9(3):219–24.

    Article  PubMed  Google Scholar 

  162. Vieta E, Montgomery S, Sulaiman AH, Cordoba R, Huberlant B, Martinez L, Schreiner A. A randomized, double-blind, placebo-controlled trial to assess prevention of mood episodes with risperidone long-acting injectable in patients with bipolar I disorder. Eur Neuropsychopharmacol. 2012;22(11):825–35.

    Article  PubMed  CAS  Google Scholar 

  163. Bowden CL, Vieta E, Ice KS, Schwartz JH, Wang PP, Versavel M. Ziprasidone plus a mood stabilizer in subjects with bipolar I disorder: a 6-month, randomized, placebo-controlled, double-blind trial. J Clin Psychiatry. 2010;71(2):130–7.

    Article  PubMed  CAS  Google Scholar 

  164. Popovic D, Reinares M, Goikolea JM, Bonnin CM, Gonzalez-Pinto A, Vieta E. Polarity index of pharmacological agents used for maintenance treatment of bipolar disorder. Eur Neuropsychopharmacol. 2012;22(5):339–46.

    Article  PubMed  CAS  Google Scholar 

  165. Popovic D, Torrent C, Goikolea JM, Cruz N, Sánchez-Moreno J, Gonzalez-Pinto A, Vieta E. Clinical implications of predominant polarity and the polarity index in bipolar disorder: a naturalistic study. Acta Psychiatrica Scand (in press).

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Acknowledgments

Professor Vieta and Dr. Valentí declare no sources of funding were used to prepare this review.

Professor Vieta has received research grants and served as consultant, advisor, or speaker for Alexza, Almirall, AstraZeneca, Bial, Bristol-Myers Squibb, Elan, Eli Lilly, Ferrer, Forest Research Institute, Gedeon Richter, Glaxo-Smith-Kline, Janssen-Cilag, Jazz, Johnson & Johnson, Lundbeck, Merck-Sharp and Dohme, Novartis, Organon, Otsuka, Pfizer, Pierre Fabre, Qualigen, Roche, Sanofi-Aventis, Servier, Sherling-Plough, Shire, Solvay, Takeda, Teva, United Biosource Corporation, and Wyeth; and has received research funding from the Catalan, Spanish, and European Governments. Dr. Valentí has served as a speaker for Abbott, and Bristol-Myers Squibb.

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    Eduard Vieta & Marc Valentí

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Vieta, E., Valentí, M. Pharmacological Management of Bipolar Depression: Acute Treatment, Maintenance, and Prophylaxis. CNS Drugs 27, 515–529 (2013). https://doi.org/10.1007/s40263-013-0073-y

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