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Essential Pharmacotherapies for Bipolar Disorder

  • Hilja RueggEmail author
  • Caleb Adler
  • L. Rodrigo Patino Duran
  • Suzanne Watson
  • Melissa DelBello
Mental Health in Primary Care (P Diller, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Mental Health in Primary Care

Abstract

Purpose of Review

The evidence basis for treatment of bipolar disorder, both for adults and children, is fairly varied and while Federal Drug Administration (FDA) approval provides one marker of evidence, many psychotropic medications are used for off-label indications. Primary care providers are increasingly at the forefront of initiating treatment for patients with mental health disorders. The purpose of this review is to discuss the current state of evidence for medications treating bipolar disorder, highlighting the evidence, exploring contraindications, side effects, and monitoring requirements for each of the major agents available.

Recent Findings

Currently, there are three major classes of medication to treat bipolar disorder: lithium, anti-seizure drugs, and a growing range of second-generation antipsychotics. The guiding principle in initiation of treatment is to target treatment to the primary phase of illness while balancing side effect profiles with patient characteristics and comorbidities.

Summary

While FDA approval of medications for the treatment of bipolar disorder is somewhat limited for both children and adults, in practice, a wider range of medications have shown to be useful. Increasing second-generation antipsychotic medications can be used as first-line agents for both bipolar mania and bipolar depression.

Keywords

Bipolar pharmacotherapy Medications and bipolar disorder Evidence-based treatment and bipolar disorder 

Notes

Compliance with Ethical Standards

Conflict of Interest

Caleb Adler declares that he has no conflict of interest. L. Rodrigo Patino Duran declares that he has no conflict of interest. Hilja Ruegg declares that she has no conflict of interest. Suzanne Watson declares that she has no conflict of interest. Melissa DelBello declares that she has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: ••Of major importance

  1. 1.
    Hirschfeld RM, Lewis L, Vornik LA. 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. J Clin Psychiatry. 2003;64(2):161–74.CrossRefGoogle Scholar
  2. 2.
    Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924–6.  https://doi.org/10.1136/bmj.39489.470347.AD.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Ebell MH, Siwek J, Weiss BD, Woolf SH, Susman J, Ewigman B, et al. Strength of recommendation taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician. 2004;69(3):548–56.PubMedGoogle Scholar
  4. 4.
    Bowden CL, Brugger AM, Swann AC, Calabrese JR, Janicak PG, Petty F, et al. Efficacy of divalproex vs lithium and placebo in the treatment of mania. The Depakote Mania Study Group. JAMA. 1994;271(12):918–24.CrossRefGoogle Scholar
  5. 5.
    Bowden CL, Grunze H, Mullen J, Brecher M, Paulsson B, Jones M, et al. A randomized, double-blind, placebo-controlled efficacy and safety study of quetiapine or lithium as monotherapy for mania in bipolar disorder. J Clin Psychiatry. 2005;66(1):111–21.CrossRefGoogle Scholar
  6. 6.
    Keck PE, Orsulak PJ, Cutler AJ, Sanchez R, Torbeyns A, Marcus RN, et al. Aripiprazole monotherapy in the treatment of acute bipolar I mania: a randomized, double-blind, placebo- and lithium-controlled study. J Affect Disord. 2009;112(1–3):36–49.  https://doi.org/10.1016/j.jad.2008.05.014.CrossRefPubMedGoogle Scholar
  7. 7.
    Kushner SF, Khan A, Lane R, Olson WH. Topiramate monotherapy in the management of acute mania: results of four double-blind placebo-controlled trials. Bipolar Disord. 2006;8(1):15–27.  https://doi.org/10.1111/j.1399-5618.2006.00276.x.CrossRefPubMedGoogle Scholar
  8. 8.
  9. 9.
    Young AH, McElroy SL, Bauer M, Philips N, Chang W, Olausson B, et al. 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.  https://doi.org/10.4088/JCP.08m04995gre.CrossRefPubMedGoogle Scholar
  10. 10.
    Amsterdam JD, Shults J. Efficacy and safety of long-term fluoxetine versus lithium monotherapy of bipolar II disorder: a randomized, double-blind, placebo-substitution study. Am J Psychiatry. 2010;167(7):792–800.  https://doi.org/10.1176/appi.ajp.2009.09020284.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Bowden CL, Calabrese JR, McElroy SL, Gyulai L, Wassef A, Petty F, et al. 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.CrossRefGoogle Scholar
  12. 12.
    Bowden CL, Calabrese JR, Sachs G, Yatham LN, Asghar SA, Hompland M, et al. 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.  https://doi.org/10.1001/archpsyc.60.4.392.CrossRefPubMedGoogle Scholar
  13. 13.
    Calabrese JR, Bowden CL, Sachs G, Yatham LN, Behnke K, Mehtonen OP, et al. 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.CrossRefGoogle Scholar
  14. 14.
    Prien RF, Caffey EM Jr, Klett CJ. Prophylactic efficacy of lithium carbonate in manic-depressive illness. Report of the Veterans Administration and National Institute of Mental Health collaborative study group. Arch Gen Psychiatry. 1973;28(3):337–41.CrossRefGoogle Scholar
  15. 15.
    Weisler RH, Nolen WA, Neijber A, Hellqvist A, Paulsson B, Trial 144 Study, I. Continuation of quetiapine versus switching to placebo or lithium for maintenance treatment of bipolar I disorder (trial 144: a randomized controlled study). J Clin Psychiatry. 2011;72(11):1452–64.  https://doi.org/10.4088/JCP.11m06878.CrossRefPubMedGoogle Scholar
  16. 16.
    Severus E, Taylor MJ, Sauer C, Pfennig A, Ritter P, Bauer M, et al. Lithium for prevention of mood episodes in bipolar disorders: systematic review and meta-analysis. Int J Bipolar Disord. 2014;2:15.  https://doi.org/10.1186/s40345-014-0015-8.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Emrich HM, von Zerssen D, Kissling W, Moller HJ. Therapeutic effect of valproate in mania. Am J Psychiatry. 1981;138(2):256.  https://doi.org/10.1176/ajp.138.2.256.CrossRefPubMedGoogle Scholar
  18. 18.
    Emrich HM, von Zerssen D, Kissling W, Moller HJ, Windorfer A. Effect of sodium valproate on mania. The GABA-hypothesis of affective disorders. Arch Psychiatr Nervenkr (1970). 1980;229(1):1–16.CrossRefGoogle Scholar
  19. 19.
    McElroy SL, Keck PE Jr, Pope HG Jr, Hudson JI. Valproate in psychiatric disorders: literature review and clinical guidelines. J Clin Psychiatry. 1989;50 Suppl:23–9.PubMedGoogle Scholar
  20. 20.
    Bowden CL, Swann AC, Calabrese JR, Rubenfaer LM, Wozniak PJ, Collins MA, et al. A randomized, placebo-controlled, multicenter study of divalproex sodium extended release in the treatment of acute mania. J Clin Psychiatry. 2006;67(10):1501–10.CrossRefGoogle Scholar
  21. 21.
    Hirschfeld RM, Bowden CL, Vigna NV, Wozniak P, Collins M. A randomized, placebo-controlled, multicenter study of divalproex sodium extended-release in the acute treatment of mania. J Clin Psychiatry. 2010;71(4):426–32.  https://doi.org/10.4088/JCP.08m04960yel.CrossRefPubMedGoogle Scholar
  22. 22.
    McElroy SL, Martens BE, Creech RS, Welge JA, Jefferson L, Guerdjikova AI, et al. Randomized, double-blind, placebo-controlled study of divalproex extended release loading monotherapy in ambulatory bipolar spectrum disorder patients with moderate-to-severe hypomania or mild mania. J Clin Psychiatry. 2010;71(5):557–65.  https://doi.org/10.4088/JCP.08m04854yel.CrossRefPubMedGoogle Scholar
  23. 23.
    Pope HG Jr, McElroy SL, Keck PE Jr, Hudson JI. Valproate in the treatment of acute mania. A placebo-controlled study. Arch Gen Psychiatry. 1991;48(1):62–8.CrossRefGoogle Scholar
  24. 24.
    Tohen M, Vieta E, Goodwin GM, Sun B, Amsterdam JD, Banov M, et al. Olanzapine versus divalproex versus placebo in the treatment of mild to moderate mania: a randomized, 12-week, double-blind study. J Clin Psychiatry. 2008;69(11):1776–89.CrossRefGoogle Scholar
  25. 25.
    Cipriani A, Barbui C, Salanti G, Rendell J, Brown R, Stockton S, et al. Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis. Lancet. 2011;378(9799):1306–15.  https://doi.org/10.1016/S0140-6736(11)60873-8.CrossRefPubMedGoogle Scholar
  26. 26.
    Davis LL, Bartolucci A, Petty F. Divalproex in the treatment of bipolar depression: a placebo-controlled study. J Affect Disord. 2005;85(3):259–66.  https://doi.org/10.1016/j.jad.2004.09.009.CrossRefPubMedGoogle Scholar
  27. 27.
    Ghaemi SN, Gilmer WS, Goldberg JF, Zablotsky B, Kemp DE, Kelley ME, et al. Divalproex in the treatment of acute bipolar depression: a preliminary double-blind, randomized, placebo-controlled pilot study. J Clin Psychiatry. 2007;68(12):1840–4.CrossRefGoogle Scholar
  28. 28.
    Muzina DJ, Gao K, Kemp DE, Khalife S, Ganocy SJ, Chan PK, et al. Acute efficacy of divalproex sodium versus placebo in mood stabilizer-naive bipolar I or II depression: a double-blind, randomized, placebo-controlled trial. J Clin Psychiatry. 2011;72(6):813–9.  https://doi.org/10.4088/JCP.09m05570gre.CrossRefPubMedGoogle Scholar
  29. 29.
    Bond DJ, Lam RW, Yatham LN. Divalproex sodium versus placebo in the treatment of acute bipolar depression: a systematic review and meta-analysis. J Affect Disord. 2010;124(3):228–34.  https://doi.org/10.1016/j.jad.2009.11.008.CrossRefPubMedGoogle Scholar
  30. 30.
    Calabrese JR, Shelton MD, Rapport DJ, Youngstrom EA, Jackson K, Bilali S, et al. A 20-month, double-blind, maintenance trial of lithium versus divalproex in rapid-cycling bipolar disorder. Am J Psychiatry. 2005;162(11):2152–61.  https://doi.org/10.1176/appi.ajp.162.11.2152.CrossRefPubMedGoogle Scholar
  31. 31.
    Findling RL, McNamara NK, Youngstrom EA, Stansbrey R, Gracious BL, Reed MD, et al. 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.  https://doi.org/10.1097/01.chi.0000155981.83865.ea.CrossRefPubMedGoogle Scholar
  32. 32.
    BALANCE investigators, collaborators, Geddes JR, Goodwin GM, Rendell J, Azorin JM, et al. Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial. Lancet. 2010;375(9712):385–95.  https://doi.org/10.1016/S0140-6736(09)61828-6.CrossRefGoogle Scholar
  33. 33.
    Altamura AC, Russo M, Vismara S, Mundo E. Comparative evaluation of olanzapine efficacy in the maintenance treatment of bipolar disorder. J Clin Psychopharmacol. 2004;24(4):454–6.CrossRefGoogle Scholar
  34. 34.
    Cipriani A, Reid K, Young AH, Macritchie K, Geddes J. Valproic acid, valproate and divalproex in the maintenance treatment of bipolar disorder. Cochrane Database Syst Rev. 2013;10:CD003196.  https://doi.org/10.1002/14651858.CD003196.pub2.CrossRefGoogle Scholar
  35. 35.
    Ballenger JC, Post RM. Carbamazepine in manic-depressive illness: a new treatment. Am J Psychiatry. 1980;137(7):782–90.  https://doi.org/10.1176/ajp.137.7.782.CrossRefPubMedGoogle Scholar
  36. 36.
    Post RM, Ballenger JC, Hare TA, Bunney WE Jr. Lack of effect of carbamazepine on gamma-aminobutyric acid in cerebrospinal fluid. Neurology. 1980;30(9):1008–11.CrossRefGoogle Scholar
  37. 37.
    Weisler RH, Kalali AH, Ketter TA, Group, S. P. D. S. A multicenter, randomized, double-blind, placebo-controlled trial of extended-release carbamazepine capsules as monotherapy for bipolar disorder patients with manic or mixed episodes. J Clin Psychiatry. 2004;65(4):478–84.CrossRefGoogle Scholar
  38. 38.
    Weisler RH, Keck PE Jr, Swann AC, Cutler AJ, Ketter TA, Kalali AH, et al. Extended-release carbamazepine capsules as monotherapy for acute mania in bipolar disorder: a multicenter, randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2005;66(3):323–30.CrossRefGoogle Scholar
  39. 39.
    Zhang ZJ, Kang WH, Tan QR, Li Q, Gao CG, Zhang FG, et al. Adjunctive herbal medicine with carbamazepine for bipolar disorders: a double-blind, randomized, placebo-controlled study. J Psychiatr Res. 2007;41(3–4):360–9.  https://doi.org/10.1016/j.jpsychires.2005.06.002.CrossRefPubMedGoogle Scholar
  40. 40.
    Dilsaver SC, Swann SC, Chen YW, Shoaib A, Joe B, Krajewski KJ, et al. Treatment of bipolar depression with carbamazepine: results of an open study. Biol Psychiatry. 1996;40(9):935–7.  https://doi.org/10.1016/S0006-3223(96)00339-3.CrossRefPubMedGoogle Scholar
  41. 41.
  42. 42.
  43. 43.
  44. 44.
  45. 45.
  46. 46.
    Calabrese JR, Bowden CL, Sachs GS, Ascher JA, Monaghan E, Rudd GD. A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal 602 Study Group. J Clin Psychiatry. 1999;60(2):79–88.CrossRefGoogle Scholar
  47. 47.
    Calabrese JR, Suppes T, Bowden CL, Sachs GS, Swann AC, McElroy SL, et al. A double-blind, placebo-controlled, prophylaxis study of lamotrigine in rapid-cycling bipolar disorder. Lamictal 614 Study Group. J Clin Psychiatry. 2000;61(11):841–50.CrossRefGoogle Scholar
  48. 48.
    Seo HJ, Chiesa A, Lee SJ, Patkar AA, Han C, Masand PS, et al. Safety and tolerability of lamotrigine: results from 12 placebo-controlled clinical trials and clinical implications. Clin Neuropharmacol. 2011;34(1):39–47.  https://doi.org/10.1097/WNF.0b013e3182055c07.CrossRefPubMedGoogle Scholar
  49. 49.
    Ban TA. Fifty years chlorpromazine: a historical perspective. Neuropsychiatr Dis Treat. 2007;3(4):495–500.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Gajwani P, Kemp DE, Muzina DJ, Xia G, Gao K, Calabrese JR. Acute treatment of mania: an update on new medications. Curr Psychiatry Rep. 2006;8(6):504–9.CrossRefGoogle Scholar
  51. 51.
    Abou-Setta AM, Mousavi SS, Spooner C, Schouten JR, Pasichnyk D, Armijo-Olivo S, et al. (2012) first-generation versus second-generation antipsychotics in adults: comparative effectiveness. Rockville (MD).Google Scholar
  52. 52.
    Muench J, Hamer AM. Adverse effects of antipsychotic medications. Am Fam Physician. 2010;81(5):617–22.PubMedGoogle Scholar
  53. 53.
    •• Solmi M, Murru A, Pacchiarotti I, Undurraga J, Veronese N, Fornaro M, et al. Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review. Ther Clin Risk Manag. 2017;13:757–77.  https://doi.org/10.2147/TCRM.S117321 This paper presents a clinical review summarizing the safety and tolerability profile of second-generation antipsychotic medications.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Scherk H, Pajonk FG, Leucht S. Second-generation antipsychotic agents in the treatment of acute mania: a systematic review and meta-analysis of randomized controlled trials. Arch Gen Psychiatry. 2007;64(4):442–55.  https://doi.org/10.1001/archpsyc.64.4.442.CrossRefPubMedGoogle Scholar
  55. 55.
    Gitlin M, Frye MA. Maintenance therapies in bipolar disorders. Bipolar Disord. 2012;14(Suppl 2):51–65.  https://doi.org/10.1111/j.1399-5618.2012.00992.x.CrossRefPubMedGoogle Scholar
  56. 56.
    •• Lindstrom L, Lindstrom E, Nilsson M, Hoistad M. Maintenance therapy with second generation antipsychotics for bipolar disorder—a systematic review and meta-analysis. J Affect Disord. 2017;213:138–50.  https://doi.org/10.1016/j.jad.2017.02.012 This paper presents data from a meta-analysis of therapeutics for bipolar maintenance. The authors present data comparing efficacy between second-generation antipsychotic medications and more traditional mood stabilizers, as well as placebo. They also present data on the efficacy of these agents with regard to delaying recurrence of specific mood states.CrossRefPubMedGoogle Scholar
  57. 57.
    Fornaro M, Stubbs B, De Berardis D, Perna G, Valchera A, Veronese N, et al. Atypical antipsychotics in the treatment of acute bipolar depression with mixed features: a systematic review and exploratory meta-analysis of placebo-controlled clinical trials. Int J Mol Sci. 2016;17(2):241.  https://doi.org/10.3390/ijms17020241.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Bond DJ, Frey BN, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018;20(2):97–170.  https://doi.org/10.1111/bdi.12609.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Pereira L, Budovich A, Claudio-Saez M. Monitoring of metabolic adverse effects associated with atypical antipsychotics use in an outpatient psychiatric clinic. J Pharm Pract. 2018.  https://doi.org/10.1177/0897190017752712.
  60. 60.
    Pringsheim T, Lam D, Patten SB. The pharmacoepidemiology of antipsychotic medications for Canadian children and adolescents: 2005–2009. J Child Adolesc Psychopharmacol. 2011;21(6):537–43.  https://doi.org/10.1089/cap.2010.0145.CrossRefPubMedGoogle Scholar
  61. 61.
    Vieta E, Sanchez-Moreno J. Acute and long-term treatment of mania. Dialogues Clin Neurosci. 2008;10(2):165–79.PubMedPubMedCentralGoogle Scholar
  62. 62.
    •• Yildiz A, Nikodem M, Vieta E, Correll CU, Baldessarini RJ. A network meta-analysis on comparative efficacy and all-cause discontinuation of antimanic treatments in acute bipolar mania. Psychol Med. 2015;45(2):299–317.  https://doi.org/10.1017/S0033291714001305 This paper presents data from a network meta-analysis of data from trials of 18 anti-manic therapeutics. By utilizing a methodology allowing direct and indirect comparisons between agents, the authors provide a set of findings which may be useful in choosing between the large number of treatment options for bipolar mania.CrossRefPubMedGoogle Scholar
  63. 63.
    Tohen M, Kryzhanovskaya L, Carlson G, Delbello M, Wozniak J, Kowatch R, et al. Olanzapine versus placebo in the treatment of adolescents with bipolar mania. Am J Psychiatry. 2007;164(10):1547–56.  https://doi.org/10.1176/appi.ajp.2007.06111932.CrossRefPubMedGoogle Scholar
  64. 64.
    •• Vazquez GH, Holtzman JN, Tondo L, Baldessarini RJ. Efficacy and tolerability of treatments for bipolar depression. J Affect Disord. 2015;183:258–62.  https://doi.org/10.1016/j.jad.2015.05.016 This paper summarizes findings from the fairly limited number of randomized, placebo-controlled trials of medications for bipolar depression. However, data from studies of some newer agents, such as cariprazine, are not included.CrossRefPubMedGoogle Scholar
  65. 65.
    Detke HC, DelBello MP, Landry J, Usher RW. Olanzapine/fluoxetine combination in children and adolescents with bipolar I depression: a randomized, double-blind, placebo-controlled trial. J Am Acad Child Adolesc Psychiatry. 2015;54(3):217–24.  https://doi.org/10.1016/j.jaac.2014.12.012.CrossRefPubMedGoogle Scholar
  66. 66.
    Haas M, Delbello MP, Pandina G, Kushner S, Van Hove I, Augustyns I, et al. Risperidone for the treatment of acute mania in children and adolescents with bipolar disorder: a randomized, double-blind, placebo-controlled study. Bipolar Disord. 2009;11(7):687–700.  https://doi.org/10.1111/j.1399-5618.2009.00750.x.CrossRefPubMedGoogle Scholar
  67. 67.
    Gentile S. Clinical usefulness of second-generation antipsychotics in treating children and adolescents diagnosed with bipolar or schizophrenic disorders. Paediatr Drugs. 2011;13(5):291–302.  https://doi.org/10.2165/11591250-000000000-00000.CrossRefPubMedGoogle Scholar
  68. 68.
    Pillay J, Boylan K, Carrey N, Newton A, Vandermeer B, Nuspl M, et al. (2017) First- and second-generation antipsychotics in children and young adults: systematic review update. Rockville (MD)Google Scholar
  69. 69.
    Taylor DM, Cornelius V, Smith L, Young AH. Comparative efficacy and acceptability of drug treatments for bipolar depression: a multiple-treatments meta-analysis. Acta Psychiatr Scand. 2014;130(6):452–69.  https://doi.org/10.1111/acps.12343.CrossRefPubMedGoogle Scholar
  70. 70.
    Berwaerts J, Melkote R, Nuamah I, Lim P. A randomized, placebo- and active-controlled study of paliperidone extended-release as maintenance treatment in patients with bipolar I disorder after an acute manic or mixed episode. J Affect Disord. 2012;138(3):247–58.  https://doi.org/10.1016/j.jad.2012.01.047.CrossRefPubMedGoogle Scholar
  71. 71.
    Berwaerts J, Xu H, Nuamah I, Lim P, Hough D. Evaluation of the efficacy and safety of paliperidone extended-release in the treatment of acute mania: a randomized, double-blind, dose-response study. J Affect Disord. 2012;136(1–2):e51–60.  https://doi.org/10.1016/j.jad.2010.06.030.CrossRefPubMedGoogle Scholar
  72. 72.
    Vieta E, Nuamah IF, Lim P, Yuen EC, Palumbo JM, Hough DW, et al. A randomized, placebo- and active-controlled study of paliperidone extended release for the treatment of acute manic and mixed episodes of bipolar I disorder. Bipolar Disord. 2010;12(3):230–43.  https://doi.org/10.1111/j.1399-5618.2010.00815.x.CrossRefPubMedGoogle Scholar
  73. 73.
    Joshi G, Petty C, Wozniak J, Faraone SV, Spencer AE, Woodworth KY, et al. A prospective open-label trial of paliperidone monotherapy for the treatment of bipolar spectrum disorders in children and adolescents. Psychopharmacology. 2013;227(3):449–58.  https://doi.org/10.1007/s00213-013-2970-7.CrossRefPubMedGoogle Scholar
  74. 74.
    Buoli M, Ciappolino V, Altamura AC. Paliperidone palmitate depot in the long-term treatment of psychotic bipolar disorder: a case series. Clin Neuropharmacol. 2015;38(5):209–11.  https://doi.org/10.1097/WNF.0000000000000103.CrossRefPubMedGoogle Scholar
  75. 75.
    Pathak S, Findling RL, Earley WR, Acevedo LD, Stankowski J, Delbello MP. Efficacy and safety of quetiapine in children and adolescents with mania associated with bipolar I disorder: a 3-week, double-blind, placebo-controlled trial. J Clin Psychiatry. 2013;74(1):e100–9.  https://doi.org/10.4088/JCP.11m07424.CrossRefPubMedGoogle Scholar
  76. 76.
    DelBello MP, Kowatch RA, Adler CM, Stanford KE, Welge JA, Barzman DH, et al. A double-blind randomized pilot study comparing quetiapine and divalproex for adolescent mania. J Am Acad Child Adolesc Psychiatry. 2006;45(3):305–13.  https://doi.org/10.1097/01.chi.0000194567.63289.97.CrossRefPubMedGoogle Scholar
  77. 77.
    Delbello MP, Schwiers ML, Rosenberg HL, Strakowski SM. A double-blind, randomized, placebo-controlled study of quetiapine as adjunctive treatment for adolescent mania. J Am Acad Child Adolesc Psychiatry. 2002;41(10):1216–23.  https://doi.org/10.1097/00004583-200210000-00011.CrossRefPubMedGoogle Scholar
  78. 78.
    DelBello MP, Chang K, Welge JA, Adler CM, Rana M, Howe M, et al. A double-blind, placebo-controlled pilot study of quetiapine for depressed adolescents with bipolar disorder. Bipolar Disord. 2009;11(5):483–93.  https://doi.org/10.1111/j.1399-5618.2009.00728.x.CrossRefPubMedGoogle Scholar
  79. 79.
    Findling RL, Pathak S, Earley WR, Liu S, DelBello MP. Efficacy and safety of extended-release quetiapine fumarate in youth with bipolar depression: an 8 week, double-blind, placebo-controlled trial. J Child Adolesc Psychopharmacol. 2014;24(6):325–35.  https://doi.org/10.1089/cap.2013.0105.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Findling RL, Pathak S, Earley WR, Liu S, DelBello M. Safety, tolerability, and efficacy of quetiapine in youth with schizophrenia or bipolar I disorder: a 26-week, open-label, continuation study. J Child Adolesc Psychopharmacol. 2013;23(7):490–501.  https://doi.org/10.1089/cap.2012.0092.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Duffy A, Milin R, Grof P. Maintenance treatment of adolescent bipolar disorder: open study of the effectiveness and tolerability of quetiapine. BMC Psychiatry. 2009;9:4.  https://doi.org/10.1186/1471-244X-9-4.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    McConville B, Carrero L, Sweitzer D, Potter L, Chaney R, Foster K, et al. Long-term safety, tolerability, and clinical efficacy of quetiapine in adolescents: an open-label extension trial. J Child Adolesc Psychopharmacol. 2003;13(1):75–82.  https://doi.org/10.1089/104454603321666216.CrossRefPubMedGoogle Scholar
  83. 83.
    Findling RL, Nyilas M, Forbes RA, McQuade RD, Jin N, Iwamoto T, et al. Acute treatment of pediatric bipolar I disorder, manic or mixed episode, with aripiprazole: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2009;70(10):1441–51.  https://doi.org/10.4088/JCP.09m05164yel.CrossRefPubMedGoogle Scholar
  84. 84.
    Tramontina S, Zeni CP, Ketzer CR, Pheula GF, Narvaez J, Rohde LA. Aripiprazole in children and adolescents with bipolar disorder comorbid with attention-deficit/hyperactivity disorder: a pilot randomized clinical trial. J Clin Psychiatry. 2009;70(5):756–64.  https://doi.org/10.4088/JCP.08m04726.CrossRefPubMedGoogle Scholar
  85. 85.
    Meduri M, Gregoraci G, Baglivo V, Balestrieri M, Isola M, Brambilla P. A meta-analysis of efficacy and safety of aripiprazole in adult and pediatric bipolar disorder in randomized controlled trials and observational studies. J Affect Disord. 2016;191:187–208.  https://doi.org/10.1016/j.jad.2015.11.033.CrossRefPubMedGoogle Scholar
  86. 86.
    Miura T, Noma H, Furukawa TA, Mitsuyasu H, Tanaka S, Stockton S, et al. Comparative efficacy and tolerability of pharmacological treatments in the maintenance treatment of bipolar disorder: a systematic review and network meta-analysis. Lancet Psychiatry. 2014;1(5):351–9.  https://doi.org/10.1016/S2215-0366(14)70314-1.CrossRefPubMedGoogle Scholar
  87. 87.
    Calabrese JR, Sanchez R, Jin N, Amatniek J, Cox K, Johnson B, et al. Efficacy and safety of aripiprazole once-monthly in the maintenance treatment of bipolar i disorder: a double-blind, placebo-controlled, 52-week randomized withdrawal study. J Clin Psychiatry. 2017;78(3):324–31.  https://doi.org/10.4088/JCP.16m11201.CrossRefPubMedGoogle Scholar
  88. 88.
    Thase ME, Jonas A, Khan A, Bowden CL, Wu X, McQuade RD, et al. Aripiprazole monotherapy in nonpsychotic bipolar I depression: results of 2 randomized, placebo-controlled studies. J Clin Psychopharmacol. 2008;28(1):13–20.  https://doi.org/10.1097/jcp.0b013e3181618eb4.CrossRefPubMedGoogle Scholar
  89. 89.
    Keck PE Jr, Versiani M, Potkin S, West SA, Giller E, Ice K, et al. Ziprasidone in the treatment of acute bipolar mania: a three-week, placebo-controlled, double-blind, randomized trial. Am J Psychiatry. 2003;160(4):741–8.  https://doi.org/10.1176/appi.ajp.160.4.741.CrossRefPubMedGoogle Scholar
  90. 90.
    Potkin SG, Keck PE Jr, Segal S, Ice K, English P. Ziprasidone in acute bipolar mania: a 21-day randomized, double-blind, placebo-controlled replication trial. J Clin Psychopharmacol. 2005;25(4):301–10.CrossRefGoogle Scholar
  91. 91.
    Dubovsky SL, Dubovsky AN. Ziprasidone for maintenance treatment of bipolar I disorder in adults. Expert Opin Pharmacother. 2011;12(5):817–24.  https://doi.org/10.1517/14656566.2011.563237.CrossRefPubMedGoogle Scholar
  92. 92.
    Findling RL, Cavus I, Pappadopulos E, Vanderburg DG, Schwartz JH, Gundapaneni BK, et al. Efficacy, long-term safety, and tolerability of ziprasidone in children and adolescents with bipolar disorder. J Child Adolesc Psychopharmacol. 2013;23(8):545–57.  https://doi.org/10.1089/cap.2012.0029.CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Biederman J, Mick E, Spencer T, Dougherty M, Aleardi M, Wozniak J. A prospective open-label treatment trial of ziprasidone monotherapy in children and adolescents with bipolar disorder. Bipolar Disord. 2007;9(8):888–94.  https://doi.org/10.1111/j.1399-5618.2007.00450.x.CrossRefPubMedGoogle Scholar
  94. 94.
    DelBello MP, Versavel M, Ice K, Keller D, Miceli J. Tolerability of oral ziprasidone in children and adolescents with bipolar mania, schizophrenia, or schizoaffective disorder. J Child Adolesc Psychopharmacol. 2008;18(5):491–9.  https://doi.org/10.1089/cap.2008.008.CrossRefPubMedGoogle Scholar
  95. 95.
    Sanford M, Dhillon S. Lurasidone: a review of its use in adult patients with bipolar I depression. CNS Drugs. 2015;29(3):253–63.  https://doi.org/10.1007/s40263-015-0234-2.CrossRefPubMedGoogle Scholar
  96. 96.
    DelBello MP, Goldman R, Phillips D, Deng L, Cucchiaro J, Loebel A. Efficacy and safety of lurasidone in children and adolescents with bipolar i depression: a double-blind, placebo-controlled study. J Am Acad Child Adolesc Psychiatry. 2017;56(12):1015–25.  https://doi.org/10.1016/j.jaac.2017.10.006.CrossRefPubMedGoogle Scholar
  97. 97.
    Fornaro M, De Berardis D, Perna G, Solmi M, Veronese N, Orsolini L, et al. Lurasidone in the treatment of bipolar depression: systematic review of systematic reviews. Biomed Res Int. 2017;2017:3084859.  https://doi.org/10.1155/2017/3084859.CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Durgam S, Earley W, Lipschitz A, Guo H, Laszlovszky I, Nemeth G, et al. An 8-week randomized, double-blind, placebo-controlled evaluation of the safety and efficacy of cariprazine in patients with bipolar i depression. Am J Psychiatry. 2016;173(3):271–81.  https://doi.org/10.1176/appi.ajp.2015.15020164.CrossRefPubMedGoogle Scholar
  99. 99.
    Findlay LJ, El-Mallakh PL, El-Mallakh RS. Cariprazine for the treatment of bipolar disorder. Perspect Psychiatr Care. 2017;53(3):148–55.  https://doi.org/10.1111/ppc.12150.CrossRefPubMedGoogle Scholar
  100. 100.
    McIntyre RS, Cohen M, Zhao J, Alphs L, Macek TA, Panagides J. A 3-week, randomized, placebo-controlled trial of asenapine in the treatment of acute mania in bipolar mania and mixed states. Bipolar Disord. 2009;11(7):673–86.  https://doi.org/10.1111/j.1399-5618.2009.00748.x.CrossRefPubMedGoogle Scholar
  101. 101.
    McIntyre RS, Wong R. Asenapine: a synthesis of efficacy data in bipolar mania and schizophrenia. Clin Schizophr Relat Psychoses. 2012;5(4):217–20.  https://doi.org/10.3371/CSRP.5.4.6.CrossRefPubMedGoogle Scholar
  102. 102.
    Findling RL, Landbloom RL, Szegedi A, Koppenhaver J, Braat S, Zhu Q, et al. Asenapine for the acute treatment of pediatric manic or mixed episode of bipolar I disorder. J Am Acad Child Adolesc Psychiatry. 2015;54(12):1032–41.  https://doi.org/10.1016/j.jaac.2015.09.007.CrossRefPubMedGoogle Scholar
  103. 103.
    McIntyre RS, Cohen M, Zhao J, Alphs L, Macek TA, Panagides J. Asenapine for long-term treatment of bipolar disorder: a double-blind 40-week extension study. J Affect Disord. 2010;126(3):358–65.  https://doi.org/10.1016/j.jad.2010.04.005.CrossRefPubMedGoogle Scholar
  104. 104.
    Szegedi A, Durgam S, Mackle M, Yu SY, Wu X, Mathews M, et al. Randomized, double-blind, placebo-controlled trial of asenapine maintenance therapy in adults with an acute manic or mixed episode associated with bipolar I disorder. Am J Psychiatry. 2018;175(1):71–9.  https://doi.org/10.1176/appi.ajp.2017.16040419.CrossRefPubMedGoogle Scholar
  105. 105.
    Szegedi A, Zhao J, van Willigenburg A, Nations KR, Mackle M, Panagides J. Effects of asenapine on depressive symptoms in patients with bipolar I disorder experiencing acute manic or mixed episodes: a post hoc analysis of two 3-week clinical trials. BMC Psychiatry. 2011;11:101.  https://doi.org/10.1186/1471-244X-11-101.CrossRefPubMedPubMedCentralGoogle Scholar
  106. 106.
    Singh V, Arnold JG, Prihoda TJ, Martinez M, Bowden CL. An open trial of iloperidone for mixed episodes in bipolar disorder. J Clin Psychopharmacol. 2017;37(5):615–9.  https://doi.org/10.1097/JCP.0000000000000764.CrossRefPubMedGoogle Scholar
  107. 107.
    Poon SH, Sim K, Sum MY, Kuswanto CN, Baldessarini RJ. Evidence-based options for treatment-resistant adult bipolar disorder patients. Bipolar Disord. 2012;14(6):573–84.  https://doi.org/10.1111/j.1399-5618.2012.01042.x.CrossRefPubMedGoogle Scholar
  108. 108.
    Ciapparelli A, Dell’Osso L, Bandettini di Poggio A, Carmassi C, Cecconi D, Fenzi M, et al. Clozapine in treatment-resistant patients with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder: a naturalistic 48-month follow-up study. J Clin Psychiatry. 2003;64(4):451–8.CrossRefGoogle Scholar
  109. 109.
    Fehr BS, Ozcan ME, Suppes T. Low doses of clozapine may stabilize treatment-resistant bipolar patients. Eur Arch Psychiatry Clin Neurosci. 2005;255(1):10–4.  https://doi.org/10.1007/s00406-004-0528-8.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Hilja Ruegg
    • 1
    • 2
    Email author
  • Caleb Adler
    • 1
  • L. Rodrigo Patino Duran
    • 1
  • Suzanne Watson
    • 1
    • 2
  • Melissa DelBello
    • 1
  1. 1.Department of Psychiatry and Behavioral NeuroscienceUniversity of CincinnatiCincinnatiUSA
  2. 2.Department of Community and Family MedicineUniversity of CincinnatiCincinnatiUSA

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