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Rapid cycling bipolar disorder in adults: Treatment of mania and hypomania

Ralph Kupka, MD, PhD
Section Editor
Paul Keck, MD
Deputy Editor
David Solomon, MD


Bipolar disorder is characterized by mood episodes that are nearly always recurrent [1,2]. Patients who experience at least four episodes during a 12-month period are classified as “rapid cycling” [2]. The term was first used in 1974 to describe bipolar patients who were unresponsive to lithium [3]. However, it is now clear that pharmacotherapy is often less beneficial for rapid cycling patients than non-rapid cycling patients, and that lithium may be as effective as other drugs for rapid cycling [4].

This topic reviews the treatment of mania and hypomania in rapid cycling patients. The treatment of major depression in rapid cycling patients, and the epidemiology, pathogenesis, clinical features, and diagnosis of rapid cycling in patients with bipolar disorder are discussed separately, as is the diagnosis and general treatment of bipolar disorder:

(See "Rapid cycling bipolar disorder in adults: Treatment of major depression".)

(See "Rapid cycling bipolar disorder: Epidemiology, pathogenesis, clinical features, and diagnosis".)

(See "Bipolar disorder in adults: Assessment and diagnosis".)


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Literature review current through: Sep 2016. | This topic last updated: Jul 6, 2016.
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  1. Goodwin FK, Jamison KR. Manic-Depressive Illness: Bipolar Disorders and Recurrent Depression, Second Edition, Oxford University Press, Oxford 2007.
  2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), American Psychiatric Association, Arlington 2013.
  3. Dunner DL, Fieve RR. Clinical factors in lithium carbonate prophylaxis failure. Arch Gen Psychiatry 1974; 30:229.
  4. Tondo L, Hennen J, Baldessarini RJ. Rapid-cycling bipolar disorder: effects of long-term treatments. Acta Psychiatr Scand 2003; 108:4.
  5. Grunze H, Vieta E, Goodwin GM, et al. The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: update 2009 on the treatment of acute mania. World J Biol Psychiatry 2009; 10:85.
  6. American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry 2002; 159:1.
  7. Yatham LN, Kennedy SH, O'Donovan C, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: consensus and controversies. Bipolar Disord 2005; 7 Suppl 3:5.
  8. Pacchiarotti I, Bond DJ, Baldessarini RJ, et al. The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders. Am J Psychiatry 2013; 170:1249.
  9. Bauer M, Beaulieu S, Dunner DL, et al. Rapid cycling bipolar disorder--diagnostic concepts. Bipolar Disord 2008; 10:153.
  10. Kupka RW, Frye MA. Diagnosis and treatment of rapid cycling bipolar disorder. In: Yatham L, Kusumakar V (Ed.) Bipolar Disorder. A clinician’s guide to biological treatments, 2nd Ed. New York, Brunner-Routledge, 2009.
  11. National Institute for Health and Clinical Excellence. Bipolar disorder: The management of bipolar disorder in adults, children and adolescents, in primary and secondary care. NICE Clinical Guideline 185, 2014. http://guidance.nice.org.uk/cg185 (Accessed on December 31, 2014).
  12. Ketter TA, Wang PW. Management of rapid-cycling bipolar disorders. In: Handbook of Diagnosis and Treatment of Bipolar Disorders, Ketter TA. (Ed), American Psychiatric Publishing, Inc, Washington, DC 2010. p.331.
  13. Schneck CD. Treatment of rapid-cycling bipolar disorder. J Clin Psychiatry 2006; 67 Suppl 11:22.
  14. Schneck CD, Miklowitz DJ, Miyahara S, et al. The prospective course of rapid-cycling bipolar disorder: findings from the STEP-BD. Am J Psychiatry 2008; 165:370.
  15. Goodwin GM, 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.
  16. Maj M, Pirozzi R, Magliano L, Bartoli L. The prognostic significance of "switching" in patients with bipolar disorder: a 10-year prospective follow-up study. Am J Psychiatry 2002; 159:1711.
  17. Maj M, Pirozzi R, Formicola AM, Tortorella A. Reliability and validity of four alternative definitions of rapid-cycling bipolar disorder. Am J Psychiatry 1999; 156:1421.
  18. Calabrese JR, Shelton MD, Rapport DJ, et al. A 20-month, double-blind, maintenance trial of lithium versus divalproex in rapid-cycling bipolar disorder. Am J Psychiatry 2005; 162:2152.
  19. Sajatovic M, Elhaj O, Youngstrom EA, et al. Treatment adherence in individuals with rapid cycling bipolar disorder: results from a clinical-trial setting. J Clin Psychopharmacol 2007; 27:412.
  20. Kemp DE, Gao K, Ganocy SJ, et al. 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; 70:113.
  21. Perlis RH, Ostacher MJ, Miklowitz DJ, et al. Clinical features associated with poor pharmacologic adherence in bipolar disorder: results from the STEP-BD study. J Clin Psychiatry 2010; 71:296.
  22. Coryell W. Rapid cycling bipolar disorder: clinical characteristics and treatment options. CNS Drugs 2005; 19:557.
  23. Yatham LN, Kennedy SH, Parikh SV, et al. 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.
  24. American Psychiatric Association Practice Guideline for Treatment of Patients with Bipolar Disorder (Revision), 2002 http://www.psych.org/MainMenu/PsychiatricPractice/PracticeGuidelines_1.aspx (Accessed on April 25, 2011).
  25. Suppes T, Eudicone J, McQuade R, et al. Efficacy and safety of aripiprazole in subpopulations with acute manic or mixed episodes of bipolar I disorder. J Affect Disord 2008; 107:145.
  26. Baldessarini RJ, Hennen J, Wilson M, et al. Olanzapine versus placebo in acute mania: treatment responses in subgroups. J Clin Psychopharmacol 2003; 23:370.
  27. Perlis RH, Baker RW, Zarate CA Jr, et al. Olanzapine versus risperidone in the treatment of manic or mixed States in bipolar I disorder: a randomized, double-blind trial. J Clin Psychiatry 2006; 67:1747.
  28. Cipriani A, Barbui C, Salanti G, et al. Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis. Lancet 2011; 378:1306.
  29. Raedler TJ. Cardiovascular aspects of antipsychotics. Curr Opin Psychiatry 2010; 23:574.
  30. Keck PE Jr, Marcus R, Tourkodimitris S, et al. A placebo-controlled, double-blind study of the efficacy and safety of aripiprazole in patients with acute bipolar mania. Am J Psychiatry 2003; 160:1651.
  31. Sachs G, Sanchez R, Marcus R, et al. Aripiprazole in the treatment of acute manic or mixed episodes in patients with bipolar I disorder: a 3-week placebo-controlled study. J Psychopharmacol 2006; 20:536.
  32. Tohen M, Sanger TM, McElroy SL, et al. Olanzapine versus placebo in the treatment of acute mania. Olanzapine HGEH Study Group. Am J Psychiatry 1999; 156:702.
  33. Tohen M, Jacobs TG, Grundy SL, et al. Efficacy of olanzapine in acute bipolar mania: a double-blind, placebo-controlled study. The Olanzipine HGGW Study Group. Arch Gen Psychiatry 2000; 57:841.
  34. Kupka RW, Luckenbaugh DA, Post RM, et al. Rapid and non-rapid cycling bipolar disorder: a meta-analysis of clinical studies. J Clin Psychiatry 2003; 64:1483.
  35. Tohen M, Ketter TA, Zarate CA, et al. Olanzapine versus divalproex sodium for the treatment of acute mania and maintenance of remission: a 47-week study. Am J Psychiatry 2003; 160:1263.
  36. Suppes T, Brown E, Schuh LM, et al. Rapid versus non-rapid cycling as a predictor of response to olanzapine and divalproex sodium for bipolar mania and maintenance of remission: post hoc analyses of 47-week data. J Affect Disord 2005; 89:69.
  37. Goldberg JF, Kelley ME, Rosenquist KJ, et al. Effectiveness of quetiapine in rapid cycling bipolar disorder: a preliminary study. J Affect Disord 2008; 105:305.
  38. Vieta E, Parramon G, Padrell E, et al. Quetiapine in the treatment of rapid cycling bipolar disorder. Bipolar Disord 2002; 4:335.
  39. 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; 64:442.
  40. Perlis RH, Welge JA, Vornik LA, et al. Atypical antipsychotics in the treatment of mania: a meta-analysis of randomized, placebo-controlled trials. J Clin Psychiatry 2006; 67:509.
  41. Smith LA, Cornelius V, Warnock A, et al. Acute bipolar mania: a systematic review and meta-analysis of co-therapy vs. monotherapy. Acta Psychiatr Scand 2007; 115:12.
  42. Bauer M, Berghöfer A, Bschor T, et al. Supraphysiological doses of L-thyroxine in the maintenance treatment of prophylaxis-resistant affective disorders. Neuropsychopharmacology 2002; 27:620.
  43. Kupka RW. Treatment options for rapid cycling bipolar disorder. Clinical Approaches in Bipolar Disorders, 2006; 5: 22-29.
  44. Bauer MS, Whybrow PC. Rapid cycling bipolar affective disorder. II. Treatment of refractory rapid cycling with high-dose levothyroxine: a preliminary study. Arch Gen Psychiatry 1990; 47:435.
  45. Frye MA, Altshuler LL, Bitran JA. Clozapine in rapid cycling bipolar disorder. J Clin Psychopharmacol 1996; 16:87.
  46. Suppes T, Webb A, Paul B, et al. Clinical outcome in a randomized 1-year trial of clozapine versus treatment as usual for patients with treatment-resistant illness and a history of mania. Am J Psychiatry 1999; 156:1164.
  47. Suppes T, Ozcan ME, Carmody T. Response to clozapine of rapid cycling versus non-cycling patients with a history of mania. Bipolar Disord 2004; 6:329.
  48. Calabrese JR, Kimmel SE, Woyshville MJ, et al. Clozapine for treatment-refractory mania. Am J Psychiatry 1996; 153:759.
  49. Medda P, Toni C, Perugi G. The mood-stabilizing effects of electroconvulsive therapy. J ECT 2014; 30:275.
  50. Fountoulakis KN, Kontis D, Gonda X, Yatham LN. A systematic review of the evidence on the treatment of rapid cycling bipolar disorder. Bipolar Disord 2013; 15:115.
  51. Macfadden W, Haskins T, Kujawa M, et al. Adjunctive risperidone long-acting injectable is effective in delaying relapse to a mood episode in patients with frequently relapsing bipolar disorder (abstract 584). Biol Psychiatry 2008; 63 (suppl):186S.
  52. Keck PE Jr, Calabrese JR, McIntyre RS, et al. Aripiprazole monotherapy for maintenance therapy in bipolar I disorder: a 100-week, double-blind study versus placebo. J Clin Psychiatry 2007; 68:1480.
  53. Muzina DJ, Momah C, Eudicone JM, et al. Aripiprazole monotherapy in patients with rapid-cycling bipolar I disorder: an analysis from a long-term, double-blind, placebo-controlled study. Int J Clin Pract 2008; 62:679.
  54. Tohen M, Calabrese JR, Sachs GS, et al. Randomized, placebo-controlled trial of olanzapine as maintenance therapy in patients with bipolar I disorder responding to acute treatment with olanzapine. Am J Psychiatry 2006; 163:247.
  55. Weisler RH, Nolen WA, Neijber A, et al. 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; 72:1452.