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Indian J Psychiatry. 2003 Jan-Mar; 45(1): 10–15.
PMCID: PMC2951532

The use of atypical antipsychotics in Bipolar Spectrum disorders


Viewed in the context of ever-expanding conceptual boundaries for the diagnosis of bipolar disorder including the spectrum concept of DSM-IV, or even beyond (Akiskal and Pinto, 1999), it becomes obvious that lithium is the treatment of choice in a minority′ of patients only (Bowden et al, 2000). This article reviews what additional benefit atypical antipsychotics may provide in patients with bipolar disorder.

Due both to tradition and to the regulatory requirements in the USA (FDA) and European Union (EMEA), the main target of clinical trials with atypical antipsychotics has been typical manic disorder. More recently, a significant subgroup of atypical patients, e.g., with mixed states, marked psychosis, or rapid cycling, have participated in these studies to allow an estimation of the value of atypical antipsychotics in these conditions. For the purposes of filing applications for registration with the regulatory agencies, the existing evidence is probably weak, however; from a clinical perspective, it is important that most atypical antipsychotics have also been tested in combination treatments.

Finally, first data are now available on long-term prophylactic efficacy of atypical antipsychotics. These combined efficacy data definitely support the use of atypical antipsychotics in bipolar disorder, and it is now the time to collect more experience with these substances in severely ill patients in clinical settings.

Keywords: antipsychotics, aripiprazole, bipolar disorder, clozapine, haloperidol, olanzapine, quetiapine, risperidone, ziprasidone

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Ahlfors UG, Baastrup PC, Dencker SJ, Elgen K, Lingjaerde O, Pedersen V, Schou M, Aaskoven O. Flupenthixol decanoate in recurrent manic-depressive illness. A comparison with lithium. Acta Psychiatr Scand. 1981 Sep;64(3):226–237. [PubMed]
  • Akiskal HS, Pinto O. The evolving bipolar spectrum. Prototypes I, II, III, and IV. Psychiatr Clin North Am. 1999 Sep;22(3):517–vii. [PubMed]
  • Angst F, Stassen HH, Clayton PJ, Angst J. Mortality of patients with mood disorders: follow-up over 34-38 years. J Affect Disord. 2002 Apr;68(2-3):167–181. [PubMed]
  • Bottlender R, Jäger M, Strauss A, Möller HJ. Suicidality in bipolar compared to unipolar depressed inpatients. Eur Arch Psychiatry Clin Neurosci. 2000;250(5):257–261. [PubMed]
  • Bowden CL, Brugger AM, Swann AC, Calabrese JR, Janicak PG, Petty F, Dilsaver SC, Davis JM, Rush AJ, Small JG, et al. Efficacy of divalproex vs lithium and placebo in the treatment of mania. The Depakote Mania Study Group. JAMA. 1994 Mar 23;271(12):918–924. [PubMed]
  • Bowden CL, Lecrubier Y, Bauer M, Goodwin G, Greil W, Sachs G, von Knorring L Maintenance therapies for classic and other forms of bipolar disorder. J Affect Disord. 2000 Sep;59 (Suppl 1):S57–S67. [PubMed]
  • Delbello Melissa P, Schwiers Michael L, Rosenberg H Lee, Strakowski Stephen M. A double-blind, randomized, placebo-controlled study of quetiapine as adjunctive treatment for adolescent mania. J Am Acad Child Adolesc Psychiatry. 2002 Oct;41(10):1216–1223. [PubMed]
  • Esparon J, Kolloori J, Naylor GJ, McHarg AM, Smith AH, Hopwood SE. Comparison of the prophylactic action of flupenthixol with placebo in lithium treated manic-depressive patients. Br J Psychiatry. 1986 Jun;148:723–725. [PubMed]
  • Findling RL, Gracious BL, McNamara NK, Youngstrom EA, Demeter CA, Branicky LA, Calabrese JR. Rapid, continuous cycling and psychiatric co-morbidity in pediatric bipolar I disorder. Bipolar Disord. 2001 Aug;3(4):202–210. [PubMed]
  • Frye MA, Ketter TA, Altshuler LL, Denicoff K, Dunn RT, Kimbrell TA, Corá-Locatelli G, Post RM. Clozapine in bipolar disorder: treatment implications for other atypical antipsychotics. J Affect Disord. 1998 Mar;48(2-3):91–104. [PubMed]
  • Frye MA, Ketter TA, Leverich GS, Huggins T, Lantz C, Denicoff KD, Post RM. The increasing use of polypharmacotherapy for refractory mood disorders: 22 years of study. J Clin Psychiatry. 2000 Jan;61(1):9–15. [PubMed]
  • Harrow M, Yonan CA, Sands JR, Marengo J. Depression in schizophrenia: are neuroleptics, akinesia, or anhedonia involved? Schizophr Bull. 1994;20(2):327–338. [PubMed]
  • Johnstone EC, Crow TJ, Frith CD, Owens DG. The Northwick Park "functional" psychosis study: diagnosis and treatment response. Lancet. 1988 Jul 16;2(8603):119–125. [PubMed]
  • Meltzer Herbert Y, Alphs Larry, Green Alan I, Altamura A Carlo, Anand Ravi, Bertoldi Alberto, Bourgeois Marc, Chouinard Guy, Islam M Zahur, Kane John, et al. Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Arch Gen Psychiatry. 2003 Jan;60(1):82–91. [PubMed]
  • Mukherjee S, Rosen AM, Caracci G, Shukla S. Persistent tardive dyskinesia in bipolar patients. Arch Gen Psychiatry. 1986 Apr;43(4):342–346. [PubMed]
  • Sachs Gary S, Grossman Fred, Ghaemi S Nassir, Okamoto Akiko, Bowden Charles L. Combination of a mood stabilizer with risperidone or haloperidol for treatment of acute mania: a double-blind, placebo-controlled comparison of efficacy and safety. Am J Psychiatry. 2002 Jul;159(7):1146–1154. [PubMed]
  • Tohen Mauricio, Baker Robert W, Altshuler Lori L, Zarate Carlos A, Suppes Trisha, Ketter Terrence A, Milton Denai R, Risser Richard, Gilmore Julie A, Breier Alan, et al. Olanzapine versus divalproex in the treatment of acute mania. Am J Psychiatry. 2002 Jun;159(6):1011–1017. [PubMed]
  • Tohen Mauricio, Chengappa K N Roy, Suppes Trisha, Zarate Carlos A, Jr, Calabrese Joseph R, Bowden Charles L, Sachs Gary S, Kupfer David J, Baker Robert W, Risser Richard C, et al. 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 Jan;59(1):62–69. [PubMed]
  • Tohen M, Jacobs TG, Grundy SL, McElroy SL, Banov MC, Janicak PG, Sanger T, Risser R, Zhang F, Toma V, et al. Efficacy of olanzapine in acute bipolar mania: a double-blind, placebo-controlled study. The Olanzipine HGGW Study Group. Arch Gen Psychiatry. 2000 Sep;57(9):841–849. [PubMed]
  • Tohen M, Sanger TM, McElroy SL, Tollefson GD, Chengappa KN, Daniel DG, Petty F, Centorrino F, Wang R, Grundy SL, et al. Olanzapine versus placebo in the treatment of acute mania. Olanzapine HGEH Study Group. Am J Psychiatry. 1999 May;156(5):702–709. [PubMed]
  • Vieta E, Goikolea JM, Corbella B, Benabarre A, Reinares M, Martínez G, Fernández A, Colom F, Martínez-Arán A, Torrent C, et al. Risperidone safety and efficacy in the treatment of bipolar and schizoaffective disorders: results from a 6-month, multicenter, open study. J Clin Psychiatry. 2001 Oct;62(10):818–825. [PubMed]

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