Current Psychiatry Reports

, 16:499 | Cite as

Excess Mortality in Bipolar Disorders

Bipolar Disorders (W Coryell, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Bipolar Disorders


Bipolar disorder is associated with high mortality, and people with this disorder on average may die 10–20 years earlier than the general population. This excess and premature mortality continues to occur despite a large and expanding selection of treatment options dating back to lithium and now including anticonvulsants, antipsychotics, and evidence-based psychotherapies. This review summarizes recent findings on mortality in bipolar disorder, with an emphasis on the role of suicide (accounting for about 15 % of deaths in this population) and cardiovascular disease (accounting for about 35–40 % of deaths). Recent care models and treatments incorporating active outreach, integrated mental and physical health care, and an emphasis on patient self-management have shown promise in reducing excess mortality in this population.


Bipolar Mortality Suicide Cardiovascular 


  1. 1.
    Andlin-Sobocki P, Wittchen HU. Cost of affective disorders in Europe. Eur J Neurol. 2005;12 Suppl 1:34–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Baldessarini RJ, Tondo L. Suicide risk and treatments for patients with bipolar disorder. JAMA. 2003;290:1517–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Peele PB, Xu Y, Kupfer DJ. Insurance expenditures on bipolar disorder: clinical and parity implications. Am J Psychiatr. 2003;160:1286–90.PubMedCrossRefGoogle Scholar
  4. 4.
    Weiner M, Warren L, Fiedorowicz JG. Cardiovascular morbidity and mortality in bipolar disorder. Ann Clin Psychiatry. 2011;23:40–7.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Chang CK, Hayes RD, Broadbent M, et al. All-cause mortality among people with serious mental illness (SMI), substance use disorders, and depressive disorders in southeast London: a cohort study. BMC Psychiatry. 2010;10:77.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Laursen TM, Wahlbeck K, Hallgren J, et al. Life expectancy and death by diseases of the circulatory system in patients with bipolar disorder or schizophrenia in the Nordic countries. PLoS One. 2013;8:e67133.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Hoang U, Stewart R, Goldacre MJ. Mortality after hospital discharge for people with schizophrenia or bipolar disorder: retrospective study of linked English hospital episode statistics, 1999–2006. BMJ Br Med J. 2011;343:d5422.CrossRefGoogle Scholar
  8. 8.
    Mitchell PB, Hadzi-Pavlovic D. Lithium treatment for bipolar disorder. Bull World Health Organ. 2000;78:515–7.PubMedPubMedCentralGoogle Scholar
  9. 9.
    McElroy SL, Keck Jr PE, Pope Jr HG, et al. Valproate in the treatment of bipolar disorder: literature review and clinical guidelines. J Clin Psychopharmacol. 1992;12:42S–52.PubMedCrossRefGoogle Scholar
  10. 10.
    Hirschfeld RMA, Kasper S. A review of the evidence for carbamazepine and oxcarbazepine in the treatment of bipolar disorder. Int J Neuropsychopharmacol. 2004;7:507–22.PubMedCrossRefGoogle Scholar
  11. 11.
    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;64:442–55.PubMedCrossRefGoogle Scholar
  12. 12.
    Cruz N, Sanchez-Moreno J, Torres F, et al. Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis. Int J Neuropsychopharmacol. 2010;13:5–14.PubMedCrossRefGoogle Scholar
  13. 13.
    De Fruyt J, Deschepper E, Audenaert K, et al. Second generation antipsychotics in the treatment of bipolar depression: a systematic review and meta-analysis. J Psychopharmacol. 2012;26:603–17.PubMedCrossRefGoogle Scholar
  14. 14.
    Smith LA, Cornelius V, Warnock A, et al. Effectiveness of mood stabilizers and antipsychotics in the maintenance phase of bipolar disorder: a systematic review of randomized controlled trials. Bipolar Disord. 2007;9:394–412.PubMedCrossRefGoogle Scholar
  15. 15.
    Perry A, Tarrier N, Morriss R, et al. Randomised controlled trial of efficacy of teaching patients with bipolar disorder to identify early symptoms of relapse and obtain treatment. BMJ Br Med J. 1999;318:149–53.CrossRefGoogle Scholar
  16. 16.
    Colom F, Vieta E, Sanchez-Moreno J, et al. Group psychoeducation for stabilised bipolar disorders: 5-year outcome of a randomised clinical trial. Br J Psychiatr. 2009;194:260–5.CrossRefGoogle Scholar
  17. 17.
    Bauer MS, Kilbourne AM, Greenwald DE, et al. Overcoming bipolar disorder. Oakland: New Harbinger Publications, Inc; 2008.Google Scholar
  18. 18.
    Miklowitz DJ, George EL, Richards JA, et al. A randomized study of family-focused psychoeducation and pharmacotherapy in the outpatient management of bipolar disorder. Arch Gen Psychiatry. 2003;60:904–12.PubMedCrossRefGoogle Scholar
  19. 19.
    Frank E, Kupfer DJ, Thase ME, et al. Two-year outcomes for interpersonal and social rhythm therapy in individuals with bipolar I disorder. Arch Gen Psychiatry. 2005;62:996–1004.PubMedCrossRefGoogle Scholar
  20. 20.
    Harris EC, Barraclough B. Suicide as an outcome for mental disorders. A meta-analysis. Br J Psychiatr. 1997;170:205–28.CrossRefGoogle Scholar
  21. 21.
    Tondo L, Isacsson G, Baldessarini R. Suicidal behaviour in bipolar disorder: risk and prevention. CNS Drugs. 2003;17:491–511.PubMedCrossRefGoogle Scholar
  22. 22.
    Pompili M, Gonda X, Serafini G, et al. Epidemiology of suicide in bipolar disorders: a systematic review of the literature. Bipolar Disord. 2013;15:457–90.PubMedCrossRefGoogle Scholar
  23. 23.
    Antypa N, Antonioli M, Serretti A. Clinical, psychological and environmental predictors of prospective suicide events in patients with bipolar disorder. J Psychiatr Res. 2013;47:1800–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Fossati A, Maffei C, Bagnato M, et al. Brief communication: criterion validity of the personality diagnostic questionnaire-4+ (PDQ-4+) in a mixed psychiatric sample. J Pers Disord. 1998;12:172–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Yoon YH, Chen CM, Yi HY, et al. Effect of comorbid alcohol and drug use disorders on premature death among unipolar and bipolar disorder decedents in the United States, 1999 to 2006. Compr Psychiatry. 2011;52:453–64.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Gonda X, Pompili M, Serafini G, et al. Suicidal behavior in bipolar disorder: epidemiology, characteristics and major risk factors. J Affect Disord. 2012;143:16–26.PubMedCrossRefGoogle Scholar
  27. 27.
    Fiedorowicz JG, Leon AC, Keller MB, et al. Do risk factors for suicidal behavior differ by affective disorder polarity? Psychol Med. 2009;39:763–71.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Rihmer A, Gonda X, Balazs J, et al. The importance of depressive mixed states in suicidal behaviour. Neuropsychopharmacol Hung. 2008;10:45–9.PubMedGoogle Scholar
  29. 29.
    Balazs J, Benazzi F, Rihmer Z, et al. The close link between suicide attempts and mixed (bipolar) depression: implications for suicide prevention. J Affect Disord. 2006;91:133–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Valtonen HM, Suominen K, Haukka J, et al. Differences in incidence of suicide attempts during phases of bipolar I and II disorders. Bipolar Disord. 2008;10:588–96.PubMedCrossRefGoogle Scholar
  31. 31.
    Valtonen HM, Suominen K, Mantere O, et al. Suicidal behaviour during different phases of bipolar disorder. J Affect Disord. 2007;97:101–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Holma KM, Haukka J, Suominen K, et al. Differences in incidence of suicide attempts between bipolar I and II disorders and major depressive disorder. Bipolar Disord. 2014.Google Scholar
  33. 33.
    Undurraga J, Baldessarini RJ, Valenti M, et al. Suicidal risk factors in bipolar I and II disorder patients. J Clin Psychiatr. 2012;73:778–82.CrossRefGoogle Scholar
  34. 34.
    Tidemalm D, Haglund A, Karanti A, et al. Attempted suicide in bipolar disorder: risk factors in a cohort of 6086 patients. PLoS One. 2014;9:e94097.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Gonda X, Fountoulakis KN, Kaprinis G, et al. Prediction and prevention of suicide in patients with unipolar depression and anxiety. Ann Gen Psychiatr. 2007;6:23.CrossRefGoogle Scholar
  36. 36.
    Barry CL, Busch SH. News coverage of FDA warnings on pediatric antidepressant use and suicidality. Pediatrics. 2010;125:88–95.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Lu CY, Zhang F, Lakoma MD, et al. Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental study. BMJ Br Med J. 2014;348:g3596.CrossRefGoogle Scholar
  38. 38.
    Leon AC, Fiedorowicz JG, Solomon DA, et al. Risk of suicidal behavior with antidepressants in bipolar and unipolar disorders. J Clin Psychiatr. 2014;75:720–7.CrossRefGoogle Scholar
  39. 39.
    Dennehy EB, Marangell LB, Allen MH, et al. Suicide and suicide attempts in the systematic treatment enhancement program for bipolar disorder (STEP-BD). J Affect Disord. 2011;133:423–7.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    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 Psychiatr. 2013;170:1249–62.PubMedCrossRefGoogle Scholar
  41. 41.
    Mitchell PB, Frankland A, Hadzi-Pavlovic D, et al. Comparison of depressive episodes in bipolar disorder and in major depressive disorder within bipolar disorder pedigrees. Br J Psychiatr. 2011;199:303–9.CrossRefGoogle Scholar
  42. 42.
    Judd LL, Akiskal HS, Schettler PJ, et al. 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.PubMedCrossRefGoogle Scholar
  43. 43.
    Judd LL, Akiskal HS, Schettler PJ, et al. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry. 2002;59:530–7.PubMedCrossRefGoogle Scholar
  44. 44.
    Tondo L, Hennen J, Baldessarini RJ. Lower suicide risk with long-term lithium treatment in major affective illness: a meta-analysis. Acta Psychiatr Scand. 2001;104:163–72.PubMedCrossRefGoogle Scholar
  45. 45.
    Ahrens B, Müller-Oerlinghausen B. Does lithium exert an independent antisuicidal effect? Pharmacopsychiatry. 2001;34(4):132–6.PubMedCrossRefGoogle Scholar
  46. 46.
    Cipriani A, Hawton K, Stockton S, et al. Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis. BMJ. 2013. doi:10.1136/bmj.f3646.PubMedGoogle Scholar
  47. 47.
    Lauterbach E, Felber W, Müller‐Oerlinghausen B, et al. Adjunctive lithium treatment in the prevention of suicidal behaviour in depressive disorders: a randomised, placebo‐controlled, 1‐year trial. Acta Psychiatr Scand. 2008;118:469–79.PubMedCrossRefGoogle Scholar
  48. 48.
    Oquendo MA, Galfalvy HC, Currier D, et al. Treatment of suicide attempters with bipolar disorder: a randomized clinical trial comparing lithium and valproate in the prevention of suicidal behavior. Am J Psychiatr. 2011;168:1050–6.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Nierenberg AA, Friedman ES, Bowden CL, et al. Lithium treatment moderate-dose use study (LiTMUS) for bipolar disorder: a randomized comparative effectiveness trial of optimized personalized treatment with and without lithium. Am J Psychiatr. 2013;170:102–10.PubMedCrossRefGoogle Scholar
  50. 50.
    Geddes JR, Goodwin GM, Rendell J, et al. Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial. Lancet. 2010;375:385–95.PubMedCrossRefGoogle Scholar
  51. 51.
    Katz IR, Liang M, Morgenstern NC. Lithium for suicidal behavior in mood disorders (Li+). United States National Institutes of Health, 2014.Google Scholar
  52. 52.
    Pagnin D, de Queiroz V, Pini S, et al. Efficacy of ECT in depression: a meta-analytic review. J ECT. 2004;20:13–20.PubMedCrossRefGoogle Scholar
  53. 53.
    Mukherjee S, Sackeim HA, Schnur DB. Electroconvulsive therapy of acute manic episodes: a review of 50 years’ experience. Am J Psychiatr. 1994;151:169–76.Google Scholar
  54. 54.
    Loo C, Katalinic N, Mitchell PB, et al. Physical treatments for bipolar disorder: a review of electroconvulsive therapy, stereotactic surgery and other brain stimulation techniques. J Affect Disord. 2011;132:1–13.PubMedCrossRefGoogle Scholar
  55. 55.
    Versiani M, Cheniaux E, Landeira-Fernandez J. Efficacy and safety of electroconvulsive therapy in the treatment of bipolar disorder: a systematic review. J ECT. 2011;27:153–64.PubMedCrossRefGoogle Scholar
  56. 56.
    Minnai GP, Salis PG, Oppo R, et al. Effectiveness of maintenance electroconvulsive therapy in rapid-cycling bipolar disorder. J ECT. 2011;27:123–6.PubMedCrossRefGoogle Scholar
  57. 57.
    Cuijpers P, de Beurs DP, van Spijker BA, et al. The effects of psychotherapy for adult depression on suicidality and hopelessness: a systematic review and meta-analysis. J Affect Disord. 2013;144:183–90.PubMedCrossRefGoogle Scholar
  58. 58.
    Gonzalez Isasi A, Echeburua E, Liminana JM, et al. Psychoeducation and cognitive-behavioral therapy for patients with refractory bipolar disorder: a 5-year controlled clinical trial. Eur Psychiatry. 2014;29:134–41.PubMedCrossRefGoogle Scholar
  59. 59.
    Costa RT, Cheniaux E, Rosaes PA, et al. The effectiveness of cognitive behavioral group therapy in treating bipolar disorder: a randomized controlled study. Rev Bras Psiquiatr. 2011;33:144–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Bouwkamp CG, de Kruiff ME, van Troost TM, et al. Interpersonal and social rhythm group therapy for patients with bipolar disorder. Int J Group Psychother. 2013;63:97–115.PubMedCrossRefGoogle Scholar
  61. 61.
    Derby IM. Manic-depressive “exhaustion” deaths. Psychiatr Q. 1933;7:436–49.CrossRefGoogle Scholar
  62. 62.
    Mendis S, Puska P, Norrving B. Global atlas on cardiovascular disease prevention and control. World Health Organization; 2011.Google Scholar
  63. 63.
    Laursen TM, Munk-Olsen T, Gasse C. Chronic somatic comorbidity and excess mortality due to natural causes in persons with schizophrenia or bipolar affective disorder. PLoS One. 2011;6:e24597.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Westman J, Hallgren J, Wahlbeck K, et al. Cardiovascular mortality in bipolar disorder: a population-based cohort study in Sweden. BMJ Open. 2013. doi:10.1136/bmjopen-2012-002373.PubMedPubMedCentralGoogle Scholar
  65. 65.
    Leucht S, Corves C, Arbter D, et al. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet 373:31–41.Google Scholar
  66. 66.
    Reist C, Mintz J, Albers LJ, et al. Second-generation antipsychotic exposure and metabolic-related disorders in patients with schizophrenia: an observational pharmacoepidemiology study from 1988 to 2002. J Clin Psychopharmacol. 2007;27:46–51.PubMedCrossRefGoogle Scholar
  67. 67.
    Newcomer JW. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs. 2005;19 Suppl 1:1–93.PubMedGoogle Scholar
  68. 68.
    Guo JJ, Keck Jr PE, Corey-Lisle PK, et al. Risk of diabetes mellitus associated with atypical antipsychotic use among patients with bipolar disorder: a retrospective, population-based, case–control study. J Clin Psychiatr. 2006;67:1055–61.CrossRefGoogle Scholar
  69. 69.
    Ngai YF, Sabatini P, Nguyen D, et al. Quetiapine treatment in youth is associated with decreased insulin secretion. J Clin Psychopharmacol. 2014;34:359–64.PubMedCrossRefGoogle Scholar
  70. 70.
    Chen CH, Lin TY, Chen TT, et al. A prospective study of glucose homeostasis in quetiapine-treated schizophrenic patients by using the intravenous glucose tolerance test. Progr Neuro Psychopharmacol Biol Psychiatr. 2011;35:965–9.CrossRefGoogle Scholar
  71. 71.
    Laursen TM, Mortensen PB, MacCabe JH, et al. Cardiovascular drug use and mortality in patients with schizophrenia or bipolar disorder: a Danish population-based study. Psychol Med. 2014;44:1625–37.PubMedCrossRefGoogle Scholar
  72. 72.
    Kilbourne AM, Lai Z, Bowersox N, et al. Does colocated care improve access to cardiometabolic screening for patients with serious mental illness? Gen Hosp Psychiatry. 2011;33:634–6.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Kilbourne AM, Goodrich DE, Lai Z, et al. Randomized controlled trial to assess reduction of cardiovascular disease risk in patients with bipolar disorder: the self-management addressing heart risk trial (SMAHRT). J Clin Psychiatr. 2013;74:e655–62.CrossRefGoogle Scholar
  74. 74.
    Goodrich DE, Kilbourne AM, Lai Z, et al. Design and rationale of a randomized controlled trial to reduce cardiovascular disease risk for patients with bipolar disorder. Contemp Clin Trials. 2012;33:666–78.PubMedCrossRefGoogle Scholar
  75. 75.
    Davis CL, Kilbourne AM, Blow FC, et al. Reduced mortality among Department of Veterans Affairs patients with schizophrenia or bipolar disorder lost to follow-up and engaged in active outreach to return for care. Am J Public Health. 2012;102 Suppl 1:S74–9.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York (outside the USA) 2014

Authors and Affiliations

  1. 1.Center for Healthcare Organization and Implementation Research, VA Boston Healthcare SystemBostonUSA
  2. 2.Department of PsychiatryHarvard Medical SchoolBostonUSA

Personalised recommendations