Lithium Treatment and the Risk of Suicide in Affective Disorders

Zoltan Rihmer
European Psychiatric Review, 2011;4(1):48-51
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Abstract

Despite suicidal behaviour being a very complex, multicausal phenomenon, untreated major affective (bipolar and unipolar) disorders are the most powerful predictors for it. As suicidal behaviour in people with mood disorders is a state-dependent phenomenon, long-term management is fundamental for suicide prevention. Naturalistic, retrospective and prospective follow-up studies, as well as randomised controlled trials, consistently show that long-term lithium treatment reduces the risk of completed and attempted suicide by approximately 80%, both in people with bipolar disorder and unipolar depression. The marked anti-suicidal potential of lithium seems to be more than the simple reflection of its phase-prophylactic effect, as a significant reduction in the number of suicide attempts was found not only in the excellent responders, but also in moderate responders and in non-responders. Current studies also show that the combination of lithium treatment with psychosocial interventions further improves the results.
Keywords
Affective disorder, bipolar disorder, lithium treatment, unipolar depression, suicide, suicide attempt, suicide prevention
Disclosure The authors have no conflicts of interest to declare.
Received: January 12, 2011 Accepted March 03, 2011
Correspondence: Zoltan Rihmer, Department of Clinical and Theoretical Mental Health and Department of Psychiatry and Psychotherapy, Semmelweis University, 1125 Kútvölgyi út 4, Budapest, Hungary. E: rihmerz@kut.sote.hu

Although suicide is very complex, multicausal behaviour, involving several medical-biological and psychosocial components, history of bipolar disorder and major depressive disorder constitute the most important risk factors.1–6 The annual suicide rate among people with bipolar disorders is around 1%, about 60 times higher than among the general population, which is partly due to the fact that suicidal acts by those with bipolar disorder have higher lethality.3,7 However, because the majority of people with affective disorder never commit (and up to 50% of them never attempt) suicide, other familial-genetic, clinical and psychosocial risk factors also play a significant contributory role. People with affective disorders, with family and/or personal history of suicidal behaviour, bipolar I and II subtype, mixed/agitated depression, insomnia, comorbid anxiety, substance-use and personality disorders, as well as those with adverse psychosocial events and aggressive, impulsive personality features, are particularly at increased risk of attempted or completed suicide.1,4–6,8–11

As suicidal behaviour is a multicausal phenomenon with many biological, psychological and cultural components, its prevention should also be complex even in the case of people with affective disorders. Since bipolar disorders usually have a peak onset between 15 and 25 years of age,12–14 early detection of the bipolar nature of the depressive episode, including the soft manifestations as well, is very important. Misdiagnosis of bipolar depression as unipolar depression results in treatment with antidepressants alone, and this can have negative effects on the course of the illness, resulting in a high rate of treatment-resistance and inducing mixed depressive episodes, hypomanic or manic switches, rapid cycling, and therefore increasing the chance of suicidal behaviour.13,15–17

Suicidal behaviour in people with major depressive and bipolar disorder occurs mostly during severe pure or mixed depressive episodes, and less frequently in the frame of dysphoric (mixed) mania, but practically never during euphoric mania and euthymia (i.e. suicidal behaviour in people with mood disorders is a state- and severity-dependent phenomenon).4,5,11 It is, therefore, logical to assume that effective acute and long-term treatment has a strong protection against suicide, suicide attempts and probably against other complications (secondary substance-use disorders, marital instability, loss of job, cardiovascular morbidity/mortality, violent behaviour etc.). However, as successful acute pharmacotherapy of depressive or mixed episodes can only prevent the risk of suicide for a given episode, it is only adequate prophylactic therapy that can provide good long-term results.

References:
  1. Akiskal H, Targeting suicide prevention to modifiable risk factors: has bipolar II been overlooked?, Acta Psychiatr Scand, 2007;116(6):395–402.
  2. Harris EC, Barraclough B, Suicide as an outcome for mental disorders. A meta-analysis, Br J Psychiatry, 1997;170:205–28.
  3. Pompili M, Rihmer Z, Innamorati M, et al., Assessment and treatment of suicide risk in bipolar disorders, Expert Rev Neurother, 2009;9(1):109–36.
  4. Rihmer Z, Prediction and prevention of suicide in bipolar disorders, Clinical Neuropsychiatry, 2005;2:48–54.
  5. Rihmer Z, Suicide risk in mood disorders, Curr Opin Psychiatry, 2007;20(1):17–22.
  6. Tondo L, Lepri B, Baldessarini RJ, Suicidal risks among 2826 Sardinian major affective disorder patients, Acta Psychiatr Scand, 2007;116(6):419–28.
  7. Baldessarini RJ, Pompili M, Tondo L, Suicide in bipolar disorder: Risks and management, CNS Spectr, 2006;11(6):465–71.
  8. Akiskal HS, Benazzi F, Perugi G, Rihmer Z, Agitated “unipolar” depression re-conceptualized as a depressive mixed state: implications for the antidepressant-suicide controversy, J Affect Disord, 2005;85(3):245–58.
  9. 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(2-3):133–8.
  10. Sanchez-Gistau V, Colom F, Mane A, et al., Atypical depression is associated with suicide attempt in bipolar disorder, Acta Psychiatr Scand, 2009;120(1):30–6.
  11. 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(5):588–96.
  12. Akiskal HS. In: Maj M, Akiskal HS, Lopez-Ibor JJ and Sartorius N (eds.), Bipolar Disorder, Chichester: John Wiley and Sons, 2002.
  13. Ghaemi SN, Boiman EE, Goodwin FK, Diagnosing bipolar disorder and the effect of antidepressants: a naturalistic study, J Clin Psychiatry, 2000;61(10):804–8; quiz 809.
  14. Szadoczky E, Papp Z, Vitrai J, et al., The prevalence of major depressive and bipolar disorders in Hungary. Results from a national epidemiologic survey, J Affect Disord, 1998;50(2-3):153–62.
  15. Benazzi F, How could antidepressants worsen unipolar depression?, Psychother Psychosom, 2003;72(2):107–8; author reply 109.
  16. Rihmer Z, Antidepressant-resistant depression and antidepressant-associated suicidality: Is mixed depression the key, Journal of Affective Disorders, in press.
  17. Rihmer Z, Akiskal H, Do antidepressants t(h)reat(en) depressives? Toward a clinically judicious formulation of the antidepressantsuicidality FDA advisory in light of declining national suicide statistics from many countries, J Affect Disord, 2006;94(1-3):3–13.
  18. Bowden CL. In: Maj M, Akiskal HS, Lopez-Ibor JJ and Sartorius N (eds.), Bipolar Disorder, Chichester: John Wiley and Sons, 2002.
  19. Fountoulakis KN, Vieta E, Sanchez-Moreno J, et al., Treatment guidelines for bipolar disorder: a critical review, J Affect Disord, 2005;86(1):1–10.
  20. Goodwin FK, Jamison KR, Manic-Depressive Illness, New York: Oxford University Press, 1990.
  21. Maj M, Tortorella A, Bartoli L. In: Marneros A and Angst J (eds.), Bipolar disorders. 100 years after manic depressive insanity, Dordrecht: Kluwer Academic Publishers, 2000.
  22. Baldessarini RJ, Tondo L, Davis P, et al., Decreased risk of suicides and attempts during long-term lithium treatment: a meta-analytic review, Bipolar Disord, 2006;8(5 Pt 2):625–39.
  23. Thies-Flechtner K, Muller-Oerlinghausen B, Seibert W, et al., Effect of prophylactic treatment on suicide risk in patients with major affective disorders. Data from a randomized prospective trial, Pharmacopsychiatry, 1996;29(3):103–7.
  24. Ahrens B, Muller-Oerlinghausen B, Does lithium exert an independent antisuicidal effect?, Pharmacopsychiatry, 2001;34(4):132–6.
  25. Muller-Oerlinghausen B, Lewitzka U, Lithium reduces pathological aggression and suicidality: a mini-review, Neuropsychobiology, 2010;62(1):43–9.
  26. Tondo L, Baldessarini RJ, Hennen J, et al., Lithium maintenance treatment of depression and mania in bipolar I and bipolar II disorders, Am J Psychiatry, 1998;155(5):638–45.
  27. Tondo L, Baldessarini RJ, Hennen J, et al., Lithium treatment and risk of suicidal behavior in bipolar disorder patients, J Clin Psychiatry, 1998;59(8):405–14.
  28. Angst F, Stassen HH, Clayton PJ, Angst J, Mortality of patients with mood disorders: follow-up over 34–38 years, J Affect Disord, 2002;68(2-3):167–81.
  29. Yerevanian BI, Koek RJ, Mintz J, Lithium, anticonvulsants and suicidal behavior in bipolar disorder, J Affect Disord, 2003;73(3):223–8.
  30. Yerevanian BI, Koek RJ, Mintz J, Bipolar pharmacotherapy and suicidal behavior. Part I: Lithium, divalproex and carbamazepine, J Affect Disord, 2007;103(1-3):5–11.
  31. Marangell LB, Dennehy EB, Wisniewski SR, et al., Case-control analyses of the impact of pharmacotherapy on prospectively observed suicide attempts and completed suicides in bipolar disorder: findings from STEP-BD, J Clin Psychiatry, 2008;69(6):916–22.
  32. Rihmer Z, Gonda X, Tondo L, Lithium and suicidal behavior in patients with bipolar disorder, J Clin Psychiatry, 2008;69(11):1831–2.
  33. Sondergard L, Lopez AG, Andersen PK, Kessing LV, Moodstabilizing pharmacological treatment in bipolar disorders and risk of suicide, Bipolar Disord, 2008;10(1):87–94.
  34. Isometsa E, Henriksson M, Lonnqvist J, Completed suicide and recent lithium treatment, J Affect Disord, 1992;26(2):101–3.
  35. Kallner G, Lindelius R, Petterson U, et al., Mortality in 497 patients with affective disorders attending a lithium clinic or after having left it, Pharmacopsychiatry, 2000;33(1):8–13.
  36. Bauer M, Bschor T, Kunz D, et al., Double-blind, placebo-controlled trial of the use of lithium to augment antidepressant medication in continuation treatment of unipolar major depression, Am J Psychiatry, 2000;157(9):1429–35.
  37. Guzzetta F, Tondo L, Centorrino F, et al., Lithium treatment reduces suicide risk in recurrent major depressive disorder, J Clin Psychiatry, 2007;68(3):380–3.
  38. Lauterbach E, Felber W, Muller-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(6):469–79.
  39. Goodwin FK, Fireman B, Simon GE, et al., Suicide risk in bipolar disorder during treatment with lithium and divalproex, Jama, 2003;290(11):1467–73.
  40. Collins JC, McFarland BH, Divalproex, lithium and suicide among Medicaid patients with bipolar disorder, J Affect Disord, 2008;107(1-3):23–8.
  41. Ohgami H, Terao T, Shiotsuki I, et al., Lithium levels in drinking water and risk of suicide, Br J Psychiatry, 2009;194(5):464–5;discussion 446.
  42. Schrauzer GN, Shrestha KP, Lithium in drinking water and the incidences of crimes, suicides, and arrests related to drug addictions, Biol Trace Elem Res, 1990;25(2):105–13.
  43. Geddes JR, Carney SM, Davies C, et al., Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review, Lancet, 2003;361(9358):653–61.
  44. Yerevanian BI, Koek RJ, Mintz J, Bipolar pharmacotherapy and suicidal behavior Part 3: impact of antipsychotics, J Affect Disord, 2007;103(1-3):23–8.
  45. Yerevanian BI, Koek RJ, Mintz J, Akiskal HS, Bipolar pharmacotherapy and suicidal behavior Part 2. The impact of antidepressants, J Affect Disord, 2007;103(1-3):13–21.
  46. Fountoulakis KN, Gonda X, Siamouli M, Rihmer Z, Psychotherapeutic intervention and suicide risk reduction in bipolar disorder: a review of the evidence, J Affect Disord, 2009;113(1-2):21–9.
  47. Leenaars AA. In: Pompili M and Tatarelli R (eds.), Evidence-Based Practice in Suicidology. A Source Book, Göttingen: Hogrefe, 2010.
  48. Rogers JR, Madura TL, Hardy LJ. In: Pompili M and Tatarelli R (eds.), Evidence-Based Practice in Suicidology. A Source Book, Göttingen: Hogrefe, 2010.
  49. Rucci P, Frank E, Kostelnik B, et al., Suicide attempts in patients with bipolar I disorder during acute and maintenance phases of intensive treatment with pharmacotherapy and adjunctive psychotherapy, Am J Psychiatry, 2002;159(7):1160–4.
  50. Wolf T, Muller-Oerlinghausen B, The influence of successful prophylactic drug treatment on cognitive dysfunction in bipolar disorders, Bipolar Disord, 2002;4(4):263–70.
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