Skip to main content
×
×
Home

Lithium and Suicide Risk in Bipolar Disorder

  • Leonardo Tondo, Ross J. Baldessarini and John Hennen
Abstract

Can timely diagnosis and treatment of depression reduce the risk of suicide? Studies of treatment effects on mortality in major mood disorders remain rare and are widely considered difficult to carry out ethically. Despite close associations of suicide with major affective disorders and related comorbidity, the available evidence provides little support for sustained reductions of suicide risk by most mood-altering treatments, including antidepressants. Studies designed to evaluate clinical benefits of mood-stabilizing treatments in bipolar disorders, however, provide comparisons of suicidal rates with and without treatment or under different treatment conditions. This emerging body of research provides consistent evidence of reduced rates of suicides and attempts during long-term treatment with lithium. This effect may not generalize to proposed alternatives, particularly carbamazepine. Our recent international collaborative studies found compelling evidence for prolonged reduction of suicidal risks during treatment with lithium, as well as sharp increases soon after its discontinuation, all in close association with depressive recurrences. Depression was markedly reduced, and suicide attempts were less frequent, when lithium was discontinued gradually. These findings indicate that studies of the effects of long-term treatment on suicide risk are feasible and that more timely diagnosis and treatment for all forms of major depression, but particularly for bipolar depression, should further reduce suicide risk.

Copyright
References
Hide All
1.Angst, J, Stassen, HH, Gross, G, Huber, G, Stone, MH. Suicide in affective and schizoaffective disorders. In: Marneros, A, Tsuang, MT, eds. Affective and Schizoaffective Disorders. Berlin, Germany: Springer-Verlag; 1990:168185.
2.Goodwin, FK, Jamison, KR. Manic-Depressive Illness. New York, NY: Oxford University Press; 1990.
3.Coppen, A. Depression as a lethal disease: prevention strategies. J Clin Psychiatry. 1994;55(suppl 4):3745.
4.Sharma, R, Markar, HR. Mortality in affective disorders. J Affect Disord. 1994;31:9196.
5.Ahrens, B, Müller-Oerlinghausen, B, Schou, M, et al.Excess cardiovascular and suicide mortality of affective disorders may be reduced by lithium prophylaxis. J Affect Disord. 1995;33:3367.
6.Tondo, L, Jamison, KR, Baldessarini, RJ. Antisuicide effects of lithium. Ann NY Acad Sci. 1997;836:836–339.
7.Angst, J, Sellaro, R, Angst, F. Long-term outcome and mortality of treated vs untreated bipolar and depressed patients: a preliminary report. Int J Psychiatr Clin Pract. 1998;2:2115.
8.Baldessarini, RJ, Tondo, L. Effects of lithium treatment in bipolar disorders and post-treatment-discontinuation recurrence risk. Clin Drug Investigation. 1998;15:15337.
9.Tondo, L, Baldessarini, RJ, Floris, G, Silvetti, F, Hennen, J, Tohen, M. Lithium treatment and risk of suicidal behavior in bipolar disorder patients. J Clin Psychiatry. 1998;59:59405.
10.Angst, J, Angst, F, Stassen, HS. Suicide risk in patients with major depressive disorder. J Clin Psychiatry. 1999;60(suppl 2):5762.
11.Baldessarini, RJ, Jamison, KR. Effects of medical interventions on suicidal behavior: summary and conclusions. J Clin Psychiatry. 1999;60(suppl 2):117122.
12.Jamison, KR, Baldessarini, RJ. Effects of medical interventions on suicidal behavior: introduction. J Clin Psychiatry. 1999;60(suppl 2):46.
13.Guze, SB, Robins, E. Suicide and primary affective disorders. Br J Psychiatry. 1970;117:117437.
14.Roy, A. Suicide in recurrent affective disorder patients. Can J Psychiatry. 1984;29:29319.
15.Taube, CA, Barrett, SA, eds. Mental Health: United States. NIMH Publication AOM-85-1378. Washington, DC: US Government Printing Office; 1985.
16.Roy, A. Suicide. In: Kaplan, HI, Sadock, BJ, eds. Comprehensive Textbook of Psychiatry. Vol 2. 9th ed. Baltimore, Md: Williams & Wilkins; 1989:14141427.
17.Tondo, L, Baldessarini, RJ, Hennen, J, et al.Suicide attempts in major affective disorder patients with comorbid substance use disorders. J Clin Psychiatry. 1999;60(suppl 2):6369.
18.Faedda, GL, Baldessarini, RJ, Suppes, T, Tondo, L, Becker, I, Lipschitz, D. Pediatric-onset bipolar disorder a neglected clinical and public health problem. Harvard Rev Psychiatry. 1995;3:3171.
19.Committee on Adolescence. Adolescent Suicide. Washington, DC: American Psychiatric Press; 1996:3955.
20.Baldessarini, RJ, Tondo, LAntisuicidal effect of lithium treatment in major mood disorders. In: Jacobs, D, ed. Harvard Medical School Guide to Assessment and Intervention in Suicide. San Francisco, Calif: Jossey-Bass; 1998:355371.
21.Baldessarini, RJ, Tondo, L, Hennen, J. Effects of lithium treatment and its discontinuation on suicidal behavior in bipolar manic-depressive disorders. J Clin Psychiatry. 1999;60(suppl 2):7784.
22.Kessler, RC, McGonigle, KA, Zhao, S, et al.Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National Comorbidity Survey. Arch Gen Psychiatry. 1994;51:51–8.
23.Tondo, L, Baldessarini, RJ, Hennen, J, Floris, G. Lithium maintenance treatment: depression and mania in bipolar I and II disorders. Am J Psychiatry. 1998;155:155638.
24.Keller, MB, Lavori, PW, Klerman, GL, et al.Low levels and lack of predictors of somatotherapy and psychotherapy received by depressed patients. Arch Gen Psychiatry. 1986;43:43458.
25.McCombs, JS, Nichol, MB, Stimmel, GL, Sclar, DA, Beasley, CM Jr, Gross, LS. Cost of antidepressant drug therapy failure: a study of antidepressant use patterns in a Medicaid population. J Clin Psychiatry. 1990;51(suppl 6):6069.
26.Isacsson, G, Boethius, G, Bergman, U. Low level of antidepressant prescription for people who later commit suicide: 15 years of experience from a population-based drug database in Sweden. Acta Psychiatr Scand. 1992;85:85444.
27.Baldessarini, RJ, Tondo, L, Suppes, T, Faedda, GL, Tohen, M. Pharmacological treatment of bipolar disorder throughout the life-cycle. In: Shulman, KI, Tohen, M, Kutcher, S, eds. Bipolar Disorder Through the Life-Cycle. New York, NY: Wiley & Sons; 1996:299338.
28.Suominen, KH, Isometsä, E, Hendriksson, MM, Ostamo, Al, Lönnqvist, JK. Inadequate treatment for major depression both before and after attempted suicide. Am J Psychiatry. 1998;155:1551778.
29.Gunell, D, Frankel, S. Prevention of suicide: aspirations and evidence. Br Med J. 1994;308:3081227.
30.Wyatt, RJ, Henter, I. An economic evaluation of manic-depressive illness. Soc Psychiatry Psychiatr Epidemiol. 1995;30:30213.
31.Müller-Oerlinghausen, B, Berghöfer, A. Antidepressants and suicidal risk. J Clin Psychiatry. 1999;60(suppl 2):9499.
32.Avery, D, Winokur, G. The efficacy of electroconvulsive therapy and antidepressants in depression. Biol Psychiatry. 1977;12:12507.
33.Teicher, MH, Glod, CA, Cole, JO. Antidepressant drugs and the emergence of suicidal tendencies. Drug Safety. 1993;3:3186.
34.Freemantle, N, House, A, Song, F, Mason, JM, Sheldon, TA. Prescribing selective serotonin reuptake inhibitors as strategy for prevention of suicide. Br Med J. 1994;309:309–249.
35.Verkes, RJ, Van der Mast, RC, Hengeveld, MW, Tuyl, JP, Zwinderman, AH, Van Kempen, GMJ. Reduction by paroxetine of suicidal behavior in patients with repeated suicide attempts but not major depression. Am J Psychiatry. 1998;155:155543.
36.Leon, AC, Keller, MB, Warshaw, MG, et al.Prospective study of fluoxetine treatment and suicidal behavior in affectively ill subjects. Am J Psychiatry. 1999;156:156195.
37.Montgomery, SA, Dunner, DL, Dunbar, GC. Reduction of suicidal thoughts with paroxetine in comparison with reference antidepressants and placebo. Eur Neuropsychopharmacol. 1995;5:55.
38.Baldessarini, RJ. Drugs and the treatment of psychiatric disorders: antimanic and antidepressant agents. In: Hardman, JG, Limbird, LE, Molinoff, PB, Ruddon, RW, Gilman, AG, eds. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill Press; 1996:431459.
39.Ohberg, A, Lonqvist, J, Sarna, S, Vuori, E, Penttila, A. Trends and availability of suicide methods in Finland: proposals for restrictive measures. Br J Psychiatry. 1995;166:166–35.
40.Mosciki, EK. Epidemiology of suicide. In: Jacobs, D, ed. Harvard Medical School Guide to Assessment and Intervention in Suicide. San Francisco, Calif: Jossey-Bass; 1998:4051.
41.Zornberg, GL, Pope, HG Jr. Treatment of depression in bipolar disorder new directions for research. J Clin Psychopharmacol. 1993;13:13397.
42.Faedda, GL, Tondo, L, Baldessarini, RJ, Suppes, T, Tohen, M. Outcome after rapid vs gradual discontinuation of lithium treatment in bipolar mood disorders. Arch Gen Psychiatry. 1993;50:50448.
43.Suppes, T, Baldessarini, RJ, Faedda, GL, Tondo, L, Tohen, M. Discontinuing maintenance treatment in bipolar manic-depression: risks and implications. Harvard Rev Psychiatry. 1993;1:1131.
44.Baldessarini, RJ, Suppes, T, Tondo, L. Lithium withdrawal in bipolar disorder: implications for clinical practice and experimental therapeutics research. Am J Therapeutics. 1996;3:3492.
45.Baldessarini, RJ, Tondo, L, Faedda, GL, Floris, G, Suppes, T, Rudas, T. Effects of the rate of discontinuing lithium maintenance treatment in bipolar disorders. J Clin Psychiatry. 1996;57:57441.
46.Baldessarini, RJ, Tondo, L, Viguera, A. Discontinuing lithium maintenance treatment in bipolar disorders: risks and implications. Bipolar Disorders. In press.
47.Viguera, AC, Baldessarini, RJ, Friedberg, J. Risks of interrupting continuation or maintenance treatment with antidepressants in major depressive disorders. Harvard Rev Psychiatry. 1998;5:5293.
48.Viguera, AC, Baldessarini, RJ, Hegarty, JM, Van Kammen, D, Tohen, M. Risk of discontinuing maintenance medication in schizophrenia. Arch Gen Psychiatry. 1997;54:54–49.
49.Modestin, J, Schwartzenbach, F. Effect of psychopharmacotherapy on suicide risk in discharged psychiatric inpatients. Acta Psychiatr Scand. 1992;85:85173.
50.Müller-Oerlinghausen, B, Müser-Causemann, B, Volk, J. Suicides and parasuicides in a high-risk patient group on and off lithium long-term medication. J Affect Disord. 1992;25:25261.
51.Crundwell, JK. Lithium and its potential benefit in reducing increased mortality rates due to suicide. Lithium. 1994;5:5193.
52.Felber, W, Kyber, A. Suizide und parasuizide während und ausserhalb einer lithium prophylaxe. In: Müller-Oerlinghausen, B, Berghöfer, A, eds. Ziele und Ergebnisse der Medikamentösen Prophylaxe Affektiver Psychosen. Stuttgart, Germany: G Thieme Verlag; 1994:5359.
53.Lenz, G, Ahrens, B, Denk, E, et al.Mortalität nach Ausschneiden aus der Lithiumambulanz [Increased mortality after drop-out from lithium clinic]. In: Müller-Oerlinghausen, B, Berghöfer, A, eds. Ziele und Ergebnisse der Medicamentösen Prophylaxe Affecktiver Psychosen. Stuttgart, Germany: G Theme Verlag; 1994:4952.
54.Nilsson, A. Mortality in recurrent mood disorders during periods on and off lithium: a complete population study in 362 patients. Pharmacopsychiatry. 1995;28:28–8.
55.Bocchetta, A, Ardau, R, Burrai, C, Chillotti, C, Quesada, G, Del Zompo, M. Suicidal behavior on and off lithium prophylaxis in a group of patients with prior suicide attempts. J Clin Psychopharmacol. 1998;18:18384.
56.Nilsson, A. Lithium therapy and suicidal risk. J Clin Psychiatry. 1999;60(suppl 2):8588.
57.Wickham, EA, Reed, FV. Lithium for the control of aggressive and self-mutilating behavior. Int Clin Psychopharmacol. 1977;2:2181.
58.Cappiello, A, Sernyak, MJ, Malison, RT, McDougle, CJ, Heninger, GR, Price, LH. Effects of acute tryptophan depletion in lithium-remitted manic patients: a pilot study. Biol Psychiatry. 1997;42:421076.
59.Mann, JJ, Oquendo, M, Underwood, MD, Arango, V. The neurobiology of suicide risk: a review for the clinician. J Clin Psychiatry. 1999;60(suppl 2):711.
60.Thies-Flechtner, K, Müller-Oerlinghausen, B, Seibert, W, Walther, A, Greil, W. Effect of prophylactic treatment on suicide risk in patients with major affective disorders. Pharmacopsychiatry. 1996;29:29103.
61.Greil, W, Ludwig-Mayerhofer, W, Erazo, N, et al.Lithium vs carbamazepine in the maintenance treatment of bipolar disorders: a randomized study. J Affect Disord. 1997;43:43151.
62.Meltzer, HY. Suicide in schizophrenia: risk factors and clozapine treatment. J Clin Psychiatry. 1998; 59 (suppl 3):95201
63.Banov, MD, Zarate, CA Jr, Tohen, M, et al.Clozapine therapy in refractory affective disorders: polarity predicts response in long-term follow-up. J Clin Psychiatry. 1994;55:55295.
64.Zarate, CA, Tohen, M, Baldessarini, RJ. Clozapine therapy in severe mood disorders. J Clin Psychiatry. 1995;56:56411.
65.Baldessarini, RJ, Frankenburg, FR. Clozapine: a novel antipsychotic agent. N Engl J Med. 1991;24:24746.
66.Meltzer, HY, Nash, JF. Effects of antipsychotic drugs on serotonin receptors. Pharmacol Rev. 1991;43:43587.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

CNS Spectrums
  • ISSN: 1092-8529
  • EISSN: 2165-6509
  • URL: /core/journals/cns-spectrums
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed