Skip to main content
×
×
Home

Long-term lithium treatment in the prevention of suicidal behavior in bipolar disorder patients

  • Leonardo Tondo and Ross J. Baldessarini
Abstract

We reviewed available research findings, including meta-analyses on effects of lithium-treatment associated with rates of suicidal behavior in bipolar disorder or unipolar major depressive disorder patients, and for comparisons of lithium to mood-stabilizing anticonvulsants. Data from meta-analyses consistently indicate marked reductions of suicidal behavior and mortality during long-term treatment with lithium salts in bipolar disorder patients, and possibly also in unipolar, recurrent major depressive, perhaps even more effectively than with anticonvulsants proposed as mood-stabilizers. Suicidal risk is frequently associated with dysphoric-agitated symptoms, anger, aggression, and impulsivity-all of which may respond better to treatment with lithium or other mood-stabilizing medicines than to antidepressants. In these conditions, antidepressant treatment may not provide a beneficial effect on risk of suicidal thoughts and perhaps attempts, particularly in juveniles, whereas, lithium, perhaps even more than anticonvulsants, seems to be remarkably effective in the preventing suicidal behavior. The mechanism of action is not well defined and may be associated with either a prevention of mood recurrences or a more specific “antisuicidal” activity.

Declaration of Interest: Dr. Tondo has received research support from Janssen and Eli Lilly Corporations and has served as a consultant to Glaxo-SmithKline and Merck Corporations. Dr. Baldessarini has recently been a consultant or investigator-initiated research collaborator with: AstraZeneca, Auritec, Biotrofix, Janssen, JDS-Noven, Lilly, Luitpold, NeuroHealing, Novartis, Pfizer, and SK-BioPharmaceutical Corporations. Neither author is a member of pharmaceutical speakers’ bureaus, nor do they or any family member hold equity positions in biomedical or pharmaceutical corporations.

Copyright
Corresponding author
Address for correspondence: Professor L. Tondo, Centro Bini, Via Cavalcanti 28, 09128 Cagliari (Italy). Fax: +39-070-496354 E-mail: ltondo@aol.com
References
Hide All
Ahrens, B. & Müller-Oerlinghausen, B. (2001). Does lithium exert an independent antisuicidal effect? Pharmacopsychiatry 34, 132136.
Akiskal, H.S., Benazzi, F., Perugi, G. & Rihmer, Z. (2005). Agitated “unipolar” depression re-conceptualized as a depressive mixed state: implications for the antidepressant-suicide controversy. Journal of Affective Disorders 85, 245258.
Angst, J., Angst, F., Gerber-Werder, R. & Gamma, A. (2005). Suicide in 406 mood-disorder patients with and without long-term medication: a 40–44 years follow-up. Archives of Suicide Research 9, 279300.
Baldessarini, R.J. & Tondo, L. (2008). Lithium and suicidal risk. Bipolar Disorders 10, 114115.
Baldessarini, R.J. & Tondo, L. (2009). Suicidal risks during treatment of bipolar disorder patients with lithium versus anticonvulsants. Pharmacopsychiatry 42, 7275.
Baldessarini, R.J., Salvatore, P., Tohen, M., Khalsa, H.M.K. & Hennen, J. (2004). Morbidity from onset in first-episode bipolar I disorder patients: The International-300 study. Neuropsychopharmacology 29, Suppl. 1, S88.
Baldessarini, R.J., Pompili, M., Tondo, L., Tsapakis, E., Soldani, F., Faedda, G.L. & Hennen, J. (2005). Antidepressants and suicidal behavior: are we hurting or helping? Clinical Neuropsychiatry 2, 7375.
Baldessarini, R.J., Tondo, L., Davis, P., Pompili, M., Goodwin, F.K. & Hennen, J. (2006). Decreased suicidal risk during long-term lithium treatment: meta-analysis. Bipolar Disorders 8, 625639.
Baldessarini, R.J., Tondo, L., Strombom, I., Dominguez, S., Fawcett, J., Oquendo, M., Tollefson, G.D., Valuck, R.J. & Tohen, M. (2007). Ecological studies of antidepressants and suicide risks. Harvard Review of Psychiatry 15, 133145.
Baldessarini, R.J., Vieta, E., Calabrese, J.R., Tohen, M. & Bowden, C. (in press). Bipolar depression: overview and commentary. Harvard Review of Psychiatry.
Barbui, C., Esposito, E. & Cipriani, A. (2009). Selective serotonin reuptake inhibitors and risk of suicide: a systematic review of observational studies. Canadian Medical Association Journal 180, 291297.
Bowden, C.L., Calabrese, J.R., Sachs, G., Yatham, L.N., Asghar, A., Hompland, M., Montgomery, P., Earl, N., Smoot, T.M. & De Veaugh-Geiss, J. (2003). Placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder. Archives of General Psychiatry 60, 392400.
Bschor, T. & Bauer, M. (2006). Efficacy and mechanisms of action of lithium augmentation in refractory major depression. Current Pharmaceutical Design 12, 29852992.
Calabrese, J.R., Bowden, C.L., Sachs, G., Yatham, L.N., Behnke, K., Mehtonen, O.P., Montgomery, P., Ascher, J., Paska, W., Earl, N. & DeVeaugh-Geiss, J. (2003). Placebo-controlled 18-month trial of lamot-rigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. Journal of Clinical Psychiatry 64, 10131024.
Cipriani, A., Pretty, H., Hawton, K. & Geddes, J.R. (2005). Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: Systematic review of randomized trials. American Journal of Psychiatry 162, 18051819.
Collins, J.C. & McFarland, B.H. (2008). Divalproex, lithium and suicide among Medicaid patients with bipolar disorder. Journal of Affective Disorders 107, 2328.
Dilsaver, S.C., Chen, Y-W., Swann, A.C., Shoaib, A.M., Dilsaver, Y.T. & Krajewski, K.J. (1997). Suicidality panic disorder and psychosis in bipolar depression, depressive-mania and pure mania. Psychiatry Research 73, 4756.
FDA (US Food and Drug Administration). (2007). Antidepressant use in children, adolescents, and adults. Retrieved February 18, 2009, from http://www.fda.gov/cder/drug/antidepressants/default.htm
Goldberg, J.F., Perlis, R.H., Bowden, C.L., Thase, M.E., Miklowitz, D.J., Marangell, L.B., Calabrese, J.R., Nierenberg, A.A. & Sachs, G.S. (2009). Manic symptoms during depressive episodes in 1,380 patients with bipolar disorder: findings from the STEP-BD. American Journal of Psychiatry 166, 173181.
Goldsmith, S.K., Pellmar, T.C., Kleinman, A.M. & Bunney, W.E. (2002). Reducing Suicide. Institute of Medicine of the US National Academy of Science: Washington, DC.
Goodwin, F.K., Fireman, B., Simon, G.E., Hunkeler, E.M., Lee, J. & Revicki, D. (2003). Suicide risk in bipolar disorder during treatment with lithium and divalproex. Journal of American Medical Association 290, 14671473.
Greil, W., Ludwig-Mayerhofer, W., Erazo, N., Schochlin, C., Schmidt, S., Engel, R.R., Czernik, A., Giedke, H., Müller-Oerlinghausen, B., Osterheider, M., Rudolf, G.A., Sauer, H., Tegeler, J. & Wetterling, T. (1997). Lithium versus carbamazepine in the maintenance treatment of bipolar disorders: randomized study. Journal of Affective Disorders 43, 151161.
Guzzetta, F., Baldessarini, R.J, Tondo, L. & Centorrino, F. (2007). Lithium treatment and suicidal risk in recurrent unipolar major depression. Journal of Clinical Psychiatry 68, 380383.
Hammad, T.A., Laughren, T.P. & Racoosin, J.A. (2006). Suicide rates in short-term randomized controlled trials of newer antidepressants. Journal of Clinical Psychopharmacology 26, 203207
Harris, E.C. & Barraclough, B. (1997). Suicide as an outcome for mental disorders. a meta-analysis. British Journal of Psychiatry 170, 205228.
Harris, E.C. & Barraclough, B. (1998). Excess mortality of mental disorder. British Journal of Psychiatry 173, 1153.
Isometsä, E.T., Henriksson, M.M., Aro, H.M., Heikkinen, M.E., Kuoppasalmi, K.I. & Lönnqvist, J.K. (1994). Suicide in major depression. American Journal of Psychiatry 151, 530536.
Joffe, R.T., Mac Queen, G.M., Marriott, M. & Trevor, Young L. (2004). Prospective, longitudinal study of percentage of time spent ill in patients with bipolar I or bipolar II disorders. Bipolar Disorders 6, 6266.
Judd, L.L., Akiskal, H.S., Schettler, P.J., Endicott, J., Maser, J., Solomon, D.A., Leon, A.C., Rice, J.A. & Keller, M.B. (2002). The longterm natural history of the weekly symptomatic status of bipolar I disorder. Archives of General Psychiatry 59, 530537.
Kessing, L.V., Søndergard, L., Kvist, K. & Andersen, P.K. (2005). Suicide risk in patients treated with lithium. Archives of General Psychiatry 62, 860866.
Kessler, R.C., Berglund, P., Borges, G., Nock, M. & Wang, P.S. (2005). Trends in suicide ideation, plans, gestures, and attempts in the United States, 1990–1992 to 2001–2003. Journal of American Medical Association 293, 24872495.
Koukopoulos, A. & Koukopoulos, A. (1999). Agitated depression as a mixed state and the problem of melancholia. Psychiatric Clinics of North America 22, 547564.
Maj, M., Pirozzi, R., Magliano, L., Fiorillo, A. & Bartoli, L. (2006). Agitated “unipolar” major depression: prevalence, phenomenology, and outcome. Journal of Clinical Psychiatry 67, 712719.
Meltzer, H.Y., Alphs, L., Green, A.I., Altamura, A.C., Anand, R., Bertoldi, A., Bourgeois, M., Chouinard, G., Islam, M.Z., Kane, J., Krishnan, R., Lindenmayer, J.P., Potkin, S. & International Suicide Prevention Trial Study Group. (2003). Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Archives of General Psychiatry 60, 8291.
Müller-Oerlinghausen, B. (2001). Arguments for the specificity of the antisuicidal effect of lithium. European Archives of Psychiatry and Clinical Neuroscience 251, Suppl. 2, 72–75.
Müller-Oerlinghausen, B., Ahrens, B. & Felber, W. (2006). The suicide-preventive and mortality-reducing effect of lithium. In Lithium in Neuropsychiatry (ed. Bauer, M., Grof, P., Müller-Oerlinghausen, B.), pp 179192. Informa Healthcare: London.
O’Donovan, C., Garnham, J.S., Hajek, T. & Alda, M. (2008). Antidepressant monotherapy in pre-bipolar depression: predictive value and inherent risk. Journal of Affective Disorders 107, 293298.
Oquendo, M.A., Chaudhury, S.R. & Mann, J.J. (2005). Pharmacotherapy of suicidal behavior in bipolar disorder. Archives of Suicide Research 9, 237250.
Post, R.M., Denicoff, K.D., Leverich, G.S., Altshuler, L.L., Frye, M.A., Suppes, T.M., Rush, A.J., Keck, P.E. Jr, McElroy, S.L., Luckenbaugh, D.A., Pollio, C., Kupka, R. & Nolen, W.A. (2003). Morbidity in 258 bipolar outpatients followed for 1 year with daily prospective ratings on the NIMH life chart method. Journal of Clinical Psychiatry 64, 680690.
Rihmer, Z. & Pestality, P. (1999). Bipolar II disorder and suicidal behavior. Psychiatric Clinics of Nord America 22, 667673.
Roy, A. (2001). Suicide. In Kaplan and Sadock’s Comprehensive Textbook of Psychiatry (ed. Sadock, B.J. and Sadock, V.A.), pp. 20312040. Lippincott-Williams & Wilkins: Philadelphia.
Simon, R.I., Hales, R.E. (2006). Textbook of Suicide Assessment and Management. American Psychiatric Press: Washington, DC.
Thies-Flechtner, K., Müller-Oerlinghausen, B., Seibert, W., Walther, A. & Greil, W. (1996). Effect of prophylactic treatment on suicide risk in patients with major affective disorders: Data from a randomized prospective trial. Pharmacopsychiatry 29, 103107.
Tondo, L. & Baldessarini, R.J. (2007). Suicidal risks among 2826 Sardinian major affective disorder patients. Acta Psychiatrica Scandinavica 116, 419428.
Tondo, L., Baldessarini, R.J., Hennen, J, Floris, G., Silvetti, F. & Tohen, M. (1998). Lithium treatment and risk of suicidal behavior in bipolar disorder patients. Journal of Clinical Psychiatry 59, 405414.
Tondo, L, Hennen, J. & Baldessarini, R.J. (2001). Reduced suicide risk with long-term lithium treatment in major affective Illness: A meta-analysis. Acta Psychiatrica Scandinavica 104, 163172.
Tondo, L., Isacsson, G. & Baldessarini, R.J. (2003). Suicide in bipolar disorder: risk and prevention. CNS Drugs 17, 491511.
Tondo, L., Albert, M.J. & Baldessarini, R.J. (2006). Suicide rates in relations to health care access in the United States: an ecological study. Journal of Clinical Psychiatry 67, 517523.
Waddington, D. & McKensie, I.P. (1994). Overdose rates in lithium-treated vs. antidepressant-treated outpatients. Acta Psychiatrica Scandinavica 90, 5052.
Yerevanian, B.I., Koek, R.J. & Mintz, J. (2003). Lithium, anticonvul-sants and suicidal behavior in bipolar disorder. Journal of Affective Disorders 73, 223228.
Zisook, S., Trivedi, M.H., Warden, D., Lebowitz, B., Thase, M.E., Stewart, J.W., Moutier, C., Fava, M., Wisniewski, S.R., Luther, J. & Rush, A.J. (2009). Clinical correlates of the worsening or emergence of suicidal ideation during SSRI treatment of depression: An examination of citalopram in the STAR-D study. Journal of Affective Disorders, Epub ahead of print.
Recommend this journal

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

Epidemiology and Psychiatric Sciences
  • ISSN: 2045-7960
  • EISSN: 2045-7979
  • URL: /core/journals/epidemiology-and-psychiatric-sciences
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