Lithium in suicide
prevention
Leonardo Tondo,
Carmen Ghiani
Dipartimento
Psicologia Università Cagliari, Italy
Harvard Medical School-McLean Hospital
Centro Bini-Stanley Medical Research Institute, Cagliari, Italy
(www.centrobini.it)
Long-term lithium treatment in mood disorders provides the strongest available evidence of reduced suicide risk compared to any other psychopharmacological treatment.[1-7] Studies reporting on the association of lithium treatment and suicide in bipolar and other major affective disorder patients have consistently found lower rates of suicides and attempts during lithium maintenance treatment than without it.[1-6] Despite some limitations, long-term lithium treatment has been associated with a nearly six-fold reduction of the crude average rate for completed suicide, and a nearly nine-fold lower multivariate computed risk in a meta-analysis of 22 studies involving a total of 5,647 patients and 33,473 patient-years of risk.[5] In 360 bipolar I and II patients evaluated before, during, and following discontinuation of maintenance lithium treatment, rates of suicide and life-threatening attempts were reduced 6.40 times (83.4%).[8] This reduction was consistent with a reduction of rates of suicidal acts by 8.85-times (85.3%) in the above-mentioned meta-analysis .[5]
A similar reduction of suicide risk has not been paralleled by long-term treatment with anticonvulsants. A recent study based on more than 20,000 bipolar patients from US Health Maintenance Organizations (1994-2001) showed a 3.2-fold higher risk of suicide in patients treated with anticonvulsants (mainly valproate) compared to lithium-treated patients [9].
The suicide preventing action of lithium is likely to be associated with the reduction of risk or severity of recurrences in depression or mixed dysphoric-agitated states, [10] although some experts have suggested a specific effect against suicide independent of its mood-stabilizing actions [11]. This specific value of lithium treatment may include reduction of impulsive, aggressive, or hostile behavior, possibly mediated through the central serotonin system. [12] Inconsistent with this hypothesis is the lack of evidence that serotonin reuptake inhibitor antidepressants have a beneficial effect on suicidality,[13] and that the central antiserotonergic agent clozapine may reduce suicide risk in schizophrenia.[14]
1. Jamison, K.R. Suicide and bipolar disorders. Ann. N.Y. Acad. Sci. 1986; 487: 301–15
2. Coppen A, Standish-Barry H, Bailey J, Houston G, Silcocks P, Hermon C. Does lithium reduce the mortality of recurrent mood disorders? J Affect Disord 1991; 23: 1–7
3. 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: 261–70
4. 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: 77–84
5. Tondo L, Hennen J, Baldessarini RJ: Reduced suicide risk with long-term lithium treatment in major affective illness: A meta-analysis. Acta Psychiatr Scand 2001; 104: 163–72
6. Nilsson A. Lithium therapy and suicide risk. J Clin Psychiatry 1999; 60 (Suppl 2): 85–8
7. Schou M. Perspectives on lithium treatment of bipolar disorder: action, efficacy, effect on suicidal behavior. Bipolar Disord 1999;1: 5-10
8. Tondo L, Baldessarini RJ, Hennen J, Floris G, Silvetti F, Tohen M. Lithium treatment and risk of suicidal behavior in bipolar disorder patients. J Clin Psychiatry 1998; 59: 405–14
9. Goodwin FK, Fireman B, Simon G, Hunkeler E, Lee J, Revicki D. Suicide attempts in bipolar patients on lithium vs. divalproex. Presented at the 42th ACNP, Puerto Rico, December 2002.
10. Baldessarini RJ, Tondo L, Hennen J. Reduced suicide risk during long-term treatment with lithium. Ann NY Acad Sci 2001; 932: 24–43
11. Müller-Oerlinghausen B. Arguments for the specificity of the antisuicidal effect of lithium. Eur Arch Psychiatry Clin Neurosci 2001;251 (Suppl 2):72-75
12. Young LT. Warsh JJ. Kish SJ. Shannak K. Hornykeiwicz O. Reduced brain 5-HT and elevated NE turnover and metabolites in bipolar affective disorder. Biol Psychiatry 1994; 35: 121–7
13. Khan A, Warner HA, Brown WA. Symptom reduction and suicide risk in patients treated with placebo in antidepressant clinical trials: An analysis of the FDA database. Arch Gen Psychiatry 2000; 57: 311–17
14. Meltzer HY, Anand R, Alphs L. Reducing suicide risk in schizophrenia: Focus on the role of clozapine. CNS Drugs 2000; 14: 355–65