Lithium Treatment Reduces Suicide Risk in Recurrent Major Depressive Disorder

Harvard University, Cambridge, Massachusetts, United States
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 04/2007; 68(3):380-3. DOI: 10.4088/JCP.v68n0304
Source: PubMed


Evidence that clinical treatment reduces suicide risk in major depressive disorder (MDD) is limited and inconsistent. Since lithium shows major antisuicidal effects in bipolar disorders and in heterogeneous mood disorder samples, we evaluated evidence of antisuicidal effects of lithium in patients with recurrent MDD.
We searched MEDLINE (January 1966 to April 2006; search terms: lithium, suicide, affective disorder, depression, major depression, and mood disorder) for studies reporting suicides or suicide attempts during treatment with and without lithium in recurrent MDD patients, and we added data for 78 new subjects, provided from the Lucio Bini Mood Disorders Research Center in Sardinia, Italy. Suicide rates were pooled and analyzed by use of incidence-rate ratios (IRRs) and meta-analytic methods.
Eight studies involved 329 MDD patients and exposure for 4.56 years (1149 person-years) with, and 6.27 years (1285 person-years) without, lithium. Overall risk of suicides and suicide attempts was 88.5% lower with vs. without lithium: 0.17%/y versus 1.48%/y (IRR = 8.71; 95% CI: 2.10 to 77.2, p = .0005); for completed suicides (85% risk reduction), IRR = 6.77 (95% CI: 1.29 to 66.8, p = .01). Meta-analysis by risk difference and risk ratio supported these findings, and sensitivity analysis yielded similar results with studies omitted serially.
This is the first meta-analysis suggesting antisuicidal effects of lithium in recurrent MDD, similar in magnitude to that found in bipolar disorders.

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    • "However, the first-line of choice antidepressant treatments, including SSRIs, and SNRIs, have drawbacks since it can take weeks to develop beneficial mood-enhancing effects, and the risk for suicidality has been reported to increase during the first weeks of treatment, especially in children and adolescents (Wasserman et al., 2012). Pharmacological treatment with lithium in mood disorders (Baldessarini et al., 2006;Guzzetta et al., 2007), clozapine in schizophrenia (Meltzer and Baldessarini, 2003), and electroconvulsive therapy in treatment-resistant depression (Kennedy et al., 2009) have proven effective in decreasing suicidal behavior. In addition, a robust and rapid (within hours) antidepressant and anti-suicidal effect is produced by intravenous injection of ketamine, which is an NMDA-receptor antagonist (Fond et al., 2014;M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 5 2013). "
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    • "Baldessarini et al. (2006) conducted a meta-analysis of 45 studies including more than 33,000 patients showing that patients treated with lithium had a 5-fold reduced risk of suicide or suicide attempts compared to patients treated with other substances. When analyzing data of 328 Sardinian patients with unipolar depression, Guzzetta et al. (2007) found a significant lower risk for suicide attempts and suicides in lithium-treated patients. "
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    • "Although over 60 years have elapsed since its effects on mania were first described, lithium (LI) is still a mainstay in the treatment of mood disorders and remains the standard against which new mood-stabilizing or thymoleptic drugs are measured (Price and Heninger 1994). LI treatment paradoxically relieves both mania and depression—conditions that appear to be opposites, and additionally, it has been reported to have specific antisuicidal effects (Baldessarini et al. 2006; Guzzetta et al. 2007). However, the mechanism by which LI effectively treats bipolar disorder (BP) and depression and reduces the risk of suicidal behaviors is largely unknown. "
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