Lithium Treatment Reduces Suicide Risk in Recurrent Major Depressive Disorder

Francesca Guzzetta, M.D.; Leonardo Tondo, M.D.; Franca Centorrino, M.D.; and Ross J. Baldessarini, M.D.

Objective: 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.

Data Sources: 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.

Data Synthesis: 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.

Conclusions: This is the first meta-analysis suggesting antisuicidal effects of lithium in recurrent MDD, similar in magnitude to that found in bipolar disorders.

(J Clin Psychiatry 2007;68:380-383)

Received June 7, 2006; accepted Aug. 4, 2006. From the Department of Psychiatry, Harvard Medical School, Boston, and the International Consortium for Bipolar Disorder Research, McLean Hospital, Belmont, Mass. (all authors); the Department of Psychiatry, University of Bologna, Bologna, Italy (Dr. Guzzetta); and the Department of Psychology, University of Cagliari, and the Lucio Bini Mood Disorders Research Center, Cagliari, Sardinia, Italy (Dr. Tondo).

This study was supported in part by a research fellowship from the University of Bologna (Dr. Guzzetta); by grants from the Bruce J. Anderson Foundation and the McLean Hospital Private Donors Psychopharmacology Research Fund (Dr. Baldessarini); and by a Stanley Medical Research Institute award, a National Alliance for Research on Schizophrenia and Depression (NARSAD) Investigator award, and a grant from the Centro Bini Private Donors Research Fund (Dr. Tondo).

We thank Bruno Müller-Oerlinghausen, M.D., Alberto Bocchetta, M.D., and Alec Coppen, M.D., for very generously providing unpublished supplementary data that give clarifications for their cited studies (references 20, 22, and 23, respectively). Theodore Whitfield, D.Sc., and Federico Soldani, M.D., Ph.D., provided valuable consultation on data analyses. Neither Dr. Whitfield nor Dr. Soldani has a potential conflict of interest.

Dr. Tondo has conducted research with Eli Lilly and Janssen. Dr. Centorrino is a consultant for, is a member of the speakers' bureaus for, or has conducted research with Abbott, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Eli Lilly, Novartis, and Pfizer. Dr. Baldessarini is a consultant for or is a research collaborator with the following industrial organizations: Alkermes, Auritec, Biotrofix, Eli Lilly, IFI, Janssen, JDS, Merck, NeuroHealing, Novartis, and Solvay, some of whom produce treatments for mood disorders. He is not a member of pharmaceutical speakers' bureaus, nor does he or any family member hold equity positions in biomedical or pharmaceutical corporations. Dr. Guzzetta has no such industrial relationships to disclose relative to the subject of this article.

Corresponding author and reprints: Ross J. Baldessarini, M.D., McLean Hospital, Mailman Research Center, 115 Mill Street, Belmont, MA 02478-9106 (e-mail: rjb@mclean.org).