Lithium Reduces Suicide in Major Depressive Disorder
381 380 J Clin Psychiatry 68:3, March 2007
10 to 20 times above general-population rates, and with
severe clinical, social, and economic impact.1–3 Neverthe-
less, there is remarkably limited evidence of effectiveness
and safety of clinical interventions aimed at suicide pre-
vention.2,3 A notable exception is that rates of suicides and
suicide attempts in bipolar disorder patients or in diagnos-
tically heterogeneous mood disorder samples are mark-
edly reduced during treatment with lithium.2–10 Antide-
pressants do not appear to reduce risk of suicide in major
depressive disorders (MDD),11–14 but there is suggestive
evidence of protective effects of long-term antidepressant
treatment in recurrent MDD.15 However, it has also been
reported that serotonin reuptake inhibitors may increase
risk of suicidality in young patients.16 Since effects of lith-
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 dis-
orders 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: lith-
ium, suicide, affective disorder, depression, major
depression, and mood disorder) for studies report-
ing suicides or suicide attempts during treatment
with and without lithium in recurrent MDD pa-
tients, 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
Conclusions: This is the first meta-analysis
suggesting antisuicidal effects of lithium in recur-
rent MDD, similar in magnitude to that found in
(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
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: firstname.lastname@example.org).
ajor mood disorders are associated with mark-
edly increased risk of suicide, typically at rates