© COPYRIGHT 2011 PHYSICIANS POSTGRADUATE PRESS, INC. © COPYRIGHT 2011 PHYSICIANS POSTGRADUATE PRESS, INC.
J Clin Psychiatry 72:12, December 2011
Letters to the Editor
Antidepressant Use and Risk for
Suicide Attempts in Bipolar Disorder
To the Editor: The use of antidepressants in bipolar disorder
remains controversial with respect to whether, and when, they may
destabilize mood and worsen clinical course. Despite previously
identified links between suicide attempts and the proportion of
time spent with depression in bipolar disorder,1 few longitudinal
studies have examined the relationship between antidepressant use
and suicidal behavior specifically in bipolar disorder. Retrospec-
tive studies have reported a greater risk for suicide attempts among
bipolar patients taking antidepressants alone than among those
taking concomitant mood stabilizers2,3 or mood stabilizers alone,3
while prospective studies have found either no link between suicidal
acts and antidepressant use4 or fewer suicide attempts when antide-
pressants are combined with mood stabilizers than during mood
stabilizer therapy alone.5 Interpretations about suicidal behavior in
most naturalistic outcome studies also may be hampered by tempo-
ral confounding when antidepressants are started because of, rather
than before, the emergence of suicidal behavior.
Leon and colleagues6 present findings from a useful and im-
portant 27-year observational study of suicide attempts and
antidepressant therapy in a large mood disorder cohort. Using a
propensity-adjusted mixed-effect survival model, they demonstrate
a 20% reduction in overall risk for suicide attempts among all sub-
jects taking versus not taking an antidepressant. However, their
model did not stratify for unipolar versus bipolar diagnosis as a cor-
relate of suicide attempt risk during antidepressant use. While the
majority of their subjects (nearly 80%) had index diagnoses of (uni-
polar) major depression, their available subgroup of 119 subjects
with index bipolar mania should nevertheless provide adequate
power for the inclusion of unipolar versus bipolar diagnosis as a
covariate of suicidal behavior. Given the potential for differences
between bipolar and unipolar patients in antidepressant response,
as well as the potential for antidepressants to exacerbate concomi-
tant manic symptoms during bipolar depressive syndromes,7 such
an analysis in this unique cohort would be of great value for deter-
mining whether antidepressants may differentially affect suicide
risk in bipolar versus unipolar patients.
1. Tondo L, Baldessarini RJ, Hennen J, et al. Lithium treatment and risk
of suicidal behavior in bipolar disorder patients. J Clin Psychiatry.
1998;59(8):405–414. doi:10.4088/JCP.v59n0802 PubMed
2. Pacchiarotti I, Valentí M, Colom F, et al. Differential outcome of bipolar
patients receiving antidepressant monotherapy versus combination with
an antimanic drug. J Affect Disord. 2011;129(1–3):321–326. doi:10.1016/j.jad.2010.07.036 PubMed
3. Yerevanian BI, Koek RJ, Mintz J, et al. Bipolar pharmacotherapy and
suicidal behavior, pt 2: the impact of antidepressants. J Affect Disord.
2007;103(1–3):13–21. doi:10.1016/j.jad.2007.05.017 PubMed
4. Gilbert AM, Garno JL, Braga RJ, et al. Clinical and cognitive correlates
of suicide attempts in bipolar disorder: is suicide predictable? J Clin
Psychiatry. 2011;72(8):1027–1033. PubMed
5. Angst F, Stassen HH, Clayton PJ, et al. Mortality of patients with mood
disorders: follow-up over 34–38 years. J Affect Disord. 2002;68(2–3):
167–181. doi:10.1016/S0165-0327(01)00377-9 PubMed
6. Leon AC, Solomon DA, Li C, et al. Antidepressants and risks of suicide
and suicide attempts: a 27-year observational study. J Clin Psychiatry.
2011;72(5):580–586. doi:10.4088/JCP.10m06552 PubMed
7. Goldberg JF, Perlis RH, Ghaemi SN, et al. Adjunctive antidepressant use
and symptomatic recovery among bipolar depressed patients with con-
comitant manic symptoms: findings from the STEP-BD. Am J Psychiatry.
2007;164(9):1348–1355. doi:10.1176/appi.ajp.2007.05122032 PubMed
Joseph F. Goldberg, MD
Author affiliations: Department of Psychiatry, Mount Sinai School of Medicine,
New York, New York, and Affective Disorders Research Program, Silver Hill Hospital,
New Canaan, Connecticut. Potential conflicts of interest: Dr Goldberg has been a con-
sultant to Dey, Grünenthal Group, and Eli Lilly; has received honoraria from AstraZeneca
and Eli Lilly; and has been on the speakers/advisory boards of AstraZeneca, Eli Lilly, Dey,
Merck, and Sunovion. Funding/support: None reported.
© Copyright 2011 Physicians Postgraduate Press, Inc.