Divalproex, lithium and suicide among Medicaid patients with
Jon C. Collinsa,b, Bentson H. McFarlanda,⁎
aDepartment of Psychiatry, CR-139, Oregon Health & Science University, Portland, Oregon 97239, United States
bAddictions and Mental Health Division, Department of Human Services, State of Oregon, Salem, Oregon 97301, United States
Received 25 October 2006; received in revised form 1 June 2007; accepted 11 July 2007
Available online 16 August 2007
Background: Suicide completion and attempted suicide are major concerns for people with bipolar disorder. Studies in the private
sector have suggested that lithium treatment may be superior to divalproex therapy with regard to minimizing suicidal behavior
among individuals with bipolar disorder. However, few data are available regarding Medicaid patients diagnosed with bipolar
Methods: Subjects were 12,662 Oregon Medicaid patients diagnosed with bipolar disorder and treated with medication between
1998 and 2003. Outcomes measures were completed suicide and emergency department visits for suicide attempts (including non-
fatal poisoning). Cox proportional hazards models were used to adjust for demographics, co-morbidity, and concurrent
psychotropic medication use.
Results: Divalproex was the most common mood stabilizer (used by 33% of subjects) followed by gabapentin (32%), lithium
(25%), and carbamazepine (3%). There were 11 suicide deaths and 79 attempts. Adjusted hazard ratios (versus lithium users) for
suicide attempts were 2.7 for divalproex users (pb0.001), 1.6 for gabapentin users (not significant) and 2.8 for carbamazepine
users (not significant). For suicide deaths, the adjusted hazard ratios were 1.5 for divalproex users (not significant), 2.6 for
gabapentin users (pb0.001), and not available for carbamazepine users.
Limitations: It should be noted that subjects were not assigned at random to medication use, data on prior suicide attempts were not
available, medication use was measured by automated pharmacy records, and duration of mood stabilizer utilization may have been
Conclusions: Lithium may have a protective effect with regard to suicide attempts among Medicaid patients with bipolar disorder.
It remains unclear whether or not lithium protects these patients against completed suicide.
© 2007 Elsevier B.V. All rights reserved.
Keywords: Mood stabilizer; Valproate; Valproic acid; Carbamazepine; Gabapentin; Community mental health; Anticonvulsant; Antiepileptic
Completed suicide and attempted suicide are major
concerns for people with bipolar disorder (Baldessarini
et al., 2006; Baldessarini and Tondo, 2003; Goodwin,
1999; Müller-Oerlinghausen et al., 2002). In the absence
Journal of Affective Disorders 107 (2008) 23–28
⁎Corresponding author. Tel.: +1 503 245 6550; fax: +1 503 494
E-mail address: firstname.lastname@example.org (B.H. McFarland).
0165-0327/$ - see front matter © 2007 Elsevier B.V. All rights reserved.
gabapentin use. This finding from the present study
needs further exploration.
In summary, results from this study are not com-
pletely consistent with those of Goodwin et al. (2003)
nor with those of Yerevanian et al. (2003). The present
project found a higher risk of suicide attempt during use
of divalproex compared to lithium but did not find
greater risk with regard to suicide death among Med-
icaid patients with bipolar disorder.
Overall, then, it remains unclear whether or not there
is differential impact on suicide deaths among the mood
stabilizing agents. Lithium may exert a protective effect
with regard to attempted suicide.
Role of funding source
Funding for this study was provided by Abbott Laboratories,
which had no further role in study design; in the collection, analysis
and interpretation of data; in the writing of the report; and in the
decision to submit the paper for publication.
Conflict of interest
This work was supported in part by Abbott Laboratories. B.H.M.
currently receives research grant funding from Eli Lilly. The authors
have no other conflicts of interest.
Baldessarini, R.J., Tondo, L., 2003. Suicide risk and treatments for
patients with bipolar disorder. JAMA 290, 1517–1519.
Baldessarini, R.J., Tondo, L., Hennen, J., 2003. Lithium treatment and
suicide risk in major affective disorders: update and new findings.
J. Clin. Psychiatry 64 (Suppl 5), 44–52.
Baldessarini, R.J., Pompili, M., Tondo, L., 2006. Suicide in bipolar
disorder: risks and management. CNS Spectr. 11, 465–471.
Bender, K.J., 1998. NCDEU report I: bipolar, stress and panic
disorders. Psychiatric Times XV. Retrieved August 5, 2006, from
Blanco, C., Laje, G., Olfson, M., Marcus, S.C., Pincus, H.A., 2002.
Trends in the treatment of bipolar disorder by outpatient psy-
chiatrists. Am. J. Psychiatry 159, 1005–1010.
Born, C., Dittmann, S., Post, R.M., Grunze, H., 2005. Newer
prophylactic agents for bipolar disorder and their influence on
suicidality. Arch. Suicide Res. 9, 301–306.
Bowden, C.L., 2000. The ability of lithium and other mood stabilizers
to decrease suicide risk and prevent relapse. Curr. Psychiatry Rep.
Bowden, C., Fawcett, J., 2004. Pharmacotherapy and risk of suicidal
behaviors among patients with bipolar disorder [Letter]. JAMA
Bowden, C.L., Calabrese, J.R., McElroy, S.L., Gyulai, L., Wassef, A.,
Petty, F., Pope Jr., H.G., Chou, J.C., Keck Jr., P.E., Rhodes, L.J.,
Swann, A.C., Hirschfeld, R.M., Wozniak, P.J., 2000. A random-
ized, placebo-controlled 12-month trial of divalproex and lithium
in treatment of outpatients with bipolar I disorder. Arch. Gen.
Psychiatry 57, 481–489.
Coryell, W., Arndt, S., Turvey, C., Endicott, J., Solomon, D., Mueller,
T., Leon, A.C., Keller, M., 2001. Lithium and suicidal behavior in
major affective disorder: a case-control study. Acta Psychiatr.
Scand. 104, 193–197.
Fenn, H.H., Robinson, D., Luby, V., Dangel, C., Buxton, E., Beattie,
M., Kraemer, H., Yesavage, J.A., 1996. Trends in pharmacother-
apy of schizoaffective and bipolar affective disorders: a 5-year
naturalistic study. Am. J. Psychiatry 153, 711–713.
Gelenberg, A.J., 2001. Can lithium help to prevent suicide? Acta
Psychiatr. Scand. 104, 161–162.
Goodwin, F.K., 1999. Anticonvulsant therapy and suicide risk in
affective disorders. J. Clin. Psychiatry 60 (Suppl 2), 89–93.
Goodwin, F.K., Fireman, B., Simon, G.E., Hunkeler, E.M., Lee, J.,
Revicki, D., 2003. Suicide risk in bipolar disorder during treatment
with lithium and divalproex. JAMA 290, 1467–1473.
Goodwin, F.K., Simon, G., Revicki, D., Hunkeler, E., Fireman, B.,
Lee, J., 2004. In reply. JAMA 291, 940.
Kaplan, M.S., McFarland, B.H., Huguet, N., Newsom, J.T., 2007.
Physical illness, functional limitations, and suicide risk: a
population-based study. Am. J. Orthopsychiatr. 77, 56–60.
Müller-Oerlinghausen, B., 2001. Arguments for the specificity of the
antisuicidal effect of lithium. Eur. Arch. Psychiatry Clin. Neurosci.
251 (Suppl 2), II72–II75.
Müller-Oerlinghausen, B., Berghöfer, A., Bauer, M., 2002. Bipolar
disorder. Lancet 359, 241–247.
Schou, M., 1999. Perspectives on lithium treatment of bipolar disorder:
action, efficacy, effect on suicidal behavior. Bipolar Disord. 1, 5–10.
Thies-Flechtner, K., Muller-Oerlinghausen, B., Seibert, W., Walther,
A., Greil, W., 1996.Effectof prophylactictreatment on suicide risk
in patients with major affective disorders: data from a randomized
prospective trail. Pharmacopsychiatry 29, 103–107.
Tondo, L., Hennen, J., Baldessarini, R.J., 2001. Lower suicide risk
with long-term lithium treatment in major affective illness: a meta-
analysis. Acta Psychiatr. Scand. 104, 163–172.
Yerevanian, B.I., Koek, R.J., Mintz, J., 2003. Lithium, anticonvul-
sants, and suicidal behavior in bipolar disorder. J. Affect. Disord.
Yerevanian, B.I., Koek, R.J., Feusner, J.D., 2004. Pharmacotherapy
and risk of suicidal behaviors among patients with bipolar disorder
[Letter]. JAMA 291, 939.
28J.C. Collins, B.H. McFarland / Journal of Affective Disorders 107 (2008) 23–28