For years, lithium has been thought to have a protective effect against
suicide in patients with bipolar disorder. Recent data show, however, that in
one sample of patients with the mood disorder, this is not the case.
Researchers conducting a new data analysis of the Systematic Treatment
Enhancement Program for Bipolar Disorder (STEP-BD) study compared subjects
with bipolar disorder who took lithium in the six months prior to a suicide
attempt or completion with subjects who did not make such an attempt and
failed to find an association between lithium and suicide attempts or
completions (p = .41).
The findings were published in the April 8 online edition of the
Journal of Clinical Psychiatry.
Lead author lauren Marangell, M.D., told Psychiatric News that for
clinicians treating patients with bipolar disorder, suicide prevention is an
important concern and that there is reason to challenge an automatic
assumption that lithium protects patients against suicide based on past
studies. "Until we have further data," she noted, "the
clinician must weigh the risks and benefits for each individual
At the time of the study analysis, Marangell was a professor of psychiatry
at Baylor College of Medicine and codirector of the National Institute of
Mental Health's Bipolar Trials Network. She is currently a distinguished
scholar at Eli Lilly and Company.
The STEP-BD study is a multisite study designed to evaluate clinical
outcomes in patients with bipolar disorder. Researchers recruited 4,360
patients with bipolar disorder from September 1998 through November 2004. They
examined the association between eight cases of suicide and 262 suicide
attempts and medications prescribed to the patients in the six months
preceding the suicidal behavior.
According to the report, there a number of published studies supporting the
use of lithium as a suicide-protective agent in patients with bipolar
disorder. One 2003 study conducted by Ross Baldessarini, M.D., also published
in the Journal of Clinical Psychiatry, showed a nearly 15-fold risk
reduction associated with lithium treatment, for example.
Marangell noted, however, that Baldessarini's analysis and other studies
showing lithium's suicide-protective effects are mostly retrospective and not
randomized, so they may reflect a bias toward those who respond positively to
In her analysis, Marangell matched 93 cases of STEP-BD participants who
attempted or completed suicide with 93 participants who did not based on
gender, age, and a propensity score that accounted for bipolar subtype,
marital status, age at illness onset, and history of psychosis. She
categorized each group by whether they were continually prescribed lithium,
had only partial exposure to lithium, or were not prescribed lithium in the
six months prior to the suicide or attempt; she also did so for controls, also
looking at the same six-month period, as indicated by clinical-monitoring
forms completed throughout the study.
Of the 53 subjects who had a suicide attempt or completion with no lithium
in the six months prior to the event, 32 matched controls also had no lithium
in the six months prior, eight had some lithium use, and 13 had steady lithium
Of the 18 subjects who had some lithium use and who attempted or completed
suicide, five matched controls had no lithium use, six had some, and seven had
continual lithium exposure.
Finally, of the 22 cases of suicide or attempt with steady lithium use,
nine had matched controls with no lithium use, four with some lithium use, and
nine with steady lithium use.
The findings do not support an association between lithium use and reduced
suicide attempts or completions, according to the report, and there was no
association between suicide events and use of valproate, carbamazepine,
lamogatrine, or atypical antipsychotic medications.
Marangell also found that in 23 cases of a suicide or attempt, there was
steady exposure to a selective serotonin reuptake inhibitor (SSRI) in the six
months prior to the event. Within the matched controls, 20 had no exposure to
an SSRI, one had some, and two had exposure throughout the six-month period."
These findings suggest that exposure to an SSRI medication is
associated with a suicide event over a six-month period prior to the event
Marangell emphasized, however, that "this study was not designed to
assess the association between SSRIs and suicide risk"; thus, these
findings must be interpreted with caution.
She also pointed out that her analysis on the association between lithium
and suicide had certain limitations: for example, the overall rate of suicides
and suicide attempts was low, she said. "Mostly the events included were
suicide attempts, with only a few completed suicides. The risk factors for
completed suicides may be different from those of suicide attempts, but I
think both are clinically important."
To further elucidate her findings, Marangell would like to conduct a
prospective, randomized clinical trial in a population at high risk for
The study was funded by the American Foundation for Suicide Prevention and
National Alliance for Research in Schizophrenia and Depression. The STEP-BD
Project was funded by the National Institute of Mental Health.
"Case-Control Analyses of the Impact of Pharmacotherapy on
Prospectively Observed Suicide Attempts and Completed Suicides in Bipolar
Disorder: Findings From the STEP-BD" is posted at<http://www.psychiatrist.com/privatepdf/oap/ej07m03621.pdf>.▪