With appropriate precautions, placebo-controlled trials of treatment for
acute manic episodes and for prevention of manic-depressive episodes can be
conducted with minimal risk of suicide.
So report Jitschak Storosum, M.D., Ph.D., and colleagues in the April
American Journal of Psychiatry.
In a review of placebo-controlled, double-blind, randomized trials of
medication for the treatment of acute manic episodes and the prevention of
manic-depressive episodes, they found that suicide was not a significant risk
among patients enrolled in placebo groups.
"The results... indicate no greater risk of suicide among patients
with acute manic episode or stabilized bipolar disorder who were treated with
placebo compared with the risk of patients who were treated with an active
compound under the conditions of the trials," Storosum wrote.
He is with the Medicines Evaluation Board of the Netherlands (a regulatory
agency similar to the U.S. Food and Drug Administration).
In the study, all placebo-controlled, double-blind, randomized trials of
medications for the treatment of acute manic episode and the prevention of
manic-depressive episode that were part of a registration dossier submitted to
the Medicines Evaluation Board between 1997 and 2003 were reviewed for
occurrence of suicide and suicide attempts.
In 11 placebo-controlled studies of the treatment for acute manic episode
that included 1,506 patients in active compound groups and 1,005 patients in
placebo groups, Storosum and colleagues found no suicides and no suicide
attempts in either group.
In four placebo-controlled studies of the prevention of manic-depressive
episode that included 943 patients in active-compound groups and 418 patients
in the combined placebo groups, there were no suicides and only two suicide
attempts among the patients in placebo groups.
In the active-compound groups in those prevention trials, there were two
suicides and eight suicide attempts, according to the report.
Storosum stated that one limitation to the study is the exclusion from
placebo-controlled trials of patients who are considered at risk for suicide.
But he noted that the suicide rate in the active-treatment arms of the
prevention studies was greater than that reported by Frederick Goodwin, M.D.,
and colleagues in "Suicide Risk in Bipolar Disorder During Treatment
With Lithium and Divalproex," published in the September 2003
This "indicates that patients with bipolar disorder are at high risk
for suicide, even if they are considered nonsuicidal and treated with an
active compound," Storosum and colleagues said.
Psychiatrist Maria Oquendo, M.D., who reviewed the report for
Psychiatric News, called it a "very well done" study that
complements similar studies that Storosum has done looking at suicide risk in
placebo-controlled studies of treatment for schizophrenia and depression.
"These studies all show the same thing—that placebo groups do
not have an increased risk for suicide," said Oquendo, a clinical
professor of psychiatry at Columbia University College of Physicians and
But she emphasized that researchers performing intervention studies
continue to be ethically bound not to include patients at risk for suicide in
placebo-controlled trials, and for that reason Storosum's conclusions about
the relative safety of placebo cannot be extended yet to high-risk
"As more and more data accumulate, we may be able to change
that," she said. "But until we have more evidence, we are
ethically bound to exclude patients at risk for suicide from these
Oquendo published a report in the August 2004 American Journal of
Psychiatry examining strategies for designing randomized, controlled
trials that minimize the risk of morbidity and mortality for suicidal patients
while providing valuable data on effectiveness of interventions
(Psychiatric News, October 1, 2004).
Among her recommendations was not to use placebo controls in such
intervention trials. Other strategies:
"Suicide Risk in Placebo-Controlled Trials of Treatment for
Acute Manic Episode and Prevention of Manic-Depressive Episode" is
posted online at<http://ajp.psychiatryonline.org/cgi/content/full/162/4/799>."
Prospective Study of Clinical Predictors of Suicidal Acts After a Major
Depressive Episode in Patients With Major Depressive Disorder or Bipolar
Disorder" is posted at<http://ajp.psychiatryonline.org/cgi/content/full/161/8/1433>.▪
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