C O SMI M

SYMP UME NOTNA R

B IYP, OcLoAnRt iDnIuSeOdR D E R

COMMENTARY: Bipolar disorder is a potentially

fatal disease

Leslie Citrome, MD, MPH Joseph F. Goldberg, MD

Suicide is among the top five causes of death in the United States for persons aged 5 to 44 years.1 In
the Epidemiologic Catchment Area survey,2 the lifetime rate of suicide attempts in persons with bipo-
lar disorder was 29.2%, compared with 15.9% in persons with unipolar depression and 4.2% in those
with other major psychiatric disorders (excluding personality disorders).

In this study, persons with bipolar disorder were six sivity and hostility traits also elevate suicide risk.6
times more likely to attempt suicide than those with Impulsivity may be the reason why patients with bipo-
a psychiatric disorder other than depression and lar disorder who abuse substances are twice as likely
about twice as likely as to attempt suicide as those
those with unipolar de- who do not.7 About two
pression.2 thirds of patients who at-
Although many per- tempt suicide make mul-
sons with bipolar disor- tiple attempts.8 In those
der who attempt suicide with bipolar disorder, 1
never actually complete out of 5 suicide attempts
it, the annual average is lethal, in contrast to 1
suicide rate in men and out of 10 to 1 out of 20 in
women with diagnosed the general population.9
bipolar disorder (0.4%) is
more than 20 times that Physician intervention
in the general popula- What can primary care
tion.3 From another per- physicians do in the face
spective, about half of all of such daunting statis-
suicides can be attributed tics? First, recognition of
to bipolar disorder.4 the possibility of bipolar
Risk factors for suicide disorder in a patient pre-
among patients with bi- senting with depressive
polar disorder include Illustration: © 2005. Cary Henrie symptoms is key. The pa-
early age at disease onset, tient may be at higher risk
high number of depressive episodes, comorbid alcohol than a patient with unipolar depression. Second, ques-
abuse, personal history of antidepressant-induced ma- tions about suicidal ideation, intent, and plans should
nia, and family history of suicidal behavior.5 Impul- be part of every assessment of patients with depressed
See symposium articles on pages 15 and 25.
or irritable mood.
It is a myth that asking about suicide places the
Financial disclosure statement is on page 15. The authors disclose no unlabeled idea into a patient’s mind, and often, patients are grate-
uses for any product mentioned in this article. ful for the opportunity to discuss their fears about
continued
VOL 117 / NO 2 / FEBRUARY 2005 / POSTGRADUATE MEDICINE 9
 COMMENTARY, continued
suicide.10 A gradual approach to such questioning
often works well:
• Do you ever feel that life is not worth living?
• Have you ever thought about ending your life?
• What methods have you thought about?
Suicidal ideation should be taken seriously; emer-
gency consultation with a psychiatrist is highly desir-
able. If prompt evaluation by a psychiatrist is not lo-
gistically possible, telephone consultation with a local
mental health center is an option. Steps that ensure
the protection of the patient are paramount.
The role of antidepressants
Medications can be helpful in decreasing suicide risk,
but not all medications have the same antisuicide prop-
erties.11 In a recent and influential report,12 the risks of
suicide attempt and suicide death during treatment with
lithium were compared with those for divalproex
sodium. The investigators conducted a retrospective
analysis of patients in two large, integrated health plans
in California and Washington (N = 20,638 patients
with bipolar disorder). After adjustment for age, sex,
health plan, year of diagnosis, comorbid medical and
psychiatric conditions, and concomitant use of other
psychotropic drugs, risk of suicide death was almost
three times higher in patients taking divalproex than
in those taking lithium. Risk of nonfatal attempts was
almost double.
With the exception of clozapine (Clozaril, FazaClo),
less is known about the ability of second-generation
antipsychotic agents to reduce suicidal ideation and
behavior. 11 Combinations of antipsychotic agents
Leslie Citrome, MD, MPH, and Joseph F. Goldberg, MD
Dr Citrome, coordinator of this symposium, is professor of psychiatry,
New York University School of Medicine, New York, and director, clinical
research and evaluation facility, Nathan S. Kline Institute for Psychiatric
Research, Orangeburg, New York. Dr Goldberg is director, bipolar disorders
research program, department of psychiatry research, Zucker Hillside Hospi-
tal, North Shore Long Island Jewish Health System, Glen Oaks, New York.
Correspondence: Leslie Citrome, MD, MPH, Nathan S. Kline Institute for
Psychiatric Research, 140 Old Orangeburg Rd, Orangeburg, NY 10962.
E-mail: citrome@nki.rfmh.org.
10
and antidepressants are used for treatment of bipolar I
depression (depressive episode and a history of ma-
nia), and the combination drug of olanzapine and
fluoxetine hydrochloride (Symbyax) has received
US Food and Drug Administration (FDA) approval
for that indication.13 Use of antidepressant mono-
therapy for bipolar disorder remains controversial,
but recent evidence suggests it may be useful in treat-
ment of bipolar II depression (depressive episode and
a history of hypomania).14
The FDA’s response
In February 2004, an FDA advisory panel identified
apparent risks associated with several antidepressants
for increasing suicide-related behaviors in children
and adolescents with depression. Although no spe-
cific risks of these behaviors were observed among
adult patients with depression, the FDA extended a
warning label advisory about the potential associa-
tion between antidepressant use and suicidality in
adults as well as children and adolescents.
The relationship between antidepressant use and
suicide is complex. Suicidal features are commonly
associated with severe depression, and most com-
pleted suicides among depressed patients seem to oc-
cur in the context of undertreatment or nonadherence
to effective antidepressant therapy.11 Another impor-
tant consideration involves the potential for antide-
pressants to unmask a biologic vulnerability to bipolar
illness in children and adolescents. Such a reaction
could result in the induction of agitation or a mixed
state of both depression and mania, during which im-
pulsivity and suicidal features may become active.
Use of mood-stabilizing pharmacotherapies, rather
than antidepressants, may warrant consideration in
children and adolescents with depression who have
signs of bipolar diathesis. Physicians who treat depressed
patients in this age-group also should remain watch-
ful for indicators of potential vulnerability to bipolar
illness, such as early age at disease onset, prepubescent
depression, psychosis, family history of bipolar disor-
der, or prior “activation”—including symptoms such
VOL 117 / NO 2 / FEBRUARY 2005 / POSTGRADUATE MEDICINE
 COMMENTARY, continued
as anxiety, agitation, panic attacks, insomnia, irrita-
bility, hostility (aggressiveness), impulsivity, akathisia
(psychomotor restlessness), hypomania, and mania—
in response to antidepressant use.15
Current treatment options
Electroconvulsive therapy may be an excellent form
of intervention—particularly for patients with mixed
states—when medication is inadequate in control-
ling symptoms. Despite the negative public attitude
in the United States about electroconvulsive therapy,
the technology has advanced greatly in recent years,
and this therapy can literally be a lifesaver.16
A patient’s adherence to a medication regimen
provides hope that episodes of depression can be pre-
vented, or at least reduced in severity. This, in turn,
reduces the risk of suicide. Special attention is war-
ranted for patients with comorbid substance abuse
who demonstrate impulsive traits.
Lithium has the most evidence of capability as an
antisuicide agent. However, some patients may not
be able to tolerate its short- or long-term side effects.
Some evidence suggests that anticonvulsants such as
valproate are superior to lithium for patients who ex-
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pharmacy with multiple mood stabilizers in addition
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The following articles in this symposium address
the current approach to diagnosis and treatment of bi-
polar disorder. “The Many Faces of Bipolar Disorder:
How to Tell Them Apart” (page 15) discusses under-
diagnosis of bipolar disorder in the clinical setting, as
well as the potential morbidity and mortality associated
with misdiagnosed bipolar disorder. “Latest Therapies
for Bipolar Disorder: Looking Beyond Lithium” (page
25) provides an overview of the wide range of pharma-
cologic therapies available to treat bipolar disorder,
from traditional mainstays such as lithium to emerg-
ing treatments, including combination therapies and
second-generation antipsychotic agents. As the un-
derstanding of bipolar disorder grows, so may the
medical options for its treatment and hence the hope
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11