Bipolar Disorder in Women - Ob.Gyn. News

Bipolar Disorder
in Women
Susan Hatters-Friedman, MD; Joy E. Stankowski, MD;
Martha Sajatovic, MD
Management of bipolar
disorder virtually always requires
medication, but these drugs
can have a substantial impact
on other life issues such as
contraception and pregnancy—
necessitating a delicate
“balancing act” for patient and
physician throughout the lifespan.
Bipolar disorder affects approximately
1% of the world’s population 1 and is
characterized by both depressive and
manic episodes. 2 Bipolar I disorder
affects women and men at similar
rates, 1 but bipolar II disorder—depressive episodes
alternating with milder manic episodes
(hypomania)—is more common in women. 3,4
PRESENTATION
Bipolar disorder should always be considered
in the differential diagnosis of depression; one
quarter of those presenting with depression
prove to have bipolar disorder. 5 There is often
Susan Hatters-Friedman, MD, is senior instructor in
psychiatry, Case Western Reserve University/University
Hospitals of Cleveland/Northcoast Behavioral Healthcare;
Joy E. Stankowski, MD, is senior instructor in
psychiatry, Case Western Reserve University/Northcoast
Behavioral Healthcare; and Martha Sajatovic, MD,
is professor, Department of Psychiatry, Case Western
Reserve University/University Hospitals of Cleveland; all
are in Cleveland, Ohio.
a 5- to 10-year delay between presentation and
diagnosis, which may shorten working life and
life expectancy. 6 Persons with high scores on a
bipolar screening test are also more likely to
have physical illnesses (eg, asthma, allergies,
headaches). 7 Furthermore, treating a bipolar
patient with antidepressants alone may precipitate
a manic episode, raising the risk of
rapid cycling. 8
DIAGNOSIS
The only definitive indication of bipolar disorder
is a manic episode which patients may
not recognize or mention. The disorder usually
presents between ages 15 and 24 years.
Onset after age 40 years is more likely to have
a medical or substance-induced etiology.
Psychiatric evaluation should include family
history, history of mood swings, and
lability. Information from collateral sources
is important, as patients often lack insight
into their behaviors. Other clues to bipolar
disorder are atypical depressive symptoms
(hyperphagia, hypersomnia), psychosis, or
lack of response to multiple antidepressant
medication trials. 9
The Mood Disorder Questionnaire can
assist in diagnosis. 10 A score of 7 or more
yields good sensitivity (0.73) and specificity
(0.90) for bipolar disorder. 10 A positive
result also indicates morbidity and functional
impairment. 7
The Table outlines common signs and
symptoms of bipolar disorder. Hypomania is
similar to mania, but episodes typically last
only 4 to 7 days and are less severe. Mixed
episodes meet symptom criteria for both
mania and depression nearly every day for a
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Bipolar Disorder
week. Psychotic symptoms may accompany
mania or depression.
Bipolar I disorder is diagnosed with the
occurrence of a manic episode, whereas bipolar
II disorder involves both depressive and
hypomanic episodes. Rapid-cycling bipolar
disorder is defined as more than four mood
episodes over 1 year and is often refractory
to treatment.
Bipolar disorder is frequently complicated
by psychiatric comorbidity (eg, anxiety, substance
abuse). 11,12 Lifetime prevalence of drug
and alcohol use in bipolar disorder is 34%
and 44%, respectively. 12 Women with bipolar
disorder often have multiple
social problems such as
partner violence, 13 criminal
”No-suicide”
contracts
are generally
not effective
because patients
determined to
kill themselves
do not reliably
feel bound by
promises made
to health care
professionals.
involvement, 14 lower rates of
marriage, and relationship and
occupational dysfunction. 7
SUICIDE RISK
Up to 19% of patients with
bipolar disorder eventually
commit suicide, while one
quarter to one half attempt
suicide. 15 Risk factors include
mixed and depressive episodes,
alcohol abuse, 15 and stressful
life events. Rates of suicide
are lower in women than in
men. Physicians should routinely
inquire about suicidal
thoughts/attempts and access
to firearms, and perform risk
assessments. “No-suicide” contracts are generally
not effective because patients determined
to kill themselves do not reliably feel bound
by promises made to health care professionals.
Patients at risk merit emergent psychiatric
evaluation; hospitalization is indicated when
there is a risk of harm to self or others.
TREATMENT
Treatment of bipolar disorder involves managing
acute manic and depressive episodes
and preventing recurrence. Current guidelines
16,17 recommend starting with a mood
stabilizer, including lithium, valproate, or an
atypical antipsychotic agent, and then tailoring
therapy according to phase. Patients with
a new diagnosis of bipolar disorder should
be referred to a psychiatrist for initial treatment
recommendations.
Lithium
Lithium is effective for both prophylaxis and
acute treatment of manic and depressive episodes.
It is excreted renally, so patients with
renal disease should be monitored carefully.
The therapeutic range is 0.6 to 1.2 mEq/L;
levels greater than 1.5 mEq/L are toxic. Lithium
can cause reversible leukocytosis, thyroid
dysfunction (including goiter), nausea,
tremor, weight gain, and peripheral edema.
Between 20% and 40% of patients do not
respond to lithium.
Valproic Acid
Valproic acid is better tolerated than lithium,
and is especially effective for mixed mania
or rapid cycling. Valproate has significant
drug-drug interactions, however, and can
cause transaminase elevation (usually reversible)
and pancreatitis. Levels should usually
be kept between 50 and 100 mcg/mL—50 to
80 mcg/mL for maintenance, and closer to
100 mcg/mL for acute mania.
Other Anticonvulsants
Trials of other anticonvulsants for treating
bipolar disorder have produced mixed results. 18
Carbamazepine is no longer considered as a
first-line agent. Oxcarbazepine is better tolerated
but studies regarding efficacy are limited.
Topiramate may be useful as an adjunct when
antipsychotic-related weight gain is a concern,
but is not efficacious as a mood stabilizer.
Antipsychotic Medications
Some guidelines support the use of atypical
antipsychotics (eg, aripiprazole, olanzapine,
quetiapine, risperidone, ziprasidone) alone in
less severe manic episodes. 17 Aripiprazole and
olanzapine have also been approved by the
US Food and Drug Administration (FDA)
for maintenance therapy, and quetiapine and
combined olanzapine-fluoxetine have been
approved for the treatment of bipolar depressive
episodes.
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Hatters-Friedman et al
More than 40% of individuals with bipolar
disorder use antipsychotic medications, and
85% of these patients use atypical antipsychotics.
19 As these drugs are likely to increase
weight and cardiovascular risk via the metabolic
syndrome (ie, hypertension, hyperglycemia,
lipid dysregulation) patients using them
should be monitored for abdominal obesity,
diabetes, and elevated triglyceride levels.
Lamotrigine and Antidepressants
Lamotrigine had been reserved for bipolar
depressive episodes but now has FDA
approval for maintenance therapy. Current
guidelines 16,17 also recommend selective serotonin
reuptake inhibitors or novel antidepressants
(bupropion). These medications may be
less likely to induce mania or rapid cycling
than older antidepressants. Such antidepressants
are generally used in combination with
a mood stabilizer. In cases of severe depression,
electroconvulsive therapy may be indicated—especially
in older patients.
GENDER ISSUES
Women with bipolar disorder may experience
more severe symptoms of both mania and
depression than men. 20 Women tend to be
depressed more frequently, 20 and more commonly
have mixed episodes. 3 Women with
bipolar disorder are also more likely to have
an initial depressed episode. 2 Further, women
represent a majority of rapid-cycling patients. 21
OTHER CONSIDERATIONS IN WOMEN
Contraceptive Planning
Contraceptive planning is imperative in women
with bipolar disorder, as many psychoactive
medications can be teratogenic. Barrier methods
may be most appropriate. Hormonal contraception
may negatively affect mood stability, and
can interact with both carbamazepine and topiramate.
In addition, two-thirds of women with
bipolar disorder have reported premenstrual
mood disturbances. 1 Women of reproductive
age who are taking carbamazepine or valproate
can be treated prophylactically with folate
because it may decrease risk of neural tube
defects in offspring of unexpected pregnancies.
TABLE. Signs and Symptoms of
Bipolar Episodes
Mania
• Elevated mood, euphoria, or irritable mood
• Grandiosity or inflated self-esteem
• Decreased need for sleep
• Hypertalkative
• Hypersexual
• Racing thoughts
• Distractibility
• Agitation
• Increased activities/projects (often unfinished)
• Argumentative
• Risk-taking (eg, spending sprees,
inappropriate sexual behavior)
• Psychotic symptoms (eg, hallucinations,
delusions)
• Poor insight into mania and negative
consequences
• Wearing flamboyant/revealing clothing
Depression
• Depressed mood
• Decreased interest/pleasure in activities
• Weight loss/gain
• Appetite change
• Insomnia/hypersomnia
• Tearfulness
• Hopelessness/helplessness
• Agitation
• Fatigue or loss of energy
• Lack of initiative/motivation
• Avoidance of friends or family
• Poor job/school performance
• Feelings of worthlessness/excessive guilt
• Decreased concentration (may mimic
dementia in older patients)
• Suicidal thoughts/behaviors
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Hatters-Friedman et al
Pregnancy
Almost 33% of women with bipolar disorder
will experience an episode during pregnancy,
and about 50% report severe emotional problems.
During pregnancy the risks of therapy
must be balanced against the risks of untreated
bipolar disorder. Concerns about psychotropic
medication use in pregnancy include malformations,
poor neonatal outcome, and behavioral
teratogenesis. The fetus may be exposed
before the patient knows she is pregnant.
Prenatal screening with α-fetoprotein testing,
high-resolution ultrasonography, and other
modalities is strongly advised. Physicians
should be alert to other pregnancy risks in
women with bipolar disorder such as smoking,
substance abuse, and victimization. The
goal should be control of specific symptoms
with lower doses and less polypharmacy.
Fetal risks with lithium use include Ebstein
cardiac anomaly 22-24 and neonatal toxicity
(“floppy baby syndrome”⎯ie, cyanosis and
hypotonicity). 8,22 Lithium withdrawal over
less than 2 to 4 weeks increases maternal
relapse risk. 23 Lithium can rapidly become
toxic during delivery because of fluid shifts;
levels should be monitored during labor, and
adequate hydration ensured. 22
Fetal exposure to anticonvulsants is associated
with a 2-fold increase in malformations
(neural tube defects, craniofacial anomalies,
microcephaly, growth restriction, cardiac
defects) 22 ; folic acid supplementation may be
helpful. Vitamin K should be given to mothers
and neonates exposed to carbamazepine. 8,21
Rates of malformations with lamotrigine are
similar to general-population rates but rise
when valproate is added. 22
Typical antipsychotics (eg, haloperidol) may
be useful for acute treatment of mania in
pregnancy. 22 Atypical antipsychotics (eg, olanzapine)
may induce gestational diabetes or
preeclampsia so glucose levels, blood pressure,
and weight gain should be monitored. 22
Electroconvulsive therapy is safe during pregnancy
with modifications. 22 Benzodiazepines
confer an elevated risk of cleft lip or palate but
the absolute risk remains low; high-potency
benzodiazepines are preferred due to shorter
half-life and less accumulation, 22 and are often
used on an as-needed basis.
Postpartum
The postpartum phase represents the highest
lifetime risk period for women to develop
mental illness. 25 Evidence indicates an elevated
risk of postpartum psychosis in women with
bipolar disorder. 26 Postpartum psychosis often
constitutes a psychiatric emergency, increasing
the risk of both infanticide and suicide. 27
Maintenance treatment in the postpartum
period may be prophylactic.
Treating bipolar postpartum depressive episodes
is more complex than treating unipolar
depression due to the risk of precipitating
manic episodes. In these cases a mood stabilizer
should be used, and an antidepressant
may also be needed. These women require
close monitoring.
Lactation
Communication between
treating physicians is critical
and infants should be monitored
for adverse effects,
including with laboratory
tests. Lithium should be
prescribed with caution due
to the risk of rapid dehydration.
22 Carbamazepine and
valproate are more compatible
with breast-feeding. 22
Infants exposed to lamotrigine
should be monitored
for rash. 22
Concerns
about
psychotropic
medication use
in pregnancy
include
malformations,
poor neonatal
outcome, and
behavioral
teratogenesis.
Menopause
One study noted that more
than 50% of perimenopausal
bipolar women
reported worsened mood 28
and another noted that 20% of postmenopausal
patients experienced severe
mood problems. 1
Postmenopausal patients with bipolar disorder
generally do well with valproate or
lithium treatment. Valproate is better tolerated,
and both drugs should be given at
lower dosages due to decreasing metabolic
rates. 29 Although mania can present initially
in the elderly, new-onset mania should trigger
evaluation for underlying organic disorder
or dementia.
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Bipolar Disorder
CONCLUSION
Bipolar disorder represents substantial challenges
for patients and physicians. Special considerations
such as contraception, pregnancy,
lactation, and menopause may modify treatment
options. Finally, while medications are
important, they must be accompanied by a positive
therapeutic alliance and psychotherapy.
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