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p. 1833

Bipolar disorder is a chronic progressive illness that occurs in

approximately 4% of the population. It is characterized by recurrent

mood episodes of mania and depression. Life stressors, substance use,

treatment non-adherence, and medications are common precipitants of

these mood episodes.

Case 87-1 (Questions 1–3)

Manic episodes are characterized by elevated mood, irritability,

increased goal-directed activity, inflated self-esteem, poor judgment, and

excessive motor activity.

Case 87-1 (Question 1),

Case 87-2 (Question 1)

Depressive episodes of bipolar share the same diagnostic criteria as

major depressive disorder, including depressed mood, decreased

interest, feelings of worthlessness, diminished ability to concentrate, and

recurrent thoughts of death.

Case 87-7 (Question 1)

Valproate, lithium, or atypical antipsychotics are appropriate first-line

treatments for acute mania. Depending on the severity of symptoms,

these agents may be used alone or in combination.

Case 87-1 (Questions 4, 5),

Case 87-2 (Question 1),

Case 87-5 (Question 2),

Case 87-6 (Question 1)

Lithium, lamotrigine, quetiapine, lurasidone, or the combination of these

agents is appropriate treatments for bipolar depression.

Case 87-7 (Question 1)

Maintenance treatment of bipolar disorder is imperative to prevent

disease progression. The standard of practive is to continue the acutephase treatment with gradualsimplification toward monotherapy, if

possible, with lithium, lamotrigine, valproate, or atypical antipsychotics.

Case 87-5 (Question 1),

Case 87-8 (Questions 1, 2)

Medications used to treat bipolar disorder have a wide range of adverse

effects that may impact adherence. The history of response, patient

preference, and long-term tolerability profile are important

considerations when selecting an agent. Therapeutic blood level

monitoring, as well as laboratory monitoring for adverse effects, is

commonly required for certain medications.

Case 87-1 (Questions 6–8),

Case 87-2 (Questions 1–8),

Case 87-3 (Questions 1, 2),

Case 87-4 (Questions 1, 2)

Non-pharmacologic treatments including electroconvulsive therapy

(ECT) and herbalsupplements are important considerations for the

treatment of bipolar disorder.

Case 87-8 (Questions 3, 4)

INTRODUCTION

Bipolar disorder (BD), once known as manic depression, is a severe life-threatening

psychiatric condition that is commonly misdiagnosed and too often insufficiently

treated.

1,2 BD is associated with high rates of healthcare utilization, suicidal

behavior, and use of public assistance.

3 The global burden of BD is immense,

exceeding many chronic diseases including human immunodeficiency virus, diabetes

mellitus, and asthma.

4

Epidemiology

Using DSM-IV-TR criteria, the 12-month prevalence of bipolar I disorder is

estimated to be 0.6%; bipolar II disorder is marginally more common at 0.8%.

5 The

prevalence rate for the bipolar spectrum of illnesses, which include bipolar I,

bipolar II, and subthreshold BD (i.e., Bipolar Disorder Not Otherwise Specified

[NOS]), is 4.4%.

6 Bipolar I and II are more common in women than in men, whereas

subthreshold illness predominates in men.

6 The familial nature of BD has been well

established with an

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11-fold increased risk in first-degree relatives.

7 Twin studies add further support to

the genetic linkage. Goodwin and Jamison reported a 63% concordance rate (rate of

illness in co-twin of affected proband) for monozygotic twins compared with 13%

for dizygotic twins.

7

The estimated total U.S. economic burden of BD between 1991 and 2009 was

reported to be $151 billion.

8 Direct costs, such as hospitalization, outpatient visits,

and medications, accounted for 20% of the total. The remaining 80% was attributable

to indirect costs such as lost productivity by patients and caregivers.

The mean age of onset of symptoms for the bipolar spectrum of illnesses is 21

years.

6 Bipolar I is the earliest in onset at age 18, compared with bipolar II at age 20

and subthreshold BD occurring at age 22.

6 Approximately 20% to 30% of new cases

occur in children between 10 and 15 years old.

9,10 Late-life onset of BD is rare. After

age 60, there is a sharp reduction in the new onset of BD; therefore, a presentation of

mania at this age should alert the clinician to an underlying medical problem as the

possible cause.

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Patients may present initially with any affective episode, but it is important to note

that 75% of patients report having had multiple episodes of depression before the

development of a manic episode.

9 Not surprisingly, misdiagnosis (primarily as major

depressive disorder) is common, occurring in roughly 70% of patients.

9 By some

accounts, one in four patients visit as many as five physicians before an accurate

diagnosis is made. A significant contribution to misdiagnosis is the underreporting of

manic symptoms, which are not considered to be particularly problematic by

patients.

9

BD is a recurrent illness; single episodes of mania, unrelated to BD, occur in

fewer than 10%.

12 Most patients with BD suffer multiple episodes of mania,

hypomania, or depression separated by periods of euthymia (stable mood) throughout

the course of their lives. In the majority, mania occurs just before or immediately

after a depressive episode.

12 There may be a 5- to 10-year period from the onset of

illness until the first hospitalization or diagnosis of BD.

11