Medical Grand Rounds

Diagnosing and treating bipolar disorder in primary care

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Major depression often presents in patients with a history of both depression and mania, although patients may not have the insight to report manic symptoms as problematic. Distinguishing pure (unipolar) depression from bipolar depression is important for prognostic and treatment reasons. Once identified, bipolar depression can be adequately and safely treated.


  • Bipolar depression in its manifest and subthreshold forms is nearly as prevalent as unipolar depression and often occurs in successful professionals.
  • A manic or hypomanic episode can make a patient highly productive, but it can also be severely disruptive, leading to loss of job, marriage, and financial savings.
  • Identifying bipolar depression depends on asking about bipolar symptoms, using screening instruments, and being aware of clues from the patient’s history.
  • A major depressive episode in patients with a history of mania or hypomania should be treated with a combination of an antidepressant and a mood stabilizer or a mood stabilizer alone.



Patients presenting with depression commonly have undiagnosed bipolar depression,1–7 that is, depression with shifts to periods of mania. During manic or hypomanic episodes, people feel energetic, need little sleep, and are often happy and charming.8 But too much of a good thing can also wreak havoc on their life.

Bipolar depression (ie, depression in patients with a diagnosis of bipolar disorder) is treated differently from unipolar depression,3,9–13 making it especially important that clinicians recognize if a patient who presents with depression has a history of (hypo)manic symptoms.


A 32-year-old nurse presents to her primary care provider with depressed mood. She reports having had a single depressive episode when she was a college freshman. Her family history includes depression, bipolar disorder, and schizophrenia, and her paternal grandfather and a maternal aunt committed suicide. Upon questioning, she reveals that in the past, she has had 3 episodes lasting several weeks and characterized by insubordinate behavior at work, irritability, high energy, and decreased need for sleep. She regrets impulsive sexual and financial decisions that she made during these episodes and recently filed for personal bankruptcy. For the past month, her mood has been persistently low, with reduced sleep, appetite, energy, and concentration, and with passive thoughts of suicide.


This case illustrates many typical features of bipolar depression that are revealed only by taking a thorough history. Although the patient is high-functioning, having attained a professional career, she has serious problems with sexual and financial impulsivity and at her job. She has a strong family history of mood disorder. And she describes episodes of depression and mania in the past.

Starts in young adulthood, strong heritability

Bipolar disorder can be a devastating condition with lifelong consequences,14–20 especially as it typically starts when patients are getting an education or embarking on a career. It usually first manifests in the late teenage years and progresses in the patient’s early 20s.21,22 The first hospitalization can occur soon thereafter.23,24

Bipolar disorder is one of the most heritable conditions in psychiatry, and about 13% of children who have an afflicted parent develop it.25 In identical twins, the concordance is about 50% to 75%, indicating the importance of genetics and environmental factors.26,27

Associated with migraine, other conditions

Conditions associated with bipolar disorders

The disorder is associated with a variety of conditions (Table 1).28,29 Some conditions (eg, thyroid disease) can cause mood cycling, and some (eg, sexually transmitted infections, accidents) are the consequences of the lifestyle that may accompany mania. For unknown reasons, migraine is highly associated with bipolar disorder.


Symptoms of depression and mania are frequently viewed as opposite mood states, though many times patients report a mixture of them.17,30–35 For both states, the features of a distinct change from the patient’s normal condition and the sustained nature of the symptoms are important diagnostically and indicate a likely underlying biological cause.

Major depressive disorder: Slowing down

The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5),8 defines major depressive disorder as having either depressed mood or markedly diminished pleasure in most activities for most days during at least 2 weeks.

In addition, at least 4 of the following must be present during the same period:

  • Appetite disturbance
  • Sleep disturbance
  • Motor retardation or agitation
  • Lack of energy
  • Feelings of worthlessness or excessive guilt
  • Decreased concentration
  • Recurrent thoughts of death or suicide.

An estimated 20% of the population experience a major depressive episode over their lifetime. A surprisingly high proportion of people with depression—30% to 40%—also have had subthreshold symptoms of mania (symptoms not meeting the criteria for hypomania or mania in terms of number of symptoms or duration).21,22 Because of these odds, it is important to suspect bipolar disorder even in patients who present with depression but who may not yet have manifested episodes of mania or hypomania.

Mood disorders can be regarded as falling into a spectrum, ranging from unipolar or “pure” major depression without any features of hypomania to major depression and severe mania.17,31–36

Mania: Speeding up

The DSM-5 defines mania as the presence of persistently elevated, expansive, or irritable mood with increased activity for more than 1 week. In addition, at least 3 of the following features must be present, with impaired functioning (4 features are required if mood is only irritable)8:

  • Inflated self-esteem or grandiosity
  • Decreased need for sleep
  • Pressured speech
  • Racing thoughts
  • Distractibility
  • Excessive involvement in pleasurable, high-risk activities.

Hypomania: No functional impairment

Hypomania is a less severe condition, in which the abnormally elevated mood is of shorter duration (4–7 days) and meets the other criteria for mania but without significant functional impairment. People may, in fact, be very functional and productive during hypomanic episodes.8


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