Medical Grand Rounds

Diagnosing and treating bipolar disorder in primary care

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Bipolar disorder is categorized according to severity.24,37,38 The most severe form, bipolar I disorder, is marked by major depression and manic episodes. It affects up to 1.5% of the US population, with equal proportions of men and women.39 Bipolar II disorder is less severe. It affects 0.8% to 1.6% of the US population, predominantly women.21,40 In bipolar II disorder, depression is more prominent, with episodes of hypomania.

Subthreshold bipolar disorders are characterized by episodic symptoms that do not meet the threshold for depression or hypomania; the symptoms are fewer or of shorter duration. These minor types of bipolar disorder affect up to 6% of the US population.17

Other conditions within the spectrum of bipolar and depressive disorders include medication- and substance-induced mania, agitated or anxious depression, and mixed states.31,34–36


Considerable research has focused on finding a clear-cut clinical or biological feature to differentiate unipolar from bipolar depression, but so far none has been discovered. Distinguishing the two conditions still depends on clinical judgment. There are important reasons to identify the distinction between unipolar depression and bipolar disorder.

Prognosis differs. Bipolar disorder tends to be a more severe condition. Young people, who may initially present with only mild symptoms of mania, may develop serious episodes over the years. People may lose their savings, their marriage, and their career during a manic episode. The more critical the occupation (eg, doctor, pilot), the greater the potential consequences of impaired judgment brought on by even mild hypomania.14–20

Treatment differs. Typical antidepressants given for depression can trigger a manic episode in patients with bipolar depression, with devastating consequences. Atypical neuroleptic drugs used to treat bipolar disorder can also have serious effects (eg, metabolic and neurologic effects, including irreversible tardive dyskinesia).3,13,40–43

Despite the good reasons to do so, many doctors (including some psychiatrists) do not ask their patients about a propensity to mania or hypomania.4–6 More stigma is attached to the diagnosis of bipolar disorder than to depression44–47; once it is in the medical record, the patient may have problems with employment and obtaining medical insurance.17,44 The old term “manic-depressive” is often associated in the public mind with a person on the streets displaying severely psychotic behavior; the condition is now understood to consist of a spectrum from mild to more severe illness.

Clinical indicators of bipolarity

There are many indicators that a person who presents with depression may be on the bipolar spectrum, but this is not always easily identified.48–53

History of hypomanic symptoms or subthreshold manic symptoms. Although directly asking the patient about the defining symptoms (eg, “Have you ever had episodes of being ‘hyper’ or too happy?”) may help elicit the diagnosis, many patients with bipolar disorder only report depression, as it is psychically painful. In contrast, hypomania and even mania can be perceived as positive, as patients may have less insight into the abnormality of the condition and feel that they are functioning extremely well.

Early age of onset of a mood disorder, such as severe depression in childhood or early adulthood, points toward bipolar disorder. Diagnosing mood disorders in childhood is difficult, as children are less able to recognize or verbalize many of their symptoms.

Postpartum mood disorder, particularly with psychotic symptoms, indicates a strong possibility of a diagnosis of bipolar disorder.

Drug-induced mania, hypomania, and periods of hyperactivity are key features of bipolar disorder. If asked, patients may report feeling a “buzz” when taking an antidepressant.

Erratic patterns in work and relationships are a red flag and are viewed as “soft signs” of bipolar depression. Akiskal54 described the “rule of three” that should make one consider bipolar disorder: for example, three failed marriages, three current jobs or frequent job changes, three distinct professions practiced at the same time, and simultaneously dating three people. Such features indicate both the hyperfunctioning and the disruptive aspects of mania.

Family history of bipolar disorder or severe psychiatric illness is a very important clue. A more subtle clue described by Akiskal54 may be that several members of the family are very high-functioning in several different fields: eg, one may be a highly accomplished doctor, another a famous lawyer, and another a prominent politician. Or several members of the family may have erratic patterns of work and relationships. However, these subtle clues have been derived from clinical experiences and have not been validated in large-scale studies.

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