Misdiagnosis of Bipolar Depression in Primary Care Practices

Larry Culpepper, MD, MPH

Department of Family Medicine, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts

In primary care practices, it is surprisingly common for patients who present with depressive symptoms to be misdiagnosed with unipolar depression when they actually have bipolar disorder or bipolar depression (AV 1).1–5 For example, one-third of survey respondents reported waiting 10 years or more and seeing an average of 4 physicians before receiving the correct diagnosis6; the most frequent misdiagnosis was major depression. Other misdiagnoses included anxiety disorders, schizophrenia spectrum disorders, and personality disorders.

AV 1. Key Differences Between Unipolar Depression Vs Bipolar Depression (01:09)

Based on Bowden et al,1 Mitchell et al,2 Perlis et al,3 Goodwin et al,4 and Sadock et al5

An early, accurate diagnosis of bipolar disorder is beneficial to patients, their families, and society as a whole. A lack of treatment or the provision of treatment for the wrong diagnosis can lead to an increased risk of suicide, long-lasting functional impairment, work loss, family and legal issues, more hospitalizations, and greater healthcare costs than appropriate bipolar treatment.7–10

Two Forms of Bipolar Disease

Patients with bipolar I or bipolar II disorder cycle between episodes of depression, mania/hypomania, and euthymia, spending about half the time symptomatic.11,12 Typically, patients with bipolar I disorder have full-blown manic episodes, causing them to be dysfunctional and possibly destructive, whereas patients with bipolar II disorder have hypomanic episodes, which are less severe. Hypomanic episodes can present as heightened self-esteem and increased creativity, but patients usually continue to function productively, albeit at an accelerated pace.

Although mania/hypomania is the cardinal symptom of bipolar disorder, depressive symptomatology dominates the course of illness in both forms of the condition. For example, depressive episodes occur 32% of the time in bipolar I disorder (vs 9% manic) and 50% of the time in bipolar II disorder (vs 1% hypomanic).11,12

Furthermore, patients can have mixed episodes in which they experience a combination of manic and depressive symptomatology. Mixed states occur in less than 10% of patients with bipolar I and II disorders,11,12 and include symptoms such as increased energy, a decreased need for sleep, and an overly active and racing mind while at the same time having strong feelings of depression. Clinicians should consider patients in mixed states to be at high risk for self-destructive and suicidal behaviors.

AV 2. Conversion From Unipolar Depression to Bipolar Disorder (1:28)

Data from Goldberg et al13

Reasons for Misdiagnosis

Why is it that bipolar disorder continues to be misdiagnosed? A major reason is that, when patients with bipolar disorder present in clinical settings, they are often depressed, which may mask the true bipolar condition (see AV 1). Depression may last for several months and can appear to be chronic, leading many primary care physicians to overlook a bipolar diagnosis and incorrectly diagnose depression instead. The physician might not have the opportunity to see that same patient in a brief manic or hypomanic phase because patients who feel well often do not seek medical attention. If patients with mania do receive medical attention, it is typically either because a family member brings them in or because they are involved in accidents or other risky behaviors that require an emergency room visit. Again, the primary care physician is unlikely to see them during these times.

Another reason for misdiagnosis is that a patient’s illness may, in fact, start as unipolar depression and only later become bipolar disorder. That is, patients reporting a depressive episode may not have had a hypomanic or manic episode yet. One study13 found that, among patients hospitalized for depression who were followed for 15 years, a little less than half developed mania or hypomania over the interval (AV 2).


A third reason for misdiagnosis relates to disjointed care. Some patients with bipolar disorder lack the resources necessary to obtain medical insurance. Therefore, they are unable to seek continuous medical attention and be observed over time by the same physician, so recognizing the pattern of recurrent mood episodes that characterize bipolar disease can be difficult.

Correcting the Misdiagnosis

Several principles can be applied to improve the early recognition, diagnosis, and treatment of bipolar disease (AV 3). The major red flag that primary care physicians should look for in patients with depressive episodes is a history of hypomania or mania. However, because patients may underreport manic symptomatology,6 clinicians should look for clues in the patient’s functional level. Poor functioning, as suggested by interpersonal issues, frequent job changes, legal troubles, and social alienation, indicates the need to screen for manic and hypomanic episodes.7,10 Some of these problems may be due to frequent anger attacks, which could indicate a bipolar mixed state.14,15 Adverse consequences of manic episodes include sexually transmitted diseases or multiple unplanned pregnancies and impairments secondary to injuries from automobile accidents or other ill-advised undertakings, such as engaging in risky sporting endeavors. For example, one patient with bipolar disorder attempted rock climbing without safety equipment and experienced a serious fracture as a result.

AV 3. Accurately Diagnosing Bipolar Depression (3:11)

Another red flag is having a family history of bipolar disorder.13 Parental history of bipolar disorder increases the risk of their children having bipolar disorder by about 20%.16 If both parents are affected, one with bipolar disorder and the other with either unipolar or bipolar disorder, then the risk of a mood disorder in offspring increases to about 70%.16 When exploring a patient’s family history, primary care physicians may be able to ascertain whether a parent has behavior suggestive of bipolar disease that was not diagnosed. However, sometimes these parents are separated permanently from the family, incarcerated, or dead due to trauma or suicide. Recognizing that a relative potentially has or had bipolar disease can be a critical step in the diagnostic and treatment process.

Other red flags that indicate a need to screen for bipolarity in patients with unipolar depressive symptoms are psychosis at the index depressive episode, young age at onset of depression, and either antidepressant resistance or antidepressant-induced mania or hypomania.7,13 For example, if antidepressant treatment does not seem to be effective or, conversely, if it seems to be too effective too quickly, the patient may have undiagnosed bipolar disorder.


Patients initially diagnosed with unipolar depression may actually have bipolar disorder or develop it over time. Timely recognition and diagnosis of bipolar disease is crucial to initiate correct treatment and minimize functional impairment and treatment costs. Clinicians must watch for red flags that signal a need to screen for bipolar disorder in patients with depressive episodes. These red flags include life disruptions that arise from anger and risky behaviors, a family history of bipolar disorder (even if undiagnosed), psychosis at the index depressive episode, young age at onset of depression, and either antidepressant resistance or antidepressant-induced mania or hypomania.

Clinical Points

  • Screen patients with depressive symptoms for bipolar disorder
  • Consider whether a patient’s poor functioning could be due to manic or hypomanic symptoms
  • Ask about a family history of bipolar disorder, age at onset of depression, and history of psychosis
  • Consider bipolar disorder if antidepressant treatment either has little effect or has a strong effect too quickly


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