Improving the Early Recognition and Diagnosis of Bipolar Disorder

Roger S. McIntyre, MD, FRCPC

University of Toronto and the University Health Network, Toronto, Ontario

Bipolar disorder (BD) is a widespread and lifelong illness, affecting 4% of people in the general population at some time in their lives.1 Unfortunately, despite the high prevalence of this disorder, misdiagnosis remains common. Many patients with BD are incorrectly diagnosed as having major depressive disorder, anxiety disorders, schizophrenia, or personality disorders (AV 1).2 Bipolar disorder generally affects every aspect of patients’ lives, including their health, personal and work relationships, and finances, and has been identified as the most costly psychiatric disorder in the United States.3 Accurate and timely diagnosis of BD is key to ensuring that patients receive guideline-informed, measurement-based, stratified treatment.

AV 1. Common Misdiagnoses for Patients With Bipolar Disorder (00:40)

Data from Hirschfield et al2

Clinical Presentation of Bipolar Disorder

Most individuals with BD initially “declare” their mood disorder with depressive symptoms and episodes. This frequent pattern of index presentation contributes to the misdiagnosis of major depressive disorder in many individuals with BD.4 Moreover, depressive symptoms and episodes dominate the longitudinal course of BD despite the fact that mania and hypomania are defining features of bipolar I disorder and bipolar II disorder, respectively.5 When patients seek health care services, they often present during a depressive phase, which poses a challenge to the clinician.

Probabilistic factors that indicate an increased likelihood that someone who appears to have major depression may have BD include an earlier age at onset, the presence of psychotic features, a family history of BD,4 and atypical symptoms of depression (such as hypersomnia, hyperphagia, psychomotor retardation).6 Additionally, patients with BD tend to have a greater number of prior episodes of depression, which last for a shorter duration, than patients with unipolar depression.6 It is also worth noting that the onset and/or recurrence of mood disorders during reproductive life events (eg, pregnancy/postpartum) as well as patterns of comorbidity (eg, substance use disorders) further increase probability that the individual experiencing depressive symptoms may, in fact, be bipolar. These clinical characteristics can suggest that the patient is having an index depressive episode of BD.

A diagnosis of BD cannot be made unless the patient has a current or past history of a manic or mixed episode (bipolar II disorder can only be diagnosed when a hypomanic and a major depressive episode have occurred).7 Manic features include an increase in energy, a decreased need for sleep, grandiosity, elevated mood, and an increase in overall activity and productivity.4 Patients who present with a manic depressive episode very frequently present with contemporaneous subsyndromal hypomania. The hypomanic or manic symptoms that are most often experienced during a bipolar depressive episode include distractibility, racing thoughts or flight of ideas, and an increase in speech or overall activity.8 That is, while depressed, these individuals have overactivity of thought, of feeling, and of behavior (AV 2). These individuals often manifest phenotypically with “anxious” depression or “agitated” depression.

AV 2. Recognizing Bipolar Disorder Symptoms to Make an Appropriate Diagnosis (3:52)


Because the patient may have an imperfect recollection of his or her history of manic or hypomanic symptoms and may only seek medical care when depressed, health care providers may inadvertently be led toward a unipolar diagnosis rather than a BD diagnosis. To avoid misdiagnosis, clinicians are encouraged to screen all patients with depressive symptoms for the presence and/or history of hypomanic features as well as be informed by the probabilistic factors. For example, a screening tool (eg, Mood Disorder Questionnaire) can assist the clinician in the screening for hypomanic features but does not replace a comprehensive clinical interview augmented by collateral information from family and other individuals involved in the patient’s life.9 The DSM is also an important tool in making an accurate diagnosis, and clinicians should familiarize themselves with recent changes.

Diagnostic Criteria for Bipolar Disorder

The DSM-57 contains numerous changes in BD criteria from the DSM-IV-TR.10 Most notably, BD now has its own separate chapter (“Bipolar and Related Disorders”). Additionally, the mania criteria have been augmented. The stem question pertaining to expansive, irritable, or elevated mood has the additional requirement that change in mood must be accompanied by increased activity or energy.

The DSM-5 has also added a mixed state specifier (ie, “with mixed features”) for major depressive, manic, or hypomanic episodes, which involves the presence of 3 or more opposite-polarity symptoms.7 The DSM-5 specifically identifies depressive and hypomanic features that would count towards a BD diagnosis with mixed features. A specifier to denote anxious distress was also added.

The DSM-5 also allows for the diagnosis of BD in the context of antidepressant exposure if the manic or hypomanic episode cannot be explained by the physiological effects of the drug.7 Finally, the diagnosis of bipolar disorder not otherwise specified was replaced with 2 options: (1) other specified bipolar and related disorder and (2) unspecified bipolar and related disorder.


Probabilistic Vs Deterministic Diagnoses

A challenge in reaching an appropriate and timely BD diagnosis is that the diagnosis lacks a deterministic test, necessitating that clinicians rely on the probabilistic approach. For example, if a patient has a brain tumor that a biopsy shows is malignant, that test is deterministic of the condition. By contrast, a patient who has early-onset depression coupled with a family history of BD has some probability of having a diagnosis of bipolar depression. Furthermore, the more indicators that a patient presents with, the greater the probability that the depression is BD.6,11

BD and Metabolic Comorbidity

Another clue to recognizing BD may be metabolic abnormality. Patients with BD have an increased incidence of metabolic comorbidities compared with the general population.12 The presence of a metabolic abnormality may actually change the presentation of BD toward a more depression-prone illness. For example, patients with BD who are obese have been found to exhibit more depression-related treatment seeking, longer depressive episodes, and a history of hospitalization for depression than those who are not obese.13 Women with BD, in comparison with men, are more likely to have depression-prone phenotypes (eg, bipolar II disorder, mixed features, rapid cycling in BD) as well as metabolic comorbidity.14

The high rate of metabolic comorbidity in the mood disorder population provides the basis for recommending screening for metabolic abnormalities in all individuals with mood disorders, notably BD. The most common cause of natural death in BD patients is cardiovascular disease.15 Therefore, clinicians should regularly monitor patients for increased weight, abdominal obesity, signs of type 2 diabetes, hypertension, and dyslipidemia.16


Clinicians should take appropriate measures to avoid misdiagnosis of BD in patients presenting with clinically significant affective symptoms. Knowing that BD often initially presents as unipolar depression and asking questions about sleep changes, overactivity, and atypical symptoms of depression may help support a correct diagnosis of BD. Referencing the DSM-5 for updated criteria related to BD and considering age at onset, course, and family history is necessary. Outcomes are best for patients when a timely and accurate BD diagnosis is made and appropriate treatment is provided.

Clinical Points

  • Consider that bipolar depression can initially present as unipolar depression
  • Know that features including an earlier age at onset, the presence of psychotic features, a family history of BD, and previous antidepressant-induced switch to mania are all clues to a BD diagnosis
  • Reference DSM-5 to aid in accurately diagnosing BD
  • Understand that the probabilistic approach lacks the certainty of the deterministic approach, but probability of a BD diagnosis increases with the presence of more indicators
  • Consider a patient’s metabolic syndrome status when diagnosing BD


BD = bipolar disorder

DSM-5 = Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition

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