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How Not to Miss the Diagnosis of Bipolar Disorder in Practice

Walter Dunn, MD, PhD

Assistant Clinical Professor
Semel Institute for Neuroscience and Human Behavior
University of California, Los Angeles
Los Angeles, California

Walter Dunn, MD, PhD, has no relevant conflicts of interest to report.

View ClinicalThoughts from this Author

Released: August 23, 2021

Unipolar Depression or Bipolar Illness: The Art of Differential Diagnosis
The prevalence of bipolar disorder is estimated to be between 2% and 4%, whereas the lifetime prevalence of major depressive disorder ranges from 15% to 18%.1,2 Although depressive episodes occur in both disorders, the cardinal feature of bipolar disorder is a history of mania or hypomania. However, depressive episodes are most often the presenting complaint in both illnesses, and therefore, the challenge is distinguishing bipolar illness from unipolar depression.

The Importance of Accurate Diagnosis
Before discussing screening and diagnosis, it is worth highlighting the importance of accurate diagnosis as it relates to early intervention and treatment. Bipolar disorder is commonly misdiagnosed or missed, with unipolar depression as the most likely misdiagnosis. The delay between first onset of illness and an accurate diagnosis ranges between 6 and 13 years.3 This delay has implications, as treatment of the two disorders are distinct. Mood stabilizers or antipsychotics are the mainstay of bipolar treatment, whereas major depressive disorder is managed with antidepressants. In addition, antidepressant efficacy in bipolar disorder is limited, and there are safety issues such as the potential to cause rapid cycling or treatment-emergent affective switching (ie, triggering mania or hypomania).4 Delays in proper treatment also have long-term implications. Worse outcomes such as increased hospitalizations and suicide risk is associated with longer durations of untreated illness.5,6

Basic Features of Bipolar Disorder
The essential feature of bipolar disorder is a history of mania or hypomania. Since these episodes occur less frequently than depressive episodes, healthcare professionals are often screening for a history of manic or hypomanic events rather than observing symptoms firsthand. Three to 4 symptoms are required for diagnosis of mania or hypomania with a duration of at least 1 week in mania and 4 days in hypomania. The primary difference between mania and hypomania is that manias cause functional impairment or result in hospitalization. Although hypomanias are associated with a change in functioning compared with baseline, they are not severe enough to cause marked functional impairment. Screening for a history of manic or hypomanic symptoms should be the first step in patients who have a history of or present with depression. The Rapid Mood Screener, developed by McIntyre and colleagues, yields a sensitivity of 0.88 for bipolar I disorder with 6 questions about a history of increased rate of speech or thoughts, elevated mood or energy, and decreased need for sleep.7

Challenges of Diagnosis
There are several common scenarios that present challenges to identifying mania or hypomania. Early in the course of illness, depression is often the first presenting symptom, and there may not be a history of mania or hypomania to elicit. Second, patient insight may be impaired in recognizing such defining features, especially with less-pronounced and milder hypomanic features in bipolar II.

Several strategies exist to help recognize a bipolar diathesis. First, family history can be helpful as patients with bipolar disorder are more likely to have a family history of bipolar illness. Second, the age of illness onset trends earlier than in unipolar depression. The average age of mood episode in bipolar disorder is 22 years, whereas 26 years of age is the mean onset in major depressive disorder. The number and severity of affective episodes tends to be greater and more severe than in unipolar counterparts. An early history of suicide attempts or hospitalizations may, therefore, point toward a bipolar diagnosis.8

As depressive episodes are often first encountered and initially managed in the primary care setting, patients often arrive in psychiatrists’ offices with a history of psychotropic medication trials. It is worth obtaining a detailed history of those trials as certain features can point toward a bipolar spectrum illness. Bipolar depressions tend to respond poorly to antidepressants, and therefore, patients misdiagnosed with unipolar depression may have multiple failed antidepressant trials. Adverse reactions to antidepressants such as worsening depression and irritability or rapid mood elevation resulting in impulsive or problematic behaviors are also suggestive of bipolarity.4

A careful history of depressive symptoms may also indicate a bipolar diathesis as there is evidence of atypical features in bipolar depression. Unipolar depression is classically associated with insomnia, weight loss, and reduced appetite. Conversely, some studies suggest bipolar depression can manifest more commonly with “inverse” neuro-vegetative symptoms. These include hypersomnia, increased appetite, and weight gain.8

The Art of Diagnosis
The diagnosis of bipolar II remains a challenge for patients later in the course of illness. By definition, hypomanic symptoms are less severe and do not cause functional impairment, although there is a distinct change in level of functioning compared with baseline. Because hypomanic symptoms can be subtle or patients may have limited insight, collateral reports from close friends or family can be invaluable. Friends and family have a good sense when patients are acting “unlike themselves,” engaging in “uncharacteristic behavior,” or talking faster than usual.

How we screen for manic or hypomanic symptoms is also essential to eliciting an accurate diagnosis. Although we may ultimately define behaviors as “impulsive” or “risky,” patients may initially have difficulty appreciating or accepting those terms to describe their actions. One alternative approach includes screening for the consequences of such behaviors in terms of functional impairments. Initially screening for the negative sequelae of such behaviors and then backtracking to characterize the nature of those behaviors may elicit a more accurate history. For example, a pattern of relatively unstable personal relationships or job histories punctuated by episodic breakups or poor work performance or unprofessional behavior warrants further investigation about the circumstances around the breakups or job loss. 

Asking about financial instability or difficulties can also yield revealing information about potential manic or hypomanic episodes especially as it pertains to spending. As stated before, employment instability due to work performance problems can affect the ability to earn steady income. But increased and impulsive spending can also lead to financial stress. Although many patients have chronic difficulties managing their finances, this line of inquiry attempts to identify episodic poor or impulsive decision-making about spending clustered with other manic/hypomanic symptoms.

Recognizing one’s behavior as impulsive or risky requires a level of insight some patients may not possess; however, regret is a more commonly accepted emotion that most patients can relate to. Thus, another approach to identifying manic symptoms is inquiring if patients have a history of engaging in discrete periods of regrettable behavior. During manias, patients often exhibit lowered inhibitions and poorer insight into their immediate actions. In retrospect, once they are out of their mood episodes, they can endorse regrets and reservations about their actions. Although not pathognomonic for mania or hypomania, a positive endorsement to this screening question warrants more thorough inquiry about the nature of these behaviors and co-occurring symptoms.

Concluding Thoughts
Accurately diagnosing bipolar disorder requires a keen understanding of the illness and appreciating the art of eliciting a thorough history of symptoms. Although we strive to correctly diagnose and deliver the appropriate treatments, the best strategy for not missing a bipolar diagnosis is to retain humility regardless of how many patients we have treated and how certain we are of a diagnosis. Healthcare professionals who include bipolar disorder in the differential diagnosis for any mood disorder and are willing to revise diagnoses based on evolving patient presentations will be well positioned not to miss a diagnosis of bipolar disorder.


  1. Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. Jun;289:3095-30105.
  2. Merikangas KR, Akiskal HS, Angst J, et al. Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry. 2007;64:543-552.
  3. Dagani J, Signorini G, Nielssen O, et al. Meta-analysis of the interval between the onset and management of bipolar disorder. Can J Psychiatry. 2017;62:247-258.
  4. Cheniaux E, Nardi AE. Evaluating the efficacy and safety of antidepressants in patients with bipolar disorder. Expert Opin Drug Saf. 2019;18:893-913.
  5. Post RM, Leverich GS, Kupka RW, et al. Early-onset bipolar disorder and treatment delay are risk factors for poor outcome in adulthood. J Clin Psychiatry. 2010;71:864-872.
  6. Joyce K, Thompson A, Marwaha S. Is treatment for bipolar disorder more effective earlier in illness course? A comprehensive literature review. Int J Bipolar Disord. 2016;4:19.
  7. McIntyre RS, Patel MD, Masand PS, et al. The Rapid Mood Screener (RMS): a novel and pragmatic screener for bipolar I disorder. Curr Med Res Opin. 2021;37:135-144.
  8. Motovsky B, Pecenak J. Psychopathological characteristics of bipolar and unipolar depression - potential indicators of bipolarity. Psychiatr Danub. 2013;25:34-39.

Your Thoughts?
Tell us about your thought process when you see a patient with suspected bipolar disorder. What techniques have you used to differentiate between unipolar depression and bipolar illness? Which bipolar disorder clinical cases have been most challenging to recognize and diagnose? Please share your experiences and thoughts in the comments box.

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