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eCase: Differentiating Bipolar Disorder From Major Depressive Disorder: Clinical Conundrums and Treatment Recommendations
  • CME
  • CE

Holly Swartz, MD
Program Director
Released: October 17, 2022


Bipolar disorder (BD) is a mood disorder characterized by recurrent episodes of depression, hypomania, and mania1 that affects 2% to 4% of the population worldwide.2 Typical onset of BD is in adolescence and early adulthood and is a leading cause of disability in youth.3 Individuals with BD have marked impairments functioning,4-7 increased risk for suicide,8,9 and high rates of medical comorbidities.10,11 Globally, BD is associated with decreased work productivity, poor health-related quality of life, and significant direct and indirect costs.12-14

Mania, the sine qua non of BD type I, is defined as periods of at least 1 week marked by a cluster of pathological symptoms including elevated or irritable mood, increased energy, decreased need for sleep, engagement in activities with high potential for negative consequences, racing thoughts, and, in some instances, psychosis. Hypomania, hallmarks of BD types I and II, is a milder form of mania, notable for the absence of impairment during the episode.1 Mania and hypomania can be quite dramatic, with mania (but never hypomania) commonly resulting in hospitalization. By definition, these episodes represent a change from an individual’s baseline and, as such, are identified as problematic by both loved ones and the medical profession. It would seem, therefore, that BD should be easy to recognize and diagnose.

Unfortunately, that is not the case. BD is misdiagnosed 40% to 70% of the time.15-18 One survey found that 69% of individuals with BD were initially misdiagnosed, with more than one third of individuals experiencing more than a 10-year delay until correct diagnosis.19 Mental health professionals often fail to use best practices when diagnosing patients with mood disorders, leading to delays in appropriate diagnosis of BD.20 Delays in correct diagnosis delay appropriate treatments. For instance, patients with BD who are incorrectly diagnosed with unipolar depression may be treated with antidepressant medications rather than mood stabilizing medication that, in turn, may result in iatrogenically induced mood worsening and declines in function.15,21,22 Thus, misdiagnosis of BD is both common and very consequential.

Why, then, is the diagnosis of BD so frequently missed? Although mania and hypomania are (relatively) easy to identify, the most common feature of BD is depression. Longitudinal studies show that individuals with bipolar disorder spend at least one half of their lives with mood symptoms, with the depressive phase of the disorder predominating.23 Indeed, the depressive phase of BD dominates over mania or hypomania in a ratio of approximately 3:1,24,25 perhaps even more so in BD type II.25 Thus, most individuals with BD present for care during a major depressive episode (MDE) rather than during mania or hypomania. DSM-5-TR criteria for MDE include low mood, low interest, low libido, poor concentration, poor sleep (either insomnia or hypersomnia), and suicidal ideation.1

Unfortunately, diagnostic criteria for MDE occurring in the context of BD or major depressive disorder (MDD) are identical; cross-sectional assessment of depression cannot accurately distinguish between BD and MDD. Therefore, when a patient presents with depression, the correct diagnosis can only be made if the healthcare professional takes a good history to identify presence or absence of previous episodes of mania or hypomania over the lifetime

Table 1. Episode Types by Diagnostic Category for Mood Disorders Diagnoses1


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