Differentiating Bipolar I Disorder From Major Depressive Disorder Presents Challenges


Experts discuss the clinical and economic impact of misdiagnosing bipolar I disorder as major depressive disorder.

Differentiating bipolar I disorder (BD-I) from major depressive disorder (MDD) is a challenge in clinical practice and often results in misdiagnosis and inappropriate treatment, explained Larry Culpepper, MD, MPH, professor in the Department of Family Medicine at Boston University School of Medicine in Massachusetts, during a session at the Academy of Managed Care Pharmacy (AMCP) Nexus conference in National Harbor, Maryland.Further, Culpepper noted that misdiagnosis of BD-I can lead to higher health care costs and negative patient outcomes.

Due to the potential for misdiagnosis, it is important to recognize BD-I earlier and manage the disease appropriately using screening tools, particularly because individuals with the disease have higher rates of suicide attempts than those with MDD, Culpepper explained.

“We found that bipolar disease is highly associated with suicidal modality. If you are misdiagnosed, what that takes away is your ability to treat your suicidality,” Culpepper said.

Individuals with BD-1 are not always entirely depressed or manic but may show signs of both, along with anger and irritability. According to Culpepper, suicides occur for patients with BD-1 because, “I’m very depressed, and I’ve got the energy to do something about it.”

Additionally, Culpepper noted that this mixed stage of mania and depression is where individuals with BD-1 tend to take their own lives, while the manic stage is one in which they tend to destroy their lives, because that is when they are “highly impulsive and often not well connected to reality.”

Further, patients with BD-1 who are misdiagnosed are often treated inappropriately with antidepressant medications, Culpepper noted. This misdiagnosis drives higher rates of hospitalizations, outpatient visits, and trips to emergency departments.

Diagnostic challenges with BD-1 include substance abuse that may cause similar symptoms, symptoms that overlap with other psychiatric illnesses, and the fact that BD-1 is characterized by depressive, manic, and mixed episodes, which clouds the picture. The average patient with BD-1 has their first symptoms in childhood or early adulthood, and then does not receive a diagnosis for an average of 10 years.

Because the onset often occurs in a patient’s teens to 20s, individuals with BD-1 often have problems with employment.

“This is not the individual that gets promoted,” Culpepper said. “This is not an individual who moves ahead in their chosen field.”

Steps to establish an accurate diagnosis of BD-1 include early screening of patients with depressive symptoms, establishing the level of the patient’s depression, determining the historical course of the illness, gathering the patient’s medical history, and obtaining a family psychiatric history, Culpepper said. Specifically, making use of predictive models and screening tools has the potential to reduce misdiagnosis of BD-1.

Available screening tools for MDD available to practitioners are the Patient Health Questionnaire and the Zung Self-Rating Depression Scale. Tools to assess BD-1 are the Mood Disorder Questionnaire and the Rapid Mood Screener.


Culpepper L. Humanistic and economic burden of misdiagnosis of bipolar I disorder: predictive models, the role of screening, and the importance of getting an accurate diagnosis. Presented at: AMCP Nexus; Gaylord National Convention Center in National Harbor, Maryland: October 12, 2022.

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