Bipolar I vs Bipolar II: What are the Major Differences in Presentation and Treatment?


An expert discusses key differences and some ways to avoid missing the appropriate diagnosis in these patient populations.




“Unfortunately, in the great majority of people, both bipolar I disorder and bipolar II disorder—especially bipolar II disorder—are not detected in a timely fashion.”

Roger S. McIntyre, MD, FRCPC, discussed the major differences between bipolar I and bipolar II disorder in a presentation at the 2022 Neuroscience Education Institute (NEI) Congress on November 3. The aim of the presentation was to identify the differences in the clinical presentation and diagnostic criteria associated with each disorder, and to determine the most effective pharmacologic treatments for each one.

According to McIntyre—head of the Mood Disorders Psychopharmacology Unit and a professor of psychiatry and pharmacology at the University Health Network in Toronto, Canada, who holds additional professorships at Guangzhou Medical University, Korea University College of Medicine, SUNY Upstate Medical University, and the University of California School of Medicine—misdiagnosis and underdiagnosis are very common in patients with bipolar I and II disorders, as these patients are often diagnosed with other disorders such as depression and schizophrenia.

“When they come to our office, patients often present with low-grade depression and anxiety, they can’t sleep, they can’t focus, and often they come to us as well with a sense of no purpose and functional impairment,” McIntyre said, adding that depression in particular may be an adverse event or comorbidity that can lead to misdiagnoses. “The more the patient presents with depression, the more likely we are to miss the diagnosis because major depressive disorder (MDD) is all depression, bipolar II disorder is very much depression, and bipolar I is also predominant depression, but less than bipolar II,” he said.

Bipolar disorder also has the highest rates of comorbidity, according to McIntyre, with bipolar I being closer genetically to schizophrenia and bipolar II being closer genetically to MDD. Childhood trauma can also influence onset and presentation of both types of bipolar disorder. Generally, the greater the degree of trauma, the earlier the age of onset and the greater the earlier severity of presentation. Trauma can also contribute to additional comorbidities such as substance use, higher rates of suicide, and cognitive impairment. In terms of cognitive impairment, he stated that the more episodes of illness a patient experiences, the higher the quantitative reduction in brain volume the patient experiences.

To avoid common misdiagnoses, McIntyre suggested that clinicians be aware of what he calls the 4 As: anxiety, agitation, anger/irritability, and attention-deficit/hyperactivity disorder (ADHD). “When a patient comes to my office, and they’re depressed, and the patient says to me, ‘Dr McIntyre, I am depressed. My life sucks, and I’ve got anxiety. I’ve got agitation. I’m angry as hell, and I’ve got ADHD. I need Adderall’… this indicates to me that this person could have hypomania and mixed features as they’re described to the DSM to represent hypomanic symptoms when someone’s depressed,” McIntyre said.

McIntyre also provided an updated list of medications approved by the US Food & Drug Administration (FDA) that are reportedly efficacious across the phases of bipolar disorder. FDA-approved medications for acute bipolar depression include cariprazine, lumateperone, lurasidone, and quetiapine. FDA-approved medications for acute mania include lithium, carbamazepine, aripiprazole, and olanzapine samidorphan. And, for maintenance, FDA-approved medications include asenapine, lamotrigine, quetiapine (adjunctive), and risperidone (long-acting injectable).

McIntyre is also chair and executive director of the Brain and Cognition Discovery Foundation and director and chair of the Depression and Bipolar Support Alliance Scientific Advisory Board.

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