CONFERENCE REPORTER
Differentiating between bipolar depression and unipolar depression is essential, explained Gerald Maguire, MD, at the Southern California Psychiatry Conference in Huntington Beach, California.1
Maguire noted the differential diagnosis can be tricky,2 but an investigatory approach can often be helpful. “I wish in psychiatry we had blood tests or biomarkers, but it wouldn’t be as much fun,” Maguire said in an interview with Psychiatric Times.
“The best way we differentiate [between the diagnoses] is by history,’ he explained. “And sometimes not just from the patient, but from the family members or others around them.” Maguire advocates for a deep look longitudinally back to determine if the patient had a history of mania. If so, then he would consider bipolar I depression. However, if there is any history of hypomanic episodes, then the depressive episode may be bipolar II disorder.
Maguire looks for certain clues that might also enlighten the differential diagnosis. “If a patient has had a, let’s say, ‘a misadventure’ on an antidepressant, if they’ve been prescribed an antidepressant and they got worse—they got more agitated, they got more revved up—that may be a clue that what you’re dealing with is a bipolar depression,” he explained.
Family histories can also support the differential diagnosis, he said. For instance, if there is a family history of suicides, that may be a clue, he explained. Similarly, because patients with bipolar disorder often self-medicate, looking for a family history of substance abuse can be helpful. “iI’s important to look into these other coexisting factors that may give us clues that this is a bipolar depression as opposed to a major depressive episode of major depressive disorder, he told Psychiatric Times.
“One thing I’ve always tried to teach my residents: if your known treatments aren’t working, is the diagnosis correct?” Maguire said. “[If you’re] going three or four antidepressants and patients aren’t responding or they’re getting worse, is it really major depressive disorder?”
Once the correct diagnosis has been made, treatment options can be considered. “Most of our agents that we talk about as mood stabilizers may be effective in preventing a manic episode or treating mania or mixed states,” Maguire said. “Our options are more limited when it comes to bipolar depression, and we do have some agents that are FDA approved specifically for bipolar depression.”
References
1. Maguire G. Bipolar II Depression: Clinical Differentiation from MDD and an FDA-Approved Treatment.Presented at: Southern California Psychiatry Conference; July 11-12, 2025; Huntington Beach, California.
2. Duerr HA. To BD or Not to Diagnose BD: That’s the Question. Psychiatric Times. October 22, 2023. Accessed July 12, 2025. https://www.psychiatrictimes.com/view/to-bd-or-not-to-diagnose-bd-that-s-the-question