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How to Differentiate Bipolar Disorder from Unipolar Depression

July 08, 2013

Bipolar disorder is fraught with diagnostic difficulties. More than 1 in 3 times, patients with bipolar disorder leave the psychiatrist’s office with an incorrect diagnosis (1), and the resulting delay in proper treatment can sometimes lead to disastrous consequences, including a heightened risk of suicide.

The longer bipolar disorder stays untreated, the more difficult it becomes to treat, and the greater patients’ risk for suicide. Patients with bipolar disorder make their first suicide attempt around four years from the onset of their illness. This is in sharp contrast to a delay, up to 10 years in more than 35% of patients, that occurs between symptom onset and being correctly diagnosed with bipolar disorder. (2, 3)

“That shouldn’t be understood as acceptable,” said Vladimir Maletic, MD, MS, Clinical Professor of Neuropsychiatry and Behavioral Science, University of South Carolina School of Medicine, Columbia.  

Patients with bipolar disorder are misdiagnosed with various other disorders, including schizophrenia, anxiety disorders, borderline or antisocial personality disorder, or substance abuse disorder, but most are misdiagnosed with major depressive disorder (unipolar depression). (3)  

If such patients are treated with antidepressants, the treatment for unipolar depression, this may not only prove to be ineffective treatment but may actually worsen their condition by inducing rapid cycling or triggering a switch to a manic/mixed, manic, or  hypomanic episode. In a naturalistic study of bipolar disorder patients misdiagnosed with unipolar depression, 55% of those who received an antidepressant developed a manic or hypomanic episode. (4)  

Despite stark statistics outlining the consequences of misdiagnosis, differentiating unipolar depression from bipolar disorder can be challenging. Bipolar disorder is characterized by cyclic depressive as well as manic or hypomanic episodes, but the depressive phase of the bipolar disorder appears identical to unipolar depression.  

Adding to the diagnostic challenge, patients with bipolar disorder tend to spend a far larger proportion of their time in a depressive phase than in the manic phase or may not yet have experienced a manic or hypomanic episode.(5)  

“Physicians should understand that just because someone has a major depressive episode, that doesn’t necessarily mean they have to have a major depressive disorder. You should define a major depressive episode as a symptom of an underlying illness and not as a diagnosis itself,” said Vivek Singh, MD, Associate Professor of Psychiatry at the Texas Health Science Center at San Antonio.  

Quality Questions

The path toward a correct diagnosis begins with taking a complete patient history and understanding that patients’ responses may be skewed by confusing or judgmental questions. “Your questions determine the answers,” said Dr. Singh.  

For example, rather than assessing risky/impulsive behavior by asking whether patients have been arrested or otherwise encountered legal trouble, clinicians should consider that patients may have engaged in risky/impulsive behaviors that had the potential to cause legal consequences.  

Even the word “risky/impulsive” has a negative connotation that could inappropriately color a patient’s answer, so Dr. Singh said he might instead ask if a patient has made decisions without thinking of the consequences. “People shut down when you make a judgment of a behavior,” he said.  

Patients shy away from passing judgment on family members, too. Dr. Maletic has found that patients hesitate to consider that a relative may have had bipolar disorder and may instead attribute the family member’s behavior to a “nervous breakdown” or issues with the person’s temperament. In cases like this, Dr. Maletic carefully considers whether the patient’s family history includes an underlying pattern of erratic behavior consistent with bipolar disorder.  

Understanding and Observation

Sometimes patients may deny symptoms of bipolar disorder not because of stigma but because they lack understanding. Stephen Sobel, MD, Clinical Instructor at University of California, San Diego School of Medicine and author of Successful Psychopharmacology: Evidence-Based Treatment Solutions for Achieving Remission , prevents miscommunication by paying close attention to patients’ understanding of mania and hypomania. After an initial evaluation, he sends them home with an assignment to research mania and hypomania online and come back prepared to give him a 10-minute lecture.  

“When they come back in I don’t ask for the lecture. I ask them if they’ve had episodes or not. Most of the time when I send them home with this assignment it’s because I suspect they’ve had these episodes, and they come back and say ‘absolutely,’” said Dr. Sobel.  

To help patients structure their thinking, Dr. Sobel administers the Mood Disorder Questionnaire (MDQ) , a 17-question screening tool—not a diagnostic tool—for bipolar disorder that Drs. Singh and Maletic also administer.

Dr. Maletic uses the questionnaire as a springboard to further inquiry, though he notes that bipolar patients in the midst of a depressive episode may have inaccurate and limited memory of their hypomanic episodes, and vice versa. If a patient’s answers do not indicate a positive screen, Dr. Maletic may ask the patient to explore and elaborate on positive answers.  

But even with tools like the MDQ, common misunderstandings about the exact nature of mania may lead clinicians to incorrectly diagnose patients. “Most psychiatrists think mania is associated with someone who is elated and grandiose, but truly mania manifests more as irritability, mood swings, anxiety, and distractibility,” said Dr. Singh.  

Sometimes a patient’s response to questions will have qualities suggestive of bipolar disorder. “This is not a hard science,” said Dr. Maletic, “but I’ve found that patients with bipolar disorder are more likely to be tangential in their responses and skip from one subject to the next.” Conversely, Dr. Maletic has anecdotally noticed that patients who are slow to respond and stay on one topic are more likely to have unipolar depression.  

Spending Time

Observation, thoughtful questions, and a complete patient history require an investment of time.  Dr. Singh describes the diagnostic process as an ongoing one that is not limited to the first visit. As patients gain a better understanding of their history or talk with family members, they may eventually note that a relative had symptoms of bipolar disorder.

Dr. Sobel finds that bipolar disorder often requires a two-session evaluation. During the first session, he takes a patient history and then sends the patient home to do research. Provided the patient’s symptoms meet the criteria for bipolar disorder and the patient is not suicidal, he might make a diagnosis on the second visit, even if patients are frustrated by the additional time.  

To mitigate frustration, he explains that an inaccurate diagnosis can lead to incorrect treatment that worsens the illness. “I say that we can do something immediately or we can do something well,” he said. “We’re talking about informing a patient that they have to be on medication the rest of their life. They have to truly buy into the diagnosis. That’s why it’s so important they have time to research it and process the diagnosis before starting medication treatment.”

Dr. Maletic runs a consultative practice in which he treats patients who typically have seen other psychiatrists first, and he tends to take at least an hour and a half on the initial interview to delve into patient history.

With the extra time, he also explores a patient’s response to past treatment, particularly to antidepressants. “The fact that a patient responded well at some point in the past to antidepressants does not mean they are not bipolar,” he said.

Other treatment histories that might suggest bipolar disorder include a series of antidepressants that have not worked or a series of antidepressants that all worked rapidly and robustly but then failed to deliver sustained benefit, according to Dr. Sobel.

Future Research

Until researchers develop more advanced diagnostic procedures, Dr. Maletic advises that taking the time to gather and interpret complete patient, family, and treatment histories, hetero-anamnesis, and TEMPS scores (6) remains the best strategy for clinicians to differentiate bipolar disorder from unipolar depression.  

Dr. Maletic points out that bipolar disorder is a descriptive diagnosis but that patients with bipolar disorder do not all have the same neurobiological characteristics. More research, he said, is needed to see whether people with certain biomarkers and phenotypical characteristics will respond differently to treatment.  

The rewards for research as well as for clinical perseverance in the present day are indisputable—matching a patient with the correct treatment changes lives. Dr. Maletic recalls a distraught, suicidal woman diagnosed with unipolar depression who was “unrecognizable” a week after starting mood stabilizing treatment.

Although the woman resisted the diagnosis and attempted to taper medications on her own, Dr. Maletic helped her to eventually come to terms with the need for medication, and she remained stable for years.  

Dr. Singh agrees that patients want a correct diagnosis but struggle to accept bipolar disorder due to stigma, professional repercussions, and other reasons. Yet he persists in explaining the relationship between the right diagnosis and the right medicine. “I tell them I know it’s a hard diagnosis, but the fact that we understand the problem better allows us to initiate the correct treatments.”

—Lauren LeBano


1. Knežević V, Nedić A. Influence of misdiagnosis on the course of bipolar disorder. Eur Rev Med Pharmacol Sci . 2013;17(11):1542-1545.

2. Drancourt N, Etain B, Lajnef M, et al. Duration of untreated bipolar disorder: missed opportunities on the long road to optimal treatment. Acta Psychiatr Scand. 2013;127(2):136-144.

3. Hirschfeld RM, Lewis L, Vornik LA. Perceptions and impact of bipolar disorder: how far have we really come? Results of the national depressive and manic-depressive association 2000 survey of individuals with bipolar disorder. J Clin Psychiatry . 2003;64(2):161-174.

4. Ghaemi SN, Boiman EE, Goodwin FK. Diagnosing bipolar disorder and the effect of antidepressants: a naturalistic study . J Clin Psychiatry . 2000;61(10):804-808.

5. Judd LL, Akiskal HS, Schettler PJ, et al. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry. 2002;59(6):530-537.

6. Aguiar Ferreira Ad, Vasconcelos AG, Neves FS, et al. Affective temperaments: familiality and clinical use in mood disorders. J Affect Disord . 2013;148(1):53-56.

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