Misdiagnosis and Differential Diagnosis for Bipolar Disorder Video

Bipolar I disorder is often underdiagnosed and can be misdiagnosed even by well-trained healthcare providers. This clinical insights video will review reasons behind these diagnostic difficulties and introduce clinical tools that can aid in identifying patients at higher risk for bipolar disorder.


Hi, I’m Tony Amberg. I’m a psychiatric nurse practitioner from Chicago, and welcome. Bipolar disorder can be a challenging condition for NPs to diagnose. Not only is bipolar disorder underdiagnosed, but it is often misdiagnosed1,2 because it can be confused for other psychiatric conditions.3 Nearly 70% of patients with bipolar disorder are incorrectly diagnosed, with major depressive disorder being the most common misdiagnosis.3

Patients with bipolar disorder who do not receive the correct diagnosis will have delayed access to appropriate management,2 and this can have very serious effects on their mental health. For one, patients with untreated bipolar disorder are at a significantly increased risk of suicide.4 Additionally, they often experience a wide range of health and quality of life issues, such as disruptions in their interpersonal relationships, work, school life, and everyday functioning.5 They may also experience cognitive difficulties, including problems with memory and decision-making.5

In this video, we’re going to review how to avoid misdiagnosing patients with bipolar disorder. We will review some of the diagnoses on your differential that should be there and should be ruled out to arrive at the appropriate diagnosis for these patients, as well as the complexities that arise when patients have comorbid mental health conditions along with bipolar disorder.

Many patients with bipolar disorder are incorrectly diagnosed with major depressive disorder, or MDD.3 Remember that most patients with bipolar disorder often experience symptoms of a major depressive episode much more often than they do symptoms of a manic or hypomanic episode.6 That is, when we see these patients in the clinic, we often see someone who appears depressed rather than manic or hypomanic.

In fact, it’s the major depressive episode that brings the patient into the primary care setting. They’re seeking help, because during a manic or hypomanic episode, patients may not recognize that something may be wrong that might require medical attention.5 Moreover, major depressive episodes in bipolar disorder can look very similar to those of MDD,6 so, it can be tricky trying to differentiate between them. The DSM-5 recognizes that a substantial proportion of patients initially appearing to have MDD will ultimately be diagnosed with bipolar disorder due to the marked similarity in depressive symptoms.7 In fact, the diagnostic criteria for a major depressive episode in MDD and bipolar disorder are identical.7

When patients start describing symptoms of mania or hypomania, that alerts me to do a further assessment. I notice that they might mention feeling incredibly energetic or being a lot more active than usual sometimes.7 They might also describe things like feeling easily distracted, needing less sleep, having racing thoughts, increased talkativeness, or even feeling constantly irritable.7

The patient interview and a comprehensive review of the patient’s history are vitally important. I listen and probe for certain key characteristics that help me recognize when bipolar disorder might be present instead of MDD.1 These characteristics include the patient’s family history of bipolar disorder, if they’ve experienced frequently occurring past major depressive episodes, if their medication history includes the emergence of a full manic episode or hypomanic episode in response to antidepressants, and if they’ve experienced mixed features.6-8 What do I mean by mixed features? Mixed features in the context of MDD are when the patient reports symptoms of mania or hypomania in addition to meeting the full criteria of a major depressive episode. Mixed features are a risk factor for the development of bipolar disorder.7 

It is of paramount importance to differentiate bipolar disorder from MDD to ensure that patients are prescribed the appropriate medication. Patients improperly diagnosed may suffer negative consequences. Antidepressants can potentially trigger a manic episode or hypomanic episode, or worsen the symptoms of bipolar disorder.5

My differential diagnosis for bipolar disorder includes MDD, schizophrenia spectrum and other psychotic disorders, attention-deficit/hyperactivity disorder, which you know better as ADHD, and borderline personality disorder.7 How to evaluate and treat those disorders is beyond the scope of this video, but many of these disorders have symptoms that mimic or overlap with bipolar disorder.5

For instance, psychotic symptoms such as delusions and hallucinations can occur as part of bipolar disorder and schizophrenia and other psychotic disorders. Moreover, a major depressive episode or manic episode may also occur as part of schizoaffective disorder. Difficulties with memory and concentration are features of bipolar disorder as well as ADHD.7 Finally, problems with mood as well as irritability can be a part of bipolar disorder as well as borderline personality disorder.7

How do you determine whether any of these symptoms are due to bipolar disorder versus another disorder on the differential? Clinical probes are a good way to explore the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, better known as DSM-5, diagnostic criteria in a way that is conversational. Be sure your probes focus on the core symptoms of each disorder.

A few other factors should be considered when making a differential diagnosis for bipolar disorder. First, does the patient have rapid cycling of mood episodes? Rapid cycling is a feature of bipolar disorder in which a person experiences as least 4 mood episodes that meet criteria for a major depressive episode, manic episode, or hypomanic episode within a 12-month period.7 Rapid cycling is unique to bipolar disorder and is not present in the other disorders on the differential that feature mood episodes or mood instability, such as schizoaffective disorder and borderline personality disorder.

Second, explore whether the person has psychotic features of delusions or hallucinations. Some people with bipolar disorder may experience these symptoms of psychosis during a mood episode, resulting in what may be a more severe form of bipolar disorder.9 However, the presence of psychotic symptoms and mood episodes could be due to schizoaffective disorder instead. Note that unlike schizoaffective disorder, in bipolar disorder, delusions and hallucinations occur only during a mood episode.9

Remember also that because people with 1 mental health condition can have other psychiatric disorders, the possibility of comorbidities should be considered. Some of these comorbidities overlap with diagnoses on the differential for bipolar disorder. Some psychiatric conditions that commonly co-occur with bipolar disorder include ADHD, personality disorders, substance use disorders, impulse-control disorders, anxiety disorders, and eating disorders.10 In particular, in patients with bipolar I disorder, 42% have comorbid lifetime substance use disorders, and 42% also have comorbid lifetime anxiety disorders.10

Bipolar disorder is a lifelong condition that requires ongoing management. Patients can lead fulfilling lives, but receiving an appropriate diagnosis is a necessary first step toward this goal. NPs face an uphill battle in getting to the right diagnosis—namely that of differentiating bipolar disorder from MDD and a host of other psychiatric disorders.

To properly diagnose bipolar disorder, NPs need to know the key diagnostic features not just of bipolar disorder and MDD but also of other diagnoses on the differential for bipolar disorder, such as schizophrenia spectrum and other psychotic disorders, ADHD, and borderline personality disorder.

Moreover, standardized psychiatric rating scales can be helpful in screening patients for these conditions. Some examples of screening tools used commonly in clinical practice include the Mood Disorder Questionnaire, better known as the MDQ, the Patient Health Questionnaire-9, better known as the PHQ-9, and the Scales for the Assessment of Positive and Negative Symptoms.11,12

Finally, I would add that bipolar disorder is something that should always be on our radar, because it overlaps with so many other psychiatric disorders and is frequently missed. Keeping in mind how frequently bipolar disorder occurs with comorbid psychiatric conditions will put us in a much better position to properly screen patients and arrive at the correct diagnosis.

Thanks for watching. I’m Tony Amberg, and be sure to check out the other great resources available here at NP Psych Navigator. 

Alan "Tony" Amberg, MSN, APRN, PMHNP-BC

Alan “Tony” Amberg, APRN, PMHNP-BC, is a full-practice authority psychiatric nurse practitioner (NP) and the owner of Alan Tony Amberg PLLC Psychiatry in Chicago, with patients in Illinois and Florida. He is a popular speaker and trainer for national, state, and local conferences. Prior to working in private practice, he was the psychiatric NP liaison at Northwestern Memorial Hospital, and before that, served as the psychiatric provider for Rush Oak Park Hospital. In his roles, he has worked with a wide range of psychiatric conditions combined with physical comorbidities. Tony has precepted many NPs and registered nurses (RNs) and has provided education for physician’s assistants, psychologists, chaplains, and social workers. He holds nursing degrees from Rush University and DePaul University in Chicago.   


  1. Bobo WV. The diagnosis and management of bipolar I and II disorders: clinical practice update. Mayo Clin Proc. 2017;92(10):1532-1551.

  2. Fritz K, Russell AMT, Allwang C, Kuiper S, Lampe L, Malhi GS. Is a delay in the diagnosis of bipolar disorder inevitable? Bipolar Disord. 2017;19:396-400.
  3. McIntyre RS, Calabrese JR. Bipolar depression: the clinical characteristics and unmet needs of a complex disorder. Curr Med Res Opin. 2019;35:1993-2005.
  4. Dome P, Rihmer Z, Gonda X. Suicide risk in bipolar disorder: a brief review. Medicina. 2019;55(8):403.
  5. Stiles BM, Fish AF, Vandermause R, Malik AM. The compelling and persistent problem of bipolar disorder disguised as major depression disorder: an integrative review. J Am Psychiatr Nurses Assoc. 2018;24(5):415-425.
  6. Hirschfeld RM. Differential diagnosis of bipolar disorder and major depressive disorder. J Affect Disord. 2014;160(51)512-516.
  7. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th Ed. American Psychiatric Association; 2013.
  8. Culpepper L. The diagnosis and treatment of bipolar disorder: decision-making in primary care. Prim Care Companion CNS Disord. 2014;16(3). doi:10.4088/PCC.13r01609
  9. Burton CZ, Ryan KA, Kamali M, et al. Psychosis in bipolar disorder: does it represent a more ‘severe’ illness? Bipolar Disord. 2018; 20(1):18-26. doi:10.1111/bdi.12527
  10. McIntyre RS, Konarski JZ, Yatham LN. Comorbidity in bipolar disorder: a framework for rational treatment selection. Hum Psychopharmacol Clin Exp. 2004;19:369-386.
  1. Sasdelli A, Lia L, Luciano CC, Nespeca C, Berardi D, Menchetti M. Screening for bipolar disorder symptoms in depressed primary care attenders: comparison between mood disorder questionnaire and hypomania checklist (HCL-32). Psychiatry J. 2013;2013:548349. doi:10.1155/2013/548349
  2. Rating scales and safety measurements in bipolar disorder and schizophrenia - a reference guide. Psychopharmacol Bull. 2017;47(3):77-109. 

This resource is intended for educational purposes only and is intended for US healthcare professionals. Healthcare professionals should use independent medical judgment. All decisions regarding patient care must be handled by a healthcare professional and be made based on the unique needs of each patient.

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