Major Depressive Disorder (MDD) and Bipolar Depression: Recognizing the Differences in Primary Care

Summary

This expert-led video explores how bipolar depression may be mistaken for major depressive disorder (MDD), given that the two share a highly similar depressive symptom profile. This makes the differential diagnosis more complex in a primary care visit. The discussion examines how this overlap may lead to misdiagnosis and a delay in appropriate treatment, and the video provides practical probes to screen for prior manic or hypomanic episodes in everyday practice. 

Transcript

Erin Crown: Hello and welcome to Major Depressive Disorder and Bipolar Depression: Recognizing the Differences in Primary Care. My name is Erin Crown, and I’m a psychiatric physician assistant from State College Pennsylvania. 

To distinguish a depressive episode associated with bipolar depression from one associated with major depressive disorder, or MDD, we have to first begin by reviewing the defining features of each of these diagnoses.

Bipolar I disorder is characterized by the presence of at least one full manic episode in a patient’s lifetime. Bipolar II disorder is characterized by a clinical history of at least one hypomanic episode alongside at least one major depressive episode, or MDE.¹ MDD, or major depressive disorder, by contrast, is diagnosed in the absence of any manic or hypomanic symptoms in a person’s lifetime.¹

Patients with bipolar disorder experience mood symptoms roughly 50% of the time. Those that are diagnosed with bipolar I disorder spend approximately 70% of that disrupted mood time in a depressed state, while it is estimated to be about 82% of disrupted mood time is experienced as depression for those with bipolar II disorder. Depression is what may typically prompt someone to seek care, what primary care clinicians are likely to see first. This underscores the importance of screening for and accurately diagnosing bipolar depression at this initial presentation.^2,3

In a national survey, 60% of individuals with bipolar disorder said they were first misdiagnosed with MDD. Nearly one third of respondents waited over 10 years until initial presentation and treatment.⁴

A Depressive and Manic-Depressive Association (DMDA) survey conducted in 2000 found that 69% of individuals with bipolar disorder received an average of 3.5 incorrect diagnoses, and many saw at least four physicians before receiving an accurate diagnosis. This delay in diagnosis can also delay access to the appropriate treatment approaches for bipolar depression—a distinction that will be discussed a little later on.^4,5

Clinicians can help close this diagnostic gap by incorporating probing questions into a standard visit for a patient presenting with depressive symptoms.^1,6

Additional probing questions can be focused on this important differential diagnosis between MDD and bipolar depression by asking about the presence of manic or hypomanic symptoms. These can include either of the core diagnostic symptoms such as elevated or irritable mood, or asking about increased energy, as well as the additional symptoms such as racing thoughts, pressured or rapid speech, or impulsivity, to name a few.⁴

While bipolar disorder can be differentiated from MDD by the presence of manic or hypomanic symptoms, the central diagnostic challenge, as previously mentioned, is that most patients with bipolar disorder may initially present with depressive symptoms. 

A major depressive episode in bipolar disorder is defined by the same diagnostic criteria as major depressive episode in MDD because it contains the same depressive symptoms. Without probing for hypomanic or subthreshold bipolar features, bipolar disorder may go unrecognized or misdiagnosed as MDD for years.⁷

This diagnostic overlap can be consequential.

Studies show that among patients presenting with depressive symptoms, including anxiety, in primary care, roughly one in four have an underlying bipolar disorder diagnosis.^8,9

As previously mentioned, it is estimated that individuals with bipolar II disorder spend approximately 82% of their symptomatic time in depressive episode. This means hypomanic periods can be easy to miss during a routine clinical visit.²

Additionally, hypomanic symptoms may not cause marked impairment and therefore can go unreported unless specifically explored during an assessment.⁴ In a national DMDA self-completed survey of 600 individuals with bipolar disorder, 79% of respondents agreed that their mania increased their productivity before it had a negative impact on their performance. 

In that same survey, fewer than 50% of respondents reported certain manic symptoms such as racing thoughts or reckless behavior to a physician—highlighting the need for targeted clinical probes.⁴

Differentiating bipolar depression from MDD relies on a comprehensive clinical assessment and longitudinal history, rather than a single-visit symptom check.⁶

This can start with structured inventory-taking built around two categories of clinical probes: first, course of illness, including history of manic/hypomanic symptoms, and second, family history of mood disorders.

As shown here, probabilistic features of an MDD diagnosis may include later age of onset and more frequent lifetime depressive episodes. On the other hand, an earlier age of onset, a pattern of recurrent depressive episodes, and a family history of bipolar disorder are probabilistic features of a bipolar disorder diagnosis. These probabilistic features may help provide a foundation for possible insight gathering during a routine clinical evaluation.^6,10

Bipolar disorder is also associated with a significantly greater likelihood of suicidal ideation, attempts, and completed suicide compared with MDD.¹¹ People diagnosed with bipolar disorder are over 20 times more likely to die by suicide compared with the general population.¹²

Probing for a history of mania or hypomania includes asking about core symptoms such as elevated or expansive mood, and irritability. Patients with bipolar disorder may not recognize manic/hypomanic symptoms as pathological; therefore, these clinical probes can help uncover context that may not otherwise be volunteered. A simple example to incorporate into practice is asking, “In addition to the depressive symptoms you are experiencing, has there been a period of irritable mood or unusually increased energy that lasted for a period of at least 4 days?” A “yes” response to this core mania and hypomania criterion can prompt further probing for additional symptoms or criteria.¹⁰

Depressive symptom quality can also add additional insight: hypersomnia, hyperphagia, leaden paralysis, and prominent psychomotor slowing have been shown to be more consistent with bipolar depression than major depressive disorder.⁶

Lastly, structured screening tools can be a consistent way to help support measurement-based care. 

One example includes the Mood Disorder Questionnaire, or MDQ, which is a brief screening tool that can be completed either by the patient or together with the patient and their provider. The scale contains 13 “yes or no” probes to assess a lifetime history of manic or hypomanic symptoms; a score of at least 7 represents a positive screen of bipolar disorder.¹³

The Rapid Mood Screener, or RMS is a screening tool that was developed to differentiate bipolar I disorder from MDD in patients with depressive symptoms who have been diagnosed with MDD already. This tool contains 6 “yes or no” probes to assess both depressive and manic features, and a score of at least 4 indicates a positive screen.⁵

Using these screening tools consistently—alongside the appropriate clinical probes—can help close the diagnostic gap for patients who may not otherwise proactively volunteer this information before a treatment plan is established that may not be appropriate for their underlying diagnosis.

Recognizing this distinction matters because treatment approaches for MDD and bipolar depression are not interchangeable.

Antidepressant therapy is a guideline-recommended, first-line treatment for MDD. In bipolar depression, however, antidepressant monotherapy is not recommended, given concerns about the potential for mood destabilization and the risk of precipitating a hypomanic or manic episode.¹⁰

Guideline-directed treatment for bipolar depression centers around mood stabilizers and atypical antipsychotics with established efficacy in this patient population.¹⁰

This is one of the key reasons an accurate bipolar diagnosis matters early: it shapes which management approaches are most likely to benefit the patient and which approaches may carry added risk.¹⁰

A longitudinal assessment of a patient’s mood—not just their symptoms from a single visit—along with considering their family history is often what can help to effectively diagnose bipolar depression, which might otherwise present as MDD. Applying this approach supports an accurate differential diagnosis and, in turn, appropriate treatment selection for patients with bipolar depression, resulting in optimal outcomes for patients.^6,10

Thank you for joining us for this important session on differentiating bipolar depression from major depressive disorder. And thank you for what you do every day.

Disclaimer

This content has been created for US health care professionals and is intended for information and educational purposes only. It should not be used to replace clinical judgment or a discussion with the patient’s health care team. All decisions regarding patient diagnosis and care must be made by a qualified health care professional based on each patient’s individual needs.

Referenced tools are adjunctive aids and are not diagnostic on their own, and this resource does not endorse or recommend any specific drug, treatment, or manufacturer.