Early vs Delayed Diagnosis: The BP-1 Patient Journey Podcast

Major depressive disorder (MDD) is one of the most common mental disorders in the United States. Primary care clinicians and mental health nurse practitioners are integral to addressing this common and chronic condition, as they are often at the front lines of diagnosing and managing patients with MDD. This peer exchange podcast featuring Linda Cabage, APRN, PMHNP-BC, and Katherine Sullivan, PMHNP-BC, allows busy practitioners to listen to a review of diagnostic challenges around this common and complex condition.

Transcript: 

Pradeep Manudhane (PM): Hello and welcome! I am Pradeep Manudhane, a clinical associate professor of psychiatry at Northeast Ohio Medical University and a community mental health psychiatrist at Phoenix Rising Behavioral Health in Canton, Ohio. 

Alan “Tony” Amberg (TA): And I am Alan Tony Amberg, a psychiatric mental health nurse practitioner in Chicago, Illinois, but please just call me Tony. Thanks for joining us as we discuss one of the most challenging aspects of managing bipolar I disorder, or BP-1, the difficulty in arriving at a timely and accurate diagnosis.  

PM: Tony, even though we’ve heard this before, it can’t be stressed enough. Most patients with BP-1 experience a substantial delay in receiving an accurate diagnosis. In a large-scale survey, misdiagnosed patients with bipolar disorder were shown to have had an average of three other diagnoses and to have consulted an average of four physicians.¹ It took approximately five to 10 years to receive a correct diagnosis.² 

TA: Five to 10 years! Imagine having symptoms and trying medications that may not be appropriate for so long. Such delays in accurate diagnosis and appropriate treatment of bipolar I can have a significant downstream impact on a patient’s overall journey and associated outcomes. Longitudinal studies have shown that the longer a patient with bipolar remains untreated, the greater the risk of more frequent depressive episodes and a longer duration of each episode. Patients with longer untreated bipolar were also shown to have a higher frequency of rapid cycling and a greater number of hospitalizations than those who received treatment earlier. In addition, the risk of suicide was higher, with nearly double in odds.³ 

PM: Delayed diagnosis of BP-1 may also result in impaired psychosocial functioning in professional and social settings^4,5 and lead to higher healthcare utilization, such as hospitalization.⁴ Overall, delays in accurate diagnosis of bipolar disorder can be associated with greater clinical, social, and economic burdens.   

TA: It’s also worth mentioning that medical comorbidities, such as cardiovascular disease, hypertension, obesity, metabolic syndrome, and diabetes, can be common in patients with bipolar disorder,⁶ and a delay in the diagnosis of BP-1 may result in a greater risk of developing chronic medical comorbidities.⁷  

PM: As you can see, a delayed diagnosis of BP-1 can have a significant impact on patient outcomes. Now, let’s examine what may be contributing to these delays.   

TA: While multiple factors may play a role in the delayed diagnosis of bipolar I, part of the challenge arises from how BP-1 manifests. Although bipolar I disorder is defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) as the occurrence of at least one manic episode,⁸ most patients initially seek help for their depressive symptoms. In addition, the majority of mood episodes in patients with BP-1 are depressive in nature. A follow-up study of the Systematic Treatment Enhancement Program for Bipolar Disorder, known as the STEP-BD study, showed that in 3,658 patients with bipolar, depressive episodes occurred approximately 72% of the time, while manic episodes only occurred about 11% of the time.⁹ 

Clinically, this presents a challenge of distinguishing the depressive episode of BP-1 from that of major depressive disorder (MDD), precisely because the DSM-5 diagnostic criteria for depressive episodes are identical.^4,8,10 This difficulty is reflected in the statistics showing that patients who initially present with depressive symptoms experience a significantly longer delay to accurate diagnosis compared to those who present with mania.^4,11 

PM: Patients often do not recognize symptoms of mania as needing treatment, as many may view them as normal mood fluctuations.¹² In fact, for some patients with BP-1, the energy and productivity of mania may feel welcomed to them, but they might not realize the negative impact on others. Because mania can be associated with memory issues,¹³ some may not remember mania at all, or they may only recall changes in sleep patterns or increased energy or productivity. These signs may not be thought of as needing treatment.^1,4,11,14  

TA: Another factor that may contribute to the misdiagnosis of BP-1 is the overlap of symptoms of BP-1 with those of other psychiatric comorbidities, such as post-traumatic stress disorder, attention-deficit hyperactivity disorder, and substance use disorders. Family members may mistake mania for intoxication, and indeed, there may be both.^15-17 Patients with BP-1 also have high rates of medical and psychiatric comorbidities, which can complicate diagnosis. It is estimated that approximately 90% of individuals with bipolar disorder will have psychiatric and/or medical comorbidities at some point in their lives.¹⁸ On average, a patient with BP-1 has two medical comorbidities,¹⁹ and between 50% to 70% of bipolar I patients have one or more psychiatric comorbidities.²⁰ 

PM: It is important for mental healthcare providers to evaluate differential diagnoses carefully. Now, let’s discuss the strategies that healthcare professionals can implement that may help them to arrive at an accurate diagnosis of BP-1.  

TA: One of the most important ways to mitigate the diagnostic delay is to conduct a thorough patient assessment. Studies have shown that there are clinical and familial characteristics that can vary between bipolar I and major depressive disorder, which may help the healthcare provider in differentiating between the two. A detailed history of past depressive and manic symptoms can help gather information that may be useful in the diagnostic process. For example, studies have shown that compared to those with MDD, patients with BP-1 are more likely to have an earlier onset of the first episode, often before the age of 25 years. Patients with bipolar disorder were also shown to have a greater number of prior episodes, often five or more, and a much shorter duration of episodes, compared to those with MDD.²¹ 

PM: One thing to keep in mind during the patient interview is that, as we discussed earlier, often patients may not remember or recognize past manic symptoms.^13,14 Therefore, probing for manic symptoms, such as changes in sleep patterns, activity levels, changes in appetite or weight, and feelings of irritability or agitation, during the patient interview can provide critical information that may suggest a BP-1 diagnosis.^22,23  

TA: If you can, speak to a knowledgeable family member, both for patient history and for family history. Bipolar disorder is thought to be highly heritable, so a history of bipolar disorder in first-degree relatives should raise your index of suspicion. Don’t overlook second-degree family members such as uncles, aunts, or grandparents.^21,24  

PM: Also important is addressing any potential gaps in the care process that can lead to missed opportunities for timely diagnosis. For example, research has shown that patients can experience longer diagnostic delays when their care is shared between outpatient and inpatient providers. Important details about BP-1 symptoms or history can sometimes get lost during these transitions. Therefore, improving the flow of information and communication between care teams may help address this gap and support earlier, more accurate diagnoses.⁵ 

TA: Now, inaccurate information about a patient’s symptoms or history may be documented in the hospital charts and remain, sometimes for years, without the deep dive to work up the problem. So, I would advise healthcare providers to always verify diagnoses that come to them through a chart.  

Reaching an accurate diagnosis for patients with bipolar I earlier in the course of illness can lead to a timely implementation of appropriate treatment for BP-1. As we discussed earlier, a significant proportion of patients with bipolar disorder who present with depressive symptoms may be diagnosed with MDD. This can result in misdiagnosed patients with bipolar I receiving antidepressant monotherapy as their first treatment. This is the first-line treatment for MDD.²⁵ When a patient with depressive symptoms of BP-1 is treated with antidepressant monotherapy, it may not only be ineffective but may lead to a switch in affective state from depression to mania, called a treatment-emergent affective switch.^6,15,26,27   

PM: Yes, and treatment-emergent affective switch can be associated with negative patient outcomes, including a higher risk of rapid cycling,^26-28 which may negatively impact their course of illness.²⁹ Therefore, it is important to evaluate whether the patient has any history with antidepressants causing hypomanic symptoms in the past.  

TA: One key strategy to help improve the timely and accurate diagnosis of BP-1 is incorporating measurement-based care with the use of standardized, validated assessment tools and screeners.²²  

PM: I agree. One example of a validated tool healthcare professionals can leverage is the Mood Disorder Questionnaire, also known as MDQ. The MDQ is a brief, self-rated questionnaire that can be used to screen patients at risk for bipolar disorder. It includes 13 items evaluating manic symptoms and two items assessing co-occurrence of symptoms and functional impairment.³⁰ In my opinion, the MDQ is easy to use, and it has helped me identify probable bipolar I patients when it is combined with a clinical interview, review of records from previous offices and hospitals, and interviews with loved ones of patients. Doing all of these together maximizes the likelihood of achieving an accurate diagnosis as early as possible. Reviewing how patients answered the MDQ helped me identify many patients with BP-1 over the approximately 10 years I have been using the MDQ in my practice.   

However, the MDQ needs to be carefully cross-checked with symptoms of other disorders that can have similar presentations, such as substance use or severe trauma.  

TA: Another bipolar I screener that healthcare providers can use is the Rapid Mood Screener, otherwise known as the RMS. The RMS is a validated screening tool developed to help screen for BP-1 in patients who are diagnosed with major depressive disorder.^11,31 It can be self-administered in less than two minutes by patients, which makes it a useful screening tool for clinical practice.¹¹   

TA: The RMS consists of 6 questions: three items screening for depressive features and three items screening for manic symptoms, and it has a sensitivity of 88% and specificity of 80%. One thing that should be noted is that the RMS is not a diagnostic tool, and therefore, a complete diagnostic evaluation should be performed to confirm the diagnosis of BP-1.¹¹ It’s been my experience that symptoms like irritability, getting into arguments, and having functional problems may be indeed symptoms of mania.⁸ In order to differentially diagnose, it is prudent to ask the patient to give you examples and describe the situations.  

PM: Tony, today, we examined the reasons why a timely and accurate diagnosis of BP-1 can be clinically challenging, leaving a significant proportion of patients with BP-1 experiencing delayed diagnosis. Delayed diagnosis can not only result in patients receiving inappropriate treatment, as discussed earlier, but it may also lead to a patient having the belief that they will never get better, which may be less likely if the proper diagnosis had been established as early as possible. Patients who believe they will not get better may self-medicate with substances, and this can lead to even worse outcomes.³²   

TA: We have all seen the patient who comes into the office glum and sure that we cannot help them. The common line I hear is “I’ve tried them all, and nothing works.” They have suffered for a long time, and they have frequently tried medications that either did not help or made them feel worse. We have to go slow and appreciate that the patient was willing to let us try one more time.  

PM: I totally agree. To help improve the timely and accurate diagnosis of BP-1, we, healthcare professionals, no matter how busy we are, need to conduct a thorough patient assessment and incorporate measurement-based care in our practice by using validated screening tools that can help identify patients who may have BP-1.  

TA: Absolutely. Thank you, Pradeep! And thank you to our listeners. We hope that you found today’s discussion on the importance of making a timely and accurate diagnosis of bipolar I helpful for your clinical practice.  

PM: Thank you!