Burden of Misdiagnosis in Bipolar I Disorder
The results of a large, real-world study suggest that misdiagnosis of bipolar I disorder as major depressive disorder can be associated with significantly greater healthcare resource utilization and higher costs, particularly for mental health–related services, highlighting the importance of timely and accurate diagnosis.
- Patricia Bursnall, DNP, APRN, FNP-C, PMHNP-BC
What do the results of this study mean for a practicing NP?
“For mental healthcare providers (HCPs) working with mood disorders, this study emphasizes how important it is to strive for early and accurate diagnosis of bipolar I disorder (BP-1). In my experience, some patients previously misdiagnosed with major depressive disorder (MDD) may have symptoms of BP-1 that were not properly managed. These patients might experience more hospitalizations and may be at risk of developing negative clinical outcomes.1,2 However, with an accurate diagnosis of BP-1 and an appropriate treatment plan, they may be able to reduce symptoms and decrease hospital visits, as well as impact on overall function. To help reduce the risk of potential negative patient outcomes and the economic burden of misdiagnosis of BP-1, it is essential for providers to incorporate strategies that can help identify patients with BP-1. Some of the strategies may include conducting a thorough patient interview—including history of symptom onset, history of manic symptoms, family psychiatric history, and treatment response history—and incorporating measurement-based care with the use of screening instruments in routine clinical practice.3 Additionally, collaboration through integrated care across different specialties may help improve the accurate diagnosis of BP-1.”4
NP Psych Navigator contributors are paid consultants of AbbVie Inc.
Why was the research needed?
BP-1 can often be misdiagnosed as MDD, primarily because many individuals initially seek treatment for depressive symptoms, which present very similarly to those of MDD.3 Misdiagnosis of BP-1 can result in patients with BP-1 receiving inappropriate treatment, such as antidepressant monotherapy, which can potentially increase the risk of a manic switch, known as treatment-emergent affective switch (TEAS). TEAS can be associated with negative patient outcomes.5-7 While the clinical implications of misdiagnosis have been discussed in the literature, real-world evidence quantifying the healthcare utilization and economic burden of misdiagnosis of BP-1 has been limited. The objective of this study was to compare healthcare resource utilization (HRU) among patients with BP-1 who were initially misdiagnosed with MDD versus those diagnosed correctly from the outset.
What did the researchers do?
The researchers conducted a retrospective cohort study using de-identified claims data from the IBM® MarketScan® databases, which include commercial, Medicaid, and Medicare populations. The study consisted of two patient cohorts1:
- The misdiagnosed BP-1 cohort comprised adults who had an initial diagnosis of MDD followed by a diagnosis of BP-1 at a later date.
- The BP-1 only cohort included adults who received a BP-1 diagnosis without a prior MDD diagnosis on record.
Patients were followed from the index date (first MDD or BP-1 diagnosis) for at least 12 months, with an average follow-up of about 2.5 years. The outcomes assessed included both all-cause and mental health (MH)-related healthcare utilization (hospitalizations, emergency room [ER] visits, and outpatient visits) and costs. Additionally, the study examined the time to correct BP-1 diagnosis, the types of providers involved in the initial and subsequent diagnoses, and the proportion of patients who remained misdiagnosed after one year.1
What were the key results of the study?
The analysis of the patterns of diagnostic delays, which included 14,729 patients in the misdiagnosed BP-1 cohort and 16,072 in the BP-1 only cohort, showed that, on average, more than one year elapsed between initial MDD and corrected BP-1 diagnosis (range 340 to 405 days). At one year post-index, 42% of patients in the misdiagnosed cohort had still not received the correct diagnosis.1
When HRU was compared between the misdiagnosed BP-1 and BP-1 only cohorts, higher HRU was observed in the misdiagnosed group during the follow-up period. Both all-cause and MH-related hospitalization rates were nearly double in the misdiagnosed group than in the BP-1 only group. All cause-ER visit rates were 33% higher, and MH-related ER visit rates were 77% higher in the misdiagnosed group than in BP-1 only patients.1
In addition, the healthcare costs were significantly higher in the misdiagnosed BP-1 group. During the follow-up period, the misdiagnosed group incurred higher total all-cause and MH-related healthcare costs, with differences of $6,541 and $6,152, respectively, compared to the BP-1 only group. These cost differences were even greater in the first 12 months, at $7,146 and $6,619, respectively (Figure 1).1
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Figure 1. Cost differences among the BP-1 only group vs the misdiagnosed BP-1 group. Adapted from McIntyre RS, et al. J Affect Disord. 2022;316:26-33.
Limitations
- The study used administrative claims data, which rely on diagnostic coding and may not capture relevant diagnostic details.
- The analysis included only insured patients, limiting the generalizability to uninsured populations.
- The study design required 12 months of continuous enrollment post-index, potentially introducing survivorship bias.
- Lastly, some misdiagnosed patients with longer delays may not have been captured due to the relatively short observation window (≤5 years).1
Why are these results important?
These findings provide strong real-world evidence that misdiagnosing BP-1 as MDD may lead to not only poor clinical outcomes but also an increased economic burden on the healthcare system. Patients who were initially misdiagnosed required significantly more intensive and costly care, particularly in terms of hospitalizations, emergency visits, and mental health outpatient care. Notably, the excess cost was mainly driven by MH-related services, suggesting that misdiagnosis of BP-1 was the primary contributing factor.
For HCPs, these results underscore the importance of early, accurate diagnosis in patients presenting with depressive symptoms. Given that many patients may not report/present with manic episodes, and some may not recognize these episodes as needing to be treated,8 it is critical for providers to actively screen patients diagnosed with MDD, for BP-1. Incorporating the use of validated screening tools in clinical practice and educating HCPs on the importance of screening patients presenting with depressive symptoms can help differentiate BP-1 from MDD.4,9,10 This may potentially aid in improving patient outcomes and reducing the economic burden associated with misdiagnosis of BP-1.
References
McIntyre RS, Laliberté F, Germain G, et al. The real-world health resource use and costs of misdiagnosing bipolar I disorder. J Affect Disord. 2022;316:26-33. doi:10.1016/j.jad.2022.07.069
- Preuss UW, Schaefer M, Born C, Grunze H. Bipolar disorder and comorbid use of illicit substances. Medicina (Kaunas). 2021;57(11):1256. doi:10.3390/medicina57111256
- Mitchell PB, Goodwin GM, Johnson GF, et al. Diagnostic guidelines for bipolar depression: a probabilistic approach. Bipolar Disord. 2008;10(1 Pt 2):144-152. doi:10.1111/j.1399-5618.2007.00559.x
- Bursnall P, Johnson L. Bipolar disorder: screening in the primary care setting to improve referrals for care. Clin J Nurse Pract Women's Health. 2025;2:126-130. doi:10.1891/CJNPWH-2519
- American Psychiatric Association. Practice Guideline for the Treatment of Patients With Bipolar Disorder. 2nd ed. American Psychiatric Association Publishing; 2002.
- Salvadore G, Quiroz JA, Machado-Vieira R, et al. The neurobiology of the switch process in bipolar disorder: a review. J Clin Psychiatry. 2010;71(11):1488-1501. doi:10.4088/JCP.09r05259gre
- Viktorin A, Lichtenstein P, Thase ME, et al. The risk of switch to mania in patients with bipolar disorder during treatment with an antidepressant alone and in combination with a mood stabilizer. Am J Psychiatry. 2014;171(10):1067-1073. doi:10.1176/appi.ajp.2014.13111501
- Regeer EJ, Kupka RW, Have MT, Vollebergh W, Nolen WA. Low self-recognition and awareness of past hypomanic and manic episodes in the general population. Int J Bipolar Disord. 2015;3(1):22. doi:10.1186/s40345-015-0039-8
- McIntyre RS, Patel MD, Masand PS, et al. The Rapid Mood Screener (RMS): a novel and pragmatic screener for bipolar I disorder. Curr Med Res Opin. 2021;37(1):135-144. doi:10.1080/03007995.2020.1860358
- Hirschfeld RM, Williams JB, Spitzer RL, et al. Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. Am J Psychiatry. 2000;157(11):1873-1875. doi:10.1176/appi.ajp.157.11.1873
This summary was prepared independently of the study’s authors.
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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