ABSTRACT
Objective
Bipolar I Disorder (BP‐I) is frequently misdiagnosed as Major Depressive Disorder (MDD), delaying appropriate treatment. This study aimed to examine treatment patterns among BP‐I patients misdiagnosed with MDD and assess the impact of these regimens on the time until BP‐I diagnosis.
Methods
A retrospective cohort study was conducted using the MarketScan Commercial Claims and Encounters database, analyzing 21,771 BP‐I patients initially misdiagnosed with MDD and 50,667 correctly diagnosed BP‐I patients. Treatment patterns and their influence on time to BP‐I diagnosis were assessed using multinomial logistic regression and Cox proportional hazards models.
Results
Among the misdiagnosed cohort, 25.1% were initially started on antidepressant monotherapy, with 8.7% continuing this regimen after BP‐I diagnosis. In contrast, 7.6% of the initially BP‐I diagnosed cohort received antidepressant monotherapy. The time to BP‐I conversion was shortest for those on mood stabilizer monotherapy (HR: 1.26, 95% CI: 1.19–1.34, p < 0.001), compared to those on antidepressant monotherapy. After BP‐I diagnosis, patients originally misdiagnosed with MDD had different prescribing patterns, exhibiting lower rates of guideline‐consistent treatments. Specifically, patients initially diagnosed with BP‐I were more likely to receive mood stabilizing therapy, either as monotherapy (OR = 2.63, p < 0.001) or in combination with an antidepressant (OR = 1.84, p < 0.001).
Conclusion
Misdiagnosis of BP‐I as MDD leads to significant delays in accurate diagnosis and inappropriate treatment regimens, highlighting the critical need for improved diagnostic accuracy at initial presentation. Prompt and accurate BP‐I diagnosis can optimize treatment approaches and improve patient outcomes.
1. Introduction
Bipolar I Disorder (BP‐I) is a psychiatric disorder that is characterized by chronic mood episodes of mania that often alternate with major depressive episodes (National Institute of Mental Health, 2024). Differentiating the symptomatic presentation of BP‐I from other common mental health disorders, particularly major depressive disorder (MDD), is challenging and often results in a broad differential diagnosis due to the complexity of presentation and multiple subjective data points involved in establishing a definitive diagnosis. BP‐I is frequently misdiagnosed as MDD because patients are more likely to seek office visits during their depressive episodes compared to their manic episodes [1]. One study showed that in a primary care clinic, 21% of patients being treated for depression screened positive for bipolar disorder [2]. Major contributions toward misdiagnosis also include lapses in history‐taking, and presence of psychiatric and medical comborbidities [3].
Diagnosis of BP‐I is often delayed, with 6.7 years elapsing prior to a conclusive diagnosis being established, oftentimes leading to negative health outcomes due to delayed, ineffective or inappropriate treatments being used [4]. For example, misdiagnosed patients may be at risk of receiving an antidepressant monotherapy, which can induce a hypomanic or manic episode in patients with BP‐I [5]. The standard of care for BP‐I patients is an atypical antipsychotic (AA) or mood stabilizer, though an antidepressant may be used in combination with these to address unresolved depressive symptoms [6]. One study examined the medical costs of misdiagnosed patients to be $6541 greater per patient‐year compared to those initially diagnosed with BP‐I, on account of higher hospitalizations, ER visits, and outpatient visits [7]. Improving diagnosis of BP‐I can alleviate some of the burden associated with BP‐I, which is estimated to be $219 billion [8].
While previous studies focused on the burden of misdiagnosing BP‐I, current literature lacks an in‐depth understanding of the treatment patterns during the misdiagnosis stage and the impact that treatment types have on the time until a definitive BP‐I diagnosis. In addition, the impact of MDD diagnosis prior to BP‐I on BP‐I treatment regimen is unknown. Hence, in this study, we aim to analyze psychotropic treatment patterns among BP‐I patients prior to a conclusive BP‐I diagnosis.
2. Methods
2.1. Study Design and Data Source
We conducted a retrospective cohort study, using health insurance claims data, to assess treatment patterns and patient characteristics during the misdiagnosis of BP‐I.
The MarketScan Commercial Claims and Encounters database was used to identify two cohorts: (1) BP‐I patients with the history of being misdiagnosed with MDD prior to BP‐I diagnosis; (2) BP‐I patients without the history of being misdiagnosed with MDD. This database contains de‐identified, patient‐specific health data of reimbursed healthcare claims for employees, retirees, and their dependents of over 250 medium and large employers and health plans, approximately 30 million individuals are covered under private insurance plans. No Medicaid or Medicare data are included.
The study period was from January 1, 2018 through December 31, 2022. The index period, defined to be the date of MDD or BP‐I diagnosis of the study cohorts, was from January 1, 2019, through October 1, 2022, to allow for 12 months of continuous enrollment before the index date and 3 months of follow‐up.
At the time of the analysis, MarketScan data met Health Insurance Portability and Accountability Act of 1996 (HIPAA) requirements for fully de‐identified data sets (IBM MarketScan Research Databases 2022). Institutional Review Board (IRB) approval at the University of Washington was not required, as the study met criteria for non‐human subjects' research as specified by the Human Subjects Division at the University of Washington.
2.2. Sample Selection
2.2.1. Misdiagnosed Cohort
Primary group of interest was patients with initial MDD diagnosis who were later diagnosed with BP‐I. We included patients who were at least 18 years old, and who were diagnosed with MDD (ICD‐10‐CM: Appendix 1), defined as ≥ 1 inpatient OR ≥ 2 outpatient medical diagnosis followed by ≥ 1 inpatient OR ≥ 2 outpatient medical claims with a diagnosis of BP‐I (ICD‐10‐CM: Appendix 1). MDD and BP‐I diagnosis defined the first and second index date in this cohort, respectively. We excluded all patients with prior diagnosis of schizophrenia before the first index date. We included patients with continuous enrollment in medical and prescription benefits 12 months prior to MDD diagnosis, throughout misdiagnosis, and 3 months after BP‐I diagnosis (Appendix 2).
2.2.2. Initially BP‐I Diagnosed Cohort
Our comparator group was BP‐I without history of MDD misdiagnosis. For initially BP‐I diagnosed patients, we included patients who were at least 18 years old and who were diagnosed with BP‐I, defined as ≥ 1 inpatient OR ≥ 2 outpatient medical claims. We defined the index date to be the date of BP‐I diagnosis in this group. We excluded patients with prior diagnosis of MDD and/or schizophrenia before index dates. We required continuous enrollment in medical and prescription benefits 12 months prior and 3 months after BP‐I diagnosis.
2.3. Study Measures and Outcomes
We described the baseline characteristics including patient age, sex, geographic region, insurance plan type, healthcare setting of diagnosis, provider type at diagnosis, Elixhauser comorbidity score, and Diagnostic and Statistical Manual of Mental Disorders (DSM‐5) comorbidity score on the date of BP‐I diagnosis. Elixhauser scores measure overall severity of comorbidities (Appendix 3; Agency for Healthcase Research and Quality). DSM‐5 index is a measure of comorbid psychiatric disorders (Appendix 4; [9]). We calculated a modified Elixhauser and DSM‐5 Comorbidity Index, which excluded depressive and bipolar disorders, using ICD‐10 diagnosis codes on medical claims collected during the 12‐month pre‐index period.
The main outcomes of interest were treatment patterns observed during misdiagnosis and assessing the association between treatment type and time until BP‐I conversion among the misdiagnosed cohort. We investigated the five most common treatment regimens that were used during misdiagnosis, which were identified as either monotherapy (1 medication) or combination therapy (2+ medications) from the following seven psychotropic drug classes: (1) antidepressants; (2) anxiolytics; (3) mood stabilizers; (4) psychostimulants; (5) atypical antipsychotics; (6) sedative/hypnotics; and (7) typical antipsychotics. We grouped anticonvulsants with mood stabilizers because they are frequently used as mood stabilizers. Our primary focus was the percentage of patients who received antidepressant monotherapy. Additionally, we compared the first regimen after BP‐1 diagnosis between the two cohorts.
2.4. Statistical Analysis
Baseline characteristics and treatment patterns were calculated using means and standard deviations for continuous variables and frequency (n, %) for all categorical variables.
We assessed the association between the first treatment regimen after MDD diagnosis and patient and provider characteristics in the misdiagnosed cohort by employing multinomial logistic regression. Patient, provider and clinical covariates include age, sex, place of diagnosis, provider type, DSM‐5 comorbidity index score, and Elixhauser comorbidity index score. We defined the first treatment after MDD diagnosis to be all treatments given within 14 days of diagnosis, with at least one subsequent refill taken for ≥ 30 days. We defined the last treatment of the misdiagnosis period as the final medication being taken in the 14 days leading up to BP‐I diagnosis. Additionally, we expanded the multinomial logistic regression analysis to the entire study population (misdiagnosed and initially BP‐I diagnosed cohort) and included misdiagnosis history as an additional covariate to assess the impact of MDD misdiagnosis prior to BP‐I diagnosis on the first treatment regimen after BP‐I diagnosis.
In the misdiagnosed group we employed Cox proportional hazards regression analysis to calculate the differential hazard rate ratio of BP‐I diagnosis based on the first treatment regimen while adjusting for patient and provider characteristics. The outcome variable is the diagnosis of BP‐I (binary). The first treatment regimen is a categorical variable which included the five most common psychotropic drug class combinations and an others category at MDD diagnosis: (1) Antidepressant monotherapy (reference level), (2) Antidepressant + Anxiolytics, (3) Anxiolytics monotherapy, (4) Antidepressant + Mood Stabilizer, (5) Mood stabilizer monotherapy, and(6) Others. Patients and provider covariates include age, sex, place of diagnosis, provider type, DSM‐5 comorbidity index score, and Elixhauser comorbidity index score.
We performed cohort selection and descriptive statistics using SAS version 9.4 (SAS Institute, Cary, NC), and all statistical analyses in R 4.4.0 (R Core Team, 2024).
3. Results
3.1. Baseline Characteristics
We identified 21,771 eligible BP‐I patients who were previously misdiagnosed with MDD (Table 1). The average age at MDD diagnosis was 34.8 years old and the average age at BP‐I diagnosis was 36.3 years old. Females comprised 68.1% of the misdiagnosed cohort. In this cohort, 78.0% of the MDD diagnosis prior to BP‐I diagnosis were in an outpatient setting though that number dropped to 64.9% at BP‐I diagnosis. Acute care providers were the most frequent to diagnose MDD (18.4%), followed by family practice (15.4%), and psychiatrists (14.8%). After excluding depressive disorders from the Elixhauser comorbidity index average score was 0.34, with 27% of patients having at least one comorbidity and 6.1% having 2 or more. After excluding depressive and bipolar disorders from the DSM‐5 comorbidity index, the average score was 0.60, with 43.6% having at least one comorbidity and 14.3% having 2 or more. In contrast, our initially BP‐I diagnosed cohort had 50,667 individuals and average age was 37.1 years old with females making up 65% of this population. Psychiatrists were the most frequent to diagnose BP‐I (25.4%) in this cohort. The average Elixhauser comorbidity index was 0.29, while the average DSM‐5 comorbidity index was 0.51.
TABLE 1.
Demographic and clinical characteristics of study population.
| Misdiagnosed cohort (n = 21,771) | Correctly diagnosed cohort (n = 50,667) | ||||
|---|---|---|---|---|---|
| All patients (n = 72,438) | at MDD Dx | at BP‐I Dx | at BP‐I Dx | ||
| Demographic characteristics | |||||
| Age, mean (SD) | 36.5 (14.2) | MDD dx: 34.8 (14.1) | 37.1 (14.1) | ||
| BP‐I dx: 36.3 (14.0) | |||||
| Sex, male (%) | 34.30% | 31.9% | 35.00% | ||
| Elixhauser comorbidity index | 0: 75.6% | 0: 73.0% | 0: 76.7% | ||
| 1 = 19.2% | 1 = 20.9% | 1 = 18.5% | |||
| 2 = 4.6% | 2 = 5.4% | 2 = 4.2% | |||
| 3 + = 0.6% | 3 + = 0.7% | 3 + = 0.6% | |||
| Mean = 0.30 (0.59) | Mean = 0.34 (0.61) | Mean = 0.29 (0.57) | |||
| DSM‐5 comorbidity index | 0 = 60.6% | 0: 56.4% | 0 = 62.5% | ||
| 1 = 27.1% | 1: 29.4% | 1 = 26.0% | |||
| 2 = 10.4% | 2: 12.0% | 2 = 9.7% | |||
| 3 + = 1.9% | 3 +: 2.3% | 3 + = 1.7% | |||
| Mean = 0.54 (0.76) | Mean = 0.60 (0.79) | Mean = 0.51 (0.74) | |||
| Geographic region (%) | Northeast | 14.2% | 12.4% | 14.5% | |
| North Central | 21.1% | 22.0% | 20.1% | ||
| South | 45.7% | 45.8% | 45.6% | ||
| West | 18.8% | 19.4% | 18.7% | ||
| Plan type (%) | PPO | 50.5% | 50.7% | 50.4% | |
| CDHP | 13.8% | 14.6% | 13.5% | ||
| HMO | 13.0% | 12.9% | 13.1% | ||
| HDHP | 10.2% | 10.2% | 10.2% | ||
| POS | 8.0% | 7.0% | 8.4% | ||
| Comprehensive | 3.3% | 3.6% | 3.3% | ||
| EPO | 0.7% | 0.6% | 0.7% | ||
| POS w/capitation | 0.5% | 0.4% | 0.5% | ||
| Setting of first diagnosis | Telehealth | 8.8% | 4.4% | 11.1% | 8.1% |
| Outpatient | 70.9% | 78.0% | 64.9% | 72.7% | |
| Inpatient Hospital | 9.9% | 5.9% | 13.1% | 8.9% | |
| Emergency Room | 1.2% | 3.6% | 1.3% | 1.1% | |
| Other | 9.2% | 8.1% | 9.6% | 9.2% | |
| Type of provider to initiate diagnosis | Acute Care Hospital | 13.0% | 18.4% | 15.2% | 12.4% |
| Mental Health Facility | 3.7% | 2.0% | 4.6% | 3.4% | |
| Internal Medicine | 3.8% | 5.5% | 3.6% | 3.9% | |
| Family Practice | 10.4% | 15.4% | 10.1% | 10.5% | |
| Psychiatrist | 24.4% | 14.8% | 21.3% | 25.4% | |
| Nurse Practitioner | 7.4% | 4.8% | 8.7% | 7.0% | |
| Therapist | 10.4% | 11.4% | 10.4% | 10.4% | |
| Other | 26.9% | 27.7% | 26.1% | 27.0% | |
Note: This table compares key demographic and clinical characteristics between patients misdiagnosed with Major Depressive Disorder (MDD) and those initially diagnosed with Bipolar‐I Disorder (BP‐I). It includes mean age, sex distribution, Elixhauser and DSM‐5 comorbidity indices, and healthcare settings where diagnoses were made.
Abbreviations: CDHP, consumer driven health plan; DSM‐5, diagnostic and statistical manual of mental disorders; EPO, exclusive provider organization; HDHP, high deductible health plan; HMO, health maintenance organization; POS, point of service plan; PPO, preferred provider organization; SD, standard deviation.
3.2. Association Between Patient and Provider Characteristics and First Treatment Regimen After MDD Diagnosis in the Misdiagnosed Group
Younger patients are more likely to receive an antidepressant monotherapy (p < 0.001) than all other psychotropic drug classes as a first treatment regimen (Table 2) in the misdiagnosed group. Males had a 13% decrease in odds of receiving an antidepressant and mood stabilizer combination therapy instead of an antidepressant monotherapy compared to females (OR = 0.87, p < 0.05). The odds of receiving a mood stabilizer monotherapy instead of antidepressant monotherapy are 61% lower when prescribed by family practice (OR = 0.39, p < 0.001), 37% lower when prescribed by a nurse practitioner (OR = 0.63, p < 0.01), and 45% lower when prescribed by an internal medicine provider (OR = 0.55, p < 0.001) compared to when prescribed by a psychiatrist.
TABLE 2.
Cox proportional hazards regression for time to BP‐I diagnosis.
| First regimen post MDD Dx | Last Regimen of MDD Dx | |
|---|---|---|
| Adjusted model | Adjusted model | |
| Hazard ratio (95% CI) p | Hazard ratio (95% CI) p | |
| Tx regimen (reference: antidepressant) | ||
| Antidepressant + anxiolytic | 1.13 (1.08–1.19)*** | 1.04 (0.99–1.10) |
| Anxiolytic | 1.17 (1.10–1.24)*** | 0.97 (0.92–1.03) |
| Antidepressant + mood stabilizer | 1.17 (1.10–1.24)*** | 1.05 (1.00–1.10) |
| Mood stabilizer | 1.26 (1.19–1.34)*** | 1.01 (0.97–1.06) |
| Other | 1.10 (1.06–1.13)*** | 1.09 (1.05–1.12)*** |
| Age | 1.00 (1.00–1.00)*** | 1.00 (1.00–1.00)** |
| Sex male | 1.09 (1.06–1.12)*** | 1.08 (1.05–1.12)*** |
| BP‐I diagnosis setting (Reference: Outpatient) | ||
| Inpatient | 1.30 (1.22–1.39)*** | 1.31 (1.22–1.40)*** |
| Telehealth | 1.60 (1.50–1.71)*** | 1.60 (1.50–1.71)*** |
| Emergency room | 1.24 (1.14–1.35)*** | 1.24 (1.14–1.35)*** |
| Other | 1.04 (0.98–1.10) | 1.04 (0.98–1.09) |
| Provider type (reference: psychiatrist) | ||
| Family practice | 1.05 (1.00–1.10)* | 1.04 (0.99–1.09) |
| Nurse practitioner | 1.23 (1.14–1.32)*** | 1.22 (1.12–1.31)*** |
| Therapist | 1.08 (1.02–1.13)** | 1.08 (1.02–1.14)** |
| Internal medicine | 1.13 (1.06–1.21)*** | 1.12 (1.05–1.19)** |
| Mental health facility | 1.18 (1.06–1.32)** | 1.19 (1.07–1.32)** |
| Acute care hospital | 1.18 (1.12–1.24)*** | 1.18 (1.12–1.24)*** |
| Other | 1.10 (1.05–1.15)*** | 1.10 (1.05–1.14)*** |
| DSM‐5 comorbidity score | 0.95 (0.93–0.97)*** | 0.94 (0.93–0.95)*** |
| Elixhauser comorbidity score | 0.98 (0.95–1.00)* | 0.98 (0.96–1.00)*** |
Note: Hazard ratios for the association between treatment regimen and time to BP‐I diagnosis in patients initially misdiagnosed with MDD. Adjusted models include age, sex, comorbidities (Elixhauser and DSM‐5 scores), and healthcare setting, providing insights into predictors of earlier BP‐I diagnosis. p‐value: < 0.05*, < 0.01**, < 0.001***.
3.3. Association Between Misdiagnosis History and First Treatment Regimen After BP‐I Diagnosis
Prescribing patterns after BP‐I diagnosis were substantially different depending on whether the patients initially were diagnosed with MDD (Table 3). Compared to those who were misdiagnosed with MDD, patients initially diagnosed with BP‐I were 84% more likely (OR = 1.84, p < 0.001) to be prescribed an antidepressant and a mood stabilizer combination therapy. They also had 2.63 times the likelihood (OR = 2.63, p < 0.001) of being prescribed mood stabilizer monotherapy over antidepressant monotherapy.
TABLE 3.
Multinomial logistic regression for first treatment regimen in misdiagnosed patients.
| Antidepressant + anxiolytic | Anxiolytic | Antidepressant + mood stabilizer | Mood stabilizer | Other | |
|---|---|---|---|---|---|
| Intercept | −1.44 (−1.64, −1.25)*** | −2.67 (−2.92, −2.42)*** | −1.80 (−2.02, −1.58)*** | −1.80 (−2.02, −1.57)*** | −0.13 (−0.26, 0.00)* |
| Age | 0.014 (0.01, 0.02)*** | 0.03 (0.03, 0.04)*** | 0.02 (0.02, 0.03)*** | 0.02 (0.01, 0.02)*** | 0.02 (0.02, 0.02)*** |
| Sex male | −0.16 (−0.27, −0.05)** | −0.21 (−0.35, −0.07)** | −0.14 (−0.27, −0.02)* | 0.03 (−0.15, 0.10) | −0.09 (−0.16, −0.02)* |
| Setting of Diagnosis (Ref: Outpatient) | |||||
| Inpatient | 0.63 (0.40, 0.86)*** | 0.02 (−0.31, 0.35) | 0.28 (0.01, 0.56)* | 0.03 (−0.28, 0.33) | 0.27 (0.11, 0.44)** |
| Telehealth | −0.08 (−0.32, 0.17) | −0.14 (−0.46, 0.18) | −0.05 (−0.35, 0.22) | −0.05 (−0.33, 0.23) | −0.18 (−0.34, −0.03)* |
| Emergency room | 0.32 (0.00, 0.65)* | 0.24 (−0.15, 0.63) | 0.28 (−0.08, 0.64) | 0.2 (−0.17, 0.57) | 0.25 (0.04, 0.47)* |
| Other | −0.18 (−0.38, 0.03) | −0.07 (−0.32, 0.17) | −0.03 (−0.24, 0.19) | −0.21 (−0.44, 0.02) | −0.05 (−0.17, 0.07) |
| Provider type (Ref: Psychiatrist) | |||||
| Family practice | −0.40 (−0.57, −0.23)*** | −0.43 (−0.65, −0.21)*** | −0.72 (−0.92, −0.52)*** | −0.94 (−1.06, −0.61)*** | −0.57 (−0.69, −0.46)*** |
| Nurse practitioner | −0.06 (−0.30, 0.18) | −0.13 (−0.45, −0.18) | −0.45 (−0.75, −0.16)** | −0.46 (−0.78, −0.14)** | −0.40 (−0.57, −0.23)*** |
| Therapist | −0.25 (−0.47, −0.03)* | 0.28 (0.03, 0.53)* | −0.00 (−0.23, 0.22) | 0.44 (0.22, 0.67)*** | 0.43 (0.29, 0.56)*** |
| Internal Medicine | −0.51 (−0.76–0.26)*** | −0.33 (−0.62, −0.03)* | −0.75 (−1.04, −0.46)*** | −0.60 (−0.90, −0.29)*** | −0.44 (−0.60, −0.28)*** |
| Mental health facility | 0.20 (−0.17, 0.57) | −0.48 (−1.11, 0.16) | 0.25 (−0.16, 0.65) | 0.03 (−0.45, 0.51) | 0.06 (−0.21, 0.33) |
| Acute care hospital | −0.19 (−0.38, 0.01) | 0.12 (−0.11, 0.36) | −0.17 (−0.38, 0.05) | 0.01 (−0.21, 0.23) | 0.18 (0.05, 0.31)** |
| Other | −0.27 (−0.43, −0.11)*** | −0.27 (−0.36, 0.04) | −0.25 (−0.43, −0.08)** | −0.03 (−0.22, 0.15) | −0.06 (−0.17, 0.04) |
| DSM‐5 score | 0.12 (0.06, 0.18)*** | 0.11 (0.04, 0.19)** | −0.08 (−0.15, −0.00)* | −0.14 (−0.22, −0.06)*** | 0.05 (0.00, 0.09)* |
| Elixhauser Score | 0.07 (−0.01, 0.16) | 0.15 (0.05, 0.25)** | 0.01 (−0.08, 0.11) | −0.03 (−0.13, 0.07) | 0.07 (0.01, 0.12)* |
Note: This table presents the likelihood of receiving various psychotropic drug regimens based on patient and provider characteristics after an MDD diagnosis in the misdiagnosed cohort. Covariates include age, sex, healthcare setting, provider type, and comorbidity indices. p‐value: < 0.05*, < 0.01**, < 0.001***.
3.4. Treatment Patterns and Time From MDD Misdiagnosis to BP‐I Conversion
In our misdiagnosed cohort, we identified the 13 most common treatment regimens at MDD diagnosis (Appendix 5). Among these, antidepressant was the most common, with 25.1% of patients starting on an antidepressant monotherapy, and 8.7% continuing to take it after BP‐I diagnosis (Figure 1). Surprisingly, in our initially BP‐I diagnosed cohort, 7.6% received an antidepressant monotherapy at index. At MDD diagnosis, only 8.7% of patients were on 3+ unique drug classes, and after BP‐I diagnosis that number rose to 16.6% (Figure 2). At BP‐I diagnosis, AA monotherapy was utilized in approximately 4.3% of the misdiagnosed cohort and 9.4% of the initially BP‐I diagnosed cohort. Similarly, mood stabilizers were used in about 6.4% of the misdiagnosed cohort and 11.1% of the initially BP‐I diagnosed cohort, despite both being primary guideline‐recommended therapies. The five most common treatment regimens in both of our cohorts were Antidepressant monotherapy, Antidepressant + Anxiolytic, Antidepressant + Mood Stabilizer, Mood Stabilizer monotherapy, and Atypical Antipsychotics.
FIGURE 1.
Psychotropic Medication Utilization by Initial Diagnosis and Treatment Stage: Proportional breakdown of the most common treatment regimens (antidepressants, mood stabilizers, and their combinations) in patients misdiagnosed (n = 21,771) with MDD and those initially diagnosed with BP‐I (n = 50,667), both before and after BP‐I diagnosis. Abbreviations: AA, atypical antipsychotic; AD; antidepressant, Anx; anxiolytic, BP‐I; bipolar I‐disorder, Dx; diagnosis, MDD; major depressive disorder, MS; mood stabilizer.
FIGURE 2.
Psychotropic Drug Classes Utilization by Initial Diagnosis and Treatment Stage: Proportional breakdown for the number of drug classes in patients misdiagnosed (n = 21,771) with MDD (at 3 time points) and those initially diagnosed with BP‐I (n = 50,667).
In the misdiagnosed group, time until BP‐I conversion varied based on their initial treatment regimen (Figure 3). Mood stabilizer monotherapy was associated with the highest hazard compared to antidepressant monotherapy (1.26, 95% CI: 1.19–1.34, p < 0.001), implying that mood stabilizer monotherapy as the first post‐MDD diagnosis treatment is associated with an earlier BP‐I conversion after misdiagnosis (Table 4). Compared to females, males had a significantly higher rate of BP‐I conversion (1.09, 95% CI: 1.06–1.12, p < 0.001). Additionally, higher comorbidity scores were associated with a reduced rate of BP‐I conversion. Specifically, the DSM‐V comorbidity score was associated with a rate ratio of 0.95 (95% CI: 0.93–0.97, p < 0.001), while Elixhauser comorbidity score had a rate ratio of 0.98 (95% CI: 0.95–1.00, p < 0.05), suggesting that higher comorbidity may delay the time to BP‐I diagnosis.
FIGURE 3.
Kaplan–Meier Analysis of Time to BP‐I Conversion by Initial Treatment Regimen: A Kaplan–Meier curve demonstrating the time to BP‐I conversion for patients misdiagnosed with MDD, stratified by their first psychotropic treatment regimen. Mood stabilizers, antidepressants, and combination therapies are compared for their impact on earlier BP‐I conversion.
TABLE 4.
Multinomial logistic regression for first treatment regimen after BP‐I diagnosis.
| Antidepressant + anxiolytic | Anxiolytic | Antidepressant + mood stabilizer | Mood stabilizer | Other | |
|---|---|---|---|---|---|
| Intercept | −1.52 (−1.67, −1.37)*** | −1.60 (−1.74, −1.46)*** | −0.93 (−1.04, −0.81)*** | −0.55 (−0.66, −0.44)*** | 0.24 (0.16, 0.33)*** |
| correct Dx | 0.06 (−0.02, 0.14) | 0.48 (0.41, 0.56)*** | 0.61 (0.55, 0.68)*** | 0.97 (0.91, 1.03)*** | 1.29 (1.24, 1.34)*** |
| Age | 0.01 (0.01, 0.01)*** | 0.01 (0.01, 0.01)*** | 0.01 (0.00, 0.01)*** | 0.00 (0.00, 0.00)** | 0.00 (0.00, 0.00)** |
| Sex Male | −0.28 (−0.37, −0.20)*** | −0.10 (−0.17, −0.02)* | 0.03 (−0.04, 0.09) | 0.25 (0.20, 0.31)*** | 0.12 (0.07, 0.16)*** |
| Setting of diagnosis (Ref: outpatient) | |||||
| Inpatient | 0.43 (0.26, 0.60)*** | −0.08 (−0.26, 0.10) | 0.18 (0.03, 0.33)* | −0.02 (−0.16, 0.12) | 0.29 (0.18, 0.40)*** |
| Telehealth | −0.09 (−0.25, −0.08) | −0.09 (−0.24, 0.06) | −0.15 (−0.28, −0.01)* | −0.10 (−0.21, 0.01) | −0.13 (−0.22, −0.04)** |
| Emergency room | 0.27 (−0.01, 0.56) | 0.06 (−0.23, 0.35) | 0.14 (−0.11, 0.39) | −0.15 (−0.40, 0.09) | 0.31 (0.13, 0.49)*** |
| Other | −0.056 (−0.20, 0.091) | −0.08 (−0.22, 0.06) | 0.15 (0.04, 0.27)** | 0.06 (−0.05 0.16) | 0.03 (−0.05, 0.12) |
| Provider type (Ref: Psychiatrist) | |||||
| Family practice | −0.13 (−0.26, 0.00) | −0.15 (−0.27, −0.03)* | −0.47 (−0.58, −0.36)*** | −0.34 (−0.44, −0.25)*** | −0.35 (−0.42, −0.27)*** |
| Nurse practicioner | 0.06 (−0.11, 0.24) | 0.01 (−0.15, 0.17) | −0.16 (−0.30, −0.02)* | −0.14 (−0.27, −0.01)* | −0.18 (−0.28, −0.08)*** |
| Therapist | −0.24 (−0.39, −0.09)** | −0.22 (−0.36, −0.09)** | −0.33 (−0.45, −0.22)*** | −0.21 (−0.31, −0.11)*** | −0.05 (−0.13, 0.03) |
| Internal Medicine | −0.19 (−0.38, −0.00)* | −0.16 (−0.33, 0.02) | −0.33 (−0.49, −0.18)*** | −0.23 (−0.37, −0.09)*** | −0.25 (−0.36, −0.14)*** |
| Mental health facility | 0.16 (−0.10, 0.42) | −0.34 (−0.63, −0.06)* | −0.09 (−0.31, 0.12) | −0.22 (−0.42, −0.01)* | −0.01 (−0.17, 0.15) |
| Acute care hospital | −0.03 (−0.17, 0.12) | 0.01 (−0.13, 0.14) | −0.09 (−0.21, 0.03) | −0.00 (−0.11, 0.11) | 0.02 (−0.06, 0.11) |
| Other | 0.04 (−0.08, 0.15) | 0.02 (−0.09, 0.12) | −0.13 (−0.22, −0.04)** | −0.02 (−0.10, 0.06) | −0.03 (−0.09, 0.04) |
| DSM | 0.21 (0.16, 0.27)*** | 0.20 (0.14, 0.26)*** | 0.06 (0.00, 0.11)* | 0.03 (−0.02, 0.08) | 0.19 (0.16, 0.23)*** |
| Elixhauser | −0.04 (−0.11, 0.03) | −0.06 (−0.13, 0.01) | −010 (−0.16, −0.03)** | −0.09 (−0.15, −0.03)** | −0.03 (−0.07, 0.02) |
Note: Multinomial logistic regression results showing the influence of initial misdiagnosis on the likelihood of receiving different drug regimens after a BP‐I diagnosis. Covariates include age, sex, healthcare setting, provider type, and comorbidity indices. p‐value: < 0.05*, < 0.01**, < 0.001***.
4. Discussion
We conducted a retrospective cohort study to describe patient characteristics, treatment patterns and assess time until BP‐I conversion in patients who were initially misdiagnosed with MDD. We found that most patients were initially diagnosed with MDD in an outpatient setting (78.0%) though that number was lower (64.9%) at the conversion to BP‐I. Consistent with that finding, we had seen over a 2‐fold increase in converted BP‐I diagnoses in an inpatient setting and through telehealth, which may be explained by a more severe event taking place that led to BP‐I diagnosis (i.e., manic episode leading to a hospitalization; [10]). The increase in telehealth diagnosing may also be due to our study timeline overlapping with the Covid‐19 pandemic.
Bipolar‐I disorder presents a diagnostic conundrum in clinical practice, often masquerading as MDD during initial presentation. Previous literature has highlighted liabilities with misdiagnosis, particularly the risk of initiating ineffective treatments, such as antidepressant monotherapy in individuals with BP‐I [11]. Literature has shown that antidepressant monotherapy, which 25% of our misdiagnosed cohort was taking at their MDD diagnosis, lacks efficacy in treating bipolar depression [12]. Our study underlines these findings, emphasizing the need for accurate identification of BP‐I to mitigate risks associated with inappropriate treatments. We noticed that even after BP‐I diagnosis following an initial MDD diagnosis, patients were still receiving treatments that do not align with evidence‐based treatment guidelines, including antidepressant monotherapy [13]. Our study also revealed that BP‐I patients with a history of MDD diagnosis are more likely to continue antidepressant monotherapy than those initially diagnosed with BP‐I.
Given the risk of mania associated with antidepressant monotherapy, it was initially expected that patients would convert to BP‐I more quickly [14]. Contrarily, recent literature has shown that antidepressant‐induced mania is negligible [15]. We found that patients on antidepressant monotherapy had faster time to BP‐I conversion compared to those taking antidepressants in combination with either anxiolytics or mood stabilizer, and those taking mood stabilizer monotherapy. This outcome might be explained by patients with an MDD diagnosis displaying clinical manifestations or histories indicative of a potential BP‐I diagnosis. Additionally, this study did not differentiate the MDD cohort by specifiers, and according to the DSM‐5, mixed features associated with a major depressive episode have been found to be a significant risk factor for the development of bipolar I or bipolar II disorder [16]. Consequently, patients within this cohort who were already at increased risk for BP‐I may have more frequently received mood stabilizer monotherapy instead of antidepressant monotherapy.
There are several limitations of our study. First, the diagnosis of BP‐I is not possible until the first presence of manic or mixed symptoms, thus many patients first present with an acute depressive episode, without experiencing a manic episode [17]. This can be indicative that some patients were not misdiagnosed through poor assessment, but that their illness trajectory had not converted to a definitive BP‐I diagnosis yet. Additionally, the study's criteria may not fully reflect real‐world clinical settings, and the timeline may not have been long enough to capture the full duration of misdiagnosis, which existing literature estimates to average around 6.7 years. Importantly we grabbed snapshots in time via claims, and therefore cannot make conclusion about what was happening in between these time points. Finally, this analysis was on full‐time employees with employer sponsored private insurance which may not be generalizable to the full U.S. population. This is especially important in our population because low levels of household income are associated with several lifetime mental disorders including bipolar disorder [18].
BP‐I can be extremely challenging due to the complexity of presentation and subjective diagnostic criteria, though there are more common presentations of symptoms in BP‐I patients [19, 20]. For example, earlier onset of first depressive episode, shorter depressive episodes, and family history of BP‐I are all factors that can guide clinicians toward a BP‐I diagnosis. Previous literature also reveals disparities in screening tools between MDD and BP‐I. Most healthcare providers rely on tools to screen for depression but do not use any to assess BP‐I [21]. There is a need for more frequent use of screening tools like the Mood Disorder Questionnaire (MDQ) or the Rapid Mood Screener (RMS) in patients suspected to have MDD to increase the likelihood of capturing BP‐I. Our study highlights the need to correctly diagnose BP‐I early and efficiently. By prioritizing initial correct diagnosis of BP‐I, we can mitigate the risks associated with misdiagnosis, optimize treatment selection, and improve overall patient care.
5. Conclusion
Among the 21,771 BP‐I patients who were misdiagnosed with MDD, a significant proportion (28.5%) were started on antidepressant monotherapy at MDD diagnosis, in contrast to the 11.2% in the initially BP‐I diagnosed cohort of 50,667 patients. Additionally, 13.3% continued this treatment even after an established BP‐I diagnosis. About 1% of misdiagnosed patients received an Atypical Antipsychotic When these patients received mood stabilizer monotherapy they had a 26% higher hazard for earlier onset of a BP‐I diagnosis (HR: 1.26, 95% CI: 1.19–1.34, p < 0.001).
Odds of receiving the first treatment regimen also significantly differed based on initial diagnosis. Patients initially correctly diagnosed with BP‐I had 61% greater odds of being prescribed anxiolytic monotherapy (OR = 1.61, p < 0.001), 84% greater odds of being prescribed an antidepressant combined with a mood stabilizer (OR = 1.84, p < 0.001), and were 2.63 times more likely to be prescribed mood stabilizer monotherapy (OR = 2.63, p < 0.001) compared to those initially misdiagnosed with MDD.
Acknowledgments
We would like to thank Mousam Parikh for her valuable contributions to this work. We also acknowledge the support of AbbVie for facilitating this research by providing access to MarketScan data, which was instrumental in conducting our analyses. Special thanks to Lakshmi Kandukuri and Shihan Jin for their insight and feedback throughout this project.
Appendix 1. ICD‐10 Codes for Bipolar‐I Disorder and Major Depressive Disorder.
| ICD‐10‐CM Code | Code description |
|---|---|
| BP‐I Disorder | |
| F30 | Manic episode |
| F30.1 | Manic episode without psychotic symptoms |
| F30.10 | Manic episode without psychotic symptoms, unspecified |
| F30.11 | Manic episode without psychotic symptoms, mild |
| F30.12 | Manic episode without psychotic symptoms, moderate |
| F30.13 | Manic episode, severe, without psychotic symptoms |
| F30.2 | Manic episode, severe with psychotic symptoms |
| F30.3 | Manic episode in partial remission |
| F30.4 | Manic episode in full remission |
| F31 | Bipolar disorder |
| F31.0 | Bipolar disorder, current episode hypomanic |
| F31.1 | Bipolar disorder, current episode manic without psychotic features |
| F31.10 | Bipolar disorder, current episode manic without psychotic features, unspecified |
| F31.11 | Bipolar disorder, current episode manic without psychotic features, mild |
| F31.12 | Bipolar disorder, current episode manic without psychotic features, moderate |
| F31.13 | Bipolar disorder, current episode manic without psychotic features, severe |
| F31.2 | Bipolar disorder, current episode manic severe with psychotic features |
| F31.3 | Bipolar disorder, current episode depressed, mild or moderate severity |
| F31.30 | Bipolar disorder, current episode depressed, mild or moderate severity, unspecified |
| F31.31 | Bipolar disorder, current episode depressed, mild |
| F31.32 | Bipolar disorder, current episode depressed, moderate |
| F31.4 | Bipolar disorder, current episode depressed, severe, without psychotic features |
| F31.5 | Bipolar disorder, current episode depressed, severe, with psychotic features |
| F31.6 | Bipolar disorder, current episode mixed |
| F31.60 | Bipolar disorder, current episode mixed, unspecified |
| F31.61 | Bipolar disorder, current episode mixed, mild |
| F31.62 | Bipolar disorder, current episode mixed, moderate |
| F31.63 | Bipolar disorder, current episode mixed, severe, without psychotic features |
| F31.64 | Bipolar disorder, current episode mixed, severe, with psychotic features |
| F31.7 | Bipolar disorder, currently in remission |
| F31.71 | Bipolar disorder, in partial remission, most recent episode hypomanic |
| F31.72 | Bipolar disorder, in full remission, most recent episode hypomanic |
| F31.73 | Bipolar disorder, in partial remission, most recent episode manic |
| F31.74 | Bipolar disorder, in full remission, most recent episode manic |
| F31.75 | Bipolar disorder, in partial remission, most recent episode depressed |
| F31.76 | Bipolar disorder, in full remission, most recent episode depressed |
| F31.77 | Bipolar disorder, in partial remission, most recent episode mixed |
| F31.78 | Bipolar disorder, in full remission, most recent episode mixed |
| Major Depressive Disorder | |
| F32 | Major depressive disorder, single episode |
| F32.0 | Major depressive disorder, single episode, mild |
| F32.1 | Major depressive disorder, single episode, moderate |
| F32.2 | Major depressive disorder, single episode, severe without psychotic features |
| F32.3 | Major depressive disorder, single episode, severe with psychotic features |
| F32.4 | Major depressive disorder, single episode, in partial remission |
| F32.5 | Major depressive disorder, single episode, in full remission |
| F32.9 | Major depressive disorder, single episode, unspecified |
| F33 | Major depressive disorder, recurrent |
| F33.0 | Major depressive disorder, recurrent, mild |
| F33.1 | Major depressive disorder, recurrent, moderate |
| F33.2 | Major depressive disorder, recurrent severe without psychotic features |
| F33.3 | Major depressive disorder, recurrent, severe with psychotic symptoms |
| F33.4 | Major depressive disorder, recurrent, in remission |
| F33.40 | Major depressive disorder, recurrent, in remission, unspecified |
| F33.41 | Major depressive disorder, recurrent, in partial remission |
| F33.42 | Major depressive disorder, recurrent, in full remission |
| F33.9 | Major depressive disorder, recurrent, unspecified |
| Schizophrenia | |
| F20 | Schizophrenia |
| F20.0 | Paranoid schizophrenia |
| F20.1 | Disorganized schizophrenia |
| F20.2 | Catatonic schizophrenia |
| F20.3 | Undifferentiated schizophrenia |
| F20.5 | Residual schizophrenia |
| F20.8 | Other schizophrenia |
| F20.81 | Schizophreniform disorder |
| F20.89 | Other schizophrenia |
| F20.9 | Schizophrenia, unspecified |
| F25 | Schizoaffective disorders |
| F25.0 | Schizoaffective disorder, bipolar type |
| F25.1 | Schizoaffective disorder, depressive type |
| F25.8 | Other schizoaffective disorders |
| F25.9 | Schizoaffective disorder, unspecified |
Note: A detailed list of ICD‐10 diagnosis codes used to identify BP‐I and MDD in the study population.
Appendix 2. Study Population Attrition and Cohort Selection.
Flowchart and accompanying table detailing the criteria for inclusion/exclusion at each stage of cohort selection, including the number of patients removed at each step.
Appendix 3. Elixhauser Comorbidity Index: ICD‐10 Codes.
| ICD‐10‐CM Code | Code description |
|---|---|
| Congestive heart failure | I09.9, I11.0, I13.0, I13.2, I25.5, I42.0, I42.5–I42.9, I43, I50, P29.0 |
| Cardiac arrhythmias | A52.0, I05–I08, I09.1, I09.8, I34–I39, Q23.0–Q23.3, Z95.2–Z95.4 |
| Valvular disease | A52.0, I05–I08, I09.1, I09.8, I34–I39, Q23.0–Q23.3, Z95.2–Z95.4 |
| Pulmonary circulation disorders | I26, I27, I28.0, I28.8, I28.9 |
| Peripheral vascular disease | I70, I81, I73.1, I73.8, I73.9, I77.1, I79.0, I79.2, K55.1, K55.8, K55.9, Z95.8, Z95.9 |
| Hypertension (combine uncomplicated and complicated) | Hypertension, uncomplicated: I10 Hypertension, complicated: I11–I13, I15 |
| Paralysis | G04.1, G11.4, G80.1, G80.2, G81, G82, G83.0–G83.4, G83.9 |
| Other neurological disorders | G10–G13, G20–G22, G25.4, G25.5, G31.2, G31.8, G31.9, G32, G35–G37, G40, G41, G93.1, G93.4, R47.0, R56 |
| Chronic pulmonary disease | I27.8, I27.9, J40–J47, J60–J67, J68.4, J70.1, J70.3 |
| Diabetes without chronic complications | E10.0, E10.1, E10.9, E11.0, E11.1, E11.9, E12.0, E12.1, E12.9, E13.0, E13.1, E13.9, E14.0, E14.1, E14.9 |
| Diabetes with chronic complications | E10.2–E10.8, E11.2–E11.8, E12.2–E12.8, E13.2–E13.8, E14.2–E14.8 |
| Hypothyroidism | E00–E03, E89.0 |
| Renal failure | I12.0, I13.1, N18, N19, N25.0, Z49.0–Z49.2, Z94.0, Z99.2 |
| Liver disease | B18, I85, I86.4, I98.2, K70, K71.1, K71.3–K71.5, K71.7, K72–K74, K76.0, K76.2–K76.9, Z94.4 |
| Chronic peptic ulcer disease | K25.7, K25.9, K26.7, K26.9, K27.7, K27.9, K28.7, K28.9 |
| HIV and AIDS | B20–B22, B24 |
| Lymphoma | C81–C85, C88, C96, C90.0, C90.2 |
| Metastatic cancer | C77–C80 |
| Solid tumor without metastasis | C00–C26, C30–C34, C37–C41, C43, C45–C58, C60–C76, C97 |
| Rheumatoid arthritis/collagen vascular diseases | L94.0, L94.1, L94.3, M05, M06, M08, M12, M12.3, M30, M31–M31.3, M32–M35, M45, M46, M46.8, M46.9 |
| Coagulation deficiency | D65–D68, D69.1, D69.3–D69.6 |
| Obesity | E66 |
| Weight loss | E40–E46, R63.4, R64 |
| Fluid and electrolyte disorders | E22.2, E86, E87 |
| Blood loss anemia | D50.0 |
| Deficiency anemias | D50.8, D50.9, D51–D53 |
| Alcohol abuse | F10, E52, G62.1, I42.6, K29.2, K70.0, K70.3, K70.9, T51, Z50.2, Z71.4, Z72.1 |
| drug abuse | F11–F16, F18, F19, Z71.5, Z72.2 |
| psychoses | F20, F22–F25, F28, F29, F30.2, F31.2, F31.5 |
| Depression | F20.4, F31.3–F31.5, F32, F33, F34.1, F41.2, F43.2 |
Note: A comprehensive list of ICD‐10 codes used to define the comorbidities included in the Elixhauser Comorbidity Index, which measures the overall burden of comorbid conditions in the study population.
Appendix 4. DSM‐5 Comorbidity Index: Psychiatric Disorders.
| Sleep–wake disorders | G47.00, G47.09, G47.10, G47.19, G47.8, G47.9, G47.419, G47.411, G47.429, G47.33, G47.31, R06.3, G47.37, G47.34, G47.35, G47.36, G47.21, G47.22, G47.23, G47.24, G47.26, G47.20, F51.3, F51.4, F51.5, G47.52, G25.81 |
| Anxiety disorders | F93.0, F94.0, F40.218, F40.228, F40.230, F40.231, F40.232, F40.233, F40.248, F40.298, F40.10, F41.0, F40.00, F41.1, F06.4, F41.8, F41.9 |
| Trauma‐ and stressor‐related disorders | F94.1, F94.2, F43.10, F43.0, F43.21, F43.22, F43.23, F43.24, F43.25, F43.20, F43.9, F43.8 |
| Neurodevelopmental disorders | F70, F71, F72, F73, F79, F88, F80.9, F80.0, F80.89, F80.81, F80.9, F84.0, F90.2, F90.1, F90.8, F90.9, F90.0, F81.0, F81.81, F81.2, F82, F98.4, F95.2, F95.1, F95.0, F95.8, F95.9, F89 |
| Medication‐induced movement disorders and other adverse effects of medication | G21.11, G21.19, G21.0, G24.02, G24.09, G25.71, G25.79, G24.01, G25.1, T43.205A, T43.205D, T43.205S, T50.905A, T50.905D, T50.905S |
| Bipolar and related disorders | F31.11, F31.12, F31.13, F31.2, F31.73, F31.74, F31.9, F31.0, F31.31, F31.32, F31.4, F31.5, 31.75, F31.76, F31.9, F31.81, F31.89, F34.0, F06.33, F06.34, F06.31, F06.32, F31.9 |
| Neurocognitive disorders | F05, R41.0, G31.84, G31.9, F02.81, F02.80, F01.50, F01.51, R41.9 |
| Obsessive‐compulsive and related disorders | F42, F63.2, L98.1, F06.8 |
| Sexual dysfunctions | F52.32, F52.21, F52.22, F52.31, F52.6, F52.0, F52.4, F52.8, F52.9 |
| Schizophrenia spectrum and other psychotic disorders | F21, F22, F23, F20.81, F20.9, F25.0, F25.1, F06.2, F06.0, F06.1, F28, F29 |
| Depressive disorders | F34.8, F32.0, F32.1, F32.2, F32.3, F32.4, F32.5, F32.9, F33.0, F33.1 F33.2, F33.3, F33.41, F33.42, F33.9, F34.1, N94.3, F32.8, F32.9 |
| Elimination disorders | F98.0, F98.1, N39.498, R32, R15.9 |
| Personality disorders | F60.0, F60.1, F60.3, F60.4, F60.81, F60.6, F60.7, F60.5, F07.0, F60.89, F60.9 |
| Somatic symptom and related disorders | F45.1, F45.9, F45.21, F45.22, F44.4, F44.5, F44.6, F44.7, F54, F68.10, F45.8 |
| Dissociative disorders | F44.81, F44.0, F44.1, F48.1, F44.89, F44.9 |
| Feeding and eating disorders | F98.3, F50.8, F98.21, F50.01, F50.02, F50.2, F50.9 |
| Disruptive, impulse‐control, and conduct disorders | F91.3, F63.81, F91.1, F91.2, F63.3, F91.9, F91.8, F60.2, F63.1, F91.9 |
| Gender dysphoria | F64.2, F64.8, F64.9, F64.1 |
| Paraphilic disorders | F65.3, F65.2, F65.81, F65.89, F65.51, F65.52, F65.4, F65.0, F65.1, F65.9 |
| Gambling disorder | F63.0 |
| Other mental disorders | F09, F99 |
| Other conditions that may be a focus of clinical attention | Z62.820, Z62.891, Z62.29, Z63.8, Z62.898, Z63.0, Z63.5, Z63.4, T74.12XA, T74.12XD, T76.12XA, T76.12XD, T74.22XA, T74.22XD, T76.22XA, T76.22XD, T74.02XA, T74.02XD, T76.02XA, T76.02XD, T74.32XA, T74.32XD, T76.32XA, T76.32XD, Z69.010, Z69.020, Z69.011, Z62.812, Z62.811, Z91.412, Z91.411, T74.11XA, T74.11XD, T76.11XA, T76.11XD, T74.31XA, T74.31XD, T76.31XA, T76.31XD, T74.21XA, T74.21XD, T76.21XA, T76.21XD, T74.01XA, T74.01XD, T76.01XA, T76.01XD, Z69.11, Z69.81, Z69.12, Z70.9, Z69.81, Z69.82, Z69.021, Z62.810, Z91.410, Z55.9, Z56.82, Z56.9, Z59.0, Z59.1, Z59.2, Z59.3, Z59.4, Z59.5, Z59.6, Z59.7, Z59.9, Z60.0, Z65.4, Z65.8, Z64.4, R41.83 V, Z60.2, Z60.3, Z60.4, Z60.5, Z65.0, Z65.1, Z65.2, Z65.3, Z64.0, Z64.1, Z65.5, Z91.82, Z60.9, Z65.9, Z71.9, Z91.49, Z91.5, Z91.89, Z72.9, Z72.811, Z72.810, Z75.3, Z75.4, Z91.19, E66.9, Z76.5, Z91.83 |
| Mental retardation | F70, F71, F72, F73, F74, F75, F76, F78, F79 |
Note: A list of DSM‐5 psychiatric comorbidities (e.g., anxiety disorders, neurodevelopmental disorders) included in the study's comorbidity analysis, with corresponding ICD‐10 codes.
Appendix 5. Extended Treatment Patterns by Regimen and Diagnosis Stage.
| Misdiagnosed (n = 21,771) | Control (n = 50,667) | |||
|---|---|---|---|---|
| 1st Regimen after MDD(%) | Final regimen of MDD(%) | 1st Regimen after BP‐I(%) | 1st Regimen after BP‐I(%) | |
| Treatment Regimen | ||||
| Antidepressant | 25.1 | 14.0 | 8.7 | 7.6 |
| Antidepressant + Anxiolytic | 7.7 | 4.3 | 3.1 | 2.3 |
| Antidepressant + Mood Stabilizer | 5.5 | 6.7 | 6.8 | 6.5 |
| Mood stabilizer | 5.1 | 8.3 | 6.4 | 11.1 |
| Anxiolytic | 5.5 | 6.6 | 4.3 | 5.6 |
| Antidepressant + Atypical Antipsychotic | 4.6 | 6.1 | 6.0 | 4.9 |
| Atypical Antipsychotic | 4.3 | 7.4 | 6.0 | 9.4 |
| Antidepressant + Anxiolytic + Mood Stabilizer | 3.0 | 4.1 | 5.4 | 3.8 |
| Psychostimulant | 2.7 | 2.7 | 2.7 | 3.2 |
| Antidepressant +Psychostimulant | 2.3 | 1.7 | 2.0 | 1.3 |
| Anxiolytic + Mood Stabilizer | 2.1 | 3.3 | 3.3 | 4.0 |
| Atypical Antipsychotic + Mood Stabilizer | 1.6 | 3.2 | 4.5 | 6.0 |
| Sedative/Hypnotic | 0.7 | 0.6 | 0.5 | 0.7 |
| Other | 29.8 | 31.0 | 40.3 | 33.6 |
Note: *Other consisted of 5000+ potential combinations of psychotropics for the seven drug classes: Antidepressant, Anxiolytics, Mood Stabilizers, Psychostimulants, Atypical Antipsychotics, Typical Antipsychotics, and Sedative/Hypnotics. This appendix provides a detailed breakdown of psychotropic treatment patterns in patients misdiagnosed with MDD and those correctly diagnosed with BP‐I, comparing treatment changes before and after BP‐I diagnosis.
Data Availability Statement
The data that support the findings will be available in IBM MarketScan Commercial Claims and Encounters Database at https://www.ibm.com/products/marketscan%E2%80%90research%E2%80%90databases following an embargo from the date of publication to allow for commercialization of research findings.
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Data Availability Statement
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