Abstract
BACKGROUND:
Bipolar I disorder (BP-I) is a chronic and recurrent mental health disorder, broadly characterized by patients who alternate between the extremes of the mood spectrum: mania or hypomania; and depression. In 2015, the total estimated annual cost of BP-I in the United States reached more than $200 billion, approximately 2.5 times higher than the general population, largely driven by the increased use of acute health care services. Long-acting injectable antipsychotics such as aripiprazole were developed to significantly reduce patient burden for treatment adherence compared with oral formulations, to allow consistent dosing and improved outcomes. Previous real-world evidence studies have shown the benefits of starting aripiprazole once-monthly injection (AOM) at an early stage in patients diagnosed with schizophrenia; however, the effect of early initiation in the BP-I population remains unknown.
OBJECTIVE:
To evaluate the impact of initiating AOM 400 mg (AOM 400) in adults at an early stage (<180 days) following a diagnosis of BP-I compared with late initiation (>365 days) in a real-world setting, via a retrospective analysis using claims data from the MarketScan Medicaid database.
METHODS:
Study outcomes included the numbers of emergency department, hospitalization, outpatient, and pharmacy visits, together with the associated costs over a 1-year time horizon. A generalized linear model was used to compare the annualized costs associated with early, intermediate, and late initiators of treatment, using late initiators as the main reference group.
RESULTS:
Among 866 patients diagnosed with BP-I (median age, 36 years), 161 early initiators had significantly lower risks of emergency department visits (incidence rate ratio = 0.76; 95% CI, 0.61-0.94) and outpatient pharmacy visits (incidence rate ratio = 0.82; 95% CI, 0.73-0.93) compared with 591 late initiators. Early initiators also incurred lower pharmacy visit costs ($18,787 vs $23,503; P = 0.03) and lower medical costs ($13,898 vs $18,277; P = 0.01). Overall, early initiators incurred much lower total health care costs than late initiators during the follow-up ($31,086 vs $40,599, respectively; P < 0.001). Early initiators also incurred significantly lower total health care costs than intermediate initiators ($31,086 vs $40,892; P = 0.01).
CONCLUSIONS:
This real-world study demonstrates that early initiation of AOM 400 among patients living with BP-I may offer a significant advantage of lower health care resource utilization and associated costs when compared with late initiation.
Plain language summary
Aripiprazole (aripiprazole once-monthly 400 mg [AOM 400]) is a once-monthly medication for the treatment of bipolar I disorder (BP-I). This study found that patients who started AOM 400 early in their illness used fewer health care services than those who started treatment later. This included fewer emergency department visits and outpatient pharmacy visits. Starting treatment earlier, rather than later, was related to lower overall health care costs.
Implications for managed care pharmacy
Long-acting injectable antipsychotic medications are recommended in clinical guidelines for maintenance treatment of BP-I to control symptoms and reduce recurrence rates. The use of AOM 400 for patients diagnosed with early-stage BP-I has been shown to significantly prolong the time to recurrence of mood episodes. This study showed that early initiation of AOM 400 also results in lower health care resource utilization, fewer pharmacy visits, and lower medical costs than later initiation.
Bipolar disorder (BD) is a severe, recurrent, lifelong episodic psychiatric disorder characterized by episodes of mania, hypomania, and/or depression. The lifetime prevalence of BD was estimated to be 2.1% in the United States in 2017,1 most often emerging during adolescence or early adulthood.2 BD is a leading cause of disability among young people and can negatively impact personal, social, and occupational functioning and quality of life.3 Furthermore, BD substantially impedes psychosocial functioning and is associated with a loss of approximately 10 to 20 potential years of life.4
Bipolar I disorder (BP-I) is a subtype of BD that is characterized by the presence of 1 or more manic episodes and accounts for approximately one-quarter of all BD cases.2,3 In a prospective, randomized controlled trial evaluating tailored psychological interventions in young patients diagnosed with BP-I, early disease was defined as at least 1 manic episode in the previous 2 years, with no more than 5 lifetime treated/untreated manic or hypomanic episodes.5 “Early” BP-I has since been defined according to the number of manic or hypomanic episodes, while a systematic review of interventions in the early course of BP-I or type 2 BD (BP-II) defined early disease as seeking help for the first time for a manic episode, a lifetime history of up to 3 manic episodes, or up to 6 lifetime mood episodes.6
The total annual economic burden of BP-I in the United States was estimated to be more than $200 billion in 2015, equating to an average of $82,000 per individual, which included $51 billion in direct health care expenses and $159 billion in indirect costs associated with unemployment or lost work productivity for patients and caregivers.7 The largest contributors to excess costs were caregiving (36%), direct health care costs (21%), and unemployment (20%).
Antipsychotic therapies, particularly long-acting injectable (LAI) antipsychotic medications with or without mood-stabilizing properties, are recommended in the current clinical guidelines for the maintenance treatment of BP-I. These medications have been shown to be important in achieving and maintaining symptom control, reducing recurrence rates in BP-I, and maximizing patients’ quality of life.8-10 LAI formulations of antipsychotic medications that can be administered biweekly, monthly, once every 2 months, or at longer intervals are available. These offer several advantages compared with oral medications, including patients not needing to remember to take medications daily, reducing the risk of unintentional or deliberate overdose, and improving adherence. Real-world evidence suggests that, compared with oral antipsychotics, LAI antipsychotics are associated with significant improvements in treatment adherence in patients with BD.8 They also provide clinical benefits such as lower rates of relapse, a reduced risk of hospitalization, and fewer visits to emergency departments, accompanied by improved functioning and better quality of life.11
Aripiprazole once-monthly 400 mg (AOM 400) is a third-generation LAI antipsychotic formulation that was approved in the United States in 2017 for the maintenance monotherapy treatment of BP-I in adult patients.12 AOM 400 is administered via a single intramuscular injection once monthly. The efficacy of AOM 400 as a maintenance treatment for BP-I was established in 2 randomized, placebo-controlled studies.13,14 A post hoc analysis of data from a 52-week multicenter, double-blind, placebo-controlled, randomized trial in patients diagnosed with BP-I14 showed that the use of AOM 400 in patients with earlier-stage BP-I significantly prolonged the time to recurrence of any mood episode, compared with placebo.15 However, although previous real-world evidence studies have shown the benefits of starting AOM 400 early in patients with schizophrenia,16,17 the effect of early initiation in the general BP-I population remains unknown.
The objective of this study was to examine the association between the timing of AOM 400 treatment initiation and health care resource utilization, hospitalization, and associated costs in individuals with a diagnosis of BP-I in a real-world setting.
Methods
STUDY DESIGN
This retrospective cohort study used the Merative MarketScan Multi-State Medicaid real-world database to identify patients diagnosed with BP-I who had received AOM 400. The MarketScan Multi-State Medicaid database captures real-world treatment trends and costs by monitoring millions of patients as they navigate the health care system, providing comprehensive insights into their care journey. The closed-claims database contains the medical, surgical, and prescription drug experience of Medicaid enrollees and provides a rich source of data on patients with BP-I.
The study includes data on patients who received AOM 400 between January 2017 and December 2021. The first initiation of AOM 400 after a diagnosis of BP-I during the inclusion period was identified as the index date. The period prior to AOM 400 initiation was defined as the pre-index period, and the period after AOM 400 as post-index. The pre-index period was 30 months prior to AOM 400 initiation including a baseline period of 6 months. The post-index period (follow-up) was the subsequent 12 months during which the primary objectives were evaluated (Supplementary Figure 1 (98.8KB, pdf) , available in online article).
STUDY POPULATION AND SETTING
To be included in the study, patients were required to have received AOM 400 in the identification period from January 1, 2017, to December 31, 2021. The first AOM 400 claim during the identification period was defined as the index date. A continuous enrollment criterion of 30 months pre-index and 12 months post-index was applied to accurately capture all the claims activities related to patients’ BP-I diagnoses and health care resource utilization (HCRU). Patients were required to have at least 1 inpatient or 2 outpatient claims for BP-I (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]: 296.0X, 296.1X, 296.4X, 296.5X, 296.6X, 296.7X, 296.80, 296.81; International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM]: F31.0, F31.1X, F31.2, F31.3X, F31.4, F31.5, F31.6X, F31.7X, F31.89, F31.9, excluding F31.81), within 24 months prior to the index date and were required to be aged at least 18 years at the time of diagnosis.
Patients were excluded if they had a diagnosis (1 or more claims) of schizophrenia (ICD-9-CM: 295.X; ICD-10-CM: F20.X) or schizoaffective disorder during the study period (Supplementary Figure 1 (98.8KB, pdf) ). Patients who received AOM 400 within 6 months prior to their BP-I diagnosis were excluded. A 30-month pre-index enrollment window allowed us to effectively account for a BP-I diagnosis time frame of 24-month and 6-month washout periods for AOM before BP-I diagnosis.
EXPOSURE
The categorization of initiators of AOM 400 was based on earlier work by Waters et al that evaluated the cost and HCRU burden among patients receiving AOM 400 within 1 year after diagnosis.17 Three cohorts were defined based on the timing between BP-I diagnosis and a new episode of care with AOM 400 during the study period, which served as the main exposure in this study. Patients diagnosed with BP-I who initiated AOM 400 less than 180 days after diagnosis were categorized as “early initiators,” those receiving AOM 400 between 180 and 365 days as “intermediate initiators,” and those receiving AOM 400 more than 365 days after BP-I diagnosis as “late initiators.”
STUDY VARIABLES
The following baseline measures were reported for patients with a diagnosis of BP-I during the 6 months prior to the index date (Supplementary Table 1 (98.8KB, pdf) ): patient demographic characteristics (age, sex, comorbidities [Charlson Comorbidity Index; CCI]); psychiatric comorbidities (major depressive disorder, anxiety, personality disorder, substance abuse disorders, posttraumatic stress disorder); psychiatric medications (oral antipsychotics, LAI antipsychotics, antidepressants, anxiolytics, sedatives or hypnotics, mood stabilizers); nonpsychiatric comorbidities associated with antipsychotic use (obesity, diabetes mellitus, hyperlipidemia, hypertension, asthma, chronic obstructive pulmonary disease, obstructive sleep apnea); and nonpsychiatric medications associated with the treatment of metabolic disorders (antidiabetic medications, lipid-lowering agents, antihypertensives).
OUTCOME MEASURES
The primary outcome measures of patients who initiated AOM 400 collated for analysis over a 1-year follow-up (post-index) period were the all-cause HCRU and associated costs, including the number of outpatient and emergency department visits, outpatient pharmacy visits, and hospitalizations.
DATA ANALYSIS
Descriptive statistics included mean, SD, and relative frequencies and percentages for continuous and categorical data, respectively. The overall differences between early, intermediate, and late initiators were assessed using the Kruskal-Wallis test for continuous variables, or the χ2 test, as appropriate, based on distributional assumptions for categorical variables. HCRU was analyzed using negative binomial regression, and incidence rate ratios (IRRs) together with 95% CIs were reported. Negative binomial regression was selected over Poisson regression owing to the presence of overdispersion in the data. To model the annualized cost for the 3 exposure categories, a generalized linear model (GLM) was used to assess the adjusted costs associated with outpatient, emergency department, hospitalization, and pharmacy visits. Total health care costs were calculated from the sum of the health care visit costs and pharmacy visit costs. In the GLM, a log link with γ distribution was used to account for skewness and heteroscedasticity that are commonly present in cost data.
All costs were also adjusted for inflation using the consumer price index for 2023. Both HCRU and cost models were adjusted using baseline variables that were significantly different between the 3 exposure categories and included age, CCI score, major depressive disorder, anxiety, antidepressant use, and chronic obstructive pulmonary disorder. P values for both the HCRU-based data model (negative binomial) and the cost-based GLM model were derived using late initiators as a reference group. All tests were 2-sided, and P < 0.05 was used to indicate statistical significance. All analyses were conducted using SAS 9.4 and R studio version 2022.07.1 (SAS Institute Inc.).
ETHICAL CONSIDERATIONS
The study was performed in full accordance with relevant legislation at the time of data collection, including the US Health Insurance Portability and Accountability Act 1996,18 and Health Information Technology for Economic and Clinical Health Act legislation.19 This study was noninterventional and only employed retrospective data collection; no tests, treatments, or investigations were performed as part of this survey, and no identifiable protected health information was extracted during the study.
Results
DEMOGRAPHIC AND CLINICAL CHARACTERISTICS
More than 15,000 patients diagnosed with BP-I treated with AOM 400 were identified in the MarketScan Medicaid database, of whom 866 fulfilled the criteria for inclusion in our study (Figure 1). The baseline and clinical characteristics of included patients are shown in Table 1. Differences in age were observed between early, intermediate, and late initiators (32, 34, and 37 years, respectively). Most patients in each category were male (≥70%), and differences were observed for CCI score, with a CCI of 3+ in 4%, 11%, and 12% of early, intermediate, and late initiators, respectively. A greater proportion of patients in the early initiator group had psychiatric diagnoses, with similar medications, mainly antipsychotics, in each cohort (Table 1). The most frequent nonpsychiatric comorbidity was hypertension, with antihypertensive agents also being the most frequent medications in each cohort (Table 1).
FIGURE 1.
Patient Selection
AOM 400 = aripiprazole once-monthly 400 mg; BP-I = bipolar I disorder; HCRU = health care resource utilization; ICD-9/10-CM = International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification; NDC = National Drug Code.
TABLE 1.
Baseline Demographic and Clinical Characteristics
| Variable | Early initiators (n = 161) | Intermediate initiators (n = 114) | Late initiators (n = 591) | P value |
|---|---|---|---|---|
| Age, median (IQR), years | 34 (25-41) | 32 (25-44) | 37 (28-47) | < 0.001 |
| Sex | 0.900 | |||
| Male | 113 (70) | 83 (73) | 427 (72) | |
| Female | 48 (30) | 31 (27) | 164 (28) | |
| CCI, n (%) | 0.033 | |||
| 0 | 116 (73) | 71 (62) | 340 (58) | |
| 1 | 31 (19) | 24 (21) | 142 (24) | |
| 2 | 7 (4) | 7 (6) | 40 (7) | |
| 3+ | 7 (4) | 12 (11) | 69 (12) | |
| Psychiatric comorbidities, n (%) | ||||
| Major depressive disorder | 90 (56) | 47 (41) | 220 (37) | < 0.001 |
| Anxiety | 118 (73) | 66 (58) | 364 (62) | 0.011 |
| Personality disorder | 24 (15) | 16 (14) | 92 (16) | 0.900 |
| Substance abuse disorder | 94 (58) | 44 (39) | 239 (40) | < 0.001 |
| Posttraumatic stress disorder | 57 (35) | 32 (28) | 190 (32) | 0.400 |
| Psychiatric medications, n (%) | ||||
| Anxiolytic | 44 (27) | 29 (25) | 144 (24) | 0.700 |
| Antidepressant | 117 (73) | 73 (64) | 355 (60) | 0.013 |
| Hypnotic | 24 (15) | 19 (17) | 97 (16) | 0.900 |
| Long-acting antipsychotic | 122 (76) | 81 (71) | 438 (74) | 0.700 |
| Oral antipsychotic | 130 (81) | 94 (82) | 482 (82) | 0.900 |
| Mood stabilizer | 19 (12) | 24 (21) | 102 (17) | 0.110 |
| Nonpsychiatric comorbidities, n (%) | ||||
| Diabetes | 13 (8.1) | 12 (11) | 86 (15) | 0.068 |
| Hyperlipidemia | 19 (12) | 12 (11) | 100 (17) | 0.093 |
| Hypertension | 37 (23) | 24 (21) | 152 (26) | 0.500 |
| Asthma | 16 (9.9) | 18 (16) | 81 (14) | 0.300 |
| Chronic obstructive pulmonary disease | 10 (6.2) | 6 (5.3) | 73 (12) | 0.013 |
| Nonpsychiatric medications, n (%) | ||||
| Antidiabetic | 10 (6.2) | 12 (11) | 64 (11) | 0.200 |
| Antihypertensive | 50 (31) | 30 (26) | 177 (30) | 0.700 |
| Lipid-lowering agent | 21 (13) | 16 (14) | 104 (18) | 0.300 |
P values represent overall differences among early, intermediate, and late initiators.
CCI = Charlson Comorbidity Index.
HEALTH CARE RESOURCE UTILIZATION
When comparing the visit-level information, early initiators had significantly lower emergency department and pharmacy visits compared with late initiators of AOM 400 (Table 2). Early initiators during 12-month follow-up post-index had 27% lower emergency visits (IRR = 0.76; 95% CI, 0.61-0.94; P = 0.01), whereas an 18% reduction in pharmacy visits was observed (IRR = 0.82; 95% CI, 0.73-0.93; P = 0.002). However, no differences were observed between early vs late treatment initiator categories on other HCRU metrics including outpatient visits (IRR = 0.87; 95% CI, 0.74-1.04; P = 0.12) and hospitalization (IRR = 0.90; 95% CI, 0.66-1.21; P = 0.47).
TABLE 2.
Impact of Time of Initiation of AOM 400 Treatment on Health Care Resource Utilization
| Time of initiation | IRR | 95% CI | P valuea | |
|---|---|---|---|---|
| Lower bound | Upper bound | |||
| Pharmacy visits | ||||
| Late | Reference population | |||
| Intermediate | 1.08 | 0.94 | 1.24 | 0.20 |
| Early | 0.82 | 0.73 | 0.93 | 0.002b |
| Outpatients | ||||
| Late | Reference population | |||
| Intermediate | 1.01 | 0.83 | 1.22 | 0.94 |
| Early | 0.87 | 0.74 | 1.04 | 0.12 |
| Emergency department | ||||
| Late | Reference population | |||
| Intermediate | 0.90 | 0.72 | 1.14 | 0.38 |
| Early | 0.76 | 0.61 | 0.94 | 0.01b |
| Hospitalization | ||||
| Late | Reference population | |||
| Intermediate | 1.26 | 0.87 | 1.81 | 0.21 |
| Early | 0.90 | 0.66 | 1.21 | 0.47 |
| Total medical visitsc | ||||
| Late | Reference population | |||
| Intermediate | 1.00 | 0.84 | 1.21 | 0.90 |
| Early | 0.87 | 0.74 | 0.97 | 0.09 |
P values are estimated using late initiators as the reference population. Model adjusted for age, comorbidity score, anxiety, antidepressant use, major depressive disorder, substance abuse disorder, and chronic obstructive pulmonary disease.
P < 0.05.
Total medical visits include outpatient and emergency department visits and number of hospitalizations.
AOM 400 = aripiprazole once-monthly 400 mg; IRR = incidence rate ratio.
When compared across all the categories of AOM 400 initiators, early initiation was consistently associated with lower all-cause health care costs. In adjusted GLM, early initiators incurred significantly lower pharmacy visit costs compared with late initiators ($18,787 vs $23,503, respectively; P = 0.03) (Table 3). Similarly, the outpatient-related cost was also lower for early initiators ($10,765 vs $14,356, respectively; P = 0.008). However, no differences were observed in the health care costs related to emergency department visits ($1,217 vs $1,564; P = 0.08) and hospitalization ($10,373 vs $13,816; P = 0.2) during the follow-up between early and late initiators (Table 3). Overall, when outpatient, emergency department, hospitalization, and pharmacy visit costs were combined to reflect the total health care cost, early initiators incurred much lower total health care costs than late initiators during the follow-up ($31,086 vs $40,599, respectively; P < 0.001) (Figure 2). Early initiators also incurred significantly lower total health care costs than intermediate initiators ($31,086 vs $40,892; P = 0.01).
TABLE 3.
Adjusted All-Cause Health Care Cost During the 1-Year Follow-Up Period After Initiation of AOM 400
| Estimated cost (US$) | 95% CI (US$) | P valuea | ||
|---|---|---|---|---|
| Lower bound | Upper bound | |||
| Pharmacy visit cost | ||||
| Late | 23,503 | 21,384 | 25,835 | |
| Intermediate | 24,810 | 19,998 | 30,779 | 0.65 |
| Early | 18,787 | 15,679 | 22,510 | 0.032b |
| Outpatient cost | ||||
| Late | 15,256 | 13,915 | 16,727 | |
| Intermediate | 15,489 | 12,560 | 19,099 | 0.89 |
| Early | 11,453 | 9,529 | 13,765 | 0.006b |
| Emergency department cost | ||||
| Late | 1,564 | 1,376 | 1,777 | |
| Intermediate | 1,246 | 939 | 1,654 | 0.15 |
| Early | 1,217 | 949 | 1,561 | 0.083 |
| Hospitalization cost | ||||
| Late | 13,816 | 11,123 | 17,161 | |
| Intermediate | 13,006 | 7,102 | 23,818 | 0.85 |
| Early | 10,373 | 6,924 | 15,540 | 0.24 |
Estimated costs for all-cause health care utilization are derived from an adjusted GLM.
The GLM used to estimate cost was adjusted for age, comorbidity score, anxiety, antidepressant use, major depressive disorder, substance abuse disorder, and chronic obstructive pulmonary disease.
P values are estimated using late initiators as the reference population. Model adjusted for age, comorbidity score, anxiety, antidepressant use, major depressive disorder, substance abuse disorder, and chronic obstructive pulmonary disease.
P < 0.05.
AOM 400 = aripiprazole once-monthly 400 mg; GLM = generalized linear model.
FIGURE 2.
Annualized Adjusted Costs of Management of Patients After Initiation of AOM 400
Estimated costs for all-cause health care utilization are derived from a GLM adjusted for age, comorbidity score, anxiety, antidepressant use, major depressive disorder, substance abuse disorder, and chronic obstructive pulmonary disease.
aTotal medical cost includes cost associated with outpatient and emergency department visits and hospitalizations.
bTotal health care cost includes total medical cost and pharmacy visit cost.
AOM 400 = aripiprazole once-monthly 400 mg; GLM = generalized linear model.
Discussion
Previous research has indicated that early-onset BD and a delay before receiving initial treatment are both associated with unfavorable treatment outcomes. These outcomes can include longer and more severe episodes of depression, increased mood cycling frequency, and shorter intervals between episodes of major depression and mania.20 Our retrospective cohort study of real-world claims data in the United States provides evidence that early initiation of AOM 400 within 1 year after diagnosis of BP-I is also associated with lower HCRU and reduced health care costs compared with later initiation of treatment. Although late initiators had statistically higher emergency department utilization, the associated higher emergency department costs were not statistically significant, which may have been due to differences in the type of service used during the emergency department visits.
These findings are consistent with previous evidence that pharmacotherapy is more effective if initiated early in the course of BP-I and that treatment should be tailored according to the stage of the illness.21 The results support the evidence from a phase 3 clinical trial that showed that earlier treatment of patients with BD with aripiprazole once-monthly injection can prolong time to the recurrence of mood episodes and reduce functional impairment, irrespective of age or disease duration.15 It is recognized that BD has a progressive nature, which makes an early intervention strategy important, especially considering that symptoms of BD manifest in adolescence or early adulthood.22
A recent expert consensus panel recommended that, if antipsychotic therapy is part of a treatment plan, LAIs should be initiated as early as possible in the disease course—ideally at the first manic episode—to improve long-term outcomes.11 The expert panel also concluded that additional evidence for the use of LAIs early in the disease course of BP-I is critical for supporting regional practice guidelines and health care systems.11 This was supported by a recent systematic literature review of interventions in the early course of BP-I or BP-II, which concluded that the evidence of the benefits of pharmacological and psychological interventions suggests that patients at an early stage in the course of their illness should be offered access to safe and effective interventions.6 The implementation of early intervention strategies may help change the outcome of the illness and avert potentially irreversible harm to patients with BP-I, as early phases of the disorder may be more responsive to treatment and require less aggressive therapies.
LIMITATIONS
This study was affected by the inherent limitations of claims-based analyses, as claims data are intended for administrative purposes rather than as a tool for research. For instance, it was not possible to determine whether a patient’s first episode of care for BP-I during the study period was the true first diagnosis of BP-I, and data relating to baseline clinical characteristics (such as BP-I severity and duration of BP-I diagnosis) were not available.
Additionally, this study used claims-based outcomes to assess the impact of time-to-initiation categories on HCRU. Therefore, further validation of these timing categories in future studies may be warranted. Additionally, studies using time to treatment to define exposure categories for treatment initiators require a longer pre-index period.23 Therefore, it is difficult to ascertain the optimal lookback length pre-index period to capture the diagnosis date. The earlier work by Seetasith et al adopted a similar study design with a longer pre-index period.23 Their analysis used a 36-month period to account for both diagnosis and first-line treatment dates. We followed a similar approach in this study and used a 30-month pre-index period (24 months for diagnosis and 6 months for washout). Because we are only accounting for pre-index diagnosis to calculate time to treatment initiation from the diagnosis date, a 30-month pre-index period was sufficient for this study. However, caution is warranted when varying the length of the pre-index period as these findings may be susceptible to changes in future studies.
The study population was also limited to patients with Medicaid health benefits (excluding those with Medicare and Medicaid dual eligibility). Lastly, the threshold between early and late AOM 400 initiation was set at 1 year, an arbitrary choice, but with the addition of a cohort of intermediate initiators, corroborated the findings of a prior claims database study.17
Conclusions
Previous placebo-controlled trials have shown that treatment at earlier stages of BP-I can prolong time to recurrence of mood episodes and reduce functional impairment15 and, as a progressive illness, it is recommended that BP-I should be the target of early intervention.11 Our real-world study of the timing of initiation of AOM 400 after diagnosis of BP-I, without consideration of disease progression, demonstrated that early initiation of AOM 400 among patients living with BP-I may also offer the significant advantage of lower HCRU and associated costs. This study demonstrated the desired outcomes of early initiation within a relatively short period of time, although observational claims data studies with longer follow-up are necessary to establish whether the effects of early initiation are sustained over time.
Disclosures
This study was sponsored by Otsuka Pharmaceutical Development & Commercialization Inc. Drs Awasthi, Huang, Bell Lynum, and Nag are full-time employees of Otsuka Pharmaceutical Development & Commercialization Inc.
Acknowledgments
Medical writing support was provided by K. Ian Johnson, BSc, MBPS, SRPharmS, under contract to Prime Access (a division of Prime, Knutsford, UK). Editorial support was provided by Prime Access and funded by Otsuka Pharmaceutical Development & Commercialization Inc.
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