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Major depressive disorder (MDD) is a common and serious disorder with significant impact on patients and families. The goal of this retrospective cohort study was to determine the economic burden among patients with MDD stratified by number of treatment lines needed for episode resolution.
A total of 73,597 patients with MDD comprising the commercial (n = 66,459) and Medicare (n = 7138) populations met selection criteria. Patients who completed treatment for their episode with a single line of antidepressant had the lowest total adjusted direct costs (commercial $9975; Medicare $14,628) followed by those who completed with two lines (commercial $11,723; Medicare $15,526) and those treated with three or more lines of antidepressant regimens (commercial $21,259; Medicare $20,964). Patients who completed treatment with two lines as opposed to one incurred significantly higher direct costs (commercial +$1748, p p = 0.0092). Patients who completed treatment with one line had the lowest employment-related costs compared to other groups.
Major depressive disorder (MDD) is a brain health disorder that is characterized by distinct episodes of at least 2 weeks in duration and often associated with changes in affect, cognition, and function [1]. The American Psychiatric Association (APA) recommends treating MDD initially with psychotherapy and antidepressant medication [2]. An estimated 17 million adults in the United States experience at least one major depressive episode each year, of which approximately 7 million receive treatment with pharmacotherapy [3,4,5]. Antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs), and should be continued for at least 4 months after remission, for up to a lifetime depending on patient characteristics, according to the APA [2].
While the economic burden of treatment-resistant depression has been well studied [52,53,54,55,56,57], the direct and indirect financial impact of patients across increasing numbers of pharmacotherapy treatments in MDD has not been fully explored. Namely, the increased total costs associated with delayed episode resolution and the potential economic benefit of patients achieving early disease resolution within one pharmacotherapy treatment regimen have been overlooked. The goal of this retrospective cohort study was to evaluate the direct costs as well as employment-related costs and resource use among patients diagnosed and treated for a new MDD episode, stratified by the number of pharmacotherapy steps needed to meet episode resolution.
This retrospective cohort study demonstrated an incremental increase in direct costs, employment-related costs, and healthcare resource utilization with delays in achieving completion of guideline-recommended treatment of depressive episodes. Completion of the continuation phase of treatment (indicative of episode resolution in guidelines) on earlier lines of antidepressant therapy was associated with lower annual total cost of care when controlling for demographics and the presence of comorbidities. A consistent trend was observed across both Medicare and commercial populations, suggesting that the incremental economic burden exists regardless of payer type.
Prior analyses involving claims data reported healthcare cost differences between treatment-resistant and non-treatment-resistant depression patients ranging from $3042 to $6742 among commercial populations [52,53,54, 56, 57]. In our study, the adjusted difference in direct costs between patients who received three or more antidepressant regimens versus completing treatment with fewer antidepressant regimens ranged between $9537 and $11,285 in commercial patients. The high direct and employment-related costs observed in patients receiving three or more antidepressant regimens were comparable to those reported in other recent retrospective studies in treatment-resistant depression populations that are typically characterized by two or more failed antidepressant treatments [52,53,54,55,56,57]. While our study proxied patients achieving episode resolution using prescription treatment patterns, these ranges are aligned with previously observed costs in broader MDD and treatment-resistant depression patient cohorts [52,53,54, 56, 57].
While there are clear benefits to early episode resolution, identifying the best initial pharmacotherapy option for each MDD patient remains a major challenge [11, 65] since remission with the first pharmacotherapy treatment is difficult to achieve with current treatment options [7, 8]. Approximately two-thirds of patients do not achieve full symptom resolution on their first antidepressant pharmacotherapy [7, 66]. In addition, approaches to selecting an effective second pharmacotherapy are often inconsistent, due to considerations of safety and tolerability [67] and the limited efficacy superiority of any specific antidepressants over others [6, 65]. Therefore, a substantial unmet need exists for more rapid and effective pharmacotherapy options that promote treatment response and remission within an early line of pharmacotherapy after diagnosis.
There are several wider limitations in this study due to the inherent nature of claims analyses, including the inability to control for certain unknowns such as disease severity. Differences in health risk, such as MDD episode severity, number of prior episodes, and other underlying health conditions that may be more likely in patients on more lines of pharmacotherapy, are not captured by the claims data, but this analysis did control for baseline demographics/characteristics (age, gender, year, census regions, plan type, setting of first MDD diagnosis) and the Charlson Comorbidity Index. The use of the negative binomial distribution rather than using a continuous gamma distribution was due to the latter requiring positive values. As the two models demonstrate consistency in analyzing cost data (Supplemental Table 2, see the electronic supplementary material) [68], the negative binomial distribution was chosen to accommodate zero costs, which were observed in the 12 cost categories for some patients.
Since true clinical resolution is difficult to assess from claims data, completion of the guideline-recommended treatment continuation phase was used as a proxy for episode resolution. Employment-related costs were only examined in the commercial population as it was not available for the Medicare population. Long-term disability days and payments were not reported as they were not well represented in the dataset. Other factors not available in claims data could not be controlled for.
The association between increased number of treatment lines and increased total cost of care even between one and two lines of therapy highlights that there is an economic burden associated with a lack of early MDD episode resolution. These costs are not limited to MDD pharmacotherapy but also include inpatient and outpatient direct costs and employment-related costs. Early achievement of episode resolution may help avert higher total cost of care for patients with MDD. These results support the critical need for rapid and effective pharmacotherapy options for optimizing treatment stability early after MDD diagnosis.
Aims: Nocturnal asymptomatic hypoglycemia (NAH) is a serious complication of diabetes, but it is difficult to be detected clinically. This study was conducted to determine the largest amplitude of glycemic excursion (LAGE) to predict the episodes of NAH in outpatients with type 2 diabetes.
Methods: Data were obtained from 313 outpatients with type 2 diabetes. All subjects received continuous glucose monitoring (CGM) for consecutive 72 hours. The episodes of NAH and glycemic variability indices (glucose standard deviation [SD], mean amplitude of plasma glucose excursion [MAGE], mean blood glucose [MBG]) were accessed via CGM. LAGE was calculated from self-monitoring blood glucose (SMBG).
Notes: the sample for column (1) is total sample of 2616 episodes which has no missing information of covariates, and the sample for columns (2) to (6) includes the episodes that use each contraceptive method. The clustered standard error by woman is used. 2ff7e9595c
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