Healthcare Resource Utilization and Costs Associated with Non-Adherence to Pharmacotherapy for Major Depressive Disorder
BACKGROUND: Major Depressive Disorder (MDD) affects more than 16 million adults in the United States (US) and accounted for $210 billion in direct and indirect costs in the US in 2010. Pharmacological treatments for MDD include selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), and other antidepressants; however, non-adherence to MDD pharmacotherapy is common and is associated with poorer clinical outcomes. OBJECTIVE: To assess the impact of non-adherence to MDD pharmacotherapy on healthcare resource use (HCRU) and costs in MDD patients enrolled in commercial, Medicare Supplemental, and Medicaid insurance. METHODS: This was a retrospective cohort study conducted using administrative claims data from the IBMÂ® MarketScanÂ® Commercial, Medicare Supplemental, and Medicaid Multi-State databases from January 1, 2010 – December 31, 2017. We identified adult MDD patients ≥ 18 years with an initial diagnosis of MDD and who newly initiated antidepressant therapy between January 1, 2011 and December 31, 2016. Included patients were required to have no MDD or antidepressant claims in the 12-month baseline period prior to initial MDD diagnosis and have ≥ 12 months of continuous medical, pharmacy, and mental health/substance abuse benefits prior to the initial diagnosis date and following the index prescription date (date of first antidepressant fill within 60 days after the initial diagnosis date). Adherence to MDD pharmacotherapy at 6 months following the index prescription date was calculated using the Proportion of Days Covered (PDC) metric and included all antidepressants and augmentation agents. Adherent patients were defined as having PDC for MDD pharmacotherapy ≥ 80%. Twelve-month total all-cause HCRU by setting of care (inpatient, emergency room (ER), outpatient) and costs (total healthcare, medical, pharmacy, adjusted to 2018 US dollars) were characterized for patients who were adherent and non-adherent to MDD pharmacotherapy at 6 months. Multivariable negative binomial regression and generalized linear models with a log-link function and gamma distribution were used to estimate incidence rate ratios (IRRs) for HCRU and incremental costs of non-adherence compared to adherence, respectively. All multivariable analyses were adjusted for age, sex, geographic region, insurance type, index year, Charlson Comorbidity Index (CCI) score (continuous), and 12-month baseline costs. RESULTS: A total of 5,988,383 adult MDD patients were identified, of which 163,410 patients met study inclusion criteria. Mean [standard deviation (SD)] age was 42  years and the majority of patients were female (61%), had commercial insurance (87%), and were enrolled in Preferred Provider Organization (PPO) plans (53%). Forty-eight percent of adult MDD patients were non-adherent to MDD pharmacotherapy at 6 months, and mean [SD] PDC among non-adherent and adherent patients was 42% [20%] and 95% [6%], respectively (p<0.001). In the 12-month period following index antidepressant initiation, non-adherent patients experienced more all-cause inpatient hospitalizations (1.5 vs. 1.4, p<0.001), ER visits (1.9 vs 1.6, p<0.001), and other outpatient visits (7.7 vs. 7.2, p<0.001) compared to adherent patients. Non-adherent patients incurred non-significantly higher 12-month total all-cause medical costs ($10,240 vs. $9,891; mean unadjusted difference: $349, 95% CI: -$19, $716), but lower total 12-month total all-cause healthcare costs ($12,242 vs. $12,587; mean unadjusted difference: -$345, 95% CI: -$735, $45) as a result of lower all-cause pharmacy costs ($2,003 vs. $2,697; mean unadjusted difference: -$694, 95% CI: -$788, $600). Adjusted analyses revealed that non-adherent patients were 1.19 (95% CI: 1.15, 1.23), 1.37 (95% CI: 1.34, 1.40), and 0.86 (95% CI: 0.86, 0.88) times as likely to have inpatient hospitalizations, ER visits, and outpatient visits compared to adherent patients, respectively. Adjusted incremental total medical, total pharmacy, and total healthcare costs associated with non-adherence to MDD pharmacotherapy were $367 (95% CI: $26, $708), -$984 (95% CI: -$1107, -$861), and -$508 (95% CI: -$881, -$135), respectively. CONCLUSIONS: This study found higher all-cause inpatient and ER utilization and total medical costs, but lower total healthcare costs among patients who were non-adherent to MDD pharmacotherapy at 6 months. Non-adherent patients spent less on medications and received care in more expensive settings (inpatient and ER) than adherent patients.