Abstract
Introduction: Depression is a prevalent mental health condition among patients with sickle cell disease (SCD) and is associated with poor clinical outcomes. The purpose of this study was to determine if comorbid depression and antidepressant adherence are related to adherence to disease-modifying therapies (DMTs) among patients with SCD.
Methods: A retrospective analysis of Texas Medicaid data from 01/01/2016 to 08/31/2023 included patients who: had ≥3 medical claims for SCD, had ≥1 prescription claim for an SCD DMT, were aged 8-63 years, and were continuously enrolled for 6 months before and 12 months after the index date (first claim for an SCD DMT). In addition to the above, patients with SCD and comorbid depression had ≥1 medical claim for a depressive disorder, and patients with SCD and comorbid depression with treatment had ≥1 prescription claim for a selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI). Proportion of days covered (PDC) was used to estimate adherence. Inferential statistics and logistic regression were used.
Results: Of the 1,005 patients (mean age = 22.9±11.7, 52.4% female) included, 35.3% had depression, while 37.7% had anxiety. Compared to patients with SCD only, patients with SCD and comorbid depression were significantly older (20.4±11.3 vs. 27.4±10.9), with adults aged 27-34 having the highest prevalence of depression (22.8%), and a higher proportion were female (64.5% vs. 46.5%). Compared to patients with SCD only, patients with SCD and comorbid depression had a significantly higher mean number of SCD-related complications (1.5±1.5 vs. 2.2±1.7), vaso-occlusive crisis (VOC) events (1.5±2.3 vs. 2.8±3.0), SCD-related hospitalizations (0.2±0.7 vs. 0.5±1.5), and non-SCD-related comorbid medical conditions (0.4±0.8 vs. 0.9±1.1) in the pre-index period. Additionally, patients with SCD and comorbid depression had a significantly higher proportion of patients with a diagnosis of anxiety (76.6% vs. 16.5%) and serious mental health conditions (31.8% vs. 4.0%) during the study period.
Among patients with SCD, mean adherence for each SCD DMT was: 38.7±26.7% (hydroxyurea), 37.5±29.5% (L-glutamine), 33.9±30.4% (crizanlizumab), and 60.9±34.1% (voxelotor). Proportion of patients taking hydroxyurea who were adherent (PDC≥80%) was 11.0%, and overall adherence to SCD DMTs was suboptimal (11.7%). In the unadjusted analysis, compared to adherent patients, a significantly higher proportion of non-adherent patients had comorbid depression (22.9% vs. 37.0%) and anxiety (24.6% vs. 39.5%). Compared to adherent patients, non-adherent patients were approximately 5 years older, and adolescents aged 10-15 comprised the highest proportion of adherent patients (45.8%), while young adults aged 22-26 were the lowest (<3%). The proportion of adherent patients was highest among patients with an index year of 2020 (31.3%). Compared to adherent patients, non-adherent patients had significantly higher numbers of SCD-related complications (1.1±1.5 vs.1.9±1.6) and VOC events (0.8±1.4 vs. 2.1±2.7). After adjustment, increasing number of VOC events (OR = 0.763; 95% CI: 0.642-0.907) in the pre-index period was associated with a lower odds of being adherent to SCD DMTs among patients with SCD.
Among patients with SCD and comorbid depression with treatment, mean adherence to SSRIs and SNRIs was 43.2±29.1% and 42.3±30.8%, respectively. Overall mean adherence to antidepressants was 43.3±29.8%, and 20.5% (PDC≥80%) and 23.5% (PDC≥70%) of patients were adherent. After adjustment, antidepressant-adherent (PDC≥70%) patients had higher odds of adhering to SCD DMTs (PDC≥70%) (OR = 16.699; 95% CI: 3.966-70.309). After adjustment, increasing age and number of VOC events in the pre-index period were associated with a lower odds of being adherent to SCD DMTs. In addition, an increasing number of SCD-related complications in the pre-index period was associated with a higher odds of being adherent to SCD DMTs among patients with SCD and comorbid depression with treatment.
Conclusion: The prevalence of depression among patients with SCD is high and associated with lower adherence to SCD DMTs. Antidepressant-adherent patients were more likely to adhere to SCD DMTs. SCD providers should regularly screen for depression, initiate depression treatment when appropriate, and encourage adherence to antidepressants, as this may improve adherence to SCD DMTs and overall health outcomes for this population.
