(CSPOT47) Do Selective Serotonin Reuptake Inhibitors differ in depression treatment outcomes in Older Adults with Chronic Somatic Diseases? Evidence from a Danish Target Trial Emulation Study

Background: Depression is a common comorbidity in older adults with chronic somatic diseases and is often treated with selective serotonin reuptake inhibitors (SSRIs). However, SSRIs' comparative effectiveness has rarely been studied in this vulnerable population.

Objectives: To investigate the comparative effectiveness of commonly prescribed SSRIs for comorbid depression in older adults with chronic somatic diseases by emulating a randomized controlled trial in a real-world setting.

Methods: We applied a target-trial-emulation framework and included 43,061 individuals aged ≥65 years (54.1% females, mean age 77.8 years) who received their first prescription for depression of either sertraline (n=6,673), escitalopram (n=7,104), or citalopram (n=29,284) between 2006 and 2017. These individuals had at least one somatic disease of cancer, cardiovascular diseases (CVD), chronic obstructive pulmonary disease (COPD)/asthma, diabetes, neurodegenerative disorders, or osteoporosis. During a one-year follow-up (since the first prescription), we assessed four outcomes, including treatment switching, combination/augmentation therapy, psychiatric hospital contacts for depression, and psychiatric hospital admissions. Adjusted hazard rate ratios (HRR) for each outcome, separately for each somatic disease group, were estimated using Cox regression analyses.

Results: In our analyses of four outcomes in all six disease groups, citalopram use showed lower risks compared to sertraline in several analyses, with statistically significant results in cancer, CVD, COPD/asthma, and diabetes (e.g., HRRs for psychiatric hospital contacts/admissions ranging between 0.47 and 0.61). Regarding escitalopram, some analyses indicated unfavorable outcomes with significantly higher risks for combination/augmentation treatment than sertraline (HRRs ranging between 1.15 and 1.40). The results were consistent in various sensitivity analyses.

Conclusions: This real-world emulated target trial suggests clinically relevant differences between frequently used SSRIs, particularly favoring citalopram, in treating comorbid depression among older adults. However, the findings should be interpreted cautiously because of the study's observational nature.