Comparing adherence and persistence of common selective serotonin reuptake inhibitors in veterans with major depressive disorder: a retrospective analysis of Veterans Affairs healthcare data

Depression has a high prevalence and increasing incidence in the USA. Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), are the most commonly used treatments. To be effective, SSRIs must be taken consistently. This study evaluated adherence and persistence among veterans diagnosed with major depressive disorder (MDD) who initiated SSRI monotherapy within 90 days of diagnosis. Using Veterans Affairs healthcare data from 2000 to 2023, we identified veterans with MDD who filled a prescription for one of the five most common SSRIs: citalopram, escitalopram, fluoxetine, paroxetine, or sertraline. Adherence was measured as the proportion of days covered during the first year, with greater than or equal to 80% considered adherent. Persistence was measured as time to discontinuation, defined as a 90-day gap in supply. Among 300 628 eligible patients, 29.3% were adherent and 49.6% persisted on treatment for more than 180 days. Escitalopram, fluoxetine, and sertraline had significantly higher adherence and lower discontinuation hazards compared with citalopram and paroxetine. These results suggest that escitalopram, fluoxetine, and sertraline support better long-term adherence and persistence in veterans with MDD. Enhanced understanding of these dynamics can improve patient education and support systems that address specific adherence barriers, including side effects and lack of information about treatment duration and expectations.