Abstract
To examine the incidence of antidepressant medication reinitiation following a ≥ 6-month gap as a proxy for relapse in patients with major depressive disorder (MDD) discharged from hospital and followed in primary care, and to assess patterns of antidepressant use before and after reinitiation, as well as associations with socio-demographic and clinical variables. We conducted a population-based cohort study using seven linked administrative health databases from Newfoundland and Labrador, Canada. Adults (≥18 years) with a first hospitalization for MDD between June 2017 and March 2023 and a post-discharge antidepressant prescription of ≥30 days were included. The primary outcome was reinitiation of antidepressant pharmacotherapy following a ≥ 6-month treatment gap. Antidepressant treatment groups were defined as SSRI monotherapy (reference), SNRI monotherapy, other monotherapy, two-medication combination therapy, and three or more medication combinations. Time-varying Cox regression models were used to assess associations with reinitiation risk, adjusted for age, sex, socioeconomic status (SES), and length of hospital stay. Sensitivity and exploratory age-stratified analyses were conducted. Among 2,734 patients, 61% reinitiated antidepressant treatment after a ≥ 6-month gap. SSRI monotherapy was the most common initial regimen (34.3%), followed by 2-medication combinations (18.1%). Combination therapy was associated with lower reinitiation risk compared to SSRIs: HR = 0.67 (95% CI: 0.50-0.90) for 2-medication combinations and HR = 0.49 (95% CI: 0.40-0.60) for 3 + medication combinations. SNRI monotherapy conferred modest protection (HR = 0.84, 95% CI: 0.72-0.99). Age, sex, and SES were independently associated with reinitiation. Younger adults, males, and individuals in both high and low-income quintiles were at increased risk. Reinitiation of antidepressants after a ≥ 6-month gap was common following hospitalization for MDD. Combination therapy maybe associated with reduced reinitiation risk compared to SSRI monotherapy, with age-specific treatment effects, although residual confounding cannot be excluded. Further research, ideally RCTs, is needed before informing clinical decision-making.