Objective: The purpose of this study was to compare the use of antidepressants over 6 years between family caregivers providing high-intensity care and a matched control population using register-based data. Methods: The study includes all individuals, who received family caregiver’s allowance in Finland in 2012 (n = 29,846 females, mean age 66 years; n = 12,410 males, mean age 71 years) and a control population matched for age, sex, and municipality of residence (n = 59,141 females; n = 24,477 males). Information on purchases of antidepressants, including the number of defined daily doses (DDD) purchased, between 2012 and 2017 was obtained from the national drugs reimbursement register. Results: During the follow-up, 28.5% of female caregivers and 23.5% of the female controls used antidepressants, while the numbers for males were 21.1% and 16.4%, respectively. Adjusted for socioeconomic status, female caregivers used 43.7 (95% confidence interval 42.4–45.0) and their controls used 36.2 (35.3–37.2) DDDs of antidepressants per person-year. Male caregivers used 29.6 (27.6–31.6) and their controls used 21.6 (20.2–23.0) DDDs of antidepressants per person-year. Among female caregivers, the relative risk for use of antidepressants was similar (about 1.3) from 20 to 70 years, after which the relative risk declined. In male caregivers, the relative risk was highest (about 1.4–1.5) between 45 and 65 years. Conclusions: Family caregivers providing high-intensity care use more antidepressants and hence, are likely to have poorer mental health than the age-matched general population in virtually all age groups. However, the magnitude of the higher use varies as a function of age and gender.