This study investigated the association between the duration of pharmacotherapy treatment for depression, or discontinuation from treatment, and work functioning impairment. This was a retrospective cohort study examining 30,409 workers. Work functioning impairment was assessed using a questionnaire, and treatment status was assessed using medical claims data. Odds ratios (ORs) of workers with severe work functioning impairment compared with healthy workers (control group) were calculated using logistic regression analysis. Continuous medical treatment was associated with severely impaired work functioning regardless of treatment period [continuous medical treatment; 4 months <: OR = 3.2, 4 months ≥, 10 months <: OR = 2.6, 10 months ≥, 14 months <: OR = 2.3, 14 months ≥, 16 months <: OR = 2.3, which are all statistically significant (p < 0.05)]. Workers who initially received pharmacotherapy treatment but discontinued in < 11 months had a significantly higher OR (treatment discontinuation period; 3 months <: OR = 2.3, 3 months ≥, 8 months <; OR = 2.0, 8 months ≥, 11 months <; OR = 3.0), while those who discontinued at ≥ 11 months did not (OR = 1.4, 95% CI 0.6-3.5). The sensitivity analysis excluding participants with at least one psychiatric comorbidity other than depression did not change the final result. It is important for the occupational health practitioners and attending psychiatrists to follow up in cooperation with each other, paying attention to the decrease in work functioning in addition to the symptoms.