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BackgroundNaturalistic studies regarding clinical outcomes associated with antidepressant treatment duration have yielded conflicting results, possibly because they did not consider the occurrence of treatment changes. This nation-wide population-based study examined the association between the number of filled prescriptions and treatment changes and long-term psychiatric outcomes after antidepressant treatment initiation.MethodsBased on the French national health insurance database, 842,175 adults who initiated an antidepressant treatment in 2011 were included. Cox proportional-hazard multi-adjusted regression models examined the association between the number of filled prescriptions and the occurrence of treatment changes 12 months after initiation and four outcomes during a 5-year follow-up: psychiatric hospitalizations, suicide attempts, sick leaves for a psychiatric diagnosis, new episodes of antidepressant treatment.ResultsDuring a mean follow-up of 4.5 years, the incidence rates of the four above-mentioned outcomes were 13.49, 2.47, 4.57, and 92.76 per 1,000 person-years, respectively. The number of filled prescriptions was associated with each outcome (adjusted HRs [95% CI] for one additional prescription ranging from 1.01 [1.00–1.02] to 1.10 [1.09–1.11]), as was the occurrence of at least one treatment change vs. none (adjusted HRs [95% CI] ranging from 1.18 [1.16–1.21] to 1.57 [1.79–1.65]). Furthermore, the adjusted HRs [95% CI] of the number of filled prescriptions were greater in patients with (vs. without) a treatment change for psychiatric hospitalizations (1.12 [1.11–1.14] vs. 1.09 [1.08–1.10], p for interaction = 0.002) and suicide attempts (1.12 [1.09–1.15] vs. 1.06 [1.04–1.08], p for interaction = 0.006).LimitationsLack of clinical data about the disorders warranting the prescriptions or their severity.ConclusionConsidering treatment changes is critical when using administrative claims database to examine the long-term psychiatric outcomes of antidepressant treatments in real-life settings.