3 months of psychotherapy, antidepressants are recommended as part of a combined treatment approach. This combination with psychotropic drugs and psychotherapy appears to be indicated from baseline in patients with moderate, severe or recurrent depression. In the last decade, antidepressant prescription rates in general practice have increased between 4 and 10 times. Depression presents high rates of relapse and recurrence. Treatment is often interrupted prematurely, leading to increases in both relapse rates and health care costs. Few studies have analysed the chronic use of antidepressant drugs and long-term adherence. Objective: To evaluate compliance with antidepressant treatment between 2003 and 2011 and to explore the associated factors. Methods: Retrospective cohort study of antidepressant dispensing. Setting: Health Region of Lleida between 2003 and 2011. Participants: Patients with chronic prescription of antidepressants (ATC code NO6A) during 2003 were followed up until December 2011. The sample comprised 3684 subjects. Main measures: The compliance rate was calculated on the basis of the number of units withdrawn from the pharmacy and the theoretical number of units required according to the scheduled duration of treatment: compliance was defined in cases with scores greater than or equal to 80 %. Results: 12.5 % of patients received chronic antidepressant treatment for at least 4 years. Mean age was 54 years, and 73.2 % of patients were female. Almost a third (32.4 %) presented anxiety disorders and 26.5 % mood disorders. The overall compliance rate was 22 % (28 % in patients with depression, and 21 % in patients with anxiety). According to gender, compliance rates were 21.4 % for males and 22.4 % for females. Compliance was more likely in patients with polypharmacy. Conclusions: One in 4 patients complied with treatment. Factors associated with better compliance were polypharmacy and diagnosis of depressive or mixed anxiety-depressive disorder.