The federal Agency for Health Care Policy and Research (AHCPR) recommends 12 weeks of acute treatment and 4 to 9 months of continuation treatment with antidepressant medication in patients having a new episode of depression. OBJECTIVE: To evaluate antidepressant medication adherence in patients with depression. METHODS: This was a retrospective cohort study using a 24-month pharmacy claims database. Eligible patients must be enrolled continuously in the health plan for at least 12 months with at least one antidepressant prescription during the study period. A washout period of 90 days was applied to the front and back end of the database. This allowed elimination of bias in summary results due to early or late starters in the database. Main outcome: proportion of patients adhered to antidepressant medication therapy recommended by the AHCPR. RESULTS: A total of 5105 patients were included in the study. The average days of therapy was 140 days, persistence over time was 75%, 70%, 65%, 63%, 54%, and 50% at month 2, 3, 4, 5, 6, and 7 respectively. These results indicated 70% of patients adhered to their antidepressant drug regimen during the acute phase of therapy and 50% complied with therapy during the continuation phase. The possession ratio analysis demonstrated that patients only obtained 54% of the expected number of doses at 6 months. This was supported by the median gap (11.78 days) analysis that patients typically had prescriptions refilled at less than half the expected frequency. Adherence outcomes were similar in patients who received tricyclic antidepressants when compared to patients who received selective serotonin reuptake inhibitors during acute phase, 68% vs 70% (p = 0.18) and during continuation phase, 50% vs 52% (p = 0.23). CONCLUSIONS: Our study showed that many patients ceased medication use at an earlier than expected rate, especially during the first 3 months of therapy.