OBJECTIVES: The purpose of this study was to quantify the extent of nonadherence across antidepressants and to determine the rate of switching within the class. METHODS: Blinded prescription data from two national retail pharmacy chains was analyzed for 417,002 patients taking sertraline, venlafaxine, paroxetine, and escitalopram. Cumulative drug consumption (total days supply) during the one year follow up period was employed as the measure of adherence. Kaplan Meier estimates of survival (persistence) curves were used to assess the time to discontinuation and to calculate the one year rate of discontinuation. Baseline patient characteristics, including age, gender, geographic region, median income, index quantity dispensed, population density, co-pay, and index refill and days supply prescribed were analyzed. RESULTS: Adherence data across these antidepressants showed that escitalopram patients obtained the fewest days of medication (161.26), and venlafaxine patients had the greatest number of days of therapy (191.54). At day 60, 30% of venlafaxine patients, 34% of sertraline patients, and 40% of paroxetine and escitalopram patients discontinued therapy. After 6 months, 60% of venlafaxine patients, 64% of sertraline patients, 68% of paroxetine patients, and 70% of escitalopram patients discontinued therapy. The rate of switching to another agent was 3.67% for paroxetine, 3.14% for venlafaxine, 2.95% for escitalopram, and 2.1% for sertraline. CONCLUSION: Even though antidepressant medications are effective in controlling depression, their effectiveness is reduced by the lack of adherence to therapy. Adherence can vary significantly across the agents within a class. Efforts to maintain patients on antidepressant therapy at the initiation of treatment are needed and most likely will affect future adherence.