OBJECTIVES: Pharmacologic treatment has a major role in the management of depression, but concerns about the safety of antidepressants, and in particular the increased risk of suicide, have prompted FDA blackbox warnings.  The objective of this analysis was to describe the trends in utilization of prescription antidepressants over the past decade and interpret these in the context of FDA actions over that same time period. METHODS: National prescription data were obtained from IMS XponentTM database for the period January 1999-December 2009 (inclusive).  Total prescription counts were determined for TCAs, SSRIs, and SNRIs.  The FDA website was reviewed to identify the dates of new warnings or safety-related labeling changes, including major warnings in 2004 and 2007. RESULTS: Total prescriptions for antidepressants grew from 10.9 million in 1999 to 19.3 million in 2009, with only a temporary decline occurring in 2004-2005 which corresponds with the initial FDA warning.  While the warnings applied to all antidepressants, differences in utilization patterns between classes are apparent.  TCAs declined in use, while both SNRI and SSRI prescriptions increased over the decade, although SNRI utilization leveled-off after the 2007 expansion of the FDA blackbox warning that applied to young adults (18-24). CONCLUSIONS: Despite continuing expansion of the scope of the FDA blackbox warnings, overall antidepressant utilization increased over the decade, although the rate of increase appears to have slowed in the past two years.