The aim of this work was to study time trends of antidepressant drug (AD) prescriptions in a geographically defined US population between 2005 and 2011 for men and women separately. Using the Rochester Epidemiology Project medical records-linkage system, we identified all Olmsted County, MN residents who received AD outpatient prescriptions between 2005 and 2011 (7 years). We calculated the annual age- and sex-specific prevalence over 7 years and used generalized estimating equation models to test for time trends. The prevalence of subjects receiving at least one AD prescription was approximately two times higher in women than in men consistently across the 7 years of the study. The standardized annual prevalence increased from 10.8 % in 2005 to 14.4 % in 2011 overall, from 7.0 % in 2005 to 9.9 % in 2011 for men, and from 14.4 % in 2005 to 18.6 % in 2011 for women. The absolute percent increase was greater in women (4.2 vs. 2.9 %; standardized); however, the relative percent increase was greater in men (41.4 vs. 29.2 %; standardized). The relative percent increase was greater in the age group 65+ years for both men and women. AD prescriptions are increasing over time, especially in the elderly. Women receive more AD prescriptions than men. However, the relative increase in AD prescriptions over time is greater in men than women.