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OBJECTIVE: This study investigated whether the trend of increasing rates of antidepressant use in the 1990s continued into 2000-2004. Antidepressant treatment rates were examined by age group and by the class of antidepressant in order to identify whether any observed trends were being driven by a particular age group of patients or class of medication. METHODS: Secondary analysis was performed on data from the 2000-2004 Medical Panel Expenditure Surveys, a nationally representative survey of U.S. households, to examine trends in antidepressant use by age group and medication class in the total sample (N=166,435). Trends in the rates of antidepressant use among individuals with self-reported depression (N=10,959) and self-reported anxiety disorders without comorbid depression (N=6,899) were also examined. RESULTS: Antidepressant use increased among all Americans, from 6.6% in 2000 to 8.1% in 2004 (p<.001). Rates of antidepressant use by individuals with anxiety disorders without comorbid depression increased from 30.8% in 2000 to 39.0% in 2002, before declining to 33.2% in 2004. However, antidepressant use decreased among individuals with self-reported depression, from 63.1% in 2000 to 56.7% in 2004 (p<.001). This downward trend in antidepressant use was largely driven by a decrease in use of selective serotonin reuptake inhibitors, especially among children and middle-aged adults with depression. Rates of adequate antidepressant treatment (defined as receiving at least four antidepressant prescriptions at the minimum adequate daily dosage) peaked in 2002 (36.9%), and there was a significant decline by 2004 (31.7%) (p=.003). CONCLUSIONS: After years of increased use of antidepressant therapy to treat depression, a trend reversal in the beginning of the 21st century was observed, including decreasing rates of adequate antidepressant treatment. This downward trend preceded the black-box warnings included on antidepressant labels beginning in 2004