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Guidelines for antidepressant drug therapy recommend continuing treatment for several months, even after recovery. Premature termination of medication is viewed as a significant reason for chronicity in depressive disorders. To study the scope and type of this problem, routine treatment cases must be observed in sufficient numbers. In four subsequent drug utilization observation studies, the time course and reasons for early termination (i.e., during the first weeks of fluoxetine treatment for depression) were investigated in (1) 15,601 patients of 4,696 general practitioners; (2) 2,401 patients of all ages treated by 479 neuropsychiatrists from 1990 to 1991; (3) 757 patients of all ages treated by 213 neuropsychiatrists from 1992 to 1993; and (4) in 977 geriatric subjects treated by 216 neuropsychiatrists. In study 1, treatment was terminated during the first 10 weeks in 32.9% of cases; in study 2, in 48.0%; in study C, in 31.2%; and in study D, in 31.0%. When treatment was discontinued because of adverse events, the median of treatment duration was approximately 15 days; in cases of clinical deterioration, 20 days; in cases of poor response, 40 days; and when the reason was good response, the median of treatment duration was approximately 43 days. This is the largest field study on early termination of antidepressant treatment available to date. The consistency of results, which were collected from a large number of patients of different ages and from specialists as well as general practitioners, speaks for the validity and stability of the observed phenomena. The different forms of early treatment termination are discussed and addressed separately because they each have special risks and are differently associated with treatment failure.