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Pharmacotherapy is an effective treatment for generalized anxiety disorder (GAD), but few studies have examined the nature of decline of anxiety and depression during pharmacotherapy for GAD and even fewer studies have examined predictors of symptom decline. This study examined the decline in symptoms of anxiety and depression in patients with GAD during a 6-week open trial of fluoxetine. Growth curve analyses indicated that pharmacotherapy with fluoxetine led to significant declines in symptoms of anxiety and depression over the 6 weeks of treatment. However, the decay slope observed for anxiety symptoms was significantly greater than that for depressive symptoms. Further analyses revealed that the decline in anxiety remained significant after accounting for the changes in symptoms of depression. However, the effect of treatment on depression was no longer significant after controlling for the reduction in anxiety symptoms. Overall anxiety sensitivity (AS) did not moderate the level of reduction in symptoms of anxiety or depression during pharmacotherapy. However, AS specific to physical concerns demonstated a marginal negative association with decline in anxiety and depression. AS specific to social concerns also demonstrated a marginal negative association with decline in anxiety symptoms. These findings suggest that the decline in anxiety symptoms is independent of the decline in symptoms of depression during pharmacotherapy for GAD and specific AS dimensions may predict symptom change in GAD.