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The use of antidepressants has risen dramatically over the past few decades. This rise is attributable, in part, to the practice of off-label prescribing, that is, the use of antidepressants to treat conditions for which they were not designed, tested, or approved. Although there is a growing body of epidemiological data on off-label use of antidepressants, little is known about how those who are prescribed antidepressant medication for a diagnosis other than depression talk about this practice and, specifically, whether and how they invoke the topic of depression when asked to account for this practice. From a discursive analysis of interviews with 13 persons who were prescribed an antidepressant for a diagnosis other than depression (e.g., insomnia, postconcussive symptoms, new daily persistent headaches, multiple sclerosis, premenstrual syndrome), I show how the interviewees worked to decouple the relation between antidepressants and depression by (a) directly or indirectly denying one was characterologically or clinically depressed, (b) differentiating the nature of one’s distress from depression, and (c) reconstructing the antidepressant. I argue that the participants drew on various discourses of depression and reconstructed the antidepressant along functional lines as a way of arguing against the possibility that they had been prescribed an antidepressant for the purposes of being treated for particular forms of depression.