OBJECTIVE The study compared distress levels among two groups of older adults who had been newly prescribed an antidepressant by their primary care physician, those with major depressive disorder (MDD) and those without MDD. METHODS This analysis used a convenience sample of participants (N=231) who had been newly prescribed an antidepressant in a randomized controlled trial of a program to improve antidepressant adherence and depression outcomes among older adults (≥55). After determining the proportion of participants with and without MDD (using the Structured Clinical Interview for DSM-IV), the authors compared groups on demographic, clinical, and psychosocial characteristics, including the 12-Item Short-Form Health Survey physical and mental component summary scores (PCS and MCS). Logistic regression was used to test the association of these characteristics with antidepressant use in the absence of MDD. RESULTS Most (57%) participants did not have MDD. This group was older (69.4 versus 64.7, p<.001), had a larger proportion of white participants (82% versus 56%, p<.001), and reported better physical (PCS, 43.4 versus 39.9, p=.03) and emotional (MCS, 40.2 versus 30.5, p<.001) well-being compared with the group with MDD. In the final regression model, white race (adjusted odds ratio [AOR]=3.11, p=.03) and better emotional well-being (AOR=1.16, p<.001) were associated with antidepressant use in the absence of MDD. CONCLUSIONS Older adults prescribed antidepressants in the absence of MDD did not report similar distress levels compared with their counterparts with MDD. Given the continued emphasis on screening for depression in primary care, it is important to consider the potential for overtreatment.