Stigma interferes with life goals of people with mental illness. Direct-to-consumer advertising (DTCA) may impact stigmatizing attitudes. The purpose of this study is to examine the effects of psychiatric medication DTCA on the stigmatizing and affirming attitudes of the general population versus individuals self-identified with mental illness. Participants (n = 272) were randomly assigned to watch a DTCA about Cymbalta, an antidepressant, embedded in two other advertisements for non-pharmaceutical products. Participants completed measures of stigmatizing and affirming attitudes before and after viewing this DTCA. Results indicate that the Cymbalta DTCA worsened the attitudes of the general public. These participants were less likely to offer help, endorse recovery, and agree with self-determination attitudes towards people with mental illness following viewing the DTCA. The self-identified group reported less blame, less dangerousness, less social avoidance, more pity, and greater willingness to help after viewing the DTCA. Moreover, there was significant improvement in their endorsement of recovery. Results suggest that DTCAs about psychiatric medication may increase the public's stigma towards people with mental illness but reduce stigma among individuals who identify as having a mental illness. Findings are somewhat limited by selection biases and self-report. Implications for further development of DTCAs are considered.