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Adult-onset Still’s disease (AOSD) is a rare multisystemic autoinflammatory disease with symptoms, including spiking fever, evanescent rash, arthralgia or arthritis, sore throat, lymphadenopathy, hepatosplenomegaly, and myalgia. The prevalence of anxiety and depressive symptoms in rheumatological diseases is quite high, which impacts social as well as occupational functioning. Depression and anxiety are known to be the most common psychiatric comorbidities in patients with arthritis and other rheumatological disorders. Here, we report the case of an adult white female with AOSD who showed improvement in symptoms of AOSD with monoclonal antibodies and steroids; however, significant worsening of pain along with depression & anxiety were noted. With the use of antidepressant serotonin-norepinephrine reuptake inhibitor (SNRI), specifically duloxetine, our patient was able to experience improvement in depression, anxiety, and pain.