OBJECTIVES We evaluated the impact of depression, anxiety, and psoriasis treatment on employability and productivity in patients with moderate-to-severe psoriasis. METHODS In PHOENIX 2, 1230 patients with moderate-to-severe psoriasis were randomized to receive ustekinumab 45mg, 90mg, or placebo at wks0 and 4, then q12wks, with placebo crossover to ustekinumab at wk12. Anxiety and depression were defined using the HADS (score >7 for each scale) and productivity and work limitations were assessed using a VAS and Work Limitations Questionnaire. Unemployable patients were defined as those who were currently unemployed and could not work even if a job was available. Spearman correlations, or multiple linear and logistic regression models were used to measure associations between employability and depression or anxiety adjusting for age, gender, disease duration, and PASI. Patients of working age (18-64 years) (N=1154) were included in this analysis. RESULTS At baseline, 40.8% of patients experienced anxiety, 26.8% experienced depression, while 8.7% were unemployable due to their psoriasis. Depression was the most significant variable associated with a higher probability of being unemployable (RR=2.7, p<0.001). Depression or anxiety were correlated with lower productivity and higher work limitations independent of PASI in the regression models (p-values<0.01). Improvement in depression or anxiety scores was significantly correlated with improvement in work limitations and work productivity, even after adjustment for improvement in PASI. Greater improvement in work productivity and work limitations were observed after treatment with ustekinumab vs. placebo at wk12 (p<0.01), especially among the subgroup with depression or anxiety at baseline. Among unemployable patients who had depression or anxiety at baseline, 44% in the combined ustekinumab group vs. 14.3% in the placebo group became employable at wk12 (p<0.05). CONCLUSIONS Depression or anxiety in patients with moderate-to-severe psoriasis is associated with poor employability and low work productivity. Treatment with ustekinumab significantly improved both employability and productivity in this comorbid population.