BACKGROUND: Recent studies have demonstrated the efficacy of adalimumab on improving psoriasis symptoms, health related quality of life (HRQoL), and depression. OBJECTIVES: To quantify the importance of depression on overall HRQoL in patients with active plaque psoriasis who were enrolled in an open label clinical study of adalimumab. METHODS: PRIDE (A Canadian Open-Label Access PRogram to Evaluate the Safety and the Effectiveness of Adalimumab When Added to InaDEquate Therapy for the Treatment of Psoriasis) was an open-label, multicenter, Phase IIIb study in Canada. Patients with active moderate to severe plaque psoriasis who failed to respond to, or were intolerant of, standard prior therapies received adalimumab (80 mg) at Week 0 followed by adalimumab (40 mg) every other week. Changes in the outcomes including the Psoriasis Area and Severity Index (PASI), Beck Depression Inventory-II (BDI) and EQ-5D VAS at baseline, weeks 16 and 24 were evaluated. A multivariate mixed-effect regression was fitted to identify the independent contribution of skin severity (PASI) and depression (BDI) on HRQoL (EQ-5D VAS). RESULTS: A total of 203 patients (61% male, mean age:46, mean PASI:20) were enrolled at 26 sites. Statistically significant improvements in PASI, EQ-5D VAS and BDI were seen at week 16 (improvements of 16.0, 10.1, 4.2, respectively all p<0.001) and 24 (improvements of 16.1, 10.7, 4.3, respectively all p<0.001). The model found that both PASI (ß=-0.40, p=0.004) and BDI (ß =-0.54, p=0.002) were independent predictors of EQ-5D VAS. The interaction between BDI and females was also significant (ß =-0.64, p=0.006). CONCLUSIONS: HRQoL in patients with plaque psoriasis is influenced independently by both skin severity and depression. While the etiology of depression is likely through skin severity, it appears likely that both contribute to the improvements in HRQoL seen with adalimumab treatment.