Atopic dermatitis is commonly associated with depressive symptoms and fatigue, which significantly impact quality of life. While clinical trials suggest beneficial effects of dupilumab on mental health, real-world evidence remains limited. This longitudinal cohort study analysed data from adult patients treated with dupilumab in the TREATgermany registry. Subgroups were defined by baseline Center for Epidemiologic Studies Depression Scale (CES D) scores ≥16 (clinically significant depressive symptoms) and Fatigue Severity Scale (FSS) scores >4 (significant fatigue). Clinical severity (Eczema Area and Severity Index [EASI], objective Scoring Atopic Dermatitis [oSCORAD]), quality of life (DLQI), psychological symptoms, treatment needs and benefits (PNQ, PBI) and drug survival were assessed over 12 months. Among 633 patients, those with elevated baseline CES-D (n=309) or FSS (n=281) scores reported greater disease burden measured by DLQI, while EASI and oSCORAD did not differ between subgroups. Both CES-D and FSS scores decreased markedly within the first 3 months. Sleep and social functioning needs were more frequently reported in high-burden subgroups and more often fulfilled after 12 months. Drug survival was comparable across subgroups. Dupilumab treatment was associated with significant improvements in depressive symptoms, fatigue and skin severity. Patients with higher baseline mental health burden showed comparable improvements in patient relevant domains, supporting the broad relevance of dupilumab in real-world atopic dermatitis care.