BACKGROUND: Major depressive disorder and anxiety disorders are associated with less productivity, earlier retirement, and more sick-days at the workplace. These associations also exist for patients with metabolic syndrome. For both, exercise is a generally recommended part of multimodal treatments. However, for individuals with metabolic syndrome, in which depression and anxiety is more prevalent and severe, evidence for the efficacy of exercise interventions is limited. METHODS: Company employees with diagnosed metabolic syndrome (n = 314, age 48 +/- 8 yrs) were randomized to a 6-month exercise intervention (150 min per week) or wait-list control. Participants received individual recommendations for exercise activities by personal meetings, telephone, or via a smartphone app. Physical activities were supervised and adapted using activity monitor data transferred to a central database. Work ability (work ability index), depression severity and anxiety severity (hospital anxiety and depression scale (HADS)), and health-related quality of life (Short Form 36 (SF-36)) were assessed. RESULTS: We included 314 subjects from which 287 finished the intervention. Total work ability, depression- and anxiety severity, and the mental component score of the SF-36 improved after 6 months exercise compared to controls. After baseline stratification for normal (HADS scores 0 to 7) and increased depression- and anxiety scores (HADS scores 8 to 21) individuals with increased severity scores had similar age, body composition, blood lipids, and cardiorespiratory fitness compared to those with normal scores, but lower total work ability and component sum scores of health-related quality of life. After 6 months total work ability increased in the exercise group compared to controls with the magnitude of the observed increase being significantly greater for subjects with increased depression- and anxiety severity at baseline compared to those with normal severity scores. CONCLUSIONS: A 6-month exercise intervention for company employees with metabolic syndrome showed strongest effects on self-perceived work ability in individuals with mild to severe depression- and anxiety severity. This suggests exercise programs offered to workers with metabolic syndrome not only reduces individual disease risk but may also reduce healthcare and employers costs arising from metabolic syndrome and mental disease conditions. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03293264.

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