The Impact Legal and Illegal Substance Use Disorders on Mortality in Patients With Eating Disorders: A Register-Based, Retrospective Cohort Study

Background: Research is lacking on the contribution of different types of substance use disorders (SUD) to excess mortality across the full spectrum of eating disorders (ED). Therefore, we assessed the association of legal and illegal SUD with mortality in anorexia nervosa (AN), bulimia nervosa (BN), and unspecified ED (USED) compared to matched controls. Methods: A retrospective cohort study was conducted using Danish nationwide registers. The study included 20759 ED patients and 83036 matched controls. Hazard ratios (HRs) were calculated to compare all-cause mortality risk between ED patients and controls both with and without lifetime SUD (alcohol, cannabis, or hard drugs abuse/dependence). Findings: In patients with AN or USED we observed a higher risk of all-cause mortality relative to controls without SUD in those who abused alcohol/cannabis (AN, adj. HR 11·28 [95% CI 7·01, 18·16]; USED, 10·86 [6·74, 17·50]), or hard drugs (AN, 22·34 [15·13, 33·00]; USED, 15·53 [10·15, 23·78), than in those without SUD (AN, 3·21 [2·43, 4·23]; USED, 4·75 [3·57, 6·31]). In patients with BN, the risk of all-cause mortality was elevated in those who abused alcohol/cannabis (5·86 [3·37, 10·1]), or hard drugs (11·43 [7·14, 18·28]), but not in those without SUD. Controls with SUD also exhibited an increased risk of all-cause mortality relative to controls without SUD, although to a much lesser extent than ED patients with SUD. Interpretation: SUD has an additive effect on excess mortality in ED patients. The prevention and treatment of SUD is thus imperative to reduce mortality. Funding Statement: This study was unconditionally funded by the Psychiatric Research Foundation, University of Southern Denmark, Region of Southern Denmark. Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: Register-based studies in Denmark do not require approval by the Research Ethics Committee or informed participant consent. The study was approved by the Danish Data Protection Agency. All data were anonymized prior to conducting the analyses.