Medication use in severe anorexia nervosa: a Danish register-based study

ABSTRACT Background Severe anorexia nervosa (AN) represents a subgroup of individuals with AN with prolonged illness duration and poor prognosis. Previous research has reported increased medication use in AN, but prescription patterns in severe AN remain unexplored. Objectives This study aimed to: (1) compare medication prescriptions between individuals with severe and less-severe AN; (2) explore the heterogeneity of prescription patterns among individuals with severe AN across different comorbidity profiles. Methods Utilizing Danish registers, this cohort study included 7,654 individuals diagnosed with AN. We assigned cases to severe or less-severe groups based on their AN Register-based Severity Index scores. First, we examined trajectories of medication prescriptions and compared patterns between groups using logistic regression models. Second, common comorbidity profiles among individuals with severe AN were identified by latent class analysis for further between-group comparisons. Sensitivity analyses were conducted to test alternative definitions of severe AN. Findings Compared to individuals with less-severe AN, those with severe AN were more likely to be prescribed various medications, including drugs targeting alimentary tract (OR = 1.4, 95% CI 1.3-1.6), cardiovascular drugs (OR = 1.1, 95% CI 1.0-1.3), analgesics (OR = 1.2, 95% CI 1.1-1.3), and psychotropic drugs (OR = 2.4, 95% CI 2.1-2.7). Notably, this pattern persisted even among individuals without diagnosed comorbidities. Within the severe group, five clusters with distinct comorbidity profiles emerged, and we consistently observed greater prescription rates than in the comorbidity-free cluster. Sensitivity analyses confirmed that our severity classification reliably distinguished severe from less-severe AN across multiple definitions. Conclusion These findings indicate that severe AN is associated with substantially higher prevalence of prescribed medications, while specific comorbidity patterns further influence prescribing patterns. This diverse and prolonged pharmacological treatment in severe AN reflects the complexity of clinical management in this population. Clinical implications Considering the widespread medication prescription in severe AN despite the lack of specific approved pharmacotherapy for the disorder, evidence-based treatment guidelines are urgently needed. Clinicians should recognize the substantial heterogeneity in severity and comorbidity burden within this population and develop comprehensive and specialized treatment strategies that evaluate risks and treatment needs across all individuals with AN, irrespective of comorbid conditions. Key messages What is already known on this topic? The treatment of anorexia nervosa remains challenging due to the poorly understood etiology, compounded by the absence of approved pharmacotherapy and limited evidence for medication effectiveness. Individuals with anorexia nervosa and eating disorders in general receive multiple medications, but prescription patterns specifically in severe AN cases have not been systematically examined. What this study add? This study is the first to focus specifically on severe anorexia nervosa with long-term follow-up, with a precise definition of severity using the Anorexia Nervosa Register-based Severity Index in comprehensive Danish national registers. Individuals with severe AN have significantly higher prescription rates and more prolonged durations of pharmacotherapy compared to less-severe cases, with substantial prescribing observed even in the absence of diagnosed comorbidities. Within the severe anorexia nervosa population, individuals with distinct comorbidity profiles show associations with different medication patterns, providing a multidimensional understanding of pharmacological management. Timeframe selection critically influences the anorexia nervosa severity classification, as 5- or 7-year post-diagnosis periods provide more robust distinctions, while a shorter assessment period insufficiently captures the full picture of illness complexity. How this study might affect research, practice, or policy? This study provides essential evidence for the need to develop evidence-based pharmacotherapy guidelines for severe anorexia nervosa, addressing the current gap between extensive medication prescriptions and the lack of approved treatments. Clinicians should consider both illness severity and individual clinical presentations to optimize personalized treatment and address potential medication-related risks in this vulnerable population.