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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: Using Danish registers, this cohort study included 7654 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 with 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 to 1.6), cardiovascular drugs (OR 1.1, 95% CI 1.0 to 1.3), analgesics (OR 1.2, 95% CI 1.1 to 1.3) and psychotropic drugs (OR 2.4, 95% CI 2.1 to 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 recognise the substantial heterogeneity in severity and comorbidity burden within this population and develop comprehensive and specialised treatment strategies that evaluate risks and treatment needs across all individuals with AN, irrespective of comorbid conditions.