Abstract: Background: Anorexia nervosa (AN) is a serious psychiatric disease. Choice of acute inpatient care for AN is driven by the severity of symptoms and the level of risk to the patient. Inpatient hospitalization of patients with AN typically includes a behavioral weight gain protocol that is designed to address the core features of the disorder: weight, appetite, and distorted thoughts and behavior. Some add-on treatments may also be included in the inpatient treatment model and may have potential benefits, including faster or greater weight gain; such treatments include psychotherapy, psychoeducation, pharmacological treatment, and nutritional replacement. Objective: The goal of this study was to systematically review randomized clinical trials (RCTs) that have compared the efficacy of different forms of add-on treatment delivered during admission to a 24-hour hospital and to summarize the existing data regarding weight gain associated with such pharmacological, medical, and psychological interventions. Methods: Systematic electronic and manual searches were conducted to identify published RCTs concerning inpatient treatment of AN. Weight gain was used as the main outcome variable. Results: Overall, no significant increase in weight recovery was reported with atypical antipsychotics compared to placebo or therapy as usual. Only one study showed slight benefits in young patients during hospitalization (d=0.77; 95% confidence interval [CI] -0.09-1.64). No significant effects on weight recovery were found for antidepressants (d=-0.10; 95% CI=-0.63-0.42). In addition, none of the add-on psychotherapy techniques that were evaluated demonstrated superiority compared with control interventions in the inpatient setting. Cyclic enteral nutrition was studied in one RCT in which it demonstrated superiority compared to oral refeeding only (d=0.97; 95% CI=0.51-1.47). Other less common treatments such as bright light therapy and lithium carbonate were not found to produce additional significant weight improvement compared with placebo. Conclusion: Most add-on treatments during the acute inpatient phase of AN treatment are not effective in increasing weight recovery. Long-term follow-up studies after the acute treatment phase are needed to make evidence-based recommendations.

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