The Efficacy of Pharmacological Treatment of Depression in Anorexia Nervosa and Underweight Patients: A Systematic Review

Abstract

OBJECTIVE: Major depressive disorder (MDD) is a frequent comorbidity in anorexia nervosa (AN). This review aimed to evaluate evidence on the effectiveness of pharmacological treatments for MDD in underweight individuals. METHOD: A systematic review was conducted using PubMed, Medline, PsycINFO, and Web of Science through March 2025. Nineteen studies with 477 underweight patients were included, involving pharmacological treatment of depressed underweight young adults. Study designs ranged from randomised controlled trials (RCTs) to open-label trials and case reports, with quality assessments performed. Most studies focused on patients with AN; a few included underweight individuals without eating disorders. RESULTS: No RCTs specifically examined antidepressant treatment for MDD in AN. Most studies prioritised weight restoration and eating disorder symptoms over depressive outcomes. Some case reports indicated potential benefits of medications such as mirtazapine and ketamine. However, evidence was mixed and generally low in quality. Overall, it shows insufficient evidence for the effectiveness of pharmacological treatments in underweight individuals. There is insufficient data to determine whether being underweight affects antidepressant efficacy. CONCLUSIONS: Evidence on pharmacological treatment of MDD in underweight individuals, particularly those with AN, is scarce and inconclusive. Well-designed RCTs are needed to assess the efficacy and safety of antidepressants in this population.