Deep Brain Stimulation in Treatment-Refractory Anorexia Nervosa: Current Targets, Emerging Techniques, and Methodological Challenges

Background: Anorexia nervosa (AN) is a severe psychiatric disorder associated with the highest mortality rate among mental illnesses. Up to 20% of patients develop Severe and Enduring Anorexia Nervosa (SE-AN), a life-threatening condition resistant to conventional psychotherapy and nutritional rehabilitation. In the absence of effective pharmacotherapy, Deep Brain Stimulation (DBS) has emerged as a potential neurosurgical intervention targeting dysfunctional circuits involved in cognitive control, reward processing, and emotion regulation. Objectives: This review evaluates the current application of DBS in treatment-refractory AN, focusing on neuroanatomical targets, clinical efficacy, safety, and methodological, technological, and ethical challenges. Methodology: A comprehensive literature search was conducted in PubMed, Scopus, ScienceDirect, Embase, and Google Scholar. Studies published between 2022 and 2026 were considered, with reference lists manually screened for additional relevant evidence. Results: DBS may improve BMI, psychiatric symptoms, and quality of life in patients with SE-AN. Although the subcallosal cingulate cortex (SCC) and nucleus accumbens (NAcc) remain the principal targets, recent approaches increasingly emphasize phenotype-driven and connectome-guided neuromodulation. Emerging closed-loop, AI-assisted, and wireless technologies may further improve stimulation precision and reduce hardware-related complications. Conclusions: DBS represents a promising harm-reduction approach for treatment-refractory SE-AN. However, limited evidence, surgical risks, and ethical concerns regarding informed consent in severely malnourished patients warrant its use only as a last-resort intervention. Robust randomized multicenter trials are needed to establish its long-term safety and target-specific efficacy.