Deep brain stimulation of the ventral anterior limb of the capsula interna in patients with treatment-refractory anorexia nervosa

Anorexia nervosa (AN) is a severe and often chronic psychiatric disorder with high morbidity and mortality [1]. Pilot studies and cases showed mixed but promising effects of deep brain stimulation (DBS) as a last-resort treatment option for life-threatening treatment-refractory AN [2,3]. The present study (N 1⁄4 4) is the first to target DBS in AN at the ventral anterior limb of the capsula interna (vALIC), part of the reward circuitry. vALIC-DBS showed strong and long-lasting effects in obsessive-compulsive disorder (OCD). We hypothesized that, due to the clinical and neurobiological similarities between AN and OCD, vALIC-DBS may exert comparable effects in treatmentrefractory AN. We included a sample of patients with exceptionally severe AN. Although challenging, they reflect the prototypical patients that may be eligible for DBS as a last resort treatment option [4]. Inclusion criteria included primary diagnosis of AN, a BodyMass Index (BMI) < 15, a Global Assessment of Function score (GAFscore) of 45 or less for 2 years [5], an illness duration of 10 years and a lack of response to 2 typical modes of treatment including 1 inpatient treatment of hospitalization. We conducted bilateral stereotactic implantation of DBS electrodes in the vALIC. In accordancewith our DBS studies [6] the study comprised four sequential phases: preoperative (T-1), surgery (T0), optimization (3e9 months; T1-T2) and maintenance phase (12 months; T2-T4) (Supplement 1, methods and statistical analysis). During the study the patients received standard medical and psychiatric care, comprised of regular visits with a nurse-practitioner and a psychiatrist. No major psychopharmacological adjustments were made. Primary outcome measures were 1) change in body mass index (BMI), 2) change in Yale-Brown-Cornell Eating Disorder Scale (YBCEDS)-score [7] and 3) change in Eating Disorder Quality of Life (EDQOL)-score [8]. We established side effects and safety through frequent and intensive monitoring by a psychiatrist, including