Drugs are widely prescribed for anorexia nervosa in the nutritional, somatic, and psychiatric fields. There is no systematic overview in the literature, which simultaneously covers all these types of medication. The main aims of this paper are (1) to offer clinicians an overview of the evidence-based data in the literature concerning the medication (psychotropic drugs and medication for somatic and nutritional complications) in the field of anorexia nervosa since the 1960s, (2) to draw practical conclusions for everyday practise and future research. Searches were performed on three online databases, namely MEDLINE, Epistemonikos and Web of Science. Papers published between September 2011 and January 2019 were considered. Evidence-based data were identified from meta-analyses, if there were none, from systematic reviews, and otherwise from trials (randomized or if not open-label studies). Evidence-based results are scarce. No psychotropic medication has proved efficacious in terms of weight gain, and there is only weak data suggesting it can alleviate certain psychiatric symptoms. Concerning nutritional and somatic conditions, while there is no specific, approved medication, it seems essential not to neglect the interest of innovative therapeutic strategies to treat multi-organic comorbidities. In the final section we discuss how to use these medications in the overall approach to the treatment of anorexia nervosa.

Dysregulation of habit formation has been recently proposed as pivotal to eating disorders. Here, we report that a subset of patients suffering from restrictive anorexia nervosa have enhanced habit formation compared with healthy controls. Habit formation is modulated by striatal cholinergic interneurons. These interneurons express vesicular transporters for acetylcholine (VAChT) and glutamate (VGLUT3) and use acetylcholine/glutamate cotransmission to regulate striatal functions. Using mice with genetically silenced VAChT (VAChT conditional KO, VAChTcKO) or VGLUT3 (VGLUT3cKO), we investigated the roles that acetylcholine and glutamate released by cholinergic interneurons play in habit formation and maladaptive eating. Silencing glutamate favored goal-directed behaviors and had no impact on eating behavior. In contrast, VAChTcKO mice were more prone to habits and maladaptive eating. Specific deletion of VAChT in the dorsomedial striatum of adult mice was sufficient to phenocopy maladaptive eating behaviors of VAChTcKO mice. Interestingly, VAChTcKO mice had reduced dopamine release in the dorsomedial striatum but not in the dorsolateral striatum. The dysfunctional eating behavior of VAChTcKO mice was alleviated by donepezil and by l-DOPA, confirming an acetylcholine/dopamine deficit. Our study reveals that loss of acetylcholine leads to a dopamine imbalance in striatal compartments, thereby promoting habits and vulnerability to maladaptive eating in mice.

The management of eating disorders (EDs) is still difficult and few treatments are effective. Recently, several studies have described the important contribution of non-invasive brain stimulation (repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and electroconvulsive therapy) and invasive brain stimulation (deep brain stimulation and vagal nerve stimulation) for ED management. This review summarizes the available evidence supporting the use of brain stimulation in ED. All published studies on brain stimulation in ED as well as ongoing trials registered at clinicaltrials.gov were examined. Articles on neuromodulation research and perspective articles were also included. This analysis indicates that brain stimulation in EDs is still in its infancy. Literature data consist mainly of case reports, cases series, open studies, and only a few randomized controlled trials. Consequently, the evidence supporting the use of brain stimulation in EDs remains weak. Finally, this review discusses future directions in this research domain (e.g., sites of modulation, how to enhance neuromodulation efficacy, personalized protocols).

Introduction: Eating disorders (ED) are associated with high rates of suicide attempts and premature mortality. However, data in large samples of adolescents and young adults are limited. This study aims to assess the risk of self‐harm and premature mortality in young people hospitalized with an ED.Methods: Individuals aged 12 to 25 years old hospitalized in 2013–2014 in France with anorexia nervosa and/or bulimia nervosa as a primary or associated diagnosis were identified from French national health records. They were compared to two control groups with no mental disorders, and with any other mental disorder than ED. The main outcomes were any hospitalization for deliberate self‐harm and mortality in the 3 years following hospitalization. Logistic regression models were used.Results: This study included 5, 452 patients hospitalized with an ED, 14,967 controls with no mental disorder, and 14,242 controls with a mental disorder other than an ED. During the three‐year follow‐up, 13.0% were hospitalized for deliberate self‐harm (vs. 0.2 and 22.0%, respectively) and 0.8% died (vs. 0.03 and 0.4%). After adjustment, hospitalization with an ED was associated with more self‐harm hospitalizations (hazard ratio [HR] = 46.0, 95% confidence interval [32.3–65.3]) and higher all‐cause mortality (HR = 12.6 [4.3–37.3]) relative to youths without any mental disorder; less self‐harm hospitalizations (HR = 0.5 [0.5–0.6]) but higher mortality (HR = 1.6 [1.0–2.4]) when compared to youths with any other mental disorder.Conclusion: Young patients hospitalized with an ED are at high risk of self‐harm and premature mortality. It is urgent to evaluate and implement the best strategies for post‐discharge care and follow‐up.Public significance: We found that the risk of being hospitalized for a suicide attempt is 46 times higher and mortality 13 times higher than the general population in adolescents and young adults during the 3 years following hospitalization with an eating disorder. Eating disorders are also associated with a 1.5 higher risk of premature mortality relative to other mental disorders. This risk is particularly high in the 6 months following hospitalization. It is therefore crucial to implement careful post‐discharge follow‐up in patients hospitalized for eating disorders.

The exact mechanisms linking metabolic and neuroendocrine adaptations to undernutrition and the pathophysiology of anorexia nervosa (AN) are not fully understood. AN is a psychiatric disorder of complex etiology characterized by extreme starvation while the disease is progressing into a chronic state. Metabolic and endocrine alterations associated to this disorder are part of a powerful response to maintain whole body energy homeostasis. But these modifications may also contribute to associated neuropsychiatric symptoms (reward abnormalities, anxiety, depression) and thus participate to sustain the disease. The current review presents data with both a clinical and basic research point of view on the role of nutritional and energy sensors with neuroendocrine actions in the pathophysiology of the disease, as they modulate metabolic responses, reproductive functions, stress responses as well as physical activity. While clinical data present a full description of changes occurring in AN, animal models that integrate either spontaneous genetic mutations or experimentally-induced food restriction with hyperactivity and/or social stress recapitulate the main metabolic and endocrine alterations of AN and provide mechanistic information between undernutrition state and symptoms of the disease. Further progress on the central and peripheral mechanism involved in the pathophysiology of eating disorders partly relies on the development and/or refinement of existing animal models to include recently identified genetic traits and better mimic the complex and multifactorial dimensions of the disease.