Eating Disorders
Number: 0511
Table Of Contents
PolicyApplicable CPT / HCPCS / ICD-10 Codes
Background
References
Policy
Scope of Policy
This Clinical Policy Bulletin addresses eating disorders.
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Medically Necessary
Aetna considers the following services and procedures medically necessary for the management of members with anorexia nervosa or bulimia nervosa:
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Assessment
- Albumin and prealbumin
- Blood count and serum chemistry (e.g., CBC, electrolytes, BUN/creatinine, glucose, magnesium, phosphorus)
- Bone density measurement (for evaluation of anorexic members)
- Electrocardiography (ECG/EKG)
- Liver function tests
- Luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol for women with amenorrhea or oligomenorrhea
- Medical evaluation (complete medical history and physical examination)
- Psychiatric / psychological consultation and testing
- Thyroid function testing (TSH)
- Urinalysis
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Treatment
- Nutritional counseling
- Psychotherapy (e.g., cognitive behavioral therapy, dialectical behavior therapy (DBT), family-based psychotherapy, interpersonal psychotherapy, and psychodynamic psychotherapy)
- Enteral nutrition as a last resort for the treatment of anorexia nervosa.
Note: Self-administered pharmacotherapies are managed under the pharmacy benefit. For additional information, refer to member's pharmacy benefit plan.
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Experimental, Investigational, or Unproven
Aetna considers the following services/procedures experimental, investigational, or unproven for the diagnosis and treatment of anorexia nervosa, bulimia nervosa, and binge-eating disorder because of insufficient evidence in the peer-reviewed literature:
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Assessment
- Blood-based serotoninergic biomarkers
- Brain imaging (e.g., MRI, PET and SPECT)
- Catechol-O-methyltransferase (COMT) Val158Met polymorphism genotyping
- Electroencephalography (EEG)
- Estrogen receptor 1 gene (ESR1) polymorphism testing
- Evaluation of genetic polymorphisms
- Evaluation of gustatory function
- Evaluation of gut microbiota
- Evaluation of multi-sensory integration
- Evaluation of olfaction
- Evaluation of melanocortin 4 receptor gene (MC4R) coding variants and mutations
- Individual Optimal Nutrition (ION) analysis/profile
- Measurement of blood levels of peripheral brain derived neurotrophic factor (BDNF)
- Measurement of betaine levels
- Measurement of plasma levels of hypothalamic neuropeptides (e.g., kisspeptin, nesfatin-1, phoenixin, and spexin)
- Measurement of plasma levels of adiponectin as a prognostic biomarker
- Measurement of plasma levels of polyunsaturated fatty acids
- Measurement of serum concentration of brain derived neurotrophic factor
- Measurement of serum levels of cytokines
- Measurements of serum zinc levels
- Proton magnetic resonance spectroscopy of neuro-metabolites
- Routine screening of asymptomatic adolescents and adults for eating disorders
- Serotonin transporter gene (5-HTTLPR) polymorphism testing
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Treatment
- Acamprosate calcium (Campral)
- Acupuncture
- Bright light therapy (includes use for night eating syndrome)
- Cannabinoids
- Chromium injection (excludes use as a supplement to intravenous solutions given during total parenteral nutrition (TPN); it is not used as a therapeutic intervention targeting the eating disorder itself)
- Deep brain stimulation
- Dehydroepiandrosterone (DHEA) injection
- Digital, single-session intervention (Help for Overcoming Problem Eating [HOPE])
- Electroconvulsive therapy
- E-therapy (via internet and mobile-device applications)
- Feedback-based (biofeedback, neurofeedback) therapies
- Food-specific inhibition training
- Ghrelin agonists injection
- Glucagon-like peptide-1 receptor agonists
- Gut microbiota modulation
- Imaginal exposure prevention (I-ERP) program
- Intranasal naloxone
- Music therapy
- Neural therapy (superficial injection of local anesthetic)
- Oxytocin
- Relaxation therapy
- Repetitive transcranial magnetic stimulation (rTMS)
- The Mandometer treatment
- Transcranial direct current stimulation.
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Related Policies
- CPB 0049 - Nutritional Counseling
- CPB 0061 - Nutritional Support
- CPB 0134 - Bone Mass Measurements
- CPB 0135 - Acupuncture and Dry Needling
- CPB 0202 - Magnetic Resonance Spectroscopy (MRS)
- CPB 0208 - Deep Brain Stimulation
- CPB 0370 - Phototherapy for Psychiatric Disorders
- CPB 0388 - Complementary and Alternative Medicine
- CPB 0445 - Electroconvulsive Therapy
- CPB 0469 - Transcranial Magnetic Stimulation and Cranial Electrical Stimulation
- CPB 0524 - Zoledronic Acid
Background
Eating disorders are psychiatric disorders characterized by persistent disturbances in eating behavior or related behaviors that result in altered consumption or absorption of food and significantly impair physical health or psychosocial functioning, including anorexia nervosa (AN), bulimia nervosa (BN), binge‑eating disorder (BED), avoidant/restrictive food intake disorder, and other specified feeding or eating disorders. These disorders are associated with abnormal body weight regulation, distorted body image, and maladaptive behaviors such as dietary restriction, binge eating, or compensatory behaviors, and they can lead to serious medical complications involving cardiovascular, gastrointestinal, endocrine, and neurologic systems, as well as increased psychiatric comorbidity and mortality. Evidence‑based guidelines describe eating disorders as multifactorial conditions influenced by biological, psychological, and social factors, with treatment typically involving nutritional rehabilitation, psychotherapy, and, in some cases, pharmacotherapy, delivered within a multidisciplinary care model (APA, 2022, Balasundaram & Santhanam, 2023; NIH/NIMH, 2024).
There are two severe forms of eating disorders - anorexia nervosa (AN) and bulimia nervosa (BN). AN typically begins during adolescence or young adulthood, with approximately 90% of patients being female. In females, the prevalence of anorexia is around 1%, and it carries a lifetime mortality rate of 15 to 20%. The disorder is characterized by three classical symptoms: a refusal to maintain a minimally normal body weight (such as weight loss resulting in a body weight less than 85% of what is expected or failure to achieve expected weight gain during growth), a distorted body image accompanied by an intense fear of gaining weight, and amenorrhea in post-menarcheal females (defined as the absence of three consecutive menstrual cycles). A diagnosis of anorexia should be considered for a young woman exhibiting symptoms of an eating disorder, amenorrhea, and a body mass index (BMI) of 17.5 kg/m² or lower, with similar considerations applying to male patients experiencing unexplained weight loss.
BN is more prevalent than anorexia, with a prevalence of 2 to 5% among females, though it has a lower mortality rate. This disorder is characterized by an excessive preoccupation with weight and body shape, recurrent episodes of binge eating followed by inappropriate compensatory behaviors such as purging, restriction, or excessive exercise, occurring at least twice a week for a minimum of three months. Unlike individuals with anorexia, those with bulimia typically maintain a normal weight, although they often experience fluctuations in their weight.
The majority of patients with eating disorders can be treated in outpatient settings. Hospitalization is usually reserved for severely symptomatic patients, such as individuals with extremely low body weight (75% or less of expected body weight) whose condition must be hemodynamically stabilized, or those with medical problems requiring intensive monitoring, such as patients with electrolyte imbalances, cardiac arrhythmias, profound hypoglycemia, self-mutilation, impaired capacity for self-care, or active suicidal ideation. Furthermore, failure of outpatient treatment may also constitute grounds for inpatient treatment. It should be noted that patients with bulimia rarely need hospitalization unless the binge-purge cycle has led to anorexia, resulting in severe metabolic deficiencies such as severe electrolyte imbalances, or suicidal depression is present.
A complete blood count may reflect anemia due to nutritional deficiency. Serum electrolyte imbalances may occur in patients with bulimia. Other laboratory tests include blood urea nitrogen/creatinine levels, serum measurements of calcium, glucose, magnesium, phosphorus, urinalysis, albumin and prealbumin levels, and liver function tests (Attia & Walsh, 2025). An electrocardiogram may aid in identifying cardiac abnormalities such as sinus bradycardia, as well as signs of hypokalemia or ipecac-induced myopathy. In general, brain imaging and bone mineral density studies are not necessary. A psychiatric assessment of patients with an eating disorder is appropriate for the identification of any concurrent psychiatric illness, evaluation of the risk of suicide, and exploration of the psychosocial context of the symptoms.
Current guidelines from the American Psychiatric Association (APA), the American Academy of Pediatrics (Hornberger, et al., 2021), and the American College of Obstetricians and Gynecologists (ACOG, 2018) recommend thyroid function testing (TSH) as part of the initial workup to exclude thyroid disease as an alternative diagnosis.
Guidelines from the American College of Obstetricians and Gynecologists (ACOG, 2018) recommend reproductive hormone testing (LH, FSH, estradiol) for women with amenorrhea or oligomenorrhea is guideline-recommended
Treatments for patients with eating disorders include nutritional counseling; psychotherapy such as cognitive behavioral therapy, family-based psychotherapy, interpersonal psychotherapy, and psychodynamic psychotherapy; as well as pharmacotherapy. Nutritional counseling, with a reasonable, graduated eating plan tied to specific weight goals, as well as psychotherapy, are essential. Medication plays an important but limited role in the management of eating disorders. In general, drug therapy is not effective in treating anorexia; zinc, cyproheptadine, antidepressants, and neuroleptic agents have not been shown to improve symptoms.
Pharmacotherapy for eating disorders is disorder-specific and is generally used as an adjunct to nutritional rehabilitation and psychotherapy, with the strongest evidence in BN and binge‑eating disorder. For AN, no medication has demonstrated consistent efficacy for weight restoration, and guidelines note that antidepressants and antipsychotics have limited benefit, though they may be used to treat comorbid anxiety, depression, or obsessive symptoms once malnutrition is corrected. For BN, selective serotonin reuptake inhibitors (SSRIs), particularly fluoxetine, have demonstrated efficacy in reducing binge‑purge behaviors and are recommended as first‑line pharmacotherapy. For BED, lisdexamfetamine is FDA‑approved and has been shown to reduce binge frequency, while SSRIs and some anticonvulsants may also reduce binge eating. Across eating disorders, medications are not recommended as monotherapy and should be integrated into a comprehensive, multidisciplinary treatment plan that prioritizes medical stability and evidence‑based psychotherapy.
Kucukgoncu et al. (2015) stated that night eating syndrome (NES) is a unique disorder characterized by a delayed pattern of food intake in which recurrent episodes of nocturnal eating and/or excessive food consumption occur after the evening meal. Night eating syndrome is a clinically important disorder due to its relationship to obesity, its association with other psychiatric disorders, and problems concerning sleep. However, NES often goes unrecognized by both health professionals and patients. The lack of knowledge regarding NES in clinical settings may lead to inadequate diagnoses and inappropriate treatment approaches. Therefore, the proper diagnosis of NES is the most important issue when identifying NES and providing treatment for this disorder. Clinical assessment tools such as the Night Eating Questionnaire may help health professionals working with populations vulnerable to NES. Although NES treatment studies are still in their infancy, antidepressant treatments and psychological therapies can be used for optimal management of patients with NES. Other treatment options, such as melatonergic medications, light therapy, and the anticonvulsant topiramate, also hold promise as future treatment options.
Attia and Walsh (2025) highlight the significance of eating disorders, which are characterized by disturbances in eating behavior and have a lifetime prevalence of 2% to 5% worldwide, with a higher occurrence in females than males. These disorders, including anorexia nervosa, bulimia nervosa, binge-eating disorder, and avoidant/restrictive food intake disorder, can lead to various medical and psychiatric complications, such as weight changes, electrolyte imbalances (e.g., hyponatremia, hypokalemia), bradycardia, hormonal disturbances (e.g., decreased estradiol levels in females), and reduced bone density. Individuals with these disorders also face high rates of depression - 76.3% for bulimia nervosa, 65.5% for binge-eating disorder, and 49.5% for anorexia nervosa, and are at a greater risk for suicide attempts. Anorexia nervosa has a mortality rate of 5.1 deaths per 1,000 person-years, nearly six times higher than that of individuals without the disorder, with 25% of deaths attributed to suicide. First-line treatments include nutritional support, psychotherapy, and pharmacotherapy, with cognitive behavioral therapy being particularly effective for bulimia nervosa and binge-eating disorder. Family-based treatment for youth with anorexia nervosa shows a higher remission rate at 6 to 12 months compared to individual treatment. Medications such as fluoxetine and other antidepressants can reduce binge-eating episodes in bulimia nervosa, while antidepressants and the stimulant lisdexamfetamine have been shown to decrease binge frequency in binge-eating disorder. However, there are currently no effective medications for anorexia nervosa, and individuals with severe medical or psychiatric complications should be hospitalized for treatment. Overall, eating disorders pose significant health risks and require comprehensive management strategies.
American Psychiatric Association Practice Guideline - Treatment of Eating Disorders
The American Psychiatric Association (Crone et al., 2023) practice guideline provide the following recommendations for the treatment of patients with eating disorders:
Guideline Statement Summary for the Assessment and Determination of Treatment Plan
- APA recommends screening for the presence of an eating disorder as part of an initial psychiatric evaluation (Strength of Recommendation (SOR: 1C).
- APA recommends that the initial evaluation of a patient with a possible eating disorder include assessment of the following (SOR: 1C):
- The patient’s height and weight history (e.g., maximum and minimum weight, recent weight changes);
- Presence of, patterns in, and changes in restrictive eating, food avoidance, binge eating, and other eating-related behaviors;
- Patterns and changes in food repertoire (e.g., breadth of food variety, narrowing or elimination of food groups);
- Presence of, patterns in, and changes in compensatory and other weight control behaviors, including dietary restriction, compulsive or driven exercise, purging behaviors, and use of medication to manipulate weight;
- Percentage of time preoccupied with food, weight, and body shape;
- Prior treatment and response to treatment for an eating disorder;
- Psychosocial impairment secondary to eating or body image concerns or behaviors; and
- Family history of eating disorders, other psychiatric illnesses, and other medical conditions (e.g., obesity, inflammatory bowel disease, diabetes mellitus).
- APA recommends that the initial psychiatric evaluation of a patient with a possible eating disorder include weighing the patient and quantifying eating and weight control behaviors (SOR: 1C).
- APA recommends that the initial psychiatric evaluation of a patient with a possible eating disorder identify co-occurring health conditions, including co-occurring psychiatric disorders (SOR: 1C).
- APA recommends that the initial psychiatric evaluation of a patient with a possible eating disorder include a comprehensive review of systems (SOR: 1C).
- APA recommends that the initial physical examination of a patient with a possible eating disorder include assessment of vital signs, height, weight, and body mass index (BMI; or percent median BMI, BMI percentile, or BMI Z-score for children and adolescents), and physical appearance, including signs of malnutrition or purging behaviors (SOR: 1C).
- APA recommends that the laboratory assessment of a patient with a possible eating disorder include a complete blood count and a comprehensive metabolic panel, including electrolytes, liver enzymes, and renal function tests (SOR: 1C).
- APA recommends that an electrocardiogram be done in patients with a restrictive eating disorder, patients with severe purging behavior, and patients who are taking medications that are known to prolong QTc intervals (SOR: 1C).
- APA recommends that patients with an eating disorder have a documented, comprehensive, culturally appropriate, and person-centered treatment plan that incorporates medical, psychiatric, psychological, and nutritional expertise, commonly via a coordinated multidisciplinary team (SOR: 1C).
Anorexia Nervosa
- APA recommends that patients with anorexia nervosa who require nutritional rehabilitation and weight restoration have individualized goals set for weekly weight gain and target weight (SOR: 1C).
- APA recommends that adults with anorexia nervosa be treated with an eating disorder–focused psychotherapy, which should include normalizing eating and weight control behaviors, restoring weight, and addressing psychological aspects of the disorder (e.g., fear of weight gain, body image disturbance) (SOR: 1B).
- APA recommends that adolescents and emerging adults with anorexia nervosa who have an involved caregiver be treated with eating disorder–focused family-based treatment, which should include caregiver education aimed at normalizing eating and weight control behaviors and restoring weight (SOR: 1B).
Bulimia Nervosa
- APA recommends that adults with bulimia nervosa be treated with eating disorder–focused cognitive-behavioral therapy and that a serotonin reuptake inhibitor (e.g., 60 mg fluoxetine daily) also be prescribed, either initially or if there is minimal or no response to psychotherapy alone by 6 weeks of treatment (SOR: 1C).
- APA suggests that adolescents and emerging adults with bulimia nervosa who have an involved caregiver be treated with eating disorder–focused family-based treatment (SOR: 2C).
Binge-Eating Disorder
- APA recommends that patients with binge-eating disorder be treated with eating disorder–focused cognitive-behavioral therapy or interpersonal therapy, in either individual or group formats (SOR: 1C).
- APA suggests that adults with binge-eating disorder who prefer medication or have not responded to psychotherapy alone be treated with either an antidepressant medication or lisdexamfetamine (SOR: 2C).
Acceptance and Commitment Therapy (ACT)-Based Treatments for Eating Disorders
Di Sante and colleagues (2022) noted that an increasing number of studies have examined the effectiveness of Acceptance and Commitment Therapy (ACT) for the reduction of dysregulated eating behaviors such as binge eating and emotional eating. However, little is known regarding their short- and long-term effectiveness as well as the underlying mechanisms of change. These researchers carried out a systematic effect size analysis to estimate the effectiveness of ACT-based treatments on measures of dysregulated eating and of psychological flexibility, a theorized ACT mechanism of change. Literature searches were performed in PsycInfo, Medline, Web of Science, and ProQuest Dissertations. Within-group and between-group SMDs were computed using Comprehensive Meta-Analysis Version 3. Additional sub-group and meta-regression analyses by study characteristics were carried out. A total of 20 publications (22 samples, n = 1,269) were included. Pre-post and pre-follow-up effects suggested that ACT-based treatments were moderately effective in reducing dysregulated eating behaviors and increasing psychological flexibility. These effects were comparable for binge-eating and emotional eating outcomes and for face-to-face interventions, Web-based interventions, and interventions that used a self-help book. Longer treatments were associated with larger outcome effect sizes, and changes in psychological flexibility were not associated with changes in dysregulated eating outcomes. Small significant effects were found in favor of ACT when compared to inactive control groups. The only 3 studies that included active control groups and did not show significant differences in outcomes between ACT and other treatments. The authors concluded that future studies should aim to compare ACT-based treatments to active treatments and to provide empirical evidence for the theoretical mediating role of psychological flexibility in reported changes in eating behavior.
Blood-Based Serotonergic Biomarkers for Tailoring Treatment in Bulimia Nervosa
Sjogren and colleagues (2019) stated that BN is a serious ED affecting 0.8 to 2.9% of the young population. The etiology is unknown and biomarkers would support in understanding the pathophysiology of BN, and in identifying BN patients that may benefit from medical treatment. In a systematic review, these investigators asked if BN deviate from healthy controls in terms of serotonin (5-HT) biomarkers in blood, and if blood-based 5-HT biomarkers could be used to tailor psycho-pharmacological therapies in BN. They carried out a literature search using PubMed, PsycINFO and Embase using the following search terms: "bulimia nervosa" and "serotonin" and "blood" or "plasma" or "serum". A total of 32 studies were included in this systematic review. Several biomarkers and challenge tests were identified and all studies described an association with BN and dysregulation of the 5-HT system compared to healthy controls. Several studies pointed to an association also to borderline symptoms in BN. The authors found BN deviated from healthy controls in terms of 5-HT biomarkers in blood supporting an abnormal 5-HT system in BN. These researchers stated that 5-HT biomarkers and associated methods could be used to tailor treatment in BN although as yet, most tests described are impractical for bedside use.
Brain-Derived Neurotrophic Factor (BDNF)
Brandys et al. (2011) noted that brain-derived neurotrophic factor (BDNF) is involved in neuroplasticity and in the homeostatic regulation of food intake and energy expenditure. It also has a role in stress responsivity and reward processing. On the basis of its involvement in these various processes, BDNF can be hypothesized to be an important factor in the development and maintenance of anorexia nervosa (AN). These researchers meta-analytically summarized investigations of serum BDNF concentrations in people currently ill with AN, in comparison to healthy controls. A total of seven studies measuring BDNF in serum of individuals with AN (n = 155) and healthy controls (n = 174) were identified and included in the meta-analysis of the mean differences between case and control groups. This study confirmed that AN is associated with decreased serum BDNF concentrations in comparison to healthy controls. The combined effect size (standardized mean difference, SMD) was large (SMD = -0.96; 95% confidence interval [CI]: -1.33 to -0.59; p < 0.001). Significant heterogeneity of effect sizes was identified (I(2) = 58.3%; p < 0.001), which emerged as being primarily attributable to the first published study on the investigated association. The authors concluded that the meta-analytical summary of studies measuring circulating BDNF concentrations in women with AN and healthy controls confirms that it is significantly reduced in this patient group. Moreover, difficulties associated with the measurement of BDNF have been identified, and potential confounding factors have been discussed. They stated that current data do not allow inferences to be made about causal links between levels of circulating BDNF and AN. However, possible explanations for the relationship between BDNF and AN have been presented.
Phillips et al. (2014) stated that there is currently limited understanding of the etiology of BN. While a multifaceted etiology is likely, several neurobiological factors may play a role. Brain-derived neurotrophic factor (BDNF), a potential biomarker linked to eating and weight disorders, is one factor of recent investigation. These investigators examined studies comparing BDNF blood levels in BN to healthy control (HC) subjects. A systematic review of the literature was conducted utilizing five databases (PubMed, CINAHL, EMBASE, PsycINFO, and Medline). Key terms included eating disorders, BDNF, and bulimia nervosa. The authors concluded that BDNF blood levels appear lower in BN than in HC subjects; however, studies are needed to examine the influence of possible correlates, including symptom severity, mood, medications, exercise, and substance use.
Bright Light Therapy for Eating Disorders
Bright light therapy is a non-invasive biological intervention that may be effective for eating disorders characterized by non-normative circadian features, such as binge-eating and night-eating patterns. Recognizing this potential, Beauchamp and Lundgren (2016) conducted a systematic review following PRISMA guidelines to evaluate the empirical treatment outcomes of bright light therapy for eating disorders. The authors aimed to understand the timing of changes in eating behavior, mood, and sleep-related symptoms, which could elucidate the mechanisms by which bright light therapy operates in the context of eating disorder treatment. A comprehensive literature search was performed in April 2016 using PsycInfo and PubMed/Medline, identifying studies published without date restrictions that utilized bright light therapy for treating eating disorders. The search included various keywords related to disordered eating and bright light therapy. After excluding duplicates, 34 articles were reviewed, and 14 studies met the inclusion criteria, which required participants to have an eating disorder or disordered eating behaviors and to be published in English. The findings indicated that bright light therapy could potentially improve disordered eating behaviors and mood in the short term, although the timing of symptom response and the duration of treatment effects remain unclear. The authors emphasized the need for future research to systematically control for placebo responses, frequently assess symptom changes across a wide range of systems, and evaluate the long-term effectiveness of bright light therapy for eating disorders.
Cannabinoids for the Treatment of Anorexia Nervosa
Rosager and colleagues (2021) noted that AN is a psychiatric disorder with a high mortality and unknown etiology, and effective treatment is lacking. For decades, cannabis has been known to cause physical effects on the human body, including increasing appetite, which may be beneficial in the treatment of AN. These investigators examined the literature for evidence of an effect of cannabinoids on weight gain and other outcomes in patients with AN. They carried out a systematic review using 3 data-bases Embase, PubMed and Psychinfo. There were 1,288 studies identified and after thorough review and exclusion of copies, 4 studies met the inclusion criteria; and 3 studies used the same AN population and utilized data from 1 original study, leaving only 2 original studies. Both of these were RCTs that examined the effects of delta-9-tetrahydrocannabinol (Δ9-THC) or dronabinol in AN, whereas 1 study was properly designed and powered and showed a weight increase of an added 1 kg over 4 weeks over placebo. The authors concluded that there were few studies and the level of evidence was low. The only properly designed, low bias and highly powered study found a weight increasing effect of dronabinol in AN, while the other, using Δ9-THC at a high dose, found no effect and where the dose may have counteracted the weight gaining effects due to AEs. These researchers stated that more research on cannabinoids in AN is needed, especially its effects on psychopathology. Level of Evidence = I.
Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism Genotyping
Collantoni and associates (2017) examined if catechol-O-methyltransferase (COMT) Val158Met polymorphism is associated with EDs. These researchers conducted a systematic literature search of studies published until January 15, 2017 and added data from the Italian “Biobanca Veneta per i Disturbi Alimentari” biobank, and performed a meta-analysis comparing COMT Val158Met genotype and allele frequencies in patients with EDs and AN or BN versus controls. A total of 10 studies plus Biobanca Veneta per i Disturbi Alimentari (ED: n = 920, controls: n = 261 controls) with 3,541 ED patients (AN = 2,388; BN = 233) and 3,684 controls were included. There were no significant group differences in COMT Val158Met alleles and genotype frequencies between patients and controls, for all EDs pooled together [range of odds ratios (ORs): 0.96 to 1.04, p : 0.46 to 0.97, I2 = 0%] and when analyzing separately patients with AN (ORs: 0.94 to 1.04, p : 0.31 to 0.61, I2 = 0%) or BN (ORs: 0.80 to 1.09, p : 0.28 to 0.64, I2 = 0 to 44%). The authors concluded that results from 11 studies and 7,225 subjects showed that COMT Val158Met polymorphism was not associated with EDs.
Chromium
In a double-blind, randomized pilot trial, Brownley et al. (2013) examined whether chromium may be useful in the treatment of BED. A total of 24 overweight adults with BED were enrolled in a 6-month double-blind placebo-controlled trial and randomly assigned to receive either 1,000 mcg chromium/day ("high dose"; n = 8) or 600 mcg chromium/day ("moderate dose"; n = 9) as chromium picolinate or placebo (n = 7). Mixed linear regression models were used to estimate mean change in binge frequency and related psychopathology, weight, symptoms of depression, and fasting glucose. Fasting glucose was significantly reduced in both chromium groups compared to the placebo group; similarly, numerically, but not significantly, greater reductions in binge frequency, weight, and symptoms of depression were observed in those treated with chromium versus placebo, although statistical power was limited in this pilot trial. For fasting glucose, the findings suggested a dose-response with larger effects in the high-dose compared to the moderate-dose group. The authors concluded that these initial findings supported further larger trials to determine chromium's effectiveness in maintaining normal glucose regulation, reducing binge eating and related psychopathology, promoting modest weight loss, and reducing symptoms of depression in individuals with BED. Studies designed to link the clinical effects of chromium with changes in underlying insulin, serotonin, and dopamine pathways may be especially informative. They stated that chromium supplementation, if effective, may provide a useful, low-cost alternative to or augmentation strategy for SSRIs, which have partial efficacy in BED.
Complementary and Alternative Medicine
In a systematic review, Fogarty and associates (2016) examined the role of complementary and alternative medicine in the treatment of individuals with eating disorders. A total of 16 studies were included in the review. The results of this review showed that the role of complementary and alternative medicine in the treatment of those with eating disorders is unclear, and further studies should be conducted. A potential role was found for massage and bright light therapy for depression in individuals with bulimia nervosa (BN), as well as a potential role for acupuncture and relaxation therapy in the treatment of state anxiety for those with eating disorders.
In a systematic review and meta-analysis, Chen et al. (2023) examined the safety and effectiveness of acupuncture at Sifeng for the treatment of pediatric anorexia. By means of seven databases, these investigators searched for randomized controlled trials (RCTs) of acupuncture at Sifeng for pediatric anorexia from their inception to October 2022. The Cochrane risk of bias evaluation tool was employed to ascertain the risk of bias in the included studies. A meta-analysis of effectiveness, including the score of food intake reduction, time to normalize food intake, body weight, leptin levels, and blood zinc levels, was carried out using Review Manager 5.3 software. The GRADE criteria were applied to assess the quality of the evidence. A total of 24 RCTs were included, involving 2,202 children. The allocation concealment, blinding, and selective reporting had a high or unclear risk of bias. All experiments compared acupuncture at Sifeng with traditional Chinese medicine or Western medicine. The results demonstrated that, compared with medicine, acupuncture at Sifeng could significantly improve effectiveness (OR = 6.44, 95% CI: 4.78 to 8.66), lower the score of food intake reduction (MD = -0.69, 95% CI: -1.00 to -0.39), decrease leptin levels (MD = -5.19, 95% CI: -8.09 to -2.29), reduce the time to normal food intake (MD = -2.22, 95% CI: -2.42 to -2.01), and increase blood zinc (MD = 0.79, 95% CI: 0.21 to 1.37) and body weight (MD = 1.28, 95% CI: 0.85 to 1.72). A total of seven studies found that the treatment was safe both during and after the procedure. Based on the GRADE criteria, the quality of the evidence for the majority of indicators was extremely poor. The authors concluded that the low certainty of evidence suggested that acupuncture at Sifeng was safe and effective in the treatment of pediatric anorexia. Moreover, these researchers stated that future high-quality clinical studies are needed to provide more reliable evidence of the safety and effectiveness of the therapy.
Deep Brain Stimulation
Anorexia nervosa (AN) is characterized by a chronic course that is refractory to treatment in many patients and has one of the highest mortality rates of any psychiatric disorder. Deep brain stimulation (DBS) has been applied to circuit-based neuropsychiatric diseases, such as Parkinson's disease and major depression, with promising results. In a pilot study, Lipsman et al. (2013) evaluated the safety of DBS to modulate the activity of limbic circuits and examined how this might affect the clinical features of AN. In this prospective trial, subcallosal cingulate DBS was administered to 6 patients with chronic, severe, and treatment-refractory AN. Eligible patients were aged 20 to 60 years, had been diagnosed with restricting or binge-purging AN, and showed evidence of chronicity or treatment resistance. Patients underwent medical optimization pre-operatively and had baseline body mass index (BMI), psychometric, and neuroimaging investigations, followed by implantation of electrodes and pulse generators for continuous delivery of electrical stimulation. Patients were followed up for 9 months after DBS activation, and the primary outcome of adverse events associated with surgery or stimulation was monitored at every follow-up visit. Repeat psychometric assessments, BMI measurements, and neuroimaging investigations were also conducted at various intervals. Deep brain stimulation was associated with several adverse events, only one of which (a seizure during programming, roughly 2 weeks after surgery) was serious. Other related adverse events included a panic attack during surgery, nausea, air embolus, and pain. After 9 months, 3 of the 6 patients had achieved and maintained a BMI greater than their historical baselines. Deep brain stimulation was associated with improvements in mood, anxiety, affective regulation, and AN-related obsessions and compulsions in 4 patients, and with improvements in quality of life in 3 patients after 6 months of stimulation. These clinical benefits were accompanied by changes in cerebral glucose metabolism (seen in a comparison of composite positron emission tomography (PET) scans at baseline and 6 months) that were consistent with a reversal of the abnormalities seen in the anterior cingulate, insula, and parietal lobe in the disorder. The authors concluded that subcallosal cingulate DBS seems to be generally safe in this sample of patients with chronic and treatment-refractory AN. The effectiveness of this approach awaits results from well-designed studies.
Shaffer et al. (2023) noted that DBS has been approved as a therapy for movement disorders and obsessive-compulsive disorder (OCD). Recently, DBS has been studied in patients with AN. Several stimulation locations have been tested without a clear indication of the best region. In a systematic review and network meta-analysis, these investigators employed patient-level data to identify stimulation targets with the greatest evidence for effectiveness in increasing BMI. They carried out a systematic search on or before August 4, 2022, using PubMed/Medline, OVID, and Scopus. Studies were included if patient-level data were presented, patients were diagnosed with AN and treated with DBS, and 6 months or more of post-operative follow-up data were reported. Quality and risk of bias were assessed with the NIH assessment tools. Patient data were collected and stratified by stimulation location. A network meta-analysis was performed. This review was written in accordance with PRISMA guidelines for systematic reviews. A total of 11 studies consisting of 36 patients were included. The mean age and BMI at the time of surgery were 38.07 (SD 11.64) years and 12.58 (SD 1.4) kg/m², respectively. After 6 months of DBS, a significant difference in percentage change in BMI was found between the nucleus accumbens and subcallosal cingulate cortex (SCC) (standardized mean difference [SMD] 0.78; 95% CI: 0.10 to 1.45) and between the SCC and ventral anterior limb of the internal capsule (SMD -1.51; 95% CI: -2.39 to -0.62). Similarly, at 9 to 12 months, a significant difference in percentage change in BMI was found between the SCC and ventral anterior limb of the internal capsule (SMD -1.18; 95% CI: -2.21 to -0.15). With hierarchical ranking, this study identified the SCC as the most supported stimulation location for BMI change at 6 and 9 to 12 months (p-scores 0.9449 and 0.9771, respectively). The authors concluded that several DBS targets have been tested for AN, and this study identified the SCC as the most supported region for BMI change. Moreover, these researchers stated that further larger, randomized studies with blinded on/off periods are needed to confirm these findings.
The authors stated that, as with any meta-analysis, this study had several drawbacks. First, the types of studies included were observational cohort studies and case series. Because of the nature of the trials, there was a potential for selection bias. Furthermore, the lack of randomized patient data, especially sham-controlled studies, presents a notable limitation. In aggregate, this reduced the power of the analysis and underscored the need to validate these findings. Second, the sample size for each stimulation location varied, and the overall sample size was limited. However, this was likely related to the lack of FDA approval for the use of DBS in AN and the limited availability of DBS. Third, patients were not stratified by subtype of AN (restrictive versus binge/purge). Stimulation location effectiveness may vary by disease subtype in addition to individual differences in patient pathophysiology. Finally, BMI was used as the primary outcome measure of effectiveness. Although BMI was used to define the severity of AN, treatment-induced increases in BMI did not necessarily reflect improvements in a patient’s mental health.
Dialectical Behavior Therapy (DBT)
Dialectical Behavior Therapy (DBT) is a manualized, cognitive‑behavioral treatment that integrates behavioral change strategies with acceptance‑based interventions and was originally developed for individuals with borderline personality disorder and chronic suicidal behavior. DBT is delivered through a multimodal structure that typically includes individual psychotherapy, group skills training, between‑session coaching, and a therapist consultation team, with core skills modules focused on mindfulness, distress tolerance, emotion regulation, and interpersonal effectiveness. Clinical trials and systematic reviews have demonstrated that DBT is effective in reducing suicidal and self‑injurious behaviors and improving emotional regulation in its primary indicated populations. DBT has been adapted for use in eating disorders, particularly binge‑eating disorder and bulimia nervosa; however, systematic reviews indicate that while DBT and other “third‑wave” therapies are associated with large within‑group symptom improvements, they have not demonstrated superiority to active comparators, including cognitive‑behavioral therapy (CBT). Accordingly, major reviews and practice guidelines continue to recommend CBT as the first‑line treatment for bulimia nervosa and binge‑eating disorder (BED), with DBT considered an adjunctive or alternative approach for selected patients, particularly those with prominent emotion dysregulation (Linardon et al., 2017; Linehan, 1993).
Masson et al. (2013) performed a randomized waitlist-controlled pilot study (n=60) that examined DBT guided self-help for binge eating disorder, delivered via a self-help manual supplemented by six brief (20-minute) telephone coaching calls over 13 weeks. At post-treatment, the DBT group had significantly fewer binge episodes per month (6.0 vs. 14.4) and a substantially higher binge abstinence rate (40% vs. 3.3%) compared to waitlist, along with improvements in quality of life and eating disorder psychopathology. At 6-month follow-up (available only for the intervention group, as the waitlist crossed over), improvements were largely maintained, though abstinence rates declined to 30%. Limitations include the small sample size, the low-intensity self-help format (which does not reflect full therapist-delivered DBT), the lack of an active comparator, and the inability to make between-group comparisons at follow-up.
Linardon et al. (2024) conducted a randomized controlled trial (n=576) that evaluated a DBT skills training smartphone application for adults with recurrent binge eating, comparing the app intervention to a waitlist control over 6 weeks with a 12-week follow-up. Participants randomized to the app demonstrated significantly fewer objective binge eating episodes (incidence rate ratio = 0.69) and greater reductions in eating disorder psychopathology (d = −0.68) compared to waitlist, with continued improvement at 12 weeks. The authors reported significant effects observed for behavioral and cognitive eating disorder symptoms, emotion regulation difficulties, and mindfulness, though no significant differences emerged for subjective binge eating, psychological distress, or distress tolerance. Key limitations include the absence of an active comparator (e.g., CBT), a high dropout rate of 48% in the intervention arm with declining engagement over time, reliance on self-report measures, and the app-based delivery format, which limits generalizability to therapist-delivered DBT.
Briggs et al. (2025) explored the acceptability and preliminary clinical effectiveness of a virtual therapist-led DBT group for binge eating disorders (BED), delivered across eight 10-week groups in a UK NHS eating disorders service. Of 108 patients offered the intervention, 51 commenced and 36 (71%) completed treatment. At post-treatment, 64.7% achieved binge abstinence, with significant reductions in eating disorder psychopathology and mood symptoms at strong effect sizes, maintained at 1-month follow-up. Acceptability ratings were high among completers. However, the absence of a control group, the high rate of non-uptake and attrition (only 33% of those offered treatment completed it), the short follow-up period, and the self-selected nature of the sample substantially limit the ability to attribute outcomes to the intervention or generalize findings.
In a single case report, Navarro-Haro et al. (2025) described the transdiagnostic application of standard DBT to a patient with comorbid borderline personality disorder and an eating disorder, illustrating how DBT's modular structure (individual therapy, skills training, phone coaching, and consultation team) can address the shared emotion dysregulation underlying both conditions. The case demonstrated clinical improvement across both BPD and eating disorder symptoms, supporting the theoretical rationale for DBT in patients with this common comorbidity. As a single case report, this study represents the lowest level of evidence, cannot establish causation or generalizability, and is subject to inherent publication bias favoring positive outcomes. Its primary value lies in hypothesis generation and clinical illustration rather than as evidence for treatment efficacy.
In a narrative review, Attia & Walsh (2025) provided a comprehensive overview of the epidemiology, pathophysiology, and treatment of eating disorders, including anorexia nervosa, bulimia nervosa, binge eating disorder, and avoidant/restrictive food intake disorder. Regarding DBT, the review noted that it has "not been extensively studied" in eating disorders but "may be useful, especially for individuals with coexisting borderline personality disorder, impulsivity, and emotional dysregulation." The review affirmed CBT as the most evidence-supported psychotherapy for binge-spectrum eating disorders and noted that no single psychological treatment has demonstrated clear superiority for anorexia nervosa. As a narrative review, the study is subject to author selection bias in the choice of evidence presented and does not provide a systematic or quantitative synthesis of the DBT literature.
Digital Single Session Intervention (Help for Overcoming Problem Eating" (HOPE)) for the Treatment of Binge-Spectrum Eating Disorders
Negi and Forbush (2025) stated that EDs are common among university students, yet most students with EDs do not have access to ED-related care on their campuses. In a pilot study, these researchers tested the initial acceptability and feasibility of Help for Overcoming Problem Eating (HOPE), the 1st digital single-session intervention designed to reduce binge eating for college students with non-low-weight binge-spectrum EDs. A total of 75 university students with non-low-weight binge-spectrum EDs completed HOPE and answered questions regarding the acceptability and user perceptions of the program following completion. They also completed baseline, 1-week, and 4-week follow-up questionnaires assessing ED symptoms. Of the eligible participants (n = 190), 70.52% (n = 134) consented to the study, 42.63% (n = 81) started HOPE, and 39.47% (n = 75) completed HOPE. Descriptive statistics showed that HOPE was highly acceptable, with a scaled mean overall acceptability score of 4.35 out of 5. Paired Sample t-tests showed that there were significant reductions in binge eating (p < 0.001, 1-week d = 0.86, 4-week d = 0.98), restricting (p < 0.001, 1-week d = 0.52, 4-week d = 0.41), and cognitive restraint (p < 0.001, 1-week d = 0.63, 4-week d = 0.87) following HOPE completion. The authors concluded that the findings of this study showed the acceptability and preliminary effectiveness of HOPE for those who completed the intervention. Moreover, these researchers stated that further investigations in a RCT design is needed. These investigators noted that although these findings provided promising pilot feasibility data, additional research is needed to identify reasons for attrition/non-participation to reduce barriers for study completion.
Electroencephalography (EEG) for the Management of Bulimia Nervosa, and Binge-Eating Disorder
To provide a basis for electroencephalography (EEG) neurofeedback protocols for BN, BED, and obesity, Blume and colleagues (2019) examined alterations in EEG-measured brain activity, specifically frequency bands. These investigators carried out a systematic literature search with pre-defined search terms, which yielded 7 studies meeting the inclusion criteria. The risk of bias was assessed for all studies. In resting-state EEG, the beta activity was elevated in fronto-central regions in individuals with obesity and co-morbid BED. In food-cue conditions, both obese individuals with and without BED showed increased beta activity, suggesting increased awareness of food cues and a heightened attentional focus towards food stimuli. The level of beta activity was positively correlated with ED psychopathology in resting and food-cue conditions. In individuals with BN, there was no evidence for altered EEG spectral power. The authors concluded that these findings indicated specific alterations in EEG-based brain activity in individuals with BED and obesity. Moreover, these researchers stated that more high-quality studies are needed to confirm these findings and to transfer them into EEG-based interventions.
Enteral Nutrition for the Treatment of Anorexia and Bulimia
Rizzo and colleagues (2019) stated that weight restoration is an important first step in treating patients with anorexia nervosa (AN) because it is essential for medical stabilization and the reversal of long-term complications. Tube feeding may help facilitate weight restoration, but its role in treatment remains unclear. These investigators reviewed the literature describing the efficacy, safety, tolerance, and long-term effects of enteral nutrition (EN) via nasogastric (NG) feeding for re-feeding patients with AN. Four electronic databases were systematically searched through May 2018. Boolean search terms included "anorexia nervosa," "refeeding," and "nasogastric tube feeding." A total of 10 studies were eligible for inclusion: 8 retrospective chart reviews, 1 prospective cohort, and 1 randomized controlled trial (RCT); 9 of the studies were performed in-hospital. In 8 studies, NG nutrition resulted in an average rate of weight gain exceeding 1 kg/week. In 4 of 5 studies that included an oral-only control group, mean weekly weight gain and caloric intake were significantly higher in tube-fed patients. Six studies provided prophylactic phosphate supplementation, all with less than a 1% occurrence rate of re-feeding hypophosphatemia; 7 studies reported on other physiological disturbances, 6 evaluated medical and gastrointestinal (GI) side effects, 3 considered psychological outcomes, and 4 assessed patients post-discharge. Results indicated that NG feeding was not associated with an increased risk for adverse outcomes. The authors concluded that NG nutrition was considered safe and well-tolerated and effectively increased caloric intake and the rate of weight gain in patients with AN. Moreover, they stated that these findings were limited by weaknesses in study designs, and more rigorous methods are needed for the development of evidence-based, standardized re-feeding protocols.
Hale and Logomarsino (2019) noted that EN is frequently used in the treatment of AN and, less commonly, bulimia nervosa (BN); yet, no standardized guidelines for treatment exist at this time. These investigators examined the efficacy of EN in the treatment of eating disorders and made recommendations for clinical practice and future research. They carried out an exhaustive literature search of 7 databases. The search strategy combined key terms such as anorexia nervosa, bulimia, and eating disorders with terms associated with EN. There were no restrictions on publication date or language. Studies that assessed the effect of EN on weight restoration, re-feeding syndrome, and binge/purge behaviors in the treatment of AN and BN were included. Of 73 full-text articles reviewed, 22 met inclusion criteria; 19 studies reported that significant short-term weight gain was achieved when EN was used for re-feeding malnourished AN patients; however, results varied for the 6 studies reporting on long-term weight gain, maintenance, and recovery. In studies with a comparator, no significant differences were found between the EN and oral refeeding cohorts regarding gastrointestinal (GI) disturbance, re-feeding syndrome, or electrolyte abnormalities. Five studies examined the effect of EN on binge/purge behaviors, suggesting that temporary exclusive EN decreased the frequency and severity of binge/purge episodes. The authors concluded that although EN was an essential life-saving treatment in severe cases of AN, it did not guarantee long-term success or recovery. These researchers stated that the findings of this systematic review highlighted the need for prospective controlled trials with adequate sample sizes to make comparisons between specific feeding methods, formulations, and defined short- and long-term outcomes. They emphasized that evidence-based standards for clinical practice are needed, along with specific guidelines for achieving the best results in the treatment of AN and BN.
Evaluation of Genetic Polymorphisms for Binge Eating Disorder
Manfredi and colleagues (2021) noted that the genetic polymorphisms involved in the physiopathology of binge eating disorder (BED) are currently unclear. In a systematic review, these investigators examined the research on polymorphisms conducted in the field of BED. They evaluated observational studies where there was a genetic comparison between adults with BED, in some cases also with obesity or overweight, and healthy controls or individuals with obesity/overweight without BED. The protocol was written using PRISMA guidelines. To identify potentially relevant documents, the following bibliographic databases were searched without a time limit, but until September 2020: PubMed, PsycINFO, Scopus, and Web of Science. A total of 21 articles were included in the qualitative analysis of the systematic review, as they met the eligibility criteria. Within the selected studies, 41 polymorphisms of 17 genes were assessed. Overall, this systematic review provided a list of potentially useful genetic polymorphisms involved in BED: 5-HTTLPR (5-HTT), Taq1A (ANKK1/DRD2), A118G (OPRM1), C957T (DRD2), rs2283265 (DRD2), Val158Met (COMT), rs6198 (GR), Val103Ile (MC4R), Ile251Leu (MC4R), rs6265 (BDNF), and Leu72Met (GHRL). The authors concluded that it is important to emphasize that Taq1A is the polymorphism that showed, in two different research groups, the most significant association with BED. The remaining polymorphisms need further evidence to be confirmed.
The authors stated that this study had several drawbacks. First, the number of studies examining associations between many genetic polymorphisms and BED is limited, and in some cases, the sample size used was small. Second, the relationship between some polymorphisms and BED could also be influenced by gene-gene or gene-environment interactions. Third, these researchers could not pool data collected for a meta-analysis due to the heterogeneity of the genetic polymorphisms observed.
Heidinger and associates (2021) stated that the genetics of BED is an emerging topic, with dopaminergic genes being implicated in its etiology due to the role that dopamine (DA) plays in food reward sensitivity and self-regulation of eating behavior. However, no study to date has examined whether DA genes influence response to behavioral treatment of BED. These researchers examined the ability of DA-associated polymorphisms to predict BED treatment response, measured using binge frequency over 12 months. As secondary objectives, this study examined cross-sectional relationships between these polymorphisms and anthropometrics in women living with and without BED and obesity. Women aged 18 to 64 years were genotyped for the DA-related SNPs DRD2/ANKK1 Taq1A (rs1800497) and COMT (rs4680), as well as the DA-related uVNTRs DAT-1 (SLC6A3) and MAO-A. A multi-locus DA composite score was formed from these four polymorphisms using genotypes known to have a functional impact resulting in modified DA signaling. Binge frequency (Eating Disorder Examination - Interview) and body composition (Tanita BC-418) were evaluated in a pre-post analysis to examine genetic predictors of treatment response in women living with obesity and BED. Secondary data analysis was carried out on a cross-sectional comparison of three groups of women enrolled in trial group treatment for BED: women living with obesity and BED (n = 72), obesity without BED (n = 27), and normal-weight women without BED (n = 45). There were no significant genotype × time interactions related to anthropometrics or binge frequency for any individual DA genotypes, nor for the composite score reflecting DA availability. At baseline, there were no significant between-group differences in frequencies of DA-related alleles, nor were there associations between genotypes and anthropometrics. The authors concluded that this study found no evidence to suggest that the DRD2/ANKK1 Taq1A, COMT, MAO-A, or DAT-1 polymorphisms are associated with response to behavioral intervention for BED as measured by changes in binge frequency. These researchers stated that future studies should examine a greater variety of dopaminergic polymorphisms, other candidate genes that target other neurotransmitter systems, as well as their impact on both behavioral and pharmacological-based treatment for BED.
Evaluation of Gustatory Function in Individuals with Eating Disorders
Chao and colleagues (2020) noted that eating disorders are a significant cause of morbidity and mortality. The etiology and maintenance of eating disorder symptoms are not well understood, and evidence suggests that there may be gustatory alterations in patients with eating disorders. In a systematic review, these researchers examined gustatory differences in patients with anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). The systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focusing on taste and eating disorders. These investigators reviewed electronic databases and identified 1,490 peer-reviewed English-language studies, of which 49 met inclusion criteria. Studies employed psychophysical measures (n = 27), self-reported questionnaires (n = 5), and neuroimaging techniques (i.e., electroencephalography, functional MRI; n = 17). Psychophysical studies showed that individuals with BN, in general, had a greater preference for sweetness than healthy controls, while those with AN had a greater aversion to fat than controls. In neuroimaging studies, findings suggested that predictable administration of sweet-taste stimuli was associated with reduced activation in taste-reward regions of the brain among individuals with AN (e.g., insula, ventral striatum, and dorsal striatum) but increased activation in BN and BED. The authors concluded that this systematic review was the first to synthesize literature on taste differences in AN, BN, and BED. These researchers noted that the inconsistency and variability in methods used across studies increased difficulties in comparing studies and disease processes. They stated that further studies with well-defined population parameters are needed to better understand how taste varies in patients with eating disorders. In addition, they noted that more research is needed on the biological factors that might influence taste, such as genetics. Improved understanding of differences in taste perception and preferences in eating disorder populations, as well as the mechanisms that underlie these differences, could have implications for the treatment and prevention of these disorders.
The authors stated that although they carried out a comprehensive systematic review of differences in taste perception, preference, and response across multiple eating disorders (AN, BN, and BED), they were unable to perform a meta-analysis. Although there were several studies in each group (i.e., self-report, psychophysical, neuroimaging), the heterogeneity of the studies made it difficult to draw strong conclusions. For example, the self-report studies employed different questionnaires and taste measures and were conducted among different eating disorder populations. Standardizing the methodology for taste evaluation among specific cohorts of eating disorder patients would likely provide more consistent and comparable findings.
Evaluation of Gut Microbiota for the Management of Eating Disorders
Kleiman and associates (2016) stated that the relevance of the microbe-gut-brain axis to psychopathology is of interest in anorexia nervosa (AN), as the intestinal microbiota plays a critical role in metabolic function and weight regulation. These researchers characterized the composition and diversity of the intestinal microbiota in AN, using stool samples collected at inpatient admission (T1; n = 16) and discharge (T2; n = 10). At T1, subjects completed the Beck Depression and Anxiety Inventories and the Eating Disorder Examination-Questionnaire. Patients with AN were compared with healthy individuals who participated in a previous study (healthy comparison group; HCG). Genomic DNA was isolated from stool samples, and bacterial composition was characterized by 454 pyrosequencing of the 16S rRNA gene. Sequencing results were processed by the Quantitative Insights Into Microbial Ecology pipeline. These investigators compared T1 versus T2 samples, samples from both time points were compared with HCG (n = 12), and associations between psychopathology and T1 samples were explored. In patients with AN, significant changes emerged between T1 and T2 in taxa abundance and beta (between-sample) diversity. Patients with AN had significantly lower alpha (within-sample) diversity than did HCG at both T1 (p = 0.0001) and T2 (p = 0.016), and differences in taxa abundance were found between AN patients and HCG. Levels of depression, anxiety, and eating disorder psychopathology at T1 were associated with the composition and diversity of the intestinal microbiota. The authors provided evidence of an intestinal dysbiosis in AN and an association between mood and the enteric microbiota in this patient population. Moreover, these researchers stated that future directions include mechanistic examinations of the microbe-gut-brain axis in animal models and the association of microbial measures with metabolic changes and recovery indices.
The authors stated that this study had several drawbacks. First, these researchers did not control for the diet of either patients with AN or HCG. The composition of the intestinal microbiota was strongly influenced by long-term dietary patterns, and short-term dietary changes could also induce dramatic microbial shifts. Because patients resided on an inpatient hospital unit, dietary intake was controlled, and all subjects consumed a standard diet, with far less variation across individuals than what would be expected from those in a free-living environment. Furthermore, the sample size limited power to detect differences between patients and controls over the course of re-nourishment. However, these investigators observed some significant compositional changes during inpatient treatment, as well as significant global changes in composition and diversity using a statistical method that provided greater explanatory power by considering the intestinal microbiota collectively. Third, all of the participants were female, limiting the generalizability of the results to males, who comprise approximately 10% of individuals with AN. Given that these researchers would be unlikely to recruit a sufficient number of male subjects to allow testing for sex differences, they focused recruitment on females in order to maximize sample size. Lastly, these researchers were unable to distinguish between changes to the intestinal microbiota that reflect weight gain versus recovery from AN, which will be important in future work, as body mass index (BMI) alone is associated with the abundance of specific bacteria.
Carbone and colleagues (2020) noted that there is growing interest in new factors contributing to the genesis of eating disorders (EDs). Research has recently focused on the study of microbiota. Dysbiosis, associated with a specific genetic susceptibility, may contribute to the development of AN, bulimia nervosa (BN), or binge eating disorder (BED), and several putative mechanisms have already been identified. Diet appeared to have an impact not only on the modification of the gut microbiota, facilitating dysbiosis, but also on its recovery in patients with EDs. In a systematic review based on the PICO strategy, these investigators searched PubMed, Embase, PsychINFO, and Cochrane Library to examine the literature on the role of altered microbiota in the pathogenesis and treatment of EDs. A total of 16 studies were included, mostly regarding AN. Alpha diversity and short-chain fatty acid (SCFA) levels were lower in patients with AN, and affective symptoms and ED psychopathology appeared to be related to changes in gut microbiota. Microbiota-derived proteins stimulated the autoimmune system, altering neuroendocrine control of mood and satiety in EDs. Microbial richness increased in AN after weight regain on fecal microbiota transplantation. The authors concluded that microbiota homeostasis appeared essential for a healthy communication network between the gut and the brain. Dysbiosis may promote intestinal inflammation, alter gut permeability, and trigger immune reactions in the hunger/satiety regulation center, contributing to the pathophysiological development of EDs. A restored microbial balance may be a possible therapeutic target for EDs. A better and more in-depth characterization of gut microbiota and gut-brain crosstalk is needed. These researchers stated that future studies may deepen the therapeutic and preventive role of microbiota in EDs.
Garcia and Gutierrez (2023) stated that recent studies have reported a gut microbiota imbalance or dysbiosis associated with AN, which has prompted an appraisal of its etiological role and the re-formulation of AN as a metabo-psychiatric disorder. In a systematic review, these investigators examined available evidence on the role of microbiota in AN. They evaluated peer-reviewed literature in four databases published between 2009 and 2022 according to PRISMA guidelines; both human and animal studies were included. A total of 18 studies were included. In animal models, both the pre-clinical and clinical findings were inconsistent regarding microbiota composition, fecal metabolite concentrations, and the effects of human fecal microbiota transplants. The authors concluded that the methodological limitations, lack of standardization, and conceptual ambiguity hinder the analysis of microbiota as a key explanatory factor for AN. These researchers stated that further research and new protocols are needed to generate new data to fully elucidate the role of microbiota in the etiology of AN. Level of Evidence = I.
Anton-Paduraru et al. (2023) noted that intestinal microbiota has recently been implicated in the development of eating disorders. Currently, there is evidence that the composition of gut microbiota is different in AN. These investigators gathered many surveys on the changes in the profile of gut microbiota in patients with AN. They examined the contemporary experimental evidence regarding the bi-directional communication between gut microbiota and the brain. Drawing from recent breakthroughs in this area of research, these researchers proposed that the gut microbiota significantly contributes to the interplay between the body and the brain, thus contributing to overall healthy homeostasis while concurrently impacting disease risk. The authors concluded that available evidence suggests a potential association between altered microbiota composition and AN in children; however, the research in this area remains limited, and further studies are needed to confirm and expand upon these findings. In particular, these investigators stated that longitudinal studies tracking changes in microbiota composition over time in children with AN are essential for better understanding the dynamic nature of this relationship and the potential for microbiota-based markers of disease progression. Furthermore, examining the potential of microbiota-based interventions and their long-term effects should be a priority in advancing the understanding and treatment of this complex disorder.
Huwart et al. (2025) stated that the link between the gut microbiome and eating behaviors, especially palatable food intake, is a growing focus of research. The complex ecosystem of microorganisms in the gut influences host metabolism, immune function, as well as neuro-behavioral signaling. These researchers examined the role of neuro-inflammation in the dysregulation of food-induced reward signaling and the potential causal role of the gut microbiota in these pro-inflammatory processes. Particular attention is given to eating disorders, specifically AN, BED, and BN, and potential links with the gut microbiota, food reward alterations, and neuro-inflammation. Lastly, these investigators proposed gut microbiota modulation as a promising therapeutic strategy in addressing food reward alterations and eating disorders.
Evaluation of Multi-Sensory Integration for the Diagnosis of Anorexia and Bulimia
Brizzi et al. (2023) noted that individuals with anorexia nervosa (AN) and bulimia nervosa (BN) present alterations in the way they experience their bodies. Body experience results from a multi-sensory integration process in which information from different sensory domains and spatial reference frames is combined into a coherent percept. Given the critical role of the body in the onset and maintenance of both AN and BN, these investigators carried out a systematic review to examine the multi-sensory integration abilities of individuals affected by these two conditions and to determine if they exhibit impairments in cross-modal integration. They searched for studies examining cross-modal integration in individuals with a current diagnosis of AN and BN compared to healthy individuals from both behavioral and neurobiological perspectives. A search of PubMed, PsycINFO, and Web of Science databases was conducted to extract relevant studies. Of the 2,348 studies retrieved, 911 were unique articles. After screening, 13 articles were included. Studies showed multi-sensory integration abnormalities in patients affected by AN; only one included individuals with BN and observed less severe impairments compared to healthy controls. Overall, results appeared to support the presence of multi-sensory deficits in AN, especially when integrating interoceptive and exteroceptive information. The authors proposed that the study of multi-sensory integration (MSI) may provide a piece of the puzzle to better understand eating disorders (EDs). This does not mean that MSI alone will be able to explain complex conditions such as EDs; however, adding this element to the existing biological and social factors involved in the etiology of such conditions may offer important opportunities to advance their understanding.
The authors stated that this review had several drawbacks. First, the limited number of included studies—only 13 studies met the inclusion criteria—showed the scarcity of research in this area and the lack of studies addressing the assessment of MSI abilities in AN and BN. These investigators found that most of the research focused on sub-clinical or non-clinical conditions. Additionally, only one of the included studies considered patients with BN, which did not allow these researchers to make comparisons and draw conclusions regarding this disorder. Second, not all included studies reported potentially relevant sample characteristics such as disease severity, disease duration, diagnostic subtype, or other clinically relevant variables (e.g., co-morbidities or medications). Given the paucity of studies, these investigators did not specifically analyze such confounders, which may limit these interpretations. Further research should better address the role of these critical factors; for example, it may be that greater ED severity is associated with greater MSI deficits. This hypothesis is supported by studies carried out in sub-clinical samples, which have found a relationship between multi-sensory integration skills, body image, and eating disorder symptoms, with greater deficits being positively associated with greater symptomatology. In this vein, it may also be the case that deficits in multi-modal integration may predict the development of body image-related disorders and individualize individuals at risk for eating disorders. This research will be essential for proposing preventive and early interventions. Furthermore, further investigation is needed to understand how the specific clinical subtype (e.g., restricting, binge/purge subtypes of AN) affects multi-modal integration ability. Third, most of the studies included in this review focused on female patients. Since eating disorders are also increasing in males, further research should include male patients to examine gender differences, thereby comparing not only male patients with healthy controls but also females with male patients with the same diagnosis. Fourth, these investigators did not find any neuroimaging and neurofunctional studies that included multi-modal tasks; this limited their ability to hypothesize and speculate on the neurobiological basis of multi-sensory integration without the possibility of anchoring behavioral findings to robust neuroscientific results. These researchers encouraged future studies to use functional MRI techniques to examine cortical activations during cross-modal tasks to better reveal cortical functional differences between patients and controls.
Evaluation of Olfaction
Islam et al. (2015) provided a systematic review on the current literature on olfactory capacity in abnormal eating behavior. The objective was to present a basis for discussion on whether research in olfaction in eating disorders may offer additional insight with regard to the complex etiopathology of eating disorders and abnormal eating behaviors. Electronic databases (Medline, PsycINFO, PubMed, Science Direct, and Web of Science) were searched using the components in relation to olfaction and combining them with the components related to abnormal eating behavior. Out of 1,352 articles, titles were first excluded by title (n = 64) and then by abstract and full-text resulting in a final selection of 14 articles (820 patients and 385 control participants) for this review. The highest number of existing literature on olfaction in ED were carried out with AN patients (78.6%) followed by BN patients (35.7%) and obese individuals (14.3%). Most studies were only conducted on females. The general findings supported that olfaction is altered in AN and in obesity and indicated toward there being little to no difference in olfactory capacity between BN patients and the general population. The authors concluded that due to the limited number of studies and heterogeneity, this review emphasized on the importance of more research on olfaction and abnormal eating behavior.
E-Therapy
Loucas et al. (2014) stated that the widespread availability of the Internet and mobile-device applications (apps) is changing the treatment of mental health problems. These investigators reviewed the research on the effectiveness of e-therapy for eating disorders, using the methodology employed by the UK's National Institute for Health and Care Excellence (NICE). Electronic databases were searched for published RCTs of e-therapies designed to prevent or treat any eating disorder in all age groups. Studies were meta-analyzed where possible, and effect sizes with confidence intervals were calculated. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to determine the confidence in the effect estimates. A total of 20 trials met the inclusion criteria. For prevention, a CBT-based e-intervention was associated with small reductions in eating disorder psychopathology, weight concern, and drive for thinness, with moderate confidence in the effect estimates. For treatment and relapse prevention, various e-therapies showed some beneficial effects, but for most outcomes, evidence came from single studies, and confidence in the effect estimates was low. The authors concluded that although some positive findings were identified, the value of e-therapy for eating disorders must be viewed as uncertain. They stated that further research, with improved methods, is needed to establish the effectiveness of e-therapy for people with eating disorders.
Feedback-Based Therapies for the Treatment of Anorexia and Bulimia
Imperatori and colleagues (2018) stated that the effectiveness of biofeedback and neurofeedback has been examined in a range of psychiatric disorders. However, there are currently few studies on the clinical usefulness of feedback-based techniques for eating disorders (EDs) and ED-related symptoms (e.g., food craving). These researchers carried out a systematic search of PubMed, Scopus, and PsychINFO, identifying 162 articles. Among these, 13 studies exploring the therapeutic use of biofeedback and neurofeedback in EDs or ED-related symptoms were included. Biofeedback and neurofeedback were implemented in 5 and 8 of all reviewed articles, respectively. No studies incorporated different feedback modalities or both biofeedback and neurofeedback. The considered studies provided preliminary data on the usefulness of feedback-based techniques in the treatment of several dysfunctional eating behaviors (e.g., food craving, rumination). Although no significant effect has been reported for other important ED-related symptoms (i.e., body image disturbance), feedback-based techniques were associated with significant modifications of both sympathetic reactions to food-related stimuli and brain activity in several regions of the reward system (e.g., insula). The authors concluded that the findings of the present review suggested that, although future studies are needed to draw definitive conclusions, feedback-based techniques may be useful in the treatment of several dysfunctional eating behaviors (e.g., food craving, binge eating) operating on both top-down and bottom-up individual coping strategies.
The authors stated that this study had several limitations. First, the search strategy was limited to articles published in English. Second, due to the high heterogeneity of samples, outcome measures, and feedback modalities, a meta-analysis to quantify the effectiveness of both biofeedback and neurofeedback was not performed. These researchers stated that despite these limitations, to the best of their knowledge, this was the first systematic review that examined both biofeedback and neurofeedback applications in the treatment of EDs and ED-related symptoms.
Food-Specific Inhibition Training for Binge Eating Disorder
Giel and colleagues (2017) noted that impulsivity might contribute to the development and maintenance of obesity and eating disorders. Patients suffering from BED show an impulsive eating pattern characterized by regular binge eating episodes. Novel behavioral interventions increasing inhibitory control could improve eating behavior in BED. In a randomized controlled, proof-of-concept study, these researchers piloted a novel food-specific inhibition training in individuals with BED (n =22). Patients according to SCID-I were randomly assigned to 3 sessions of a training or control condition. In both conditions, pictures of high-caloric food items were presented in peripheral vision on a computer screen while assessing gaze behavior. The training group had to suppress the urge to turn their gaze towards these pictures (i.e., to perform anti-saccades). The control group was allowed to freely explore the pictures. These investigators assessed self-reported food craving, food addiction, and wanting/liking of food pictures pre- and post-intervention. A total of 20 subjects completed the study. The training proved to be feasible and acceptable. Patients of the training group significantly improved inhibitory control towards high-caloric food stimuli. Both groups reported a significantly lower number of binge eating episodes in the last 4 weeks after termination of the study. No changes were found in food craving, food addiction, liking, and wanting ratings. The authors concluded that a food-specific inhibition training could be a useful element in the treatment of BED and other eating disorders; however, larger efficacy studies are needed to examine the effectiveness of this and similar training approaches.
Ghrelin Agonists
In a clinical trial, Miljic et al. (2006) evaluated the effects of ghrelin, a gastric hormone, on appetite, sleepiness, and neuroendocrine responses in patients with anorexia nervosa. A total of 25 young women, including 9 patients diagnosed with anorexia nervosa with very low body weight, 6 patients who partially recovered their body weight but were still amenorrheic, and 10 constitutionally thin female subjects without a history of eating disorder, weight loss, and with regular menstrual cycles, were included in the study. Each patient received a 300-min intravenous infusion of ghrelin at 5 pmol/kg/min and was asked to complete visual analog scale (VAS) questionnaires hourly. Main outcome measures were VAS scores for appetite and sleepiness; growth hormone (GH), prolactin, and cortisol responses were measured. At baseline, patients with anorexia nervosa had significantly higher ghrelin, GH, and cortisol levels and significantly lower leptin than constitutionally thin subjects. Responses of GH to ghrelin infusion were blunted in patients with anorexia nervosa. Ghrelin administration did not significantly affect appetite but tended to increase sleepiness in patients with anorexia nervosa. These investigators concluded that ghrelin is unlikely to be effective as a single appetite stimulatory treatment for patients with anorexia nervosa. These results suggested that patients with anorexia nervosa are less sensitive to ghrelin in terms of GH response and appetite than healthy controls. Ghrelin's effects on sleep need further studies.
Gluck et al. (2014) stated that ghrelin, a peptide hormone secreted mainly by the stomach, increases appetite and food intake. Surprisingly, ghrelin levels are lower in obese individuals with binge eating disorder (BED) than in obese non-BED individuals. Acute psychological stress has been shown to raise ghrelin levels in animals and humans. These researchers evaluated ghrelin levels after a cold pressor test (CPT) in women with BED. They also examined the relationship between the cortisol stress response and changes in ghrelin levels. A total of 21 obese (mean [standard deviation] BMI = 34.9 [5.8] kg/m²) women (10 non-BED, 11 BED) underwent the CPT, with their hands submerged in ice water for 2 minutes. Blood samples were drawn for 70 minutes and assayed for ghrelin and cortisol. There were no differences between the groups in ghrelin levels at baseline (-10 minutes). Ghrelin rose significantly after the CPT (F = 2.4, p = 0.024), peaking at 19 minutes before declining (F = 17.9, p < 0.001), but there were no differences between the BED and non-BED groups. The area under the curve for ghrelin was not related to ratings of pain, stress, hunger, or desire to eat after CPT. In addition, there were no observed relationships between the area under the curves for ghrelin or cortisol after stress. The authors concluded that although there were no differences between BED groups, there was a significant rise in ghrelin in obese humans after a stressor, consistent with other recent reports suggesting a stress-related role for ghrelin.
In a randomized, double-blind, placebo-controlled study, Fazeli and colleagues (2018) examined the effects of relamorelin, an agonist of the appetite-stimulating hormone ghrelin, which has effects on gastric emptying-on weight gain and gastric emptying in women with AN. A total of 22 out-patient women with AN (diagnosed using DSM-5 criteria) were included in this trial; 10 participants were randomly assigned to relamorelin 100 μg subcutaneously daily (mean ± SEM age of 28.9 ± 2.4 years), and 12 were randomly assigned to placebo (28.9 ± 1.9 years). These researchers measured changes in weight and gastric emptying time using a gastric emptying breath test (GEBT) for relamorelin versus placebo after 4 weeks of treatment. At baseline, subjects did not differ in weight, plasma ghrelin levels, or gastric emptying time; 3 subjects randomized to relamorelin stopped use of the study medication due to reported feelings of increased hunger. After 4 weeks, there was a trend toward an increase in weight in participants randomized to relamorelin (mean ± SEM change of 0.86 ± 0.40 kg) compared to placebo (0.04 ± 0.28 kg; p = 0.07), and gastric emptying time was significantly shorter in patients taking relamorelin (median [interquartile range (IQR)]: 58.0 [51.0 to 78.0] minutes) compared to placebo (85.0 [75.8 to 100.5] minutes; p = 0.03). The authors concluded that treatment with a ghrelin agonist in women with AN significantly decreased gastric emptying time, led to a trend in weight gain after only 4 weeks, and was well-tolerated. Moreover, they stated that further study is needed to determine the long-term safety and efficacy of a ghrelin agonist in the treatment of AN.
Imaginal Exposure Prevention (I-ERP) Program for the Treatment of Anorexia Nervosa
Smith et al. (2025) stated that anxiety due to a phobia of normal body weight is a core feature and maintenance factor of anorexia nervosa (AN). In a pilot study, these researchers examined the effectiveness and acceptability of using a novel imaginal exposure response prevention (I-ERP) group program to target fears associated with being a normal body weight to reduce anxiety in adolescents with AN. The principal author adapted an I-ERP manual used to treat AN in adults in one-on-one therapy. Content was adapted for an adolescent population, sessions were reduced from 10 to 4, and the program was delivered in a group format with audio recordings to be more accessible for patients. A total of 19 patients with AN completed the group, and the group therapist collected outcome measures before and after the intervention. A paired samples t-test was used to evaluate changes in eating disorder psychopathology (EDEQ), anxiety and depression (RCAD), and fear of food (FOFM). Qualitative feedback to examine acceptability was also gathered. A statistically significant reduction in anxiety in a variety of situations pertaining to weight and shape was found following completion of the group. There were no significant changes observed in eating disorder psychopathology. Adolescents provided qualitative feedback suggesting that the intervention was acceptable for users. The authors concluded that I-ERP, which has been adapted for adolescents with AN in a group format, appeared to improve eating disorder psychopathology and reduce weight, shape, social, as well as separation anxiety and phobias when used as an adjuvant to inpatient treatment. Moreover, these researchers stated that further controlled research is needed. Level of Evidence = III.
The authors stated that this trial had several drawbacks. First, this study was not a randomized controlled trial (RCT); thus, these investigators were unable to compare its effectiveness to “treatment as usual” (TAU) or another control group. These researchers could not conclude that I-ERP resulted in significant changes, as patients received other support and treatment as part of their inpatient care. Second, patients were not followed up, making it difficult to suggest that the results were robust. Third, the program was carried out in an inpatient setting; therefore, these investigators could not ascertain whether the results would be similar in outpatient settings. Despite this, previous research that employed I-ERP to treat adults in a community setting showed significant results; thus, there is no clear reason that these results could not be replicated in outpatient settings. Fourth, the research was conducted on a female population due to the nature of the condition. These researchers stated that further investigations are needed to examine if the treatment is of equal benefit to boys and girls. Fifth, all adolescents who participated in the study had a primary diagnosis of AN; its effectiveness in other eating disorders needs to be examined.
Individual Optimal Nutrition
The ION™ (Individual Optimal Nutrition) analysis/profile (Metametrix, Norcross, GA) is a comprehensive combination of nutritional analyses that measures blood and urine levels of amino acids, including arginine, glycine, and tryptophan (plasma), antioxidants, fatty acids including monounsaturated fatty acids, polyunsaturated omega-3 and omega-6 fatty acids (plasma), minerals/elements including calcium, copper, manganese, magnesium, potassium, selenium, and zinc (red blood cells), organic acids (urine), oxidation products, toxins, and vitamins including vitamins A, B, C, D, and E (serum for fat-soluble vitamins). It supposedly offers a complete evaluation of functions that impact patients' mental and physical well-being. However, there is a lack of evidence regarding the clinical value of the ION analysis/profile in the diagnosis and evaluation of patients with eating disorders.
Mandometer Treatment
The Mandometer treatment is a controversial program for patients with eating disorders. It is a residential program that averages approximately 12 months in duration. While the management of patients with eating disorders has often included psychiatric treatment, advocates of the Mandometer treatment assert that standard psychiatric treatment is largely ineffective for these patients. They believe anorexia and bulimia to be essentially the same disorder. The Mandometer treatment for both anorexics and bulimics consists of re-teaching eating habits with a computerized, hand-held Mandometer (which gives continuous biofeedback about food intake over the course of meals), re-learning sensations of satiety, external heating by resting in warm rooms and using warm jackets, restriction of physical activity, and social reconstruction to restore normal social interactions without the use of psychoactive drugs.
The clinical value of the Mandometer treatment for the management of patients with eating disorders has not been established. Its effectiveness needs to be validated by well-designed studies. Evidence for the effectiveness of the Mandometer treatment came primarily from a Swedish group (Bergh et al., 1996; Bergh et al., 2002; Court et al., 2005). In a RCT, Bergh and colleagues (2002) assessed the effectiveness of the Mandometer treatment. A total of 16 patients, randomly selected out of a group composed of 19 patients with anorexia nervosa and 13 with bulimia nervosa, were trained to eat and recognize satiety by using computer support. They rested in a warm room after eating, and their physical activity was restricted. The patients in the control group (n = 16) received no treatment. Remission was defined by normal body weight (anorexia), cessation of binge eating and purging (bulimia), a normal psychiatric profile, normal laboratory test values, normal eating behavior, and resumption of social activities. Fourteen patients went into remission after a median of 14.4 months (range of 4.9 to 26.5 months) of treatment, but only 1 patient went into remission while waiting for treatment (p = 0.0057). Relapse is considered a major problem in patients who have been treated to remission. Thus, these researchers reported results on a total of 168 patients who have entered their treatment program. The estimated rate of remission was 75%, and the estimated time to remission was 14.7 months (quartile range of 9.6 to greater than or equal to 32). Six patients (7%) of 83 who were treated to remission relapsed, but the others (93%) have remained in remission for 12 months (quartile range of 6 to 36 months). Because the risk of relapse is maximal in the first year after remission, the authors suggested that most patients treated with this method recover. Furthermore, these investigators noted that although these results are promising, they realized the necessity to further develop their method. For example, it is necessary to examine if one of their interventions is more important than another and if their procedures should be modified. More importantly, however, is that a RCT comparing this method with the standard of care for eating disorders is needed. Court et al. (2005) presented the case of a girl with severe anorexia nervosa who had previously been resistant to treatment and who was subsequently treated successfully by the Mandometer program.
Measurement of Plasma B12 and Betaine Levels in Women with Anorexia Nervosa
Steiger et al. (2025) noted that the phenomenology in anorexia nervosa (AN) appears to be subject to epigenetic regulation via DNA methylation. The micronutrients B12 and betaine contribute directly to DNA methylation and have been reported to be abnormally elevated in blood samples from individuals with AN. These researchers measured plasma B12 and betaine levels, as well as leukocyte DNA methylation levels, among women with active AN (AN-active group), those in 1-year remission from AN (AN-remitted group), and those who had never experienced an eating disorder (NED group). They compared the groups on micronutrient levels and on the strength of association between micronutrients and methylation. This study included 64 women in the AN-active group, 49 in the AN-remitted group, and 49 in the NED group. Relative to those with NED (B12: mean of 339.6 [SD 224.3] μmol/L; betaine: mean of 33.74 [SD 17.10] μmol/L), participants with active AN showed high B12 and betaine (B12: mean of 571.0 [SD 505.2] μmol/L; betaine: mean of 43.73 [SD 22.50] μmol/L); AN-remitted participants had elevated B12 alone (B12: mean of 588.2 [SD 379.9] μmol/L; betaine: mean of 33.50 [SD 19.20] μmol/L). There were also group-based differences in the strength of association between B12 and site-specific DNA methylation at genes regulating insulin function, glucose metabolism, cell regulation, and neurotransmitter function. These associations between B12 and methylation levels were generally stronger among those without an eating disorder than among those with either active or remitted AN. The authors concluded that elevated B12 levels in AN resembled elevations reported among patients with autoimmune, neoplastic, or other disorders. Such elevations implied that plasma B12 levels may misrepresent nutritional status among individuals with AN. Moreover, these investigators stated that observed associations between levels of B12 and methylation could indicate a direct influence of nutrient status on epigenetic mechanisms; however, they could also result from a coincidence of processes that independently affect micronutrient levels and methylation. Either way, elevated B12 and betaine levels among individuals who are actively ill with AN may have clinical ramifications, epigenetic and otherwise, that warrant further investigations.
The authors stated that this study had several drawbacks. First, these investigators examined the association between plasma micronutrient levels and site-specific DNA methylation among patients with AN. Aspects related to micronutrient levels were quite well controlled, given attention to liver function and dietary supplement use, although the absence of information ascertaining quantities or frequency of supplement use is a limitation. Second, given multiple intervening factors in the pathway linking nutrient intake to methylation of genes, it remains unclear to what extent plasma nutrient levels provide a meaningful proxy for cellular processes that affect DNA methylation. Third, these researchers did not address other factors (e.g., childhood abuse, other developmental stressors) that have a known impact on DNA methylation levels. Fourth, as with all DNA methylation studies involving peripheral tissues, implications for brain function remain uncertain. Although it was by design (to accommodate the relatively low frequency of males with AN), the authors included only biological females in this study, which limits the generalizability of the findings. Fifth, there was a small tendency toward more heterogeneous ancestry in the NED group.
Measurement of Plasma Levels of Adiponectin as a Prognostic Biomarker for Bulimia
Syk and co-workers (2017) noted that BN is characterized by dysregulated eating behavior and available data suggest that adipokines may regulate food intake. These researchers investigated a possible association between BN and adipokine levels and hypothesized that plasma (P)-adiponectin would be elevated and P-leptin and P-leptin-adiponectin-ratio would be reduced in women with BN. The study was designed as a cross-sectional study with a longitudinal arm for patients with BN. Plasma-adiponectin and leptin was measured in 148 female patients seeking psychiatric ambulatory care and 45 female controls; 15 patients were diagnosed with BN and the remaining with other affective and anxiety disorders. P-adiponectin and P-leptin levels were compared between patients with BN, patients without BN and controls. At follow-up of 1 to 2 years, adipokines were re-assessed in patients with BN and the Eating Disorder Examination (EDE) Questionnaire was used to assess symptom severity. Plasma adiponectin was elevated in patients with BN at baseline and at follow-up when compared to patients without BN and controls (p < 0.004 and p < 0.008, respectively). The difference remained significant after controlling for BMI. Plasma adiponectin was correlated to symptom severity at follow-up in patients with BN without morbid obesity (ρ = 0.72, p < 0.04). Plasma leptin-adiponectin-ratio was significantly lower in patients with BN compared to controls (p < 0.04) and P-leptin non-significantly lower. The authors concluded that the findings of this study indicated a stable elevation of P-adiponectin in women with BN; P-adiponectin at follow-up correlated to eating disorder symptom severity in patients without morbid obesity, indicating that P-adiponectin should be further investigated as a possible potential prognostic biomarker for BN.
Measurement of Plasma Levels of Hypothalamic Neuropeptides for the Diagnosis of Anorexia
Pałasz and co-workers (2018) stated that due to the dynamic development of molecular neurobiology and bioinformatic methods several novel brain neuropeptides have been identified and characterized in recent years. Contemporary techniques of selective molecular detection e.g., in-situ Real-Time PCR, micro-diffusion and some bioinformatics strategies that base on searching for single structural features common to diverse neuropeptides such as hidden Markov model (HMM) have been successfully introduced. A convincing majority of neuropeptides have unique properties as well as a broad spectrum of physiological activity in numerous neuronal pathways including the hypothalamus and limbic system. The newly discovered but uncharacterized regulatory factors kisspeptin, nesfatin-1, phoenixin, and spexin have the potential to be unique modulators of stress responses and eating behavior. Accumulating basic studies reveled an intriguing role of these neuropeptides in the brain pathways involved in the pathogenesis of anxiety behavior. Nesfatin-1, phoenixin, spexin and kisspeptin may also distinctly affect the energy homeostasis and modulate food intake not only at the level of hypothalamic centers. Moreover, in patients suffered from anxiety and AN, a significant, sex-related changes in the plasma neuropeptide levels occurred. Thus, it should be noted the targeted pharmaco-modulation of central peptidergic signaling may be potentially helpful in the future treatment of certain neuropsychiatric and metabolic disorders.
Measurement of Serum Levels of Cytokine for Diagnosis of Anorexia Nervosa
Maunder et al. (2023) stated that the underlying psychobiology contributing to the onset and progression of anorexia nervosa (AN) remains unclear. New research is emerging that suggests a possible link between inflammation and a variety of mental illnesses. Alterations in cytokines may play a role in the pathogenesis of AN. Some studies have found differences in the cytokine profile of those with AN compared to healthy controls (HCs); however, results were heterogeneous. In a systematic review, these researchers examined available evidence investigating in vivo cytokine production in individuals with AN before and after weight restoration compared to controls. They conducted a comprehensive literature search of four electronic databases (PubMed, PsychInfo, Embase, and CINAH) according to the PRISMA guidelines to identify human in vivo studies examining the relationship between AN and cytokine production. Data extracted from included studies related to population characteristics (e.g., age, gender, mean mBMI/%IBW), cytokine measurement, and relevant findings. Confounding factors (e.g., smoking status, co-morbid mental illness, menstruation status) were also collected. A total of 36 studies were eligible for this systematic review, the majority of which were carried out in Europe (77.8%) and involved female subjects (97.2%). Those with AN ranged in age from 13 to 47 years and had an illness duration of 3 months to 24 years. A total of 15 candidate cytokines and 3 receptors were identified (TNF-alpha, IL-6, IL-1B, CRP, IL-2, IL-7, IL-10, IFN-γ, TNF-R2, IL-1α, IL-15, TNF-R1, IL-17, IL-18, TGF-B1, IL-12, IL-6R, and TGF-B2) exploring in vivo levels in patients with AN and comparing them to controls. TNF-alpha and IL-6 were the most extensively studied, with IL-6 being significantly elevated in 4 out of 8 (50%) of longitudinal studies when comparing AN patients at baseline to post-weight restoration. Following weight restoration, there was no difference in IL-6 levels when comparing to HCs in 7 of 8 (87.5%) longitudinal studies examined. The authors concluded that the most promising cytokine potentially involved in the pathogenesis of AN appeared to be IL-6, and possibly TNF-alpha pathways. The heterogeneity of clinical and methodological factors impeded the generalizability of results. These researchers stated that future studies need to address these methodological shortcomings, as alterations in cytokine levels in AN could act as therapeutic targets aiding in restoring weight and may offer diagnostic potential.
The authors stated that this systematic review highlighted issues with study design, including small sample sizes, variation in cytokine sampling techniques, and confounding factors such as smoking status, psychiatric co-morbidity, duration of illness, and the presence or absence of amenorrhea, all contributing to study heterogeneity and potential bias. These researchers stated that future studies should control for these confounding factors and their role in inflammation. Further longitudinal studies may also aid in understanding how cytokines and inflammation may influence disease onset and the trajectory of AN. If researchers can identify changes in cytokine levels, they could act as biomarkers, offering diagnostic potential, indicators of treatment response, and possibly risk of relapse. Isolating further pathways involved in the inflammatory response could emerge as possible pharmacological treatment targets. Further studies are needed to examine the specific role cytokines play in the pathogenesis of AN.
Measurement of Serum Zinc Levels for the Diagnosis of Anorexia and Bulimia
Zepf and colleagues (2017) stated that research has implicated that changes in zinc (Zn) metabolism may be associated with the biological underpinnings of EDs, especially AN. However, current research on the role of Zn in patients with BN is scarce. In a cross-sectional, pilot study, these investigators examined serum Zn concentrations in young patients with BN, with a focus on the stage of the disorder, comparing acutely ill and recovered patients with BN with healthy controls. Serum Zn concentrations were obtained from healthy controls and from acutely ill and remitted young patients with BN. Mean duration of remission was 4.0 ± 3.5 years. Remitted patients showed elevated serum Zn concentrations when compared to controls (Cohen's d = 2.022), but concentrations were still in the normal range. Acutely ill patients also had higher serum Zn levels when compared to controls (all values still being within the reference range, Cohen's d = 0.882). There was no difference between acutely ill and remitted patients with BN in serum Zn concentrations. Of note, remitted patients had a significantly higher body weight when compared to the other 2 groups. Overall, there were no significant differences in dietary preferences with regard to Zn-containing foods between the groups. The authors concluded that the findings of this study provided preliminary evidence that the underlying factors for changes in Zn serum concentrations in young patients with BN did not vary with regard to the stage of illness (acute versus remitted BN). Moreover, they stated that further prospective research is needed in order to disentangle the possible interplay between serum Zn status and bulimic eating behaviors.
Melanocortin 4 Receptor Gene (MC4R) and Binge Eating Disorder
Qasim and colleagues (2019) noted that the association between coding variants in the melanocortin 4 receptor gene (MC4R) and binge eating disorder (BED) in patients with obesity is controversial. Two independent reviewers searched Medline, Embase, PsycINFO, BIOSIS Previews, Web of Science Core Collection, and Google Scholar up to February 2018, using terms describing the MC4R gene and BED; 6 of 103 identified references were included. The studies examined associations between at least one coding variant or mutation in MC4R and BED, screening for BED as per the DSM. Risk of bias was assessed using a modified version of the Q-Genie tool, and the overall quality of evidence was assessed using GRADE guidance. Meta-analysis was conducted via logistic regression models. A positive association between gain-of-function (GOF) variants in the MC4R and BED was observed (OR = 3.05; 95% CI: 1.82 to 5.04; p = 1.7 × 10^-5), while no association was detected between loss-of-function (LOF) mutations and BED (OR = 1.50; 95% CI: 0.73 to 2.96; p = 0.25). Similar results were found after accounting for study quality (GOF variants: OR = 3.15; 95% CI: 1.76 to 5.66; p = 1.1 × 10^-4; LOF mutations: OR = 1.50; 95% CI: 0.73 to 2.97; p = 0.25). The authors concluded that while this study did not support an association between MC4R LOF mutations and BED among patients with obesity, these investigators observed a positive association between GOF variants in MC4R and the risk of BED in this population. In clinical practice, allocation to gastric bypass instead of gastric banding may be guided by the identification of patients prone to developing BED based on genetic variation in MC4R. These researchers stated that future meta-analyses of high-quality studies with careful functional characterization of MC4R mutations will strengthen these promising findings.
The authors stated that this study had several drawbacks. First, as per the risk of bias assessment and GRADE evaluation, this meta-analysis drew on very low-quality evidence. Studies focusing on the association of MC4R coding variants and mutations with BED are sparse; thus, the overall estimates of effect must be interpreted with caution. These investigators acknowledged that the prevalence of BED varies across studies and that, due to sample size variability, these findings may be driven by larger studies. In addition, important differences in the prevalence of LOF mutations have been observed between certain studies. These researchers opted to pool across all studies instead of using a classic meta-analytical approach so that the overall pooled estimate would not be impacted by study-level effect estimates. Although important confounding variables (e.g., mean BMI and ethnicity) were not adequately reported in all included references, these investigators adjusted their logistic regression models by study to account for some between-study heterogeneity. BED is associated with obesity in a little over one-third of patients. To the authors’ knowledge, only two studies examined the effect of genetic variation in MC4R on BED in patients without obesity, both reporting negative results. Further studies with carefully characterized eating pathologies would aid in better understanding genetic predisposition to BED in normal-weight patients. Differences in BED prevalence based on the changes in assessment criteria between DSM-IV and DSM-V have been estimated to be negligible; however, studies have shown that some differences exist in the diagnostic accuracy of BED among different instruments. The pooled estimates of effect were based on a limited sample size and low event rate. Confounding factors such as means of BED ascertainment, age, sex, ethnicity, and BMI could not be accounted for in their logistic models. Additionally, studies included in this meta-analysis often enrolled female patients with morbid obesity awaiting bariatric surgery. BED prevalence rates were reportedly elevated in this demographic, in contrast with the general population. The authors acknowledged that BED afflicts non-obese as well as obese populations and that this study of the effect of GOF mutations on BED in individuals with obesity was limited in its generalizability.
Music Therapy for the Treatment of Eating Disorders
Chang et al. (2023) stated that EDs can be life-threatening and cause long-term adverse biopsychosocial effects; and therapeutic options are limited and treatment seeking barriers exist. In a systematic review, these investigators examined the therapeutic impacts of music-based intervention (MBIs) for individuals with diagnosed EDs. A total of 5 bibliographic databases (PsycInfo, Medline, CINAHL, CENTRAL, Open Dissertations) were searched. Eligible studies examined therapeutic outcomes of MBIs in individuals with EDs, using quantitative and/or qualitative methods. A total of 939 studies identified; 16 met the inclusion criteria (n = 349; age of 12 to 65 years); and were categorized as: music therapy (5 studies), music medicine (4 studies), and "other MBIs" (7 studies), i.e., the intervention included music and was delivered by a non-music therapist health worker and/or musician. A narrative synthesis of the studies was undertaken. Participants were diagnosed with AN, BN, BED, eating disorder otherwise not specified, or mixed symptoms. MBIs varied widely and were associated with improved mood regulation, emotional well-being, and management of meal-related distress. Vodcast (video podcast) interventions were associated with healthful eating in non-inpatient populations. Studies were assessed using critical appraisal tools. Generalizability of findings was limited due to small samples and suboptimal description of MBIs. The authors concluded that longitudinal research is needed with larger samples and informed by frameworks for quality reporting of complex MBIs. These researchers stated that these findings may encourage music therapists to further develop and examine how music therapy can help individuals with EDs to live healthier lives.
Naso-Gastric Tube Feeding for Anorexia Nervosa
Kells and Kelly-Weeder (2016) evaluated outcomes of naso-gastric (NG) tube feedings for individuals with AN and developed recommendations for future research, policy, and practice. An integrative review of the research literature was conducted. Of the 19 studies reviewed, all indicated short-term weight gain following NG feeding; 4 studies examined adherence; nearly 30% of subjects were non-adherent as evidenced by tube manipulation; 7 studies reported psychiatric outcomes, suggesting NG feeding reduced eating disorder behaviors but not overall symptomology. The authors concluded that NG feeding promoted short-term weight gain; however, long-term outcomes are poorly understood. They stated that future research, using rigorous methods, is still needed to inform practice.
Neural Therapy (Superficial Injection of Local Anesthetic) for the Treatment of Bulimia
Gurevich and colleagues (2017) noted that conventional treatment of BN is long-term, expensive, and often ineffective. Neural therapy (NT) holds promise for treating BN in a shorter term, lower cost, and more effective manner. Much of NT entails superficial injections of local anesthetic. These investigators presented 2 cases of adult BN patients who responded very quickly to out-patient therapy that included NT. A 48‐year‐old woman responded after 1 NT treatment session and had been free of BN for the last 23 months. A 29‐year‐old man’s self‐induced vomiting was eliminated after the 1st visit. He had 2 vomiting episodes at the 6‐month mark and had no vomiting episodes the past 12 months. The authors stated that the main drawbacks of this report were the small sample size (n = 2), its retrospective nature with the possibility of selection bias, and the lack of controlled replication. They stated that more vigorously designed future studies are needed to determine the contributions of the individual components and the entire regime OF NT in the treatment of BN.
Neuroimaging for the Diagnosis of Anorexia and Bulimia
Donnelly and associates (2018) noted that in recent decades, there has been growing interest in the use of neuroimaging techniques to explore the structural and functional brain changes that take place in those with eating disorders. However, to date, the majority of research has focused on patients with anorexia nervosa (AN). This systematic review addressed a gap in the literature by providing an examination of the published literature on the neurobiology of individuals who binge eat, specifically individuals with bulimia nervosa (BN) and binge eating disorder (BED). A systematic review was conducted in accordance with PRISMA guidelines using PubMed, PsycInfo, Medline, and Web of Science, along with additional hand searches through reference lists. A total of 1,003 papers were identified in the database search. Published studies were included if they were original research papers written in English, studied humans only, used samples of participants with a diagnosed eating disorder characterized by recurrent binge eating, included a healthy control sample, and reported group comparisons between clinical groups and healthy control groups. A total of 32 papers were included in the systematic review. Significant heterogeneity in the methods used in the included papers, coupled with small sample sizes, impeded the interpretation of results; 21 papers utilized functional magnetic resonance imaging (fMRI), 7 papers utilized MRI (with 1 of these using both MRI and PET), 3 studies used single-photon emission computed tomography (SPECT), and 1 study used PET only. A small number of consistent findings emerged in individuals in the acute phase of illness with BN or BED, including volume reduction and increases across a range of areas, hypoactivity in the fronto-striatal circuits, and aberrant responses in the insula, amygdala, middle frontal gyrus, and occipital cortex to a range of different stimuli or tasks. There was also a link between illness severity in BN and neural changes, diminished attentional capacity, and early learning; in SPECT studies, increased regional cerebral blood flow was observed in relation to disorder-related stimuli. The authors concluded that the studies included in this review were heterogeneous, preventing many robust conclusions from being drawn. The precise neurobiology of BN and BED remains unclear, and ongoing large-scale investigations are needed. One clear finding was that illness severity, exclusively defined as the frequency of binge eating or bulimic episodes, was related to greater neural changes. They stated that the results of this review indicated that additional research is needed, especially to extend findings of reduced cortical volumes and diminished activity in regions associated with self-regulation (fronto-striatal circuits) and to further explore responses to disorder-related stimuli in people with BN and BED.
Gianni and colleagues (2020) conducted a systematic review according to PRISMA guidelines on PubMed, PsychInfo, Medline, and Embase to fill the existing literature gap on the effectiveness of using PET and SPECT in AN, BN, and BED. A total of 22 articles were included; 4 reported an increased density of 5-hydroxytryptamine receptors (5-HT1A) in fronto-temporo-parietal regions in both affected and recovered AN, as well as in BN. The 5-HT transporter (5-HTT) binding was increased or diminished in different specific cortical areas and in relation to eating disorder subtypes. Some evidence of blunted dopamine (DA) release in the putamen in BN patients suggested that their DA function might be impaired, similar to addictive behaviors. Studies estimating the regional cerebral blood flow (rCBF) with SPECT demonstrated that temporal areas appeared to play a key role in eating disorders, corroborating the hypothesis of a cingulate-temporal cortical dysfunction in AN. Furthermore, alterations in both the parietal and prefrontal cortex provided a possible common neural substrate in AN. The authors concluded that the studies included in this review were heterogeneous, preventing robust conclusions; however, these findings added knowledge about some of the neurotransmitters involved in eating disorders.
In a systematic review, Kappou and colleagues (2021) examined neuroimaging findings in adolescents and young adults up to 24 years of age to explore alterations associated with disease pathophysiology. Eligible studies on structural and functional brain neuroimaging were sought systematically in PubMed, CENTRAL, and Embase databases up to October 5, 2020. A total of 33 studies were included, examining a total of 587 patients with a current diagnosis of AN and 663 healthy controls (HC). Global and regional grey matter (GM) volume reduction, as well as white matter (WM) microstructure alterations, were detected. The mainly affected regions were the prefrontal, parietal, and temporal cortex, hippocampus, amygdala, insula, thalamus, and cerebellum, as well as various WM tracts such as the corona radiata and superior longitudinal fasciculus (SLF). Regarding functional imaging, alterations were noted in large-scale brain networks, such as the default mode network (DMN), executive control network (ECN), and salience network (SN). Most findings appeared to reverse after weight restoration. Specific limitations of neuroimaging studies in still-developing individuals were also discussed. The authors concluded that structural and functional alterations were present in the early course of the disease, most of which were partially or totally reversible. Nonetheless, neuroimaging findings have been open to many biological interpretations; therefore, more studies are needed to clarify their clinical significance.
Berner and associates (2023) noted that the sense of “loss of control” (LOC), or a feeling of being unable to stop eating or control what or how much one is eating, is the most salient aspect of binge eating; however, the neural alterations that may contribute to this experience and eating behavior remain poorly understood. These researchers employed functional near-infrared spectroscopy (fNIRS) to measure activation in the prefrontal cortices of 23 women with BN and 23 healthy controls during two tasks: a novel go/no-go task requiring inhibition of eating responses and a standard go/no-go task requiring inhibition of button-pressing responses. Women with BN made more commission errors on both tasks. BN subgroups with the most severe LOC eating (n = 12) and those who felt most strongly that they binge ate during the task (n = 12) showed abnormally reduced bilateral ventromedial prefrontal cortex (vmPFC) and right ventrolateral prefrontal cortex (vlPFC) activation associated with eating-response inhibition. In the entire BN sample, lower eating-task activation in the right vlPFC was related to more frequent and severe LOC eating; however, no group differences in activation were observed on either task when this full sample was compared with healthy controls. BN severity was unrelated to standard-task activation. The authors concluded that the findings of this study provided initial evidence that diminished PFC activation may directly contribute to more severe eating-specific control deficits in BN. These findings supported vmPFC and vlPFC dysfunction as promising treatment targets and indicated that eating-specific tasks and fNIRS may be useful tools for identifying neural mechanisms underlying dysregulated eating.
Non-Invasive Brain Stimulation for Eating Disorders
Hall and colleagues (2017) described the state of the human research literature pertaining to the use of non-invasive brain stimulation (NIBS) procedures for modulating food cravings, food consumption, and treating disorders of eating (i.e., obesity, anorexia nervosa [AN], and bulimia nervosa [BN]). These researchers carried out a narrative review of methods, empirical findings, and current areas of controversy. Both single-session experimental and multi-session therapeutic modalities were considered, separately for repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) technologies. Single-session studies involving NIBS reported more consistent effects of rTMS than tDCS, but this advantage is clearer in relation to food cravings than actual food consumption. Multi-session therapeutic approaches have been applied to both obesity and eating disorders. With respect to obesity, the three published tDCS trials and one ongoing rTMS trial have yielded promising, though very preliminary, findings. The application of multi-session NIBS (predominantly rTMS) to eating disorders has also yielded promising but ultimately inconclusive results, both in relation to BN and binge eating disorder (BED). Findings regarding excitatory NIBS in the context of AN are more controversial, with evidence of improvement in affective functioning but a trend of iatrogenic weight loss. The authors concluded that excitatory NIBS—particularly rTMS—can reliably reduce food cravings in both single and multi-session formats. For multi-session treatment of clinical conditions, more studies are needed for both rTMS and tDCS, particularly in relation to obesity, BN, and BED. Moreover, they stated that the application of NIBS for anorexia is less clear at this point, and excitatory NIBS may be contraindicated on theoretical and empirical grounds.
Dalton and colleagues (2018) provided an update of the literature examining the effects of deep brain stimulation (DBS), rTMS, and tDCS on eating behaviors, body weight, and associated symptoms in people with eating disorders (EDs) and relevant analogue populations. Using PRISMA guidelines, these investigators reviewed articles in PubMed, Web of Science, and PsycINFO from January 1, 2013, until August 14, 2017, to update their earlier search. Studies assessing the effects of neurostimulation techniques on eating and weight-related outcomes in people with EDs and relevant analogue populations were included. Data from both searches were combined. These researchers included a total of 32 studies (526 participants); of these, 18 were newly identified by the update search. While findings were somewhat mixed for BN, neurostimulation techniques have shown potential in the treatment of other EDs in terms of reducing ED and associated symptoms. Studies exploring cognitive, neural, and hormonal correlates of these techniques are also beginning to appear. The authors concluded that neurostimulation approaches showed promise as treatments for EDs; however, large, well-conducted randomized controlled trials (RCTs) are lacking. They stated that more information is needed regarding treatment targets, stimulation parameters, and mechanisms of action.
Giel et al. (2023) stated that binge eating disorder (BED) is characterized by recurrent binge eating (BE) episodes with a loss of control. Inhibitory control impairments, including alterations in dorsolateral prefrontal cortex (dlPFC) functioning, have been described for BED. A targeted modulation of inhibitory control circuits by the combination of inhibitory control training and transcranial brain stimulation could be promising. In a randomized, double-blind, single-center, phase II clinical trial, these researchers examined the feasibility and effectiveness of tDCS-enhanced inhibitory control training to reduce BE episodes and to generate an empirical basis for a confirmatory trial. This study had two parallel arms; 41 adult outpatients with full-syndrome BED according to DSM-5 received six sessions of food-related inhibitory control training, randomly combined with 2 mA verum or sham tDCS of the right dlPFC. The main outcome was BE frequency within a four-week interval after treatment termination (T8; primary) and at 12-week follow-up (T9; secondary) compared to baseline. BE frequency was reduced in the sham group from 15.5 to 5.9 (T8) and to 6.8 (T9); in the verum group, the reduction was from 18.6 to 4.4 (T8) and 3.8 (T9). Poisson regression with the study arm as the factor and baseline BE frequency as the covariate revealed a p-value of 0.34 for T8 and 0.026 for T9. Sham and real tDCS differed at T9 in BE frequency. The authors concluded that inhibitory control training enhanced by tDCS was safe in patients with BED and resulted in a substantial and sustainable reduction in BE frequency that unfolded over several weeks post-treatment. These researchers stated that these findings constituted the empirical basis for a confirmatory trial.
Oxytocin for the Treatment of Anorexia and Bulimia
Giel and co-workers (2018) stated that the hypothalamic neuropeptide oxytocin regulates reproductive behavior and mother-infant interaction, and conclusive studies in humans indicated that oxytocin is also a potent modulator of psychosocial function. Pilot experiments had yielded first evidence that this neuropeptide influences eating behavior. Brain administration of oxytocin in animals with normal weight, but also with diet-induced or genetically induced obesity, attenuated food intake and reduced body weight. In normal-weight and obese individuals, acute intranasal oxytocin delivery curbed calorie intake from main dishes and snacks. Such effects might converge with the poignant social and cognitive impact of oxytocin to also improve dysfunctional eating behavior in the therapeutic context. This assumption has received support in first studies showing that oxytocin might play a role in the disease process of AN. In contrast, respective experiments in patients with BN and BED are still scarce. These investigators summarized currently available studies on the involvement of the oxytocin system in the pathophysiology of eating disorders, as well as on the effects of oxytocin administration in patients with these disorders. They proposed a framework of oxytocin's role and its therapeutic potential in eating disorders that aims at integrating social and metabolic aspects of its pharmacological profile, and ponder perspectives and limitations of oxytocin use in the clinical setting.
Plasma Levels of Polyunsaturated Fatty Acid and Eating Disorders
Satogami and colleagues (2019) stated that eating disorders result in poor nutrition, poor physical conditions and even suicidality and mortality. Although polyunsaturated fatty acids (PUFAs) have attracted attention in the emerging field of nutritional psychiatry, their role in eating disorders remains unknown. In a meta-analysis, these investigators examined the differences of PUFA levels between patients with eating disorders and healthy controls, and the potentially beneficial effects of PUFAs in such patients. They conducted a systematic literature search and meta-analysis under the random effects model. A total of 11 studies were included in the this meta-analysis. Compared with controls, 379 patients with eating disorders had significantly higher plasma levels of alpha-linolenic acid, eicosapentaenoic acid, stearidonic acid, osbond acid, palmitoleic acid, oleic acid, and total omega-3 fatty acids; and lower levels of total omega-6 fatty acids and omega-6/omega-3 ratio. Eating disorders were associated with significantly higher red blood cell (RBC) membrane levels of palmitoleic acid and oleic acid and lower levels of adrenic acid, arachidonic acid, and total omega-6 fatty acids. In addition, PUFA supplements were associated with a benefit to body weight outcomes but not disease severity and mood symptoms in interventional trials. The authors concluded that the findings of this meta-analysis indicated abnormal levels of PUFAs in peripheral blood tissues in patients with eating disorders. The relationship between PUFAs and eating disorders should be interpreted cautiously considering the specific lipid metabolism under starvation state. These researchers stated that to investigate the role of PUFAs on psycho-pathological and therapeutic effects in eating disorders, further larger clinical studies are needed.
Proton Magnetic Resonance Spectroscopy of Neuro-Metabolites for the Diagnosis of Anorexia Nervosa
Mitchell et al. (2023) stated that the dysregulation of excitatory and inhibitory neurotransmission is considered a pathological marker of AN; however, no systematic evaluation of the proton magnetic resonance spectroscopy (1H-MRS) literature has been conducted to-date. In a systematic review, these investigators reviewed neuro-metabolite differences between individuals with AN and HCs. They carried out a comprehensive database search (until June 2023), and identified 7 studies meeting inclusion criteria. Samples included adolescents and adults with similar mean age (AN: 22.20 HCs: 22.60), and female percentages (AN: 98%; HCs: 94%). The review found a considerable need for improving study design and the reporting of MRS sequence parameters and analysis. Reduced glutamate concentrations in the anterior cingulate cortex (ACC) and occipital cortex (OCC), and reduced glutamate/glutamine (Glx) concentrations in the ACC were reported by 1 and 2 studies, respectively. Lastly, only 1 study to-date has quantified gamma-aminobutyric acid (GABA) concentrations, with no significant differences found. The authors concluded that there is currently insufficient evidence of excitatory and inhibitory neuro-metabolites changes in AN.
Residential and Partial Hospital-Based Treatment
Friedman and colleagues (2016) reviewed the current eating disorders outcome literature after residential or partial hospitalization program (PHP) treatment. Articles were identified through a systematic search of PubMed and PsycINFO. A total of 22 PHP and 6 residential treatment studies reported response at discharge and tended to find improvement. Fewer studies (9 PHP and 3 residential) reported outcome at some interval after discharge from treatment. These tended to find sustained improvement. A substantial proportion of patients were lost to follow-up, particularly for residential treatment. Only 2 follow-up studies used controlled trials; both showed effectiveness for PHP compared with inpatient treatment with regard to maintaining symptom remission. The authors concluded that improvement at discharge may not predict long-term outcome; and long-term follow-up studies were confounded by high drop-out rates. These investigators stated that while higher levels of care may be essential for reversing malnutrition, there remains a lack of controlled trials showing long-term effectiveness, particularly for residential treatment settings.
Screening for Eating Disorders
In a systematic review, Feltner and colleagues (2022) examined the evidence on screening for eating disorders in adolescents and adults to inform the U.S. Preventive Services Task Force (USPSTF). Data sources included Medline, Cochrane Library, PsycINFO, and trial registries through December 19, 2020, with surveillance through January 1, 2022. English-language studies of screening test accuracy, randomized controlled trials (RCTs) of screening or interventions for eating disorders in populations with screen-detected or previously untreated eating disorders (trials limited to populations who were underweight were ineligible) were selected for analysis. Two researchers reviewed the abstracts, full-text articles, and study quality. A meta-analysis of test accuracy studies and intervention trials was carried out. Main outcomes and measures included test accuracy, eating disorder symptom severity, quality of life (QOL), depression, and harms. A total of 57 studies were included (n = 10,773); 3 studies (n = 1,073) were limited to adolescents (mean or median age of 14 to 15 years). No study directly examined the benefits and harms of screening; 17 studies (n = 6,804) examined screening test accuracy. The SCOFF questionnaire (cut-point greater than or equal to 2) had a pooled sensitivity of 84% (95% CI: 74% to 90%) and pooled specificity of 80% (95% CI: 65% to 89%) in adults (10 studies, n = 3,684). Forty RCTs (n = 3,969) examined interventions for eating disorders; none enrolled a screen-detected population. Lisdexamfetamine for binge eating disorder (BED) (4 RCTs; n = 900) was associated with larger reductions in eating disorder symptom severity on the Yale-Brown Obsessive Compulsive Scale modified for binge eating (YBOCS-BE) than placebo (pooled mean difference, -5.75 [95% CI: -8.32 to -3.17]). Two RCTs (n = 465) of topiramate for BED found larger reductions in YBOCS-BE scores associated with topiramate than placebo, from -6.40 (95% CI: -8.16 to -4.64) to -2.55 (95% CI: -4.22 to -0.88). Nine pharmacotherapy trials (n = 2,006) reported on harms. Compared with placebo, lisdexamfetamine was associated with higher rates of dry mouth, headache, and insomnia, while topiramate was associated with higher rates of paresthesia, taste perversion, confusion, and concentration difficulty. Twenty-four trials (n = 1,644) assessed psychological interventions. Guided self-help for BED improved eating disorder symptom severity more than control (pooled standardized mean difference, -0.96 [95% CI: -1.26 to -0.67]) (5 studies, n = 391). Evidence on other interventions was limited. The authors concluded that no studies directly assessed the benefits and harms of screening. The SCOFF questionnaire had adequate accuracy for detecting eating disorders among adults. No treatment trials enrolled screen-detected populations; guided self-help, lisdexamfetamine, and topiramate were effective for reducing eating disorder symptom severity among referred populations with BED; however, pharmacotherapies were also associated with harms.
Davidson et al. (2022) noted that eating disorders (e.g., AN, BN, and BED) are a group of psychiatric conditions defined as a disturbance in eating or eating-related behaviors that impair physical or psychosocial functioning. According to large U.S. cohort studies, the estimated lifetime prevalence for AN, BN, and BED in adult women is 1.42%, 0.46%, and 1.25%, respectively, and these rates are lower in adult men (AN, 0.12%; BN, 0.08%; BED, 0.42%). Eating disorder prevalence ranges from 0.3% to 2.3% in adolescent females and from 0.3% to 1.3% in adolescent males. Eating disorders are associated with short-term and long-term adverse health outcomes, including physical, psychological, and social problems. The USPSTF commissioned a systematic review to examine the benefits and harms of screening for eating disorders in adolescents and adults with a normal or high body mass index (BMI). Evidence limited to populations who are underweight or have other physical signs or symptoms of eating disorders was not considered. The USPSTF has not previously made a recommendation on this topic. Adolescents and adults (10 years or older) who have no signs or symptoms of eating disorders (e.g., rapid weight loss, weight gain, or pronounced deviation from growth trajectory; pubertal delay; bradycardia; oligomenorrhea; and amenorrhea) were included for analysis. The USPSTF concluded that the available evidence is insufficient to evaluate the balance of benefits and harms of screening for eating disorders in adolescents and adults. The evidence is limited, and the balance of benefits and harms could not be determined.
Serotonin Transporter Gene Polymorphism
Polsinelli et al. (2012) stated that several lines of research have found that genes in the serotonergic system may cause susceptibility to eating disorders. In particular, functional polymorphisms of the serotonin transporter gene (5-HTT) have been suspected to play a role in the pathogenesis of eating disorders. Several studies have examined the association between the 5-HTTLPR polymorphism and bulimia nervosa (BN). The results of these investigations have been unclear. In a meta-analysis, these researchers attempted to clarify the association between BN and 5-HTTLPR using statistical models not employed by previous meta-analyses and extended upon previous meta-analyses by including new samples. PsychINFO, ISI, and PubMed databases were searched for studies published up to May 2011. Ultimately, six case-control samples were included. Data were pooled using dominant and additive models. Both models showed a non-significant association between the 5-HTTLPR polymorphism and BN. However, this does not detract from recent research suggesting that the 5-HTTLPR polymorphism may be responsible for the phenotypic variability in the psychopathological symptoms observed in patients with BN. The authors concluded that future research should examine the association of BN with 5-HTTLPR using the recently proposed tri-allelic model.
Solmi and co-workers (2016) stated that growing interest focuses on the association between the 5-HTTLPR polymorphism and eating disorders (EDs), but published findings have been conflicting. The Italian BIO.VE.D.A. biobank provided 976 samples (735 ED patients and 241 controls) for genotyping. These researchers conducted a literature search of studies published up to April 1, 2015, including studies reporting on 5-HTTLPR genotype and allele frequencies in obesity and/or ED. They also performed a meta-analysis, including data from BIO.VE.D.A., and compared low- and high-functioning genotype and allele frequencies in ED versus controls. Data from 21 studies, plus BIO.VE.D.A., were extracted, providing information from 3,736 patients and 2,707 controls. Neither low- nor high-functioning genotype frequencies in ED patients, with both bi- and tri-allelic models, differed from controls. Furthermore, neither low- nor high-functioning allele frequencies in ED or in BN, in both bi- and tri-allelic models, differed from control groups. After sensitivity analysis, results were the same in anorexia nervosa (AN) versus controls. Results remained unaltered when investigating recessive and dominant models. The authors concluded that 5-HTTLPR does not seem to be associated with ED in general, or with AN or BN in particular. Moreover, they stated that future studies in ED should explore the role of ethnicity and psychiatric co-morbidity as a possible source of bias.
Talking Therapy for the Treatment of Binge Eating Disorder and Loss of Control Eating
Brothwood and Baudinet (2025) noted that despite reports of high incidence and prevalence, relatively few studies have examined outcomes for children and adolescents with binge eating disorder (BED) and loss of control (LOC) eating. These researchers carried out a systematic scoping review; 5 databases (Medline, PsycInfo, Embase, CENTRAL, and Scopus) were searched on August 23, 2024, for relevant peer-reviewed studies and dissertations. No beginning time point was specified, and August 23, 2024, was chosen as the ending time point. Restrictions were placed on age (under 20 years), diagnosis (BED, LOC eating), and study design (quantitative). A total of 10 quantitative studies were identified: 8 randomized controlled trials (RCTs) and 2 case-series studies. Outcome data for 2,400 young people were synthesized. Most studies (70%) had a sample size of fewer than 100 participants. Treatment modalities were heterogeneous and included psychological therapies such as cognitive behavioral therapy (CBT), dialectical behavioral therapy (DBT), interpersonal therapy (IPT), as well as group schema therapy. One study examined the role of medication. The results suggested that 6 different treatment modalities (CBT [group and individual], IPT, DBT, family-based IPT [FB-IPT], and medication) were associated with a reduction in the number of binge eating episodes and LOC eating. In terms of other psychological aspects such as depression, anxiety, and self-esteem, the data were sparse, making it difficult to draw meaningful conclusions. These investigators stated that more research is needed in this area, as few studies were found and BED and LOC eating are becoming more frequently diagnosed in young individuals.
The authors concluded that the findings of this systematic review highlighted a paucity of evidence-based interventions in this area for young people with BED and LOC eating. This is an emerging and important field in child and adolescent eating disorders, as it has now been 10 years since BED was introduced into the DSM-V, with prevalence estimates higher than those of other eating disorders in this population. As the onset of binge eating often occurs in late childhood or adolescence, there is a role for early intervention. Further research into the effectiveness of different therapeutic options for this age group is needed. In this review, the authors searched for studies where treatment for BED or LOC eating in young people (under the age of 20 years) had been trialed. These investigators wanted to see which treatments could improve the mental health of young individuals with these conditions. To ensure that as many studies as possible were included, 5 different databases were searched. A total of 10 studies were found, and the majority of these were small studies with fewer than 100 participants. Nine of the studies examined the role of talking therapies (e.g., CBT), and 1 study examined how medication helped. The talking therapies used in each of the 9 studies were varied. The authors found that, on the whole, talking therapy and medication helped reduce the number of binge eating episodes and LOC eating, but it was less clear whether they helped with depression and anxiety, which are both commonly associated with BED and LOC eating.
Transcranial Magnetic Stimulation (TMS)
Transcranial magnetic stimulation (TMS) has been investigated as a neuromodulatory intervention for eating disorders, primarily anorexia nervosa and bulimia nervosa, based on evidence of altered cortical and frontostriatal circuitry involved in reward, cognitive control, and affect regulation; systematic reviews and clinical trials describe TMS as an experimental or adjunctive treatment, with studies most commonly targeting the dorsolateral prefrontal cortex and reporting mixed effects on eating disorder psychopathology, craving, mood, and anxiety, and inconsistent effects on weight outcomes. Current clinical practice guidelines from the American Psychiatric Association and other expert bodies note that TMS is not an established treatment for eating disorders and should not replace nutritional rehabilitation or evidence‑based psychotherapy, emphasizing that available data are limited by small sample sizes, heterogeneity of stimulation protocols, and short follow‑up, and that further randomized controlled trials are needed to clarify efficacy, safety, and patient selection.
In a single-center, randomized, double-blind, sham-controlled study, Walpoth et al. (2008) examined the effectiveness of repetitive transcranial magnetic stimulation in the treatment of bulimia nervosa. A total of 14 women meeting Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria for bulimia nervosa (BN) were included in this trial. In order to exclude patients highly responsive to placebo, all patients were first submitted to a 1-week sham treatment. Randomization was followed by 3 weeks of active treatment or sham stimulation. The main outcome criterion was the change in binges and purges. Secondary outcome variables were the decrease of the Hamilton Depression Rating Scale (HDRS), the Beck Depression Inventory (BDI), and the Yale-Brown Obsessive Compulsive Scale (YBOCS) over time. The average number of binges per day declined significantly between baseline and the end of treatment in the two groups. There was no significant difference between sham and active stimulation in terms of purge behavior, BDI, HDRS, and YBOCS over time. The authors concluded that these findings indicated that repetitive transcranial magnetic stimulation in the treatment of BN does not exert additional benefit over placebo.
In a mixed-method systematic meta-review, Longo et al. (2025) reviewed evidence on neuromodulatory techniques in patients with eating disorders to synthesize findings from existing systematic reviews and meta-analyses, identify research gaps, and outline future directions. The review searched PubMed/Medline, EMBASE, and PsycINFO and included 18 systematic reviews, of which five were meta-analyses, with minimal primary study overlap (<5%). The scope covered anorexia nervosa, bulimia nervosa, and binge eating disorder, with most reviews focusing on anorexia nervosa, including treatment-resistant cases, and smaller numbers addressing bulimia nervosa and binge eating disorder. Outcomes assessed across reviews included body mass index, binge eating frequency, craving, eating disorder psychopathology, comorbid psychiatric symptoms, and adverse events. The review reported that randomized controlled trials of repetitive transcranial magnetic stimulation and transcranial direct current stimulation showed effects on binge eating and craving outcomes more consistently than on body mass index in anorexia nervosa, while deep brain stimulation was associated with reported changes in body mass index and psychiatric symptoms in nonrandomized studies; reported adverse events included headaches, nausea, and drowsiness for noninvasive techniques and rare events such as seizures and infections for deep brain stimulation. The authors concluded that neuromodulation held promise for the treatment of eating disorders and stated that future research should prioritize randomized controlled trials, objective outcome measures, longer follow-up, and comprehensive monitoring of adverse events. Limitations explicitly noted included critically low methodological quality in most included systematic reviews, frequent combination of observational studies with randomized controlled trials, heterogeneity in procedures and outcomes, and limited follow-up reporting.
In a systematic review and meta-analysis, Bahador et al. (2025) reviewed the efficacy and safety of TMS in individuals diagnosed with anorexia nervosa. The review analyzed 17 studies, with nine included in quantitative meta-analyses, comprising a total of 129 participants with a mean age of 32.41 ± 7.27 years and a mean illness duration of 14.57 ± 6.66 years. Outcomes assessed included changes in body mass index (BMI) and Eating Disorder Examination Questionnaire (EDE‑Q) global scores following TMS, with stimulation most frequently applied to the dorsolateral prefrontal cortex and, less commonly, to the dorsomedial prefrontal cortex, insula, or inferior parietal lobe. Meta-analysis demonstrated an increase in BMI after TMS (standardized mean difference [SMD] −0.255; 95% CI −0.505 to −0.005; P = 0.045), with mean BMI rising from 15.96 ± 0.94 to 16.54 ± 1.15 over a mean follow‑up of 6 ± 5.32 weeks, and a reduction in EDE‑Q global scores (SMD 0.634; 95% CI 0.349–0.919; P < 0.001), with mean scores decreasing from 4.60 ± 4.12 to 1.40 ± 1.25. Subgroup analysis reported larger reductions in EDE‑Q scores when session duration exceeded 20 minutes, while no between‑group differences were reported for BMI by session duration. Adverse events were reported in two studies and included stimulation‑related discomfort, headaches, health deterioration related to undernutrition, and suicide attempts. The authors found that TMS increased BMI and reduced core symptoms of anorexia nervosa. However, the authors reported limitations including inclusion of observational and pilot studies alongside randomized controlled trials, reliance on pre‑ and post‑treatment analyses when sham controls were unavailable, small sample sizes, heterogeneity of TMS targets and protocols, limited long‑term follow‑up, and lack of analyses stratified by demographic factors or comorbidities. That further investigation into other potential TMS targets is necessary. Additionally, long-term cohort studies are needed to identify the optimal TMS target and stimulation protocol.
References
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