Eating Disorders

Number: 0511

Table Of Contents

Applicable CPT / HCPCS / ICD-10 Codes


Scope of Policy

This Clinical Policy Bulletin addresses eating disorders.

  1. Medically Necessary

    Aetna considers the following services and procedures medically necessary for the management of members with anorexia or bulimia:

    1. Assessment

      • Blood count and serum chemistry (e.g., CBC, electrolytes, BUN/creatinine)
      • Bone density measurement (for evaluation of anorexic members)
      • Electrocardiography
      • Liver function tests
      • Medical evaluation (complete medical history and physical examination)
      • Psychiatric / psychological consultation and testing
      • Urinalysis
    2. Treatment

      • Nutritional counseling
      • Pharmacotherapy for the treatment of anorexia (e.g., selective serotonin reuptake inhibitors and anti-psychotics)Footnote1*
      • Pharmacotherapy for the treatment of bulimia (e.g., selective serotonin reuptake inhibitors such as fluoxetine, tricyclic anti-depressants, trazodone, topiramate)Footnote1*
      • Pharmacotherapy for the treatment of binge-eating disorder (e.g., lisdexamfetamine dimesylate (Vyvanse)) (Note: Coverage may be excluded under plans that exclude coverage of medications to decrease or increase weight. Please check benefit plan descriptions.)Footnote1*
      • Psychotherapy (e.g., cognitive behavioral therapy, family psychotherapy, interpersonal psychotherapy, and psychodynamic psychotherapy)
      • Enteral nutrition as a last resort for the treatment of anorexia.

      Footnote1* Note: Coverage of particular drugs within each class may be subjected to formulary restrictions, where applicable.

  2. Experimental and Investigational

    Aetna considers screening for eating disorders in adolescents and adults experimental and investigational because its clinical value has not been established.

    Aetna considers the following services/procedures experimental and investigational for the diagnosis and treatment of anorexia and bulimia because of insufficient evidence in the peer-reviewed literature:

    1. Assessment

      • Blood-based serotoninergic biomarkers for tailoring treatment in bulimia
      • Brain imaging (e.g., MRI, PET and SPECT)
      • Catechol-O-methyltransferase (COMT) Val158Met polymorphism genotyping
      • Electroencephalography (EEG) for the management of bulimia and binge-eating disorder
      • Estrogen receptor 1 gene (ESR1) polymorphism testing (for anorexia)
      • Evaluation of genetic polymorphisms (for binge eating disorder)
      • Evaluation of gustatory function
      • Evaluation of gut microbiota
      • Evaluation of olfaction
      • Evaluation of melanocortin 4 receptor gene (MC4R) coding variants and mutations (for binge eating disorder)
      • Individual Optimal Nutrition (ION) analysis/profile
      • Measurement of blood levels of peripheral brain derived neurotrophic factor (BDNF) (for bulimia)
      • Measurement of plasma levels of hypothalamic neuropeptides (e.g., kisspeptin, nesfatin-1, phoenixin, and spexin) (for anorexia)
      • Measurement of plasma levels of adiponectin as a prognostic biomarker for bulimia
      • Measurement of plasma levels of polyunsaturated fatty acids
      • Measurement of serum concentration of brain derived neurotrophic factor (for anorexia)
      • Measurements of serum zinc levels
      • Routine screening of asymptomatic adolescents and adults for eating disorders
      • Serotonin transporter gene (5-HTTLPR) polymorphism testing (for anorexia and bulimia)
    2. Treatment

      • Acamprosate calcium (Campral) for the treatment of binge-eating disorder
      • Acupuncture
      • Bisphosphonates and other anti-resorptive agents in the management of osteopenia in anorexic members
      • Bright light therapy for the treatment of eating disorders (including light therapy for the treatment of night eating syndrome)
      • Bupropion (Zyban), lithium, and naltrexone for the treatment of bulimia and binge eating disorder (bupropion only)
      • Cannabinoids for the treatment of anorexia nervosa
      • Cholinesterase inhibitors (e.g., donepezil) for the treatment of anorexia
      • Chromium for the treatment of binge eating disorder
      • Deep brain stimulation (treatment-refractory anorexia)
      • Dehydroepiandrosterone for the treatment of anorexia
      • Electroconvulsive therapy
      • Estrogen for the treatment of anorexia (including transdermal estradiol patch)
      • E-therapy (via Internet and mobile-device applications) for the treatment of eating disorders
      • Feedback-based (biofeedback, neurofeedback) therapies
      • Food-specific inhibition training for the treatment of binge eating disorder
      • Ghrelin agonists (for anorexia)
      • Glucagon-like peptide-1 receptor agonists (for bulimia)
      • Intranasal naloxone for the treatment of binge eating disorder
      • Liraglutide for the treatment of binge eating disorder
      • Melatonergic medications for the treatment of night eating syndrome
      • Music therapy for the treatment of eating disorders
      • Neural therapy (superficial injection of local anesthetic; for bulimia)
      • Oral contraceptives in preventing bone loss in amenorrheic persons with an eating disorder
      • Oxytocin
      • Qsymia (phentermine and topiramate ER; for bulimia)
      • Relaxation therapy
      • Repetitive transcranial magnetic stimulation
      • The Mandometer treatment
      • Transcranial direct current stimulation.
  3. Related Policies


CPT Codes / HCPCS Codes / ICD-10 Codes

Code Code Description

CPT codes covered if selection criteria are met:

76977 Ultrasound bone density measurement and interpretation,peripheral site(s), any method
77078 Computerized tomography, bone mineral density study, 1 or more sites
77080 - 77081 Dual energy x-ray absorptiometry (DXA), bone density study, 1 or more sites
80047 Basic metabolic panel (Calcium, ionized)
80048 Basic metabolic panel (Calcium, total)
80050 General health panel
80053 Comprehensive metabolic panel
80076 Hepatic function panel
81000 - 81005 Urinalysis
85025 - 85027 Blood count; complete (CBC)
90791 - 90792 Psychiatric diagnostic evaluation, without and with medical services
90832 - 90838 Psychotherapy
90845 - 90853 Other psychotherapy
90863 Pharmacologic management, including prescription and review of medication, when performed with psychotherapy services (List separately in addition to the code for primary procedure)
93000 Electrocardiogram, routine ECG with at least 12 leads; with interpretation and report
95977 Electronic analysis of implanted neurostimulator pulse generator/transmitter (eg, contact group[s], interleaving, amplitude, pulse width, frequency [Hz], on/off cycling, burst, magnet mode, dose lockout, patient selectable parameters, responsive neurostimulation, detection algorithms, closed loop parameters, and passive parameters) by physician or other qualified health care professional; with complex cranial nerve neurostimulator pulse generator/transmitter programming by physician or other qualified health care professional
96130 - 96131 Psychological testing evaluation services by physician or other qualified health care professional, including integration of patient data, interpretation of standardized test results and clinical data, clinical decision making, treatment planning and report, and interactive feedback to the patient, family member(s) or caregiver(s), when performed
96136 - 96137 Psychological or neuropsychological test administration and scoring by physician or other qualified health care professional, two or more tests, any method
96138 - 96139 Psychological or neuropsychological test administration and scoring by technician, two or more tests, any method
96146 Psychological or neuropsychological test administration, with single automated, standardized instrument via electronic platform, with automated result only
96156 Health behavior assessment, or re-assessment (ie, health-focused clinical interview, behavioral observations, clinical decision making)
96158 - 96171 Health behavior intervention

CPT codes not covered for indications listed in the CPB:

Measurement of serum concentration of brain derived nurotrophic factor, evaluation of olfaction and serotonin transporter gene (5-HTTLPR) polymorphism testing or relaxation therapy, , catechol-O-methyltransferase (COMT) Val158Met polymorphism genotyping, 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, ghrelin agonists, neural therapy, measurement of plasma levels of polyunsaturated fatty acids for the diagnosis and treatment of anorexia and bulimia, blood-based serotoninergic biomarkers for tailoring treatment in bulimia, cannabinoids for the treatment of anorexia nervosa, genetic polymorphisms, gustatory function, gut microbiota - no specific code
70450 - 70470 Computed tomography, head or brain
70496 Computed tomographic angiography, head, with contrast material(s), including non-contrast images, if peformed, and image post-processing
70551 - 70553 Magnetic resonance (e.g., proton) imaging, brain (including brain stem)
70554 - 70555 Magnetic resonance imaging, brain, functional MRI
78600 - 78610 Brain imaging
84630 Zinc
90867 Therapeutic repetitive transcranial magnetic stimulation (TMS) treatment; initial, including cortical mapping, motor threshold determination, delivery and management
90868       subsequent delivery and management, per session
90869       subsequent motor threshold re-determination with delivery and management
90870 Electroconvulsive therapy (includes necessary monitoring)
95706 - 95707 Electroencephalogram (EEG), without video, review of data, technical description by EEG technologist, 2-12 hours; with intermittent or continuous monitoring and maintenance
96160 Instrument-based health risk assessment (e.g., mini-nutritional assessment, HEADDSSS questionnaires) [Routine screening]
96900 Actinotherapy (ultraviolet light)
97810 - 97814 Acupuncture
90875 - 90876 Individual psychophysiological therapy incorporating biofeedback training by any modality (face-to-face with the patient), with psychotherapy (eg, insight oriented, behavior modifying or supportive psychotherapy)

Other CPT codes related to the CPB:

00104 Anesthesia for electroconvulsive therapy
90785 Interactive complexity (List separately in addition to the code for primary procedure)
96127 Brief emotional/behavioral assessment (eg, depression inventory, attention-deficit/hyperactivity disorder [ADHD] scale), with scoring and documentation, per standardized instrument
99507 Home visit for care and maintenance of catheter(s) (eg, urinary, drainage, and enteral)

HCPCS codes covered if selection criteria are met:

B4034 - B4036 Enteral feeding supply kit
B4102 - B4103, B4149 - B4162 Enteral Formula
B9002 Enteral nutrition infusion pump, any type
S9340 - S9343 Home therapy; enteral nutrition, enteral nutrition via gravity, enteral nutrition via pump; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (enteral formula and nursing visits coded separately), per diem

HCPCS codes not covered for indications listed in the CPB:

Food-specific inhibition training, Qsymia (phentermine and topiramate ER, Glucagon-like peptide-1 receptor agonists, Liraglutide - no specific code:

A4633 Replacement bulb/lamp for ultraviolet light therapy system, each
E0691 - E0694 Ultraviolet light therapy system, includes bulbs/lamps, timer and eye protection
G0176 Activity therapy, such as music, dance, art or play therapies not for recreation, related to the care and treatment of patient's disabling mental health problems, per session (45 minutes or more)
J1740 Injection, ibandronate sodium, 1 mg
J2310 Injection ,naloxone HCI, per 1 mg
J2311 Injection, naloxone hydrochloride (zimhi), 1 mg
J2315 Injection, naltrexone, depot form, 1 mg
J2430 Injection, pamidronate disodium, per 30 mg
J2590 Injection, oxytocin, up to 10 units
J3110 Injection, teriparatide, 10 mcg
J3489 Injection, zoledronic acid, 1 mg
S0106 Bupropion HCl sustained release tablet, 150 mg, per bottle of 60 tablets

ICD-10 codes covered if selection criteria are met:

F50.00 - F50.02 Anorexia nervosa
F50.2 Bulimia nervosa
F50.81 Binge eating disorder
F50.82 Avoidant/restrictive food intake disorder
R63.0 Anorexia

ICD-10 codes not covered if selection criteria are met:

Z13.21 Encounter for screening for nutritional disorder [eating disorders]

Deep Brain Stimulation:

CPT codes not covered for indications listed in the CPB:

61863 Twist drill, burr hole, craniotomy, or craniectomy with stereotactic implantation of neurostimulator electrode array in subcortical site (e.g., thalamus, globus pallidus, subthalamic nucleus, periventricular, periaqueductal gray), without use of intraoperative microelectrode recording; first array
+61864     each additional array (List separately in addition to primary procedure)
61867 Twist drill, burr hole, craniotomy, or craniectomy with stereotactic implantation of neurostimulator electrode array in subcortical site (e.g., thalamus, globus pallidus, subthalamic nucleus, periventricular, periaqueductal gray), with use of intraoperative microelectrode recording; first array
+61868     each additional array (List separately in addition to primary procedure)
61880 Revision or removal of intracranial neurostimulator electrodes
61885 Insertion or replacement of cranial neurostimulator pulse generator or receiver, direct or inductive coupling; with connection to a single electrode array
+61886     with connection to 2 or more electrode arrays
90867 Therapeutic repetitive transcranial magnetic stimulation (TMS) treatment; initial, including cortical mapping, motor threshold determination, delivery and management
90868     subsequent delivery and management, per session
90869     subsequent motor threshold re-determination with delivery and management
95836 Electrocorticogram from an implanted brain neurostimulator pulse generator/transmitter, including recording, with interpretation and written report, up to 30 days
95970 Electronic analysis of implanted neurostimulator pulse generator system (eg, rate, pulse amplitude, pulse duration, configuration of wave form, battery status, electrode selectability, output modulation, cycling, impedance and patient compliance measurements); simple or complex brain, spinal cord, or peripheral (ie, cranial nerve, peripheral nerve, sacral nerve, neuromuscular) neurostimulator pulse generator/transmitter, without programming
95971     simple spinal cord, or peripheral (ie, peripheral nerve, sacral nerve, neuromuscular) neurostimulator pulse generator/transmitter, with intraoperative or subsequent programming
95976 Electronic analysis of implanted neurostimulator pulse generator/transmitter (eg, contact group[s], interleaving, amplitude, pulse width, frequency [Hz], on/off cycling, burst, magnet mode, dose lockout, patient selectable parameters, responsive neurostimulation, detection algorithms, closed loop parameters, and passive parameters) by physician or other qualified health care professional; with simple cranial nerve neurostimulator pulse generator/transmitter programming by physician or other qualified health care professional
95983 Electronic analysis of implanted neurostimulator pulse generator/transmitter (eg, contact group[s], interleaving, amplitude, pulse width, frequency [Hz], on/off cycling, burst, magnet mode, dose lockout, patient selectable parameters, responsive neurostimulation, detection algorithms, closed loop parameters, and passive parameters) by physician or other qualified health care professional; with brain neurostimulator pulse generator/ transmitter programming, first 15 minutes face-to- face time with physician or other qualified health care professional
95984 Electronic analysis of implanted neurostimulator pulse generator/transmitter (eg, contact group[s], interleaving, amplitude, pulse width, frequency [Hz], on/off cycling, burst, magnet mode, dose lockout, patient selectable parameters, responsive neurostimulation, detection algorithms, closed loop parameters, and passive parameters) by physician or other qualified health care professional; with brain neurostimulator pulse generator/ transmitter programming, each additional 15 minutes face-to-face time with physician or other qualified health care professional (List separately in addition to code for primary procedure)
96020 Neurofunctional testing selection and administration during noninvasive imaging functional brain mapping, with test administered entirely by a physician or other qualified health care professional (ie, psychologist), with review of test results and report

HCPCS codes not covered for indications listed in the CPB :

C1767 Generator, neurostimulator (implantable), nonrechargeable
C1778 Lead, neurostimulator (implantable)
C1816 Receiver and/or transmitter, neurostimulator (implantable)
C1883 Adaptor/ extension, pacing lead or neurostimulator lead (implantable)
C1897 Lead, neurostimulator test kit (implantable)
E0745 Neuromuscular stimulator, electronic shock unit
L8680 - L8683, L8685 - L8689 Neurostimulators and accessories
L8695 External recharging system for battery (external) for use with implantable neurostimulator, replacement only

ICD-10 codes not covered for indications listed in the CPB:

F50.00 - F50.02 Anorexia nervosa

Individual Optimal Nutrition (ION) analysis/profile:

No specific code

ICD-10 codes not covered for indications listed in the CPB::

F50.00 - F50.02 Anorexia nervosa
F50.2 Bulimia nervosa


Eating disorders are characterized by marked disturbances in eating behavior.  There are 2 severe forms of eating disorders –
  1. anorexia nervosa and
  2. bulimia nervosa. 
Anorexia usually commences in the years between adolescence and young adulthood, with 90 % of the patients being female.  In the female gender, anorexia has a prevalence of approximately 1 % with a lifetime mortality rate of 15 to 20 %.  There are 3 classical symptoms associated with this eating disorder:
  1. refusal to maintain a minimally normal body weight (e.g., weight loss leading to maintenance of body weight less than 85 % of that expected; or failure to attain expected weight gain during period of growth, leading to body weight less than 85 % of that expected),
  2. disturbance of body image and intense fear of being fat, and
  3. in post-menarcheal females, amenorrhea (i.e., absence of 3 consecutive menstrual cycles). 
A diagnosis of anorexia should be considered for a young woman with symptoms of an eating disorder, amenorrhea, and a body mass index of 17.5 kg/m2 or lower.  Similar considerations apply to a male patient with unexplained weight loss.
Bulimia is more common than anorexia.  In females, bulimia has a prevalence of 2 to 5 %, but a lesser mortality rate.  It is characterized by 4 key symptoms:
  1. over-concern with weight and body shape,
  2. recurrent episodes of binge eating,
  3. recurring subsequent purging, restriction, or excessive exercise, and
  4. binge eating and subsequent inappropriate compensatory behaviors, occurring a minimum average of twice a week for at least 3 months.  
In contrast to patients with anorexia, individuals with bulimia are generally in normal weight range, although recurrent weight changes are frequently observed.

The majority of patients with eating disorders can be treated in the 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 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, magnesium, phosphorus, urinalysis, and liver function tests.  An electrocardiogram may aid to identify 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 identification of any concurrent psychiatric illness, evaluation of the risk of suicide, and exploration of the psychosocial context of the symptoms.

Treatments for patients with eating disorders include nutritional counseling; psychotherapy such as cognitive behavioral therapy, family psychotherapy, inter-personal 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, anti-depressants, and neuroleptic agents – have not been shown to improve symptoms.

On the contrary, pharmacotherapy is moderately effective in treating bulimia.  High-dose (60-mg) fluoxetine (Prozac) and other selective serotonin reuptake inhibitors (SSRIs) such as trazodone (Desyrel) have been shown to be helpful in treating bulimia.  Tricyclic anti-depressants such as imipramine (Tofranil) and desipramine (Norpramin) have been demonstrated to reduce binge eating and vomiting in bulimic patients.  Monoamine oxidase inhibitors such as phenelzine (Nardil) should not be used as initial pharmacotherapy for bulimia because of their considerable side effects.  Bupropion (Zyban) is contraindicated in the treatment of bulimia because of increased risk of seizures.  Neither naltrexone nor lithium has been shown to be effective in treating bulimia. The role of bisphosphonates (e.g., alendronate and risedronate) and other anti-resorptive agents in the management of osteopenia in anorexic patients has not been established.  In a randomized controlled trial (RCT), Golden et al (2005) concluded that in adolescents with anorexia nervosa, weight restoration is the most important determinant of bone mineral density, but treatment with alendronate did increase the bone mineral densities of the lumbar spine and femoral neck within the group receiving alendronate, but not compared with placebo in the primary analysis.  Until additional studies have demonstrated efficacy and long-term safety, the use of alendronate in this population should be confined to controlled clinical trials.  Dietary supplements are usually not recommended for anorexia.  In a RCT, Barbarich et al (2004) concluded that supplement strategies are not a substitute for adequate nutrition and are ineffective in increasing the efficacy of fluoxetine in underweight anorexia nervosa subjects.  Tube or intravenous feeding is rarely needed or recommended unless the patient's condition is life threatening.

An evidence review on the management of eating disorders prepared for the Agency for Healthcare Research and Quality (AHRQ) (Berkman et al, 2006) stated that no medications are available that effectively treat patients suffering from anorexia nervosa, but a few behavioral therapies may help prevent a relapse and offer other limited benefits.  A Cochrane review on anti-depressants for anorexia nervosa (Claudino et al, 2006) also concluded that a lack of quality information precludes definite conclusions or recommendations being rendered on the use of anti-depressants in acute anorexia nervosa.  Future studies testing safer and more tolerable anti-depressants in larger, well-designed studies are needed to provide guidance for clinical practice.

The review by AHRQ also noted that both medications (e.g., fluoxetine, tricyclic anti-depressants) and behavioral therapies were found helpful in treating bulimia nervosa; however, there was no clear information about how to combine medications with behavioral treatments (Berkman et al, 2006).

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 history of eating disorder, weight loss, with regular menstrual cycles, were included in the study.  Each patient received 300-min intravenous infusion of ghrelin 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 effects on sleep need further studies.

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 management of patients with eating disorder 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 (it 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 re-construction 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 need 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 estimated time to remission was 14.7 months (quartile range of 9.6 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.

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 2 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.

McElroy and colleagues (2009) discussed the role of anti-epileptic drugs (AEDs) in the management of patients with eating disorders.  Of the available AEDs, topiramate appears to have the broadest spectrum of action as an anti-binge eating, anti-purging and weight loss agent, as demonstrated in 2 placebo-controlled studies in BN and 3 placebo-controlled studies in binge-eating disorder (BED) with obesity.  Topiramate may also have beneficial effects in night-eating syndrome and sleep-related eating disorder, but controlled trials in these conditions are needed.  The results of 1 small controlled study suggest that zonisamide may have efficacy in BED with obesity.  However, both topiramate and zonisamide are associated with adverse effect profiles that may limit their use in patients with eating disorders.  Phenytoin may be effective in some patients with compulsive binge eating, especially if co-morbid EEG abnormalities are present, but available data are too varied to allow definitive conclusions to be made.  Carbamazepine and valproate may be effective in treating patients with BN or anorexia nervosa when they are used to treat an associated psychiatric (e.g., mood) or neurological (e.g., seizure) disorder; otherwise, both agents, particularly valproate, are associated with weight gain.  The authors concluded that AEDs have an emerging role in the management of some eating disorders.

Mehler and MacKenzie (2009) reviewed the evidence on the treatment of osteopenia and osteoporosis in patients with anorexia nervosa.  These researchers identified controlled clinical studies of interventions for low bone mass in patients with anorexia nervosa via searches of MEDLINE; the Cochrane Library; EMBASE; PsycINFO; and cumulative index to nursing and allied health literature.  Outcomes of interest were changes in bone mineral density and fracture incidence.  A total of 6 RCTs and 2 cohort trials examined 5 classes of medical therapy on bone mineral density outcomes.  One RCT of bisphosphonates showed no benefit and a second flawed RCT showed some benefit; 1 RCT showed a benefit of insulin-like growth factor-I; none of the 5 trials evaluating estrogen therapy showed benefit.  The authors concluded that although patients with anorexia nervosa are often losing bone mass when they should be optimizing bone growth, there is no good evidence to guide medicinal interventions.  Thus, early detection and weight restoration are of utmost importance whereas ongoing trials define effective therapies.

American Psychiatric Association guidelines on eating disorders (2006) state that, although hormone replacement therapy (HRT) is frequently prescribed to improve bone mineral density in female patients, no good supporting evidence exists either in adults or in adolescents to demonstrate its efficacy. Hormone therapy usually induces monthly menstrual bleeding, which may contribute to the patient's denial of the need to gain further weight. Before estrogen is offered, it is recommended that efforts be made to increase weight and achieve resumption of normal menses.

Guidelines on eating disorders from the American Psychiatric Association (2006) state that there is no indication for the use of bisphosphonates such as alendronate in patients with anorexia nervosa. Although there is no evidence that calcium or vitamin D supplementation reverses decreased bone mineral density, when calcium dietary intake is inadequate for growth and maintenance, calcium supplementation should be considered, and when the individual is not exposed to daily sunlight, vitamin D supplementation may be used. However, large supplemental doses of vitamin D may be hazardous.

NICE guidelines (2004) state that oral estrogen and oral DHEA do not appear to have a positive impact on bone density and hormone replacement therapy is not recommended in children and adolescents as it may cause premature fusion of the bones.

Halabe Bucay (2009) stated that anorexia nervosa is a serious, multi-factorial disease, characterized by psychiatric and neurological disturbances, which would appear to be similar to the manifestations of dementia.  Patients with anorexia nervosa present compromised affectivity, characterized by hypomanic, manic and depressive symptoms, and their cholinergic system is altered with a decrease in the release of acetylcholine.  Donepezil is a drug that been proven to be effective in the treatment of dementia, including Alzheimer's; it has been used for affective disorders and its mechanism of action is to inhibit the acetylcholinesterase enzyme to increase acetylcholine.  Thus, donepezil could be effective in treating anorexia nervosa.  However, there is a lack of evidence regarding the clinical value of cholinesterase inhibitors in treating anorexia.

In a review on the identification and treatment of eating disorders in the primary care setting, Sim and colleagues (2010) focused on the practical issues faced by primary care physicians in the management of these conditions and other issues central to the care of these complex patients with medical and psychiatric co-morbid conditions.  These investigators noted that there is little evidence to support the use of oral contraceptives in preventing bone loss in amenorrheic patients with an eating disorder.  They also stated that SSRIs have little benefits in treating eating disorder symptoms or preventing relapse in patients with anorexia nervosa.

In a placebo-controlled trial, McElroy and colleagues (2011) evaluated preliminarily the effectiveness of acamprosate in binge eating disorder (BED).  In this 10-week, flexible dose RCT, a total of 40 outpatients with BED received acamprosate (n = 20) or placebo (n = 20).  The primary outcome measure was binge eating episode frequency.  While acamprosate was not associated with a significantly greater rate of reduction in binge eating episode frequency or any other measure in the primary longitudinal analysis, in the endpoint analysis it was associated with statistically significant improvements in binge day frequency and measures of obsessive-compulsiveness of binge eating, food craving, and quality of life.  Among completers, weight and bone mass index decreased slightly in the acamprosate group but increased in the placebo group.  The authors concluded that although acamprosate did not separate from placebo on any outcome variable in the longitudinal analysis, results of the endpoint and completer analyses suggested the drug may have some utility in BED.

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 reserchers meta-analytically summarized investigations of serum BDNF concentrations in people currently ill with AN, in comparison to healthy controls.  A total of 7 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 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.

Dodds et al (2012) noted that the dopamine D(3) receptor is thought to be a potential target for treating compulsive disorders such as drug addiction and obesity.  These researchers used functional magnetic resonance imaging (fMRI) to investigate the effects the selective dopamine D(3) receptor antagonist GSK598809 on brain activation to food images in a sample of over-weight and obese binge-eating subjects.  Consistent with previous studies, processing of food images was associated with activation of a network of reward areas including the amygdala, striatum and insula.  However, brain activation to food images was not modulated by GSK598809.  The results demonstrated that D(3) receptor manipulation does not modulate brain responses to food images in over-weight and obese subjects.

Kontis and Theochari (2012) stated that dopamine has been implicated in the pathophysiology of AN by pre-clinical and clinical evidence.  Pre-clinical studies have examined 2 main characteristics of AN:
  1. reduction in food intake (diet restriction), and
  2. hyperactivity. 
Diet restriction has been associated with reduced dopamine levels in the hypothalamus, hippocampus, and the dorsal striatum.  Animal hyperactivity following diet restriction has been linked to increased dopamine in the hypothalamus.  Increased dopamine in the nucleus accumbens was associated with food administration, but not food expectation.  Tyrosine and dopaminergic antagonists normalized anorexia-like behaviors in animal models of AN, but did not restore body weight.  Clinical studies on the etiology of AN have produced contradictory findings.  Cerebrospinal fluid concentrations of dopamine and its metabolites have been reported to be decreased or normal under conditions of low weight, whereas they tended to normalize when the weight was restored.  Plasma and urinary levels of dopamine and its metabolites have been found to be normal, increased, and decreased.  Neuroendocrine studies suggested that dopaminergic neurotransmission is increased in AN.  However, recent neuroimaging studies lend support to the increase in binding of dopaminergic receptors in the striatum, which favors the opposite theory that intra-synaptic dopamine is indeed decreased.  Genetic studies implicate dopamine D2 receptors, the dopamine transporter, and the enzyme COMT.  The authors concluded that there are promising results with respect to the use of atypical antipsychotics against symptoms of AN beyond weight gain, but further trials are required.

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), anti-oxidants, fatty acids including monounsaturated fatty acids, polyunsaturated omega-3 and omega-t 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 vitamin 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/evaluation of patients with eating disorders. 

Zhang et al (2013) stated that estrogen plays essential roles in the regulation of food intake, adiposity, and body weight control.  The estrogen alpha receptor, encoded by estrogen receptor 1 gene (ESR1), has been implicated with AN.  A previous study indicated that the rs2295193 polymorphism in ESR1 may confer a genetic susceptibility to AN.  In a case-control study, these researchers evaluated 195 AN probands and 93 healthy controls; 99 trios were studied in a family-based association analysis through genotyping the rs2295193 polymorphism in ESR1.  Additionally, these investigators carried out a meta-analysis of the combined sample groups.  There were no significant differences in the genotype or allele frequencies of the rs2295193 polymorphism between the AN and control groups (Ps > 0.05).  In the transmission disequilibrium test (TDT) analyses, there was no evidence for biased transmission of the G allele of rs2295193 polymorphism (p = 0.32).  In female-only samples, no significant association was observed between the rs2295193 polymorphism and AN in either case-control or TDT analyses (Ps > 0.05).  The meta-analysis revealed that no excess of transmission of the G allele in AN families (pooled odds ratio = 1.10, p = 0.79).  The authors concluded that meta-analytically combined evidence from the present genotyping and the literature showed that rs2295193 polymorphism in ESR1 is not a major genetic susceptibility factor in AN.

Slof-Op 't Landt et al (2014) noted that the female preponderance and onset around puberty in the majority of eating disorders suggest that sex hormones, like estrogens, may be involved in the onset of these disorders.  An 8- single-nucleotide polymorphisms (SNP) haplotype at the ESR1 gene was found to be associated with AN and 3 SNPs from this haplotype (rs726281, rs2295193, and rs3798577) were associated with AN and/or eating disorders.  These researchers attempted to replicate these findings in an independent cohort of 520 patients with an eating disorder, of whom 244 had AN (142 restricting type) from the GenED study and 2,810 random women from the Netherlands Twin Registry.  The frequencies of the 8-SNP haplotype and 3 ESR1 SNPs were compared between patients with an eating disorder, with AN (restricting type), with BN, and the control women.  Neither the haplotype nor the 3 ESR1 SNPs were associated with eating disorders, BN, AN, or restricting type AN.  The author concluded that despite sufficient statistical power, the associations reported by Versini et al (2010) were not replicated.

Phillips et al (2014) stated that there is currently limited understanding of the etiology of BN.  While multi-faceted 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 5 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.

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 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/m(2)) women (10 non-BED, 11 BED) underwent the CPT, hand 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.  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 trial, White and Grilo (2013) evaluated the short-term effectiveness of bupropion for the treatment of BED in over-weight and obese women.  A total of 61 over-weight and obese (mean BMI = 35.8) women who met DSM-IV-TR research criteria for BED were randomly assigned to receive bupropion (300 mg/day) or placebo for 8 weeks.  Participants were enrolled from November 2006 to December 2010.  No dietary or lifestyle intervention was given.  Primary outcome measures were binge-eating frequency and percent BMI loss.  Secondary outcome measures were dimensional measures of eating disorder psychopathology, food craving, and depression levels.  A total of 54 (89 %) of randomized participants completed the trial, without differential drop-out between the bupropion and placebo groups.  Mixed-effects analyses revealed significant time effects for all outcomes but no significant differences between bupropion and placebo on any outcome measure except for weight loss.  Participants taking bupropion lost significantly more weight (1.8 % versus 0.6 % BMI loss; F = 10.57, p = 0.002).  The authors concluded that bupropion was well-tolerated and produced significantly greater-albeit quite modest-short-term weight loss in over-weight and obese women with BED.  Bupropion did not improve binge eating, food craving, or associated eating disorder features or depression relative to placebo.  These findings did not support bupropion as a stand-alone treatment for BED.  The authors stated that these preliminary findings regarding short-term weight losses suggested the need for larger and longer-term trials to evaluate the potential utility of bupropion for enhancing outcomes of psychological interventions that have demonstrated effectiveness for BED but fail to produce weight loss.

In a double-blind, randomized, pilot trial, Brownley et al (2013) examined if chromium may be useful in the treatment of BED.  A total of 24 over-weight 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 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.  The 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.

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.

McElroy et al (2015) noted that psycho-pharmacologic treatment is playing a greater role in the management of patients with eating disorders.  These investigators reviewed RCTs conducted in AN, BN, BED, and other eating disorders over the past 3 years.  Fluoxetine remains the only medication approved for an eating disorder, that being BN.  Randomized controlled trials of anti-psychotics in AN have had mixed results; the only agent with some evidence of efficacy was olanzapine.  One study suggested dronabinol may induce weight gain in AN.  Preliminary studies suggested lack of efficacy of alprazolam, dehydroepiandrosterone, or physiologic estrogen replacement in AN; erythromycin in BN; and the opioid antagonist ALKS-33 in BED.  In BED with obesity or over-weight, bupropion may cause mild weight loss without seizures, and chromium may improve glucose regulation.  Also in BED, 3 RCTs suggested the stimulant prodrug lisdexamfetamine may reduce binge eating episodes, and another RCT suggested intranasal naloxone may decrease time spent binge eating.  The authors concluded that there remains a disconnection between the size of eating disorders as a public health problem and the lack of pharmacotherapy research of these conditions.

American Psychiatric Association (2006) guidelines state that antianxiety agents used selectively before meals may be useful to reduce patients' anticipatory anxiety before eating, but because eating disorder patients may have a high propensity to become dependent on benzodiazepines, these medications should be used routinely only with considerable caution.

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, anti-depressant 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 anti-convulsant topiramate also hold promise as future treatment options.

Lisdexamfetamine Dimesylate (Vyvanse) for Binge-Eating Disorder

On January 30, 2015, the Food and Drug Administration (FDA) expanded the approved uses of Vyvanse (lisdexamfetamine dimesylate) to treat binge-eating disorder in adults.  The drug is the first FDA-approved medication to treat this condition.  The efficacy of Vyvanse in treating binge-eating disorder was shown in 2 clinical studies that included 724 adults with moderate-to-severe binge-eating disorder.  In the studies, subjects taking Vyvanse experienced a decrease in the number of binge eating days per week and had fewer obsessive-compulsive binge eating behaviors compared to those on placebo.

McElroy et al (2015) examined the safety and effectiveness of lisdexamfetamine dimesylate to treat moderate to severe binge-eating disorder (BED).  These researchers performed a randomized, double-blind, parallel-group, forced dose titration, placebo-controlled clinical trial at 30 sites from May 10, 2011, through January 30, 2012.  Safety and intention-to-treat analyses included 259 and 255 adults with BED, respectively.  Lisdexamfetamine dimesylate at dosages of 30, 50, or 70 mg/day or placebo were provided to study participants (1:1:1:1).  Dosages were titrated across 3 weeks and maintained for 8 weeks.  These investigators followed-up participants for a mean (SD) of 7 (2) days after the last dose.  They assessed the change in binge-eating (BE) behaviors measured as days per week (baseline to week 11) with a mixed-effects model using transformed log (BE days per week) + 1.  Secondary measures included BE cessation for 4 weeks.  Safety assessments included treatment-emergent adverse events, vital signs, and change in weight.  At week 11, log-transformed BE days per week decreased with the 50-mg/day (least squares [LS] mean [SE] change, -1.49 [0.066]; p = 0.008) and 70-mg/day (LS mean [SE] change, -1.57 [0.067]; p < 0.001) treatment groups but not the 30-mg/day treatment group (LS mean [SE] change, -1.24 [0.067]; p = 0.88) compared with the placebo group.  Non-transformed mean (SD) days per week decreased for placebo and the 30-, 50-, and 70-mg/day treatment groups by -3.3 (2.04), -3.5 (1.95), -4.1 (1.52), and -4.1 (1.57), respectively.  The percentage of participants achieving 4-week BE cessation was lower with the placebo group (21.3 %) compared with the 50-mg/day (42.2 % [p = 0.01]) and 70-mg/day (50.0 % [p < 0.001]) treatment groups.  The incidence of any treatment-emergent adverse events was 58.7 % for the placebo group and 84.7 % for the combined treatment group.  In the treatment groups, 1.5 % of participants had serious treatment-emergent adverse effects.  Events with a frequency of at least 5 % and changes in heart rate were generally consistent with the known safety profile.  The mean (SD) change in body weight was -0.1 (3.09), -3.1 (3.64), -4.9 (4.43), -4.9 (3.93), and -4.3 (4.09) kg for the placebo group, the 30-, 50-, and 70-mg/day treatment groups, and the combined treatment groups, respectively (p < 0.001 for each dose versus placebo group comparison in post-hoc analysis).  The authors concluded that the 50- and 70-mg/day treatment groups demonstrated efficacy compared with the placebo group in decreased BE days, BE cessation, and global improvement.  The safety profile was generally consistent with previous findings in adults with attention-deficit/hyperactivity disorder. 

Complementary and Alternative Medicine

In a systematic review, Fogarty and associates (2016) examined the role of complementary and alternative medicine in the treatment of those with an eating disorder. A total 0f 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 an eating disorder is unclear and further studies should be conducted.  A potential role was found for massage and bright light therapy for depression in those with BN and a potential role for acupuncture and relaxation therapy, in the treatment of state anxiety, for those with an eating disorder.

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.

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.

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 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 used by previous meta-analyses, and extend upon previous meta-analyses by including new samples.  PsychINFO, ISI, and PubMed databases were searched for studies published up to May 2011.  Ultimately, 6 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 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 5HTTLPR 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 AN versus controls.  Results remained unaltered when investigating recessive and dominant models.  The authors concluded that 5HTTLPR 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.

Bisphosphonates and Estradiol for Anorexia Nervosa

In a systematic review, Misra and colleagues (2016) synthesized information from key physiologic and prospective studies and trials, and provided a thorough understanding of impaired bone health in AN and its management.  Search terms included "anorexia nervosa" and "bone density" for the period 1995 to 2015, limited to articles in English.  Papers were screened manually based on journal impact factor, sample size, age of participants, and inclusion of a control group.  When necessary, these investigators included seminal papers published before 1995.  Anorexia nervosa leads to low bone mineral density (BMD), impaired bone quality and increased fracture risk.  Important determinants are low lean mass, hypogonadism, insulin-like growth factor-1 (IGF-1) deficiency, and alterations in other hormones that impact bone health.  Weight gain and menses restoration are critical for improving bone outcomes in AN.  Physiologic estrogen replacement as the transdermal patch was shown to increase bone accrual in 1 study in adolescent females with AN; however, residual deficits persist; bisphosphonates are potentially useful in adults with AN.  The authors concluded that available evidence suggested that the safest and most effective strategy to improve bone health in AN is normalization of weight with restoration of menses.  Pharmacotherapies that show promise include physiologic estradiol replacement (as the transdermal estradiol patch), and in adults, bisphosphonates.  They stated that further studies are needed to determine the best strategies to normalize BMD in AN.

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, AN, and 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 3 published (tDCS) and 1 ongoing trial (rTMS) have yielded promising though very preliminary findings.  Application of multi-session NIBS (predominantly rTMS) to eating disorders has also yielded promising but ultimately inconclusive results, both in relation to BN and 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 single and multi-session format.  For multi-session treatment of clinical conditions, more studies are needed for both rTMS and tDCS, particularly in relation to obesity, bulimia, and BED.  Moreover, they stated that 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 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 neuro-stimulation 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, neuro-stimulation techniques have shown potential in the treatment of other EDs, in terms of reduction of ED and associated symptoms.  Studies exploring cognitive, neural, and hormonal correlates of these techniques are also beginning to appear.  The authors concluded that neuro-stimulation approaches showed promise as treatments for EDs; however, large, well-conducted RCTs are lacking.  They stated that more information is needed regarding treatment targets, stimulation parameters and mechanisms of action.

Giel et al (2023) BED is characterized by recurrent binge eating (BE) episodes with 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 trans-cranial brain stimulation could be promising.  In a randomized, double-blind, single-center, phase II clinical trial, these researchers examined the feasibility and effectiveness of a tDCS-enhanced inhibitory control training to reduce BE episodes and to generate an empirical basis for a confirmatory trial.  This study had 2 parallel arms; 41 adult outpatients with full-syndrome BED according to DSM-5 received 6 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 4-week interval after treatment termination (T8; primary) and at 12-week follow-up (T9; secondary) as 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 18.6 to 4.4 (T8) resp. 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.

Bright Light Therapy for Eating Disorders

Beauchamp and Lundgren (2016) noted that bright light therapy is a non-invasive biological intervention for disorders with non-normative circadian features.  Eating disorders, particularly those with binge-eating and night-eating features, have documented non-normative circadian eating and mood patterns, suggesting that bright light therapy may be an effective stand-alone or adjunctive intervention.  In a systematic review, that used PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, these investigators
  1. evaluated the state of the empirical treatment outcome literature on bright light therapy for eating disorders, and
  2. examined the timing of eating behavior, mood, and sleep-related symptom change so as to understand potential mechanisms of bright light therapy action in the context of eating disorder treatment. 
A comprehensive literature search using PsycInfo and PubMed/Medline was conducted in April 2016 with no date restrictions to identify studies published using bright light therapy as a treatment for eating disorders.  Keywords included combinations of terms describing disordered eating (eating disorder, anorexia nervosa, bulimia nervosa, binge eating, binge, eating behavior, eating, and night eating) and the use of bright light therapy (bright light therapy, light therapy, phototherapy).  After excluding duplicates, a total of 34 articles were reviewed for inclusion; 14 published studies of bright light therapy for eating disorders met inclusion criteria (included participants with an eating disorder/disordered-eating behaviors; presented as a case study, case series, open-label clinical trial, or RCT/non-RCT; written in English; and published and available by the time of manuscript review).  Results suggested that bright light therapy is potentially effective at improving both disordered-eating behavior and mood acutely, although the timing of symptom response and the duration of treatment effects remain unknown.  The authors concluded that future research should systematically control for placebo response, assess symptom change frequently and across a broad range of systems, and evaluate the longer-term effectiveness of bright light therapy for eating disorders.

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.

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.

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.

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 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 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.

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 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 BN and BED.  A systematic review was conducted in accordance with PRISMA guidelines using PubMed, PsycInfo, Medline and Web of Science, and 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 an original research paper 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; hypo-activity 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; a link between illness severity in BN and neural changes; diminished attentional capacity and early learning; and in SPECT studies, increased regional cerebral blood flow in relation to disorder-related stimuli.  The authors concluded that 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 additional research is needed, especially extending findings of reduced cortical volumes and diminished activity in regions associated with self-regulation (fronto-striatal circuits) and further exploring 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 in 5-hydroxytryptamine receptor (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 ED subtypes.  Some evidences of blunted dopamine (DA) release in the putamen in BN patients suggested that their DA function might be impaired as in addictive behaviors.  Studies estimating the regional cerebral blood flow (rCBF) with SPECT demonstrated that temporal areas appeared to play a key role in ED corroborating the hypothesis of a cingulate-temporal cortical dysfunction in AN.  Furthermore, alterations of both parietal and prefrontal cortex provided a possible common neural substrate in AN.  The authors concluded that studies included in this review were heterogeneous preventing robust conclusions, however, these findings added knowledge on some of the neurotransmitters involved in ED.

In a systematic review, Kappou and colleagues (2021) examined neuroimaging findings in adolescents and young adults up to 24 years of age, in order 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 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 corona radiata and superior longitudinal fasciculus (SLF).  Regarding functional imaging, alterations were pointed out in large-scale brain networks, such as 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 them being 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 (2022) 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 HC during 2 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 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 HC.  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.

Ghrelin Agonists for the Treatment of Anorexia Nervosa

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.

Glucagon-Like Peptide-1 Receptor Agonists for the Treatment of Bulimia

McElroy and colleagues (2018) stated that binge eating is a defining feature of the eating disorders BED and BN.  Both BED and BN are important public health problems for which there are few medical treatments.  However, almost all drugs with central nervous system (CNS)-mediated weight loss properties studied thus far in randomized, placebo-controlled trials in persons with BED or BN have been efficacious for reducing binge eating behavior.  Glucagon-like peptide-1 (GLP-1) receptor agonists, marketed for type 2 diabetes and chronic weight management, produce weight loss in a dose-dependent manner and have favorable psychiatric adverse event (AEs) profiles.  These researchers hypothesized that GLP-1 receptor agonists will safely reduce binge eating behavior in individuals with BED or BN, including those with co-occurring psychiatric disorders, and proposed that randomized, placebo-controlled clinical trials of GLP-1 receptor agonists be conducted in persons with BED and those with BN.  To support this hypothesis, the authors reviewed studies of GLP-1 and GLP-1 receptor agonists in pre-clinical models of binge eating, studies of GLP-1 levels in individuals with BED or BN, and preliminary data of GLP-1 receptor agonists in humans with abnormal eating behavior.

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.

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.

Qsymia (Phentermine and Topiramate ER) for the Treatment of Bulimia

Dalai and associates (2018) stated that BN and BED are associated with severe psychological and medical consequences.  Current therapies are limited, leaving up to 50 % of patients symptomatic despite treatment, underscoring the need for additional therapeutic options.  Qsymia, an FDA-approved medication for obesity, combines phentermine and topiramate ER.  Topiramate has demonstrated efficacy for both BED and BN, but limited tolerability.  Phentermine is FDA-approved for weight loss.  A rationale for combined phentermine/topiramate for BED and BN is improved tolerability and efficacy.  While a prior case series exploring Qsymia for BED showed promise, randomized studies are needed to evaluate Qsymia's safety and efficacy when re-purposed in EDs.  These researchers presented a study protocol for a phase I/IIa single-center, prospective, double-blinded, randomized, cross-over trial examining safety and preliminary efficacy of Qsymia for BED and BN.  Adults with BED (n = 15) or BN (n = 15) will be randomized 1:1 to receive 12 weeks of Qsymia (phentermine/topiramate ER, 3.75 mg/23 mg to 1 5mg/92 mg) or placebo, followed by 2-weeks wash-out and 12-weeks cross-over, where those on Qsymia receive placebo and vice versa.  Subsequently, participants will receive 8 weeks follow-up off-study medications.  The primary outcome is the number of binge days/week measured by EDE Questionnaire.  Secondary outcomes include average number of binge episodes, percentage abstinence from binge eating, and changes in weight/vitals, eating psychopathology, and mood.  The authors concluded that to their knowledge this is the first randomized, double-blind protocol investigating the safety and efficacy of phentermine/topiramate in BED and BN.

Safer and associates (2020) noted that open trials suggested that phentermine/topiramate ER (PHEN/TPM-ER), an FDA-approved agent for obesity, may be useful in the treatment of BED.  In a cross-over RCT, these researchers examined the safety and effectiveness of PHEN/TPM-ERs for patients with BED or BN.  Subjects were randomized to 12-weeks PHEN/TPM-ER (3.75 mg/23 mg-15 mg/92 mg) or placebo followed by 2-weeks drug wash-out, then 12-week cross-over.  Demographics, vitals, eating disorder behaviors, mood, and side effects were measured.  Primary outcome measure was objective binge-eating (OBE) days/4-weeks; secondary outcome measures included binge abstinence.  Mixed-effect models estimated treatment effects, with fixed effects adjusting for treatment, study period, and diagnosis.  The 22 adults (BED = 18, BN = 4) were women (96 %), Caucasian (55 %), aged 42.9 (SD = 10.1) years with BMI = 31.1 (SD = 6.2) kg/m2.  Baseline OBE days/4-weeks decreased from 16.2 (SD = 7.8) to 4.2 (SD = 8.4) after PHEN/TPM-ER versus 13.2 (SD = 9.1) after placebo (p < 0.0001), with abstinence rates = 63.6 % on PHEN/TPM-ER versus 9.1 % on placebo (p < 0.0001).  Weight changes = -5.8 kg on PHEN/ TPM-ER versus +0.4 kg on placebo.  Drop-out = 2 (9 %) on PHEN/TPM-ER and 2 (9 %) on placebo, with few side effects.  Vital sign changes with PHEN/TPM-ER were minimal and similar to placebo.  Responses were not significantly different for BED versus BN.  The authors concluded that this 1st RCT to examine the  safety and effectiveness of PHEN/TPM-ER for BED/BN found this drug combination significantly more effective in reducing binge eating than placebo and well-tolerated; however, with only 4 subjects with BN, findings regarding the safety of PHEN/TPM-ER in patients with BN must be taken with caution.

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.

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 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.  Studies examined associations between at least 1 coding variant/mutation in MC4R and BED and screened for BED as per the DSM.  Risk of bias was assessed using a modified version of the Q-Genie tool, and 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 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, on the basis of 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 and 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 1/3 of patients.  To the authors’ knowledge, only 2 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 to better understand 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 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.

Enteral Nutrition for the Treatment of Anorexia and Bulimia

Rizzo and colleagues (2019) stated that weight restoration is an important 1st-step in treating patients with AN, because it is essential for medical stabilization and 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 NG 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 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 including 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 1 % occurrence rate of re-feeding hypophosphatemia; 7 studies reported on other physiological disturbances, 6 evaluated medical and 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 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 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, 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 make recommendations for clinical practice and future research.  They carried out an exhaustive literature search of 7 databases.  The search strategy combined key terms 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 gastro-intestinal (GI) disturbance, re-feeding syndrome, or electrolyte abnormalities; 5 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 stated that evidence-based standards for clinical practice are needed with specific guidelines for best results for AN and BN treatment.

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 EDs-related symptoms (e.g., food craving).  These researchers carried out a systematic search of PubMed, Scopus and PsychINF; and identified 162 articles.  Among these, 13 studies exploring the therapeutic use of biofeedback and neurofeedback in EDs or EDs-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 of 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 EDs-related symptoms (i.e., body image disturbance), feedback-based techniques were also associated with significant modifications of both sympathetic reaction 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 in order 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 both on 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 in order to quantify the effectiveness of both biofeedback and neurofeedback was not performed.   These researcher stated that despite these limitations, to the best of their knowledge, this was the 1st systematic review that examined both biofeedback and neurofeedback applications in the treatment of EDs and EDs-related symptoms.

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.

Furthermore, an UpToDate review on “Bulimia nervosa and binge eating disorder in adults: Medical complications and their management” (Mitchell and Zunker, 2020) does not mention the use of serotoninergic biomarkers as a management tool.

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.

Furthermore, an UpToDate review on “Eating disorders: Overview of prevention and treatment” (Yager, 2020) does not mention the use of cannabinoids as a therapeutic option.

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.

Furthermore, an UpToDate review on “Bulimia nervosa and binge eating disorder in adults: Medical complications and their management” (Mitchell and Zunker, 2020) does not mention the use of EEG as a management tool.

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 suggested 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 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, examining taste and eating disorders.  These investigators reviewed electronic databases and identified 1,490 peer-reviewed English-language studies; and 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 greater preference for sweetness than healthy controls, and those with AN had a greater aversion for 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, 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, as well, on the biological factors that might influence taste, such as genetics.  Improved understanding of differences in taste perception and preferences in eating-disorder populations and in the mechanisms that underlie these differences could have implications for 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.

Furthermore, UpToDate reviews on “Eating disorders: Overview of epidemiology, clinical features, and diagnosis” (Yager, 2021a), and “Eating disorders: Overview of prevention and treatment” (Yager, 2021b) do not mention evaluation of gustatory function as a management / therapeutic option.

Evaluation of Genetic Polymorphisms for Binge Eating Disorder

Manfredi and colleagues (2021) noted that the genetic polymorphisms involved in the physiopathology of BED are currently unclear.  In a systematic review, these investigators examined the research on polymorphisms that is carried out 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 obesity/overweight without BED.  The protocol was written using PRISMA.  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 (BNDF), and Leu72Met (GHRL).  The authors concluded that it is important to emphasize that Taq1A is the polymorphism that showed, in 2 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 if 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 old 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 4 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 3 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 without BED (n = 45).  There were no significant genotype × time interactions related to anthropometrics or binge frequency for any individual DA genotypes, or to 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 examine their impact on both behavioral and pharmacological-based treatment for BED.

Furthermore, an UpToDate review on “Eating disorders: Overview of epidemiology, clinical features, and diagnosis” (Yager, 2021a) does not mention genetic polymorphisms to be associated with binge eating disorder.

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 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 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 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 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 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 BMI alone is associated with abundance of specific bacteria.

Carbone and colleagues (2020) noted that there is growing interest in new factors contributing to the genesis of EDs.  Research recently focused on the study of microbiota.  Dysbiosis, associated with a specific genetic susceptibility, may contribute to the development of AN, BN, or BED, and several putative mechanisms have already been identified.  Diet appeared to have an impact not only on 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.

Furthermore, UpToDate reviews on “Eating disorders: Overview of epidemiology, clinical features, and diagnosis” (Yager, 2021a), and “Eating disorders: Overview of prevention and treatment” (Yager, 2021b) do not mention evaluation mention gut microbiota to be associated with eating disorders.

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 4 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.

Topiramate for the Treatment of Binge Eating Disorder

In a systematic review and meta-analysis, Nourredine and colleagues (2021) examined the safety and effectiveness of topiramate in the treatment of BED; RCTs evaluating topiramate versus placebo with or without adjunctive psychotherapy in BED were reviewed using a systematic search in the PubMed, Web of Science, PsycINFO, Cochrane Database of Systematic Review, and search Websites, from inception to November 2019.  Main outcome measures were the changes in binge frequency, quality of life (QOL), and weight, respectively.  Effect estimates were pooled using random-effect models and presented as risk ratios (RRs) or MDs and their 95 % CI.  Data extraction was carried out by 2 independent reviewers.  A total of 3 studies were eligible for inclusion, involving 528 BED patients.  Topiramate was found to be significantly more effective than placebo in reducing the number of binge episodes per week (MD = -1.31; 95 % CI: -2.58 to -0.03; I2 = 94 %); the number of binge days per week (MD = -0.98; 95 % CI: -1.80 to -0.16; I2 = 94 %); and weight (MD = -4.91 kg; 95 % CI: -6.42 to -3.41; I2 = 10 %).  However, subjects in the topiramate groups withdrew significantly more frequently for safety reasons, relative to subjects in the placebo group (RR = 1.90; 95 % CI: 1.13 to 3.18, I2 = 0 %).  The authors concluded that these preliminary findings support a possible efficacy of topiramate for the treatment of BED, even if safety concerns could limit the practical use of this treatment in BED subjects.

Furthermore, an UpToDate review on “Eating disorders: Overview of prevention and treatment” (Yager, 2021b) does not mention topiramate as a therapeutic option.

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.

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 entailed Medline, Cochrane Library, PsycINFO, and trial registries through December 19, 2020; surveillance through January 1, 2022.  English-language studies of screening test accuracy, RCTs of screening or interventions for eating disorders in populations with screen-detected or previously untreated eating disorders (trials limited to populations who were under-weight were ineligible) were selected for analysis.  Two researchers reviewed the abstracts, full-text articles, and study quality.  Meta-analysis of test accuracy studies and intervention trials was carried out.  Main outcomes and measures included test accuracy, eating disorder symptom severity, QOL, depression, and harms.  A total of 57 studies were included (n = 10,773); 3 (n = 1,073) 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); 40 RCTs (n = 3,969) examined interventions for eating disorders; none enrolled a screen-detected population.  Lisdexamfetamine for 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 MD, -5.75 [95 % CI: -8.32 to -3.17]); 2 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); 9 pharmacotherapy trials (n = 2,006) reported on harms.  Compared with placebo, lisdexamfetamine was associated with higher rates of dry mouth, headache, and insomnia, and topiramate was associated with higher rates of paresthesia, taste perversion, confusion, and concentration difficulty; 24 trials (n = 1,644) assessed psychological interventions.  Guided self-help for BED improved eating disorder symptom severity more than control (pooled SMD, -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 (20220 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, estimated lifetime prevalence for AN, BN, and BED in adult women are 1.42 %, 0.46 %, and 1.25 %, respectively, and 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 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 BMI.  Evidence limited to populations who are under-weight 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.

Deep Brain Stimulation

Anorexia nervosa 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 in 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 done at various intervals.  Deep brain stimulation was associated with several adverse events, only one of which (seizure during programming, roughly 2 weeks after surgery) was serious.  Other related adverse events were 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 technology (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) (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 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 strengthened the need to validate these findings.  Second, the sample size for each stimulation location varied, and the sample size overall was limited.  However, this was probably related to the lack of FDA approval for 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.  Third, 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.

Liraglutide for the Treatment of Binge Eating Disorder

In a double-blind, randomized-controlled, pilot study, Allison et al (2022) examined the effectiveness of liraglutide 3.0 mg, a glucagon-like peptide-1 (GLP-1) receptor agonist, for the treatment of BED.  Adults with a BMI of 27 kg/m2 or higher were enrolled in a 17-week trial of liraglutide 3.0 mg/day for BED.  The primary outcome was number of OBEs per week.  Binge remission, weight change, and psychosocial variables were secondary outcomes.  Mixed effect models were used for continuous variables, and generalized estimating equations were used for remission rates.  Subject (n = 27) were 44.2 ± 10.6 years of age; BMI = 37.9 ± 11.8 kg/m2; 63 % women; and 59 % White and 41 % Black.  At baseline, the liraglutide group (n = 13) reported 4.7 ± 0.7 OBEs/week, compared with 3.0 ± 0.7 OBEs/week for the placebo group, p = 0.07.  At week 17, OBEs/week decreased by 4.0 ± 0.6 in liraglutide subjects and by 2.5 ± 0.5 in placebo subjects (p = 0.37, MD = 1.2, 95 % CI: 1.3 to 2.0).  BED remission rates of 44 % and 36 %, respectively, did not differ.  Percent weight loss was significantly greater in the liraglutide versus the placebo group (5.2 % ± 1.0 % versus 0.9 % ± 0.7 %, p = 0.005).  The authors concluded that subjects in both groups reported reductions in OBEs, with the liraglutide group showing clinically meaningful weight loss.  These researchers stated that a pharmacy medication dispensing error was a significant limitation of this study.  They stated that larger trials of liraglutide are needed based on these preliminary findings.

The authors stated that the drawbacks of this trial included the impact of the misallocation of liraglutide and placebo refills to subjects by the university's Investigational Drug Service, which reduced the number of subjects with analyzable data.  Dealing with this incident also produced a large pause in the trial, from which it was difficult to recover recruitment efforts.  Ultimately, trial recruitment was terminated early.  Therefore, the sample size was small, which likely impacted our ability to detect significant differences between the groups.  Furthermore, subject in this study had a BMI of 27 kg/m2 or greater due to the approved parameters for use of the study drug; thus, this would not be applicable to individuals with BED at lower BMIs.  Finally, the placebo‐responsiveness of BED has been documented previously.  These researchers tried to limit the impact of this issue by having a 2‐week behavioral‐monitoring run‐in period; however, they still observed an improvement in the placebo group.

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.


The above policy is based on the following references:

  1. Abreu AC, Filips JK. Psychiatry: Eating disorders. In: University of Iowa Family Practice Handbook. 4th ed. Ch. 18. Iowa City, IA: University of Iowa; 2003. Available at: Accessed June 2, 2003.
  2. Aigner M, Treasure J, Kaye W, Kasper S; WFSBP Task Force On Eating Disorders. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of eating disorders. World J Biol Psychiatry. 2011;12(6):400-443.
  3. Allison KC, Chao AM, Bruzas MB, et al. A pilot randomized controlled trial of liraglutide 3.0 mg for binge eating disorder. Obes Sci Pract. 2022;9(2):127-136.
  4. American Academy of Pediatrics, Committee on Adolescence. Identifying and treating eating disorders. Pediatrics. 2003;111(1):204-211.
  5. American Dietetic Association. Position of the American Dietetic Association: Nutrition intervention in the treatment of anorexia nervosa, bulimia nervosa, and eating disorders not otherwise specified (EDNOS). J Am Diet Assoc. 2001;101(7):810-819.
  6. American Psychiatric Association. Treatment of patients with eating disorders, third edition. Am J Psychiatry. 2006;163(7 Suppl):4-54.
  7. Bacaltchuk J, Hay P, Trefiglio R. Antidepressants versus psychological treatments and their combination for bulimia nervosa. Cochrane Database Syst Rev. 2001;(4):CD003385.
  8. Barbarich NC, McConaha CW, Halmi KA, et al. Use of nutritional supplements to increase the efficacy of fluoxetine in the treatment of anorexia nervosa. Int J Eat Disord. 2004;35(1):10-15.
  9. Baron RB. Nutrition. In: Current Medical Diagnosis & Treatment. 38th ed. LM Tierney Jr, et al. eds. Stamford, CT: Appleton & Lange; 1999; Ch. 29:1174-1202.
  10. Beauchamp MT, Lundgren JD. A systematic review of bright light therapy for eating disorders. Prim Care Companion CNS Disord. 2016;18(5).
  11. Becker AE, Grinspoon SK, Klibanski A, Herzog DB. Eating disorders. N Engl J Med. 1999;340(14):1092-1098.
  12. Bergh C, Brodin U, Lindberg G, Sodersten P. Randomized controlled trial of a treatment for anorexia and bulimia nervosa. Proc Natl Acad Sci U S A. 2002;99(14):9486-9491.
  13. Bergh C, Eklund S, Eriksson M, et al. A new treatment of anorexia nervosa. Lancet. 1996;348(9027):611-612.
  14. Berkman ND, Bulik CM, Brownley KA, et al. Management of eating disorders. Evidence Report/Technology Assessment No. 135. Prepared for AHRQ by the RTI/UNC Evidence-Based Practice Center. AHRQ Publication No. 06-E010. Rockville, MD: Agency for Healthcare Quality and Research; April 2006.
  15. Berner LA, Winter SR, Ayaz H, et al. Altered prefrontal activation during the inhibition of eating responses in women with bulimia nervosa. Psychol Med. 2022 Feb 25 [Online ahead of print].
  16. Blume M, Schmidt R, Hilbert A. Abnormalities in the EEG power spectrum in bulimia nervosa, binge-eating disorder, and obesity: A systematic review. Eur Eat Disord Rev. 2019;27(2):124-136.
  17. Brandys MK, Kas MJ, van Elburg AA, et al. A meta-analysis of circulating BDNF concentrations in anorexia nervosa. World J Biol Psychiatry. 2011;12(6):444-454.
  18. Brownley KA, Von Holle A, Hamer RM, et al. A double-blind, randomized pilot trial of chromium picolinate for binge eating disorder: Results of the Binge Eating and Chromium (BEACh) study. J Psychosom Res. 2013;75(1):36-42.
  19. Carbone EA, D'Amato P, Vicchio G, et al. A systematic review on the role of microbiota in the pathogenesis and treatment of eating disorders. Eur Psychiatry. 2020;64(1):e2.
  20. Chang EX, Brooker J, Hiscock R, O'Callaghan C. Music-based intervention impacts for people with eating disorders: A narrative synthesis systematic review. J Music Ther. 2023 Apr 12 [Online ahead of print].
  21. Chao AM, Roy A, Franks AT, Joseph PV. A systematic review of taste differences among people with eating disorders. Biol Res Nurs. 2020;22(1):82-91.
  22. Claudino AM, Hay P, Lima MS, et al. Antidepressants for anorexia nervosa. Cochrane Database Syst Rev. 2006;(1):CD004365.
  23. Collantoni E, Solmi M, Gallicchio D, et al. Catechol-O-methyltransferase (COMT) val158Met polymorphism and eating disorders: Data from a new biobank and meta-analysis of previously published studies. Eur Eat Disord Rev. 2017 25(6):524-532.
  24. Cooke R, Sawyer SM. Eating disorders in adolescence. An approach to diagnosis and management. Aust Fam Physician. 2004;33(1-2):27-31.
  25. Court J, Carr-Gregg M, Bergh C, et al. An innovative treatment programme for anorexia nervosa. J Paediatr and Child Health. 2005;41(5-6):305–306.
  26. Dalai SS, Adler S, Najarian T, Safer DL. Study protocol and rationale for a randomized double-blinded crossover trial of phentermine-topiramate ER versus placebo to treat binge eating disorder and bulimia nervosa. Contemp Clin Trials. 2018;64:173-178.
  27. Dalton B, Bartholdy S, Campbell IC, Schmidt U. Neurostimulation in clinical and sub-clinical eating disorders: A systematic update of the literature. Curr Neuropharmacol. 2018;16(8):1174-1192.
  28. Di Sante J, Akeson B, Gossack A, Knauper B. Efficacy of ACT-based treatments for dysregulated eating behaviours: A systematic review and meta-analysis. Appetite. 2022;171:105929.
  29. Dodds CM, O'Neill B, Beaver J, et al. Effect of the dopamine D3 receptor antagonist GSK598809 on brain responses to rewarding food images in overweight and obese binge eaters. Appetite. 2012;59(1):27-33.
  30. Donnelly B, Touyz S, Hay P, et al. Neuroimaging in bulimia nervosa and binge eating disorder: A systematic review. J Eat Disord. 2018;6:3.
  31. Dunican KC, DelDotto D. The role of olanzapine in the treatment of anorexia nervosa. Ann Pharmacother. 2007;41(1):111-115.
  32. Eating disorders. In: Diagnostic and Statistical Manual of Mental Disorders, DSM IV. 4th ed. Washington, DC: America Psychiatric Association; 1994:539-550.
  33. Fazeli PK, Lawson EA, Faje AT, et al. Treatment with a ghrelin agonist in outpatient women with anorexia nervosa: A randomized clinical trial. J Clin Psychiatry. 2018;79(1).
  34. Feltner C, Peat C, Reddy S, et al. Screening for eating disorders in adolescents and adults: Evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2022;327(11):1068-1082.
  35. Fisher CA, Hetrick SE, Rushford N. Family therapy for anorexia nervosa. Cochrane Database Syst Rev. 2010;(4):CD004780.
  36. Fogarty S, Smith CA, Hay P.  The role of complementary and alternative medicine in the treatment of eating disorders: A systematic review. Eat Behav. 2016;21:179-188.
  37. Forman SF. Eating disorders: Overview of treatment. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed March 2015.
  38. Frank JB, Weihs K, Minerva E, Lieberman DZ. Women's mental health in primary care. Med Clin North Am. 1998;82(2):359-389.
  39. Friedman K, Ramirez AL, Murray SB, et al. A narrative review of outcome studies for residential and partial hospital-based treatment of eating disorders. Eur Eat Disord Rev. 2016;24(4):263-276.
  40. Garcia N, Gutierrez E. Anorexia nervosa and microbiota: Systematic review and critical appraisal. Eat Weight Disord. 2023;28(1):1.
  41. Gianni AD, De Donatis D, Valente S, et al. Eating disorders: Do PET and SPECT have a role? A systematic review of the literature. Psychiatry Res Neuroimaging. 2020;300:111065.
  42. Giel KE, Schag K, Max SM, et al. Inhibitory control training enhanced by transcranial direct current stimulation to reduce binge eating episodes: Findings from the randomized phase II ACCElect Trial. Psychother Psychosom. 2023 Mar 8 [Online ahead of print].
  43. Giel KE, Speer E, Schag K, et al. Effects of a food-specific inhibition training in individuals with binge eating disorder-findings from a randomized controlled proof-of-concept study. Eat Weight Disord. 2017;22(2):345-351.
  44. Giel KE, Zipfel S, Hallschmid M. Oxytocin and eating disorders: A narrative review on emerging findings and perspectives. Curr Neuropharmacol. 2018;16(8):1111-1121.
  45. Gluck ME, Yahav E, Hashim SA, Geliebter A. Ghrelin levels after a cold pressor stress test in obese women with binge eating disorder. Psychosom Med. 2014;76(1):74-79.
  46. Golden NH, Iglesias EA, Jacobson MS, et al. Alendronate for the treatment of osteopenia in anorexia nervosa: A randomized, double-blind, placebo-controlled trial. J Clin Endocrinol Metab. 2005;90(6):3179-3185.
  47. Gowers SG, Clark AF, Roberts C, et al. A randomised controlled multicentre trial of treatments for adolescent anorexia nervosa including assessment of cost-effectiveness and patient acceptability - the TOuCAN trial. Health Technol Assess. 2010;14(15):1-98.
  48. Gurevich MI, Chung MK, LaRiccia PJ. Resolving bulimia nervosa using an innovative neural therapy approach: Two case reports. Clin Case Rep. 2017;6(2):278-282.
  49. Halabe Bucay A. Donepezil (aricept) as a treatment for anorexia nervosa: A very feasible therapeutic possibility. Expert Opin Investig Drugs. 2009;18(5):569-571.
  50. Hale MD, Logomarsino JV. The use of enteral nutrition in the treatment of eating disorders: A systematic review. Eat Weight Disord. 2019;24(2):179-198. 
  51. Hall C, Hewitt G, Stevens S. Assessment and management of bone health in adolescents with anorexia nervosa. Part two: Bone health in adolescents with anorexia nervosa. J Pediatr Adolesc Gynecol. 2008;21(4):221-224.
  52. Hall PA, Vincent CM, Burhan AM. Non-invasive brain stimulation for food cravings, consumption, and disorders of eating: A review of methods, findings and controversies. Appetite. 2018;124:78-88.
  53. Hay PP, Bacaltchuk J, Claudino A, et al. Individual psychotherapy in the outpatient treatment of adults with anorexia nervosa. Cochrane Database Syst Rev. 2003;(4):CD003909.
  54. Hay PP, Bacalchuk J. Bulimia nervosa. In: BMJ Clinical Evidence. London, UK: BMJ Publishing Group; June 2007.
  55. Hay PP, Bacaltchuk J, Stefano S. Psychotherapy for bulimia nervosa and binging. Cochrane Database Syst Rev. 2004;(3):CD000562.
  56. Hay PP, Touyz S, Claudino AM, et al. Inpatient versus outpatient care, partial hospitalisation and waiting list for people with eating disorders. Cochrane Database Syst Rev. 2019;1:CD010827.
  57. Hay PP. Antidepressants versus placebo for people with bulimia nervosa. Cochrane Database Syst Rev. 2003;(4):CD003391.
  58. Hay PP, Bacaltchuk J, Stefano S, Kashyap P. Psychological treatments for bulimia nervosa and binging. Cochrane Database Syst Rev. 2009;(4):CD000562.
  59. Heidinger BA, Cameron JD, Vaillancourt R, et al. No association between dopaminergic polymorphisms and response to treatment of binge-eating disorder. Gene. 2021;781:145538.
  60. Hsu LK. Eating disorders: Practical interventions. J Am Med Womens Assoc. 2004;59(2):113-124.
  61. Imperatori C, Mancini M, Della Marca G, et al. Feedback-based treatments for eating disorders and related symptoms: A systematic review of the literature. Nutrients. 2018;10(11).
  62. Islam MA, Fagundo AB, Arcelus J, et al. Olfaction in eating disorders and abnormal eating behavior: A systematic review. Front Psychol. 2015;6:1431.
  63. Jimerson DC. Bulimia nervosa. In: Conn's Current Therapy. RE Rakel, ed. Philadelphia, PA: W.B. Saunders Co.; 1999:1130-1133.
  64. Kappou K, Ntougia M, Kourtesi A, et al. Neuroimaging findings in adolescents and young adults with anorexia nervosa: A systematic review. Children (Basel). 2021;8(2):137.
  65. Kells M, Kelly-Weeder S. Nasogastric tube feeding for individuals with anorexia nervosa: An integrative review. J Am Psychiatr Nurses Assoc. 2016;22(6):449-468.
  66. Kleiman SC, Watson HJ, Bulik-Sullivan EC, et al. The intestinal microbiota in acute anorexia nervosa and during renourishment: Relationship to depression, anxiety, and eating disorder psychopathology. Psychosom Med. 2015;77(9):969-981.
  67. Kontis D, Theochari E. Dopamine in anorexia nervosa: A systematic review. Behav Pharmacol. 2012;23(5-6):496-515.
  68. Kreipe RE, Birndorf SA. Eating disorders in adolescents and young adults. Med Clin North Am. 2000;84(4):1027-1049, viii-ix.
  69. Kucukgoncu S, Midura M, Tek C. Optimal management of night eating syndrome: Challenges and solutions. Neuropsychiatr Dis Treat. 2015;11:751-760.
  70. Legroux-Gerot I, Vignau J, Collier F, Cortet B. Bone loss associated with anorexia nervosa. Joint Bone Spine. 2005;72(6):489-495.
  71. Liburd JDA. Eating disorders. eMedicine Developmental and Behavioral Pediatrics. Topic 115. Omaha, NE:; updated March 7, 2003. Available at: Accessed June 2, 2003.
  72. Lipsman N, Woodside DB, Giacobbe P, et al. Subcallosal cingulate deep brain stimulation for treatment-refractory anorexia nervosa: A phase 1 pilot trial. Lancet. 2013;381(9875):1361-1370.
  73. Lock J, La Via MC; American Academy of Child and Adolescent Psychiatry (AACAP) Committee on Quality Issues (CQI). Practice parameter for the assessment and treatment of children and adolescents with eating disorders. J Am Acad Child Adolesc Psychiatry. 2015;54(5):412-425.
  74. Lock JD, Fitzpatrick KK. Anorexia nervosa. In: BMJ Clinical Evidence. London, UK: BMJ Publishing Group; August 2007.
  75. Loucas CE, Fairburn CG, Whittington C, et al. E-therapy in the treatment and prevention of eating disorders: A systematic review and meta-analysis. Behav Res Ther. 2014;63C:122-131.
  76. Manfredi L, Accoto A, Couyoumdjian A, Conversi D. A systematic review of genetic polymorphisms associated with binge eating disorder. Nutrients. 2021;13(3):848.
  77. McElroy SL, Guerdjikova AI, Martens B, et al. Role of antiepileptic drugs in the management of eating disorders. CNS Drugs. 2009;23(2):139-156.
  78. McElroy SL, Guerdjikova AI, Mori N, Keck PE Jr. Psychopharmacologic treatment of eating disorders: Emerging findings. Curr Psychiatry Rep. 2015;17(5):573.
  79. McElroy SL, Guerdjikova AI, Winstanley EL, et al. Acamprosate in the treatment of binge eating disorder: A placebo-controlled trial. Int J Eat Disord. 2011;44(1):81-90.
  80. McElroy SL, Hudson JI, Mitchell JE, et al. Efficacy and safety of lisdexamfetamine for treatment of adults with moderate to severe binge-eating disorder: A randomized clinical trial. JAMA Psychiatry. 2015;72(3):235-246.
  81. McElroy SL, Mori N, Guerdjikova AI, Keck PE Jr. Would glucagon-like peptide-1 receptor agonists have efficacy in binge eating disorder and bulimia nervosa? A review of the current literature. Med Hypotheses. 2018;111:90-93.
  82. McGilley BM, Pryor TL. Assessment and treatment of bulimia nervosa. Am Fam Physician. 1998;57(11):2743-2750.
  83. Mehler PS, MacKenzie TD. Treatment of osteopenia and osteoporosis in anorexia nervosa: A systematic review of the literature. Int J Eat Disord. 2009;42(3):195-201.
  84. Miljic D, Pekic S, Djurovic M, et al. Ghrelin has partial or no effect on appetite, growth hormone, prolactin, and cortisol release in patients with anorexia nervosa. J Clin Endocrinol Metab. 2006;91(4):1491-1495.
  85. Miller KK, Grieco KA, Mulder J, et al. Effects of risedronate on bone density in anorexia nervosa. J Clin Endocrinol Metab. 2004;89(8):3903-3906.
  86. Misra M, Golden NH, Katzman DK. State of the art systematic review of bone disease in anorexia nervosa. Int J Eat Disord. 2016;49(3):276-292.
  87. Misra M, Klibanski A. Evaluation and treatment of low bone density in anorexia nervosa. Nutr Clin Care. 2002;5(6):298-308.
  88. Mitchell JE, Agras S, Wonderlich S. Treatment of bulimia nervosa: Where are we and where are we going? Int J Eat Disord. 2007;40(2):95-101.
  89. Mitchell JE, Roerig J, Steffen K. Biological therapies for eating disorders. Int J Eat Disord. 2013;46(5):470-477.
  90. Mitchell JE, Zunker C. Bulimia nervosa and binge eating disorder in adults: Medical complications and their management. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed March 2020.
  91. Nakash-Eisikovits O, Dierberger A, Westen D. A multidimensional meta-analysis of pharmacotherapy for bulimia nervosa: Summarizing the range of outcomes in controlled clinical trials. Harvard Rev Psych. 2002;10(4):193-211.
  92. National Institute for Clinical Excellence (NICE). Eating disorders. Core interventions in the treatment and management of anorexia nervosa, bulimia nervosa and related eating disorders. Clinical Guideline 9. London, UK: National Health Service, National Collaborating Centre for Mental Health; January 2004.
  93. No authors listed. Eating disorders: Anorexia and bulimia. Well-Connected. Report #49. New York, NY: Nidus Information Services; 1997:1-8.
  94. Nourredine M, Jurek L, Auffret M, et al. Efficacy and safety of topiramate in binge eating disorder: A systematic review and meta-analysis. CNS Spectr. 2021;26(5):459-467.
  95. Pałasz A, Janas-Kozik M, Borrow A, et al. The potential role of the novel hypothalamic neuropeptides nesfatin-1, phoenixin, spexin and kisspeptin in the pathogenesis of anxiety and anorexia nervosa. Neurochem Int. 2018;113:120-136.
  96. Perkins SJ, Murphy R, Schmidt U, Williams C. Self-help and guided self-help for eating disorders. Cochrane Database Syst Rev. 2006;(3):CD004191.
  97. Phillips K, Keane K, Wolfe BE. Peripheral brain derived neurotrophic factor (BDNF) in bulimia nervosa: A systematic review. Arch Psychiatr Nurs. 2014;28(2):108-113.
  98. Polsinelli GN, Levitan RN, De Luca V. 5-HTTLPR polymorphism in bulimia nervosa: A multiple-model meta-analysis. Psychiatr Genet. 2012;22(5):219-225.
  99. Qasim A, Mayhew AJ, Ehtesham S, et al. Gain-of-function variants in the melanocortin 4 receptor gene confer susceptibility to binge eating disorder in subjects with obesity: A systematic review and meta-analysis. Obes Rev. 2019;20(1):13-21.
  100. Rosager EV, Moller C, Sjogren M. Treatment studies with cannabinoids in anorexia nervosa: A systematic review. Eat Weight Disord. 2021;26(2):407-415.
  101. Rizzo SM, Douglas JW, Lawrence JC, et al. Enteral nutrition via nasogastric tube for refeeding patients with anorexia nervosa: A systematic review. Nutr Clin Pract. 2019;34(3):359-370.
  102. Safer DL, Adler S, Dalai SS, et al. A randomized, placebo-controlled crossover trial of phentermine-topiramate ER in patients with binge-eating disorder and bulimia nervosa. Int J Eat Disord. 2020;53(2):266-277.
  103. Satogami K, Tseng PT, Su KP, et al. Relationship between polyunsaturated fatty acid and eating disorders: Systematic review and meta-analysis. Prostaglandins Leukot Essent Fatty Acids. 2019;142:11-19.
  104. Schützmann K, Schützmann M, Eckert J. The efficacy of outpatient client-centered psychotherapy for bulimia nervosa: Results of a randomised controlled trial. Psychother Psychosom Med Psychol. 2010;60(2):52-63.
  105. Shaffer A, Naik A, Bederson M, et al. Efficacy of deep brain stimulation for the treatment of anorexia nervosa: A systematic review and network meta-analysis of patient-level data. Neurosurg Focus. 2023;54(2):E5.
  106. Sim LA, McAlpine DE, Grothe KB, et al. Identification and treatment of eating disorders in the primary care setting. Mayo Clin Proc. 2010;85(8):746-751.
  107. Sjogren M, Nielsen ASM, Hasselbalch KC, et al. A systematic review of blood-based serotonergic biomarkers in bulimia nervosa. Psychiatry Res. 2019;279:155-171.
  108. Slof-Op 't Landt MC, van Furth EF, Meulenbelt I, et al. Association study of the estrogen receptor I gene (ESR1) in anorexia nervosa and eating disorders: No replication found. Int J Eat Disord. 2014;47(2):211-214.
  109. Sodersten P, Bergh C, Zandian M. Psychoneuroendocrinology of anorexia nervosa. Psychoneuroendocrinology. 2006;31(10):1149-1153.
  110. Solmi M, Gallicchio D, Collantoni E, et al. Serotonin transporter gene polymorphism in eating disorders: Data from a new biobank and META-analysis of previous studies. World J Biol Psychiatry. 2016;17(4):244-257.
  111. Syk M, Ramklint M, Fredriksson R, et al. Elevated total plasma-adiponectin is stable over time in young women with bulimia nervosa. Eur Psychiatry. 2017;41:30-36.
  112. U.S. Food and Drug Administration. FDA expands uses of Vyvanse to treat binge-eating disorder. Press Announcements. Silver Spring, MD: FDA; January 30, 2105.
  113. US Preventive Services Task Force; Davidson KW, Barry MJ, Mangione CM, et al. Screening for eating disorders in adolescents and adults: US Preventive Services Task Force recommendation statement. JAMA. 2022;327(11):1061-1067.
  114. Walpoth M, Hoertnagl C, Mangweth-Matzek B, et al. Repetitive transcranial magnetic stimulation in bulimia nervosa: Preliminary results of a single-centre, randomised, double-blind, sham-controlled trial in female outpatients. Psychother Psychosom. 2008;77(1):57-60.
  115. Walsh BT. The future of research on eating disorders. Appetite. 2004;42(1):5-10.
  116. White MA, Grilo CM. Bupropion for overweight women with binge-eating disorder: A randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2013;74(4):400-406.
  117. Yager J. Eating disorders: Overview of epidemiology, clinical features, and diagnosis. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed March 2021a.
  118. Yager J. Eating disorders: Overview of prevention and treatment. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed March 2020; March 2021b.
  119. Yager J. Implementing the revised American Psychiatric Association practice guideline for the treatment of patients with eating disorder. Psychiatr Clin North Am. 2001;24(2):185-199, vii.
  120. Yager J, Devlin MJ, Halmi KA, et al.; American Psychiatric Association (APA) Work Group on Eating Disorders. Practice Guideline for the Treatment of Patients with Eating Disorders. 3rd ed. Washington, DC: APA; June 2006.
  121. Zepf FD, Rao P, Runions K, et al. Differences in serum zinc levels in acutely ill and remitted adolescents and young adults with bulimia nervosa in comparison with healthy controls - a cross-sectional pilot study. Neuropsychiatr Dis Treat. 2017;13:2621-2630.
  122. Zhang C, Chen J, Jia X, et al. Estrogen receptor 1 gene rs2295193 polymorphism and anorexia nervosa: New data and meta-analysis. Asia Pac Psychiatry. 2013;5(4):331-335.