Close Window
Aetna Aetna
Clinical Policy Bulletin:
Eating Disorders
Number: 0511


Policy

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) (see CPB 0134 - Bone Mass Measurements)
    • Electrocardiography
    • Liver function tests
    • Medical evaluation (complete medical history and physical examination)
    • Psychiatric/psychological consultation and testing
    • Urinalysis.
       
  2. Treatment:

    • Nutritional counseling (see CPB 0049 - Nutritional Counseling)
    • Pharmacotherapy for the treatment of anorexia (e.g., selective serotonin reuptake inhibitors and anti-psychotics)**
    • Pharmacotherapy for the treatment of bulimia (e.g., selective serotonin reuptake inhibitors such as fluoxetine, tricyclic anti-depressants, trazodone, topiramate)**
    • Psychotherapy (e.g., cognitive behavioral therapy, family psychotherapy, interpersonal psychotherapy, and psychodynamic psychotherapy).

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

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:

    • Brain imaging
    • Estrogen receptor 1 gene (ESR1) polymorphism testing (for anorexia)
    • Individual Optimal Nutrition (ION) analysis/profile
    • Measurement of blood levels of peripheral brain derived neurotrophic factor (BDNF) (for bulimia)
    • Measurement of serum concentration of brain derived neurotrophic factor (for anorexia)
    • Serotonin transporter gene (5-HTTLPR) polymorphism testing (for bulimia)
       
  2. Treatment:

    • Acamprosate calcium (Campral) for the treatment of binge eating disorder
    • Bisphosphonates and other anti-resorptive agents in the management of osteopenia in anorexic members
    • Bupropion (Zyban), lithium, and naltrexone for the treatment of bulimia and binge eating disorder (bupropion only)
    • Cholinesterase inhibitors (e.g., donepezil) for the treatment of anorexia
    • Chromium for the treatment of binge eating disorder
    • Deep brain stimulation (treatment-refractory anorexia)
    • Oral contraceptives in preventing bone loss in amenorrheic persons with an eating disorder
    • Repetitive transcranial magnetic stimulation
    • The Mandometer treatment.


Background

Eating disorders are characterized by marked disturbances in eating behavior.  There are 2 severe forms of eating disorders -- (i) anorexia nervosa and (ii) 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: (i) 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), (ii) disturbance of body image and intense fear of being fat, and (iii) 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: (i) over-concern with weight and body shape, (ii) recurrent episodes of binge eating, (iii) recurring subsequent purging, restriction, or excessive exercise, and (iv) 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.

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.

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.

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 DSM-IV criteria for bulimia (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.

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: (i) reduction in food intake (diet restriction), and (ii) 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.

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 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.

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.  http://www.gdx.net/core/interpretive-guides/ION-IG.pdf.  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. 

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.

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.

 
CPT Codes / HCPCS Codes / ICD-9 Codes
CPT codes covered if selection criteria are met:
76977
77078
77080 - 77081
80047
80048
80050
80053
80076
81000 - 81005
85025 - 85027
90791 - 90792
90832 - 90838
90845 - 90853
90863
93000
96101 - 96103
96150 - 96151
96152 - 96155
CPT codes not covered for indications listed in the CPB:
There is no specific code for the measurement of serum concentration of brain derived nurotrophic factor:
70450 - 70470
70496
70551 - 70553
70554 - 70555
78600 - 78610
90867
90868
90869
Other CPT codes related to the CPB:
90785
HCPCS codes not covered for indications listed in the CPB:
J1740 Injection, ibandronate sodium, 1 mg
J2315 Injection, naltrexone, depot form, 1 mg
J2430 Injection, pamidronate disodium, per 30 mg
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-9 codes covered if selection criteria are met:
307.1 Anorexia nervosa
307.51 Bulimia nervosa
ICD-9 codes not covered if selection criteria are met:
783.6 Polyphagia [binge eating disorder]
Other ICD-9 codes related to the CPB :
307.50 Eating disorder, unspecified
307.52 - 307.59 Pica, rumination disorder, psychogenic vomiting, and other unspecified disorders of eating
Deep Brain Stimulation:
CPT codes not covered for indications listed in the CPB:
61863
+61864
61867
+61868
61880
61885
+61886
90867
90868
90869
95970
95971
95974
+95975
95978
95979
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-9 codes not covered for indications listed in the CPB:
307.1 Anorexia nervosa
Individual Optimal Nutrition (ION) analysis/profile:
No specific code
ICD-9 codes not covered for indications listed in the CPB:
307.1 Anorexia nervosa
307.51 Bulimia nervosa


The above policy is based on the following references:
  1. Becker AE, Grinspoon SK, Klibanski A, Herzog DB. Eating disorders. N Engl J Med. 1999;340(14):1092-1098.
  2. McGilley BM, Pryor TL. Assessment and treatment of bulimia nervosa. Am Fam Physician. 1998;57(11):2743-2750.
  3. Frank JB, Weihs K, Minerva E, Lieberman DZ. Women's mental health in primary care. Med Clin North Am. 1998;82(2):359-389.
  4. Eating disorders. In: Diagnostic and Statistical Manual of Mental Disorders, DSM IV. 4th ed. Washington, DC: America Psychiatric Association; 1994:539-550.
  5. Jimerson DC. Bulimia nervosa. In: Conn's Current Therapy. RE Rakel, ed. Philadelphia, PA: W.B. Saunders Co.; 1999:1130-1133.
  6. 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.
  7. No authors listed. Eating disorders: Anorexia and bulimia. Well-Connected. Report #49. New York, NY: Nidus Information Services; 1997:1-8.
  8. 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.
  9. 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.
  10. Kreipe RE, Birndorf SA. Eating disorders in adolescents and young adults. Med Clin North Am. 2000;84(4):1027-1049, viii-ix.
  11. 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.
  12. 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: http://www.vh.org/adult/provider/familymedicine/FPHandbook/Chapter18/06-18.html. Accessed June 2, 2003.
  13. Liburd JDA. Eating disorders. eMedicine Developmental and Behavioral Pediatrics. Topic 115. Omaha, NE: eMedicine.com; updated March 7, 2003. Available at: http://www.emedicine.com/PED/topic115.htm. Accessed June 2, 2003.
  14. American Academy of Pediatrics, Committee on Adolescence. Identifying and treating eating disorders. Pediatrics. 2003;111(1):204-211.
  15. 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. Available at: http://www.nice.org.uk/Docref.asp?d=101245. Accessed February 4, 2004.
  16. Cooke R, Sawyer SM. Eating disorders in adolescence. An approach to diagnosis and management. Aust Fam Physician. 2004;33(1-2):27-31.
  17. Hsu LK. Eating disorders: Practical interventions. J Am Med Womens Assoc. 2004;59(2):113-124.
  18. Hay PJ. Antidepressants versus placebo for people with bulimia nervosa. Cochrane Database Syst Rev. 2003;(4):CD003391.
  19. Bacaltchuk J, Hay P, Trefiglio R. Antidepressants versus psychological treatments and their combination for bulimia nervosa. Cochrane Database Syst Rev. 2001;(4):CD003385.
  20. Hay P, Bacaltchuk J, Claudino A, et al. Individual psychotherapy in the outpatient treatment of adults with anorexia nervosa. Cochrane Database Syst Rev. 2003;(4):CD003909.
  21. Hay PJ, Bacaltchuk J, Stefano S. Psychotherapy for bulimia nervosa and binging. Cochrane Database Syst Rev. 2004;(3):CD000562.
  22. Fisher CA, Hetrick SE, Rushford N. Family therapy for anorexia nervosa. Cochrane Database Syst Rev. 2010;(4):CD004780.
  23. Perkins SJ, Murphy R, Schmidt U, Williams C. Self-help and guided self-help for eating disorders. Cochrane Database Syst Rev. 2006;(3):CD004191.
  24. 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.
  25. Walsh BT. The future of research on eating disorders. Appetite. 2004;42(1):5-10.
  26. 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.
  27. 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.
  28. 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.
  29. Claudino AM, Hay P, Lima MS, et al. Antidepressants for anorexia nervosa. Cochrane Database Syst Rev. 2006;(1):CD004365.
  30. 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.
  31. Lock JD, Fitzpatrick KK. Anorexia nervosa. In: BMJ Clinical Evidence. London, UK: BMJ Publishing Group; August 2007.
  32. Hay PJ, Bacalchuk J. Bulimia nervosa. In: BMJ Clinical Evidence. London, UK: BMJ Publishing Group; June 2007.
  33. 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. Available at: http://www.psychiatryonline.com/pracGuide/pracGuideHome.aspx. Accessed August 16, 2006.
  34. Bergh C, Eklund S, Eriksson M, et al. A new treatment of anorexia nervosa. Lancet. 1996;348(9027):611-612.
  35. 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.
  36. 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.
  37. Sodersten P, Bergh C, Zandian M. Psychoneuroendocrinology of anorexia nervosa. Psychoneuroendocrinology. 2006;31(10):1149-1153.
  38. 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.
  39. Dunican KC, DelDotto D. The role of olanzapine in the treatment of anorexia nervosa. Ann Pharmacother. 2007;41(1):111-115.
  40. 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.
  41. 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.
  42. Misra M, Klibanski A. Evaluation and treatment of low bone density in anorexia nervosa. Nutr Clin Care. 2002;5(6):298-308.
  43. Legroux-Gerot I, Vignau J, Collier F, Cortet B. Bone loss associated with anorexia nervosa. Joint Bone Spine. 2005;72(6):489-495.
  44. 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.
  45. 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.
  46. 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.
  47. Hay PP, Bacaltchuk J, Stefano S, Kashyap P. Psychological treatments for bulimia nervosa and binging. Cochrane Database Syst Rev. 2009;(4):CD000562.
  48. 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.
  49. 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.
  50. 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.
  51. 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.
  52. 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.
  53. 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.
  54. Kontis D, Theochari E. Dopamine in anorexia nervosa: A systematic review. Behav Pharmacol. 2012;23(5-6):496-515.
  55. 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.
  56. 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.
  57. Mitchell JE, Roerig J, Steffen K. Biological therapies for eating disorders. Int J Eat Disord. 2013;46(5):470-477.
  58. 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.
  59. 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.
  60. 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.
  61. 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.
  62. 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.
  63. 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.


email this page   


Copyright Aetna Inc. All rights reserved. Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.
Aetna
Back to top