All guidelines which provided information on the treatment setting (n = 7) consistently recommended outpatient treatment as a first-line therapy setting for patients with AN. For determining more intense levels of care, most guidelines provided criteria for partial (n = 5) and full-time hospitalization (n = 7). The degree of detail and range of hospitalization criteria varied between guidelines. However, the guidelines consistently emphasized the necessity to decide about hospitalization on an individual basis taking multiple factors into account. Overall, hospitalization should be considered for patients who have failed at outpatient care, or who are at high risk for medical complications as determined using patient's weight status (e.g., extremely low body mass index), behavioral factors (e.g., decline in oral intake), vital signs (e.g., heart rate < 40 bpm), psychiatric comorbidity (e.g., suicide risk), or environmental aspects (e.g., family support). For very malnourished patients who do not consent to treatment, most guidelines provided some information on compulsory treatment (n = 7). Criteria for discharge from hospital were specified by the majority of guidelines (n = 7).
The majority of guidelines (n = 6) emphasized the importance to treat patients with AN and eating disorders in general, respectively, by specialized professionals and/or by professionals with substantial experience in the treatment of eating disorders. Regarding specific treatment modalities, most guidelines included recommendations for nutritional management ranging from artificial feeding (n = 8) to general nutritional counseling (n = 6). Although the extent to which information on artificial feeding was given differed among guidelines (e.g., concerning refeeding practice, duration, or indication), guidelines consistently favored oral enteral nutrition over parenteral nutrition which should only be used as a last option. Regarding general nutritional counseling, two (Germany, the United Kingdom) of six guidelines explicitly stated that it should be part of a multidisciplinary therapy approach and not used as a stand-alone treatment. Although there was substantial agreement across guidelines about the amount of recommended weight gain per week in inpatient and outpatient settings, mostly ranging between 0.5–1.5 and 0.2–0.5 kg, respectively, variation in the amount of recommended energy intake per week was apparent. Although some guidelines recommended daily energy intakes of 30–40 kcal/kg (Germany, the United States) or higher (The Netherlands), others recommended considerably lower intakes (Spain, the United Kingdom), particularly for severely malnourished patients at risk for refeeding syndrome. Among the seven guidelines which specified the use of nutritional supplements, there was a large variation of recommendations regarding the type and indication for nutritional supplements. Some guidelines specifically recommended phosphate (n = 6), thiamine (n = 3), zinc (n = 2), or potassium (n = 2), if indicated, while others made a general recommendation for mineral or vitamin supplements (n = 3).
Although psychotherapy was deemed a central part of treatment by all guidelines, only seven guidelines recommended specific psychological interventions. All seven guidelines recommended family-based therapy (for greater detail, see Herpertz-Dahlmann in this issue [40,41]), particularly for younger patients. For individual psychotherapy, most guidelines recommended cognitive-behavioral therapy (n = 6) which intervenes at the symptom level and centers on the modification of dysfunctional behaviors and cognitions that maintain the disorder . It was recommended as a first-line psychotherapy for AN by two guidelines (The Netherlands, the United Kingdom). Lesser agreement was achieved for psychodynamic therapy and interpersonal psychotherapy, which were explicitly recommended as an alternative by four and two guidelines, respectively. While psychodynamic therapy includes treatments that operate on an interpretative-supportive continuum , interpersonal psychotherapy is a focused, goal-oriented treatment which seeks to treat an eating disorder through resolving interpersonal problems in the context of what the disorder presents [44,45]. Further, the cognitive-interpersonal approach Maudsley Anorexia Nervosa Treatment for Adults  and the Specialist Supportive Clinical Management [47,48] were recommended as first-line therapies by two guidelines (The Netherlands, the United Kingdom). Although the German guideline only made a general recommendation for psychological interventions, it recommended involving the patient's family in the treatment of children and adolescents. Some guidelines noted that psychological interventions would be more effective in medically stabilized and cognitively improved patients (n = 3) or through combining psychological and nutritional interventions (n = 1).
Regarding the pharmacological treatment of AN, five of nine guidelines provided specific recommendations with some notable variations. Two guidelines made the general recommendation that medication should not be used as the sole or primary treatment for patients with AN (Spain, the United Kingdom) or that there is no specific medication to treat AN (France). Antidepressants were generally recommended for those with depressive symptoms by four guidelines. At the same time, the German guideline cautioned against the use of antidepressants for weight gain. For selective serotonin reuptake inhibitors (SSRIs), there was one guideline which recommended its use for treating depressive symptoms in conjunction with psychotherapy or after weight restoration (the United States), while two other guidelines made general recommendations against their use, particularly in children and adolescents (Australia and New Zealand, The Netherlands). The use of tricyclic antidepressants (TCAs) was not explicitly favored, given that there was one recommendation against (the United States) and one cautious recommendation in favor (France). The use of monoamine oxidase inhibitors (MAOIs) or bupropion, an atypical antidepressant, was not recommended by the guideline from the United States, the only guideline reporting on these medications. Four guidelines consistently recommended the cautious use of antipsychotics for treating obsessional thinking in patients with AN, particularly olanzapine, because evidence from randomized-controlled trials and regarding long-term effects were lacking. Conflicting results were found for weight gain, given that one guideline recommended antipsychotics for weight gain (the United States), whereas another guideline stated that antipsychotics would not be appropriate for weight gain (Germany). Promotility agents and antianxiety agents were only recommended by the guideline from the United States for treating gastrointestinal problems and to reduce anticipatory anxiety concerning food intake, respectively. The use of appetizers and lithium was not recommended by the German guideline. In addition, four guidelines consistently stated that estrogen should not be routinely offered to patients with AN, as this would depend on the patient's menarche status or chronicity of AN, for example.
Adjunctive treatment recommendations were rarely made and included meal support, eating training, and supervised physical activity, as described by the Danish guideline. Physical therapies (e.g., electroconvulsive therapy, transcranial magnetic stimulation) were not recommended by two guidelines. Of note, four guidelines included information on the medical management of AN and three guidelines additionally reported on pregnancy and pregnancy attempts. Two guidelines specifically provided information about the treatment of physical and mental comorbidities, as well as artificial feeding including refeeding syndrome.
Among the guidelines reporting on the prioritized treatment setting of BN, all recommended outpatient therapy as a first-line treatment (n = 5). Four and five guidelines provided criteria for partial and full-time hospitalization, respectively. Regarding specific treatment modalities, nutritional counseling was generally recommended by the Danish guideline, in individualized or standardized format, while two other guidelines emphasized that nutritional interventions (e.g., to help develop a structured meal plan) should not be offered as stand-alone therapy (Spain, the United States).
Other than the WFSBP guideline, all available guidelines issued recommendations on specific psychological interventions. In agreement, five guidelines recommended cognitive-behavioral therapy as a first-line psychotherapy for patients with BN, particularly in an individual format. The remaining two guidelines also made recommendations in favor of cognitive-behavioral interventions, but prioritized cognitive-behavioral, guided self-help treatment as a first-line treatment (the United Kingdom), or did not provide an explicit treatment hierarchy (Spain). Overall, among the six guidelines which recommended self-help approaches, four highlighted the use of guided self-help based on cognitive-behavioral interventions (Australia and New Zealand, Germany, The Netherlands, the United Kingdom), that is, using structured self-help manuals supplemented with brief supportive sessions . Interpersonal psychotherapy was recommended as an alternative to cognitive-behavioral therapy by most guidelines (n = 4), while psychodynamic therapy (n = 2) was rarely recommended. Family-based therapy was in particular recommended for younger patients with BN (n = 4), and only explicitly recommended for adults by the guideline from the United States. Although the German guideline recommended cognitive-behavioral therapy for children and adolescents with BN, they emphasized the importance of including the patient's family into treatment. Alternative psychological interventions were, for example, the combination of psychodynamic and cognitive-behavioral therapies (n = 1), couples therapy (n = 1), or support groups (n = 1).
Among the recommendations for pharmacological treatment, seven out of eight guidelines consistently recommended antidepressants, specifically the SSRI fluoxetine, although with some restrictions (e.g., to use antidepressants in combination with psychotherapy). Conflicting recommendations were obtained for the use of TCAs such as imipramine and desipramine, which were recommended by the WFSBP, while the guideline from the United States explicitly did not recommend TCAs for initial treatment in patients with BN. Consistently, two guidelines advised against the use of MAOIs (United States, WFSBP). The use of anticonvulsants, specifically topiramate, was consistently recommended by two guidelines, while the remaining guidelines did not report on anticonvulsants. The only guideline which made a recommendation about lithium cautioned against its use (the United States). For patients with comorbid obesity, one guideline recommended the antiobesity medication orlistat (Australia and New Zealand).
Of note, four guidelines included specific information about the treatment of comorbidities, and three guidelines made recommendations for the medical management of BN.
Only three out of seven available guidelines explicitly included the recommendation that outpatient treatment is the first-line treatment setting for BED (Germany, The Netherlands, the United Kingdom). Criteria for hospitalization were provided by four guidelines (Australia and New Zealand, Germany, The Netherlands, the United Kingdom). An explicit recommendation for nutritional counseling was made by the guideline from the United States, specifically within the context of behavioral weight loss programs. The Spanish guideline generally recommended nutritional counseling for patients with eating disorders, with a psychiatrist's approval.
All guidelines provided recommendations for specific psychological interventions, except the WFSBP guideline. Cognitive-behavioral therapy was consistently recommended by all six guidelines, followed by guided (n = 6) or unguided (n = 2) cognitive-behavioral self-help treatment and interpersonal psychotherapy (n = 4). An explicit recommendation for psychodynamic therapy was made by the German guideline only. With respect to first-line psychotherapy, four guidelines recommended cognitive-behavioral therapy, while one guideline favored guided cognitive-behavioral self-help treatment (the United Kingdom). Regarding the treatment format, guidelines varied highly, with one guideline specifically recommending individual psychotherapy (Australia and New Zealand), one prioritizing group format (the United Kingdom), and two guidelines not including any preference (The Netherlands, the United States). Family-based treatment was recommended for children and adolescents with BED by the Dutch guideline only.
The use of antidepressants was generally recommended by three guidelines (Australia and New Zealand, Spain, the United States). These three guidelines and three other guidelines (Germany, The Netherlands, WFSBP) consistently made a specific recommendation in favor of SSRIs for reducing binge-eating episodes, at least in the short-term. For TCAs, only the WFSBP recommended their use, particularly imipramine. For anticonvulsants, three guidelines (Australia and New Zealand, the United States, WFSBP) consistently recommended the use of topiramate, while the remaining guidelines did not report on it. Consistently, two out of two guidelines reporting on antiobesity medications explicitly recommended their use, specifically orlistat, for weight loss in patients with BED and comorbid obesity. In addition to weight loss, the antiobesity medication sibutramine was recommended for reducing binge eating (the United States). Two guidelines explicitly made a recommendation for pharmacological treatment in conjunction with psychological therapies (Australia and New Zealand, the United States).
Of note, three guidelines reported on the treatment of comorbidities, and two guidelines made recommendations for the medical management of BED.
The current systematic review of evidence-based clinical guidelines for eating disorders revealed many consistent recommendations, but also notable differences among the guidelines.
For the treatment of AN, the guidelines showed a substantial agreement on the amount of recommended weight gain, while recommended daily energy intakes varied considerably, which is consistent with Herpertz-Dahlmann et al. , who had narratively reviewed four European guidelines for the treatment of AN. Also in line with their findings, the recommendations for nutritional supplements varied widely, against a background of a lack of evidence. More consistently, most guidelines made recommendations for specific psychological interventions in the treatment of AN, especially for family-based therapy for younger patients, because of a large evidence base [40,50,51]. Most guidelines further supported cognitive-behavioral therapy . Cognitive-behavioral therapy, the Maudsley Anorexia Nervosa Treatment for Adults, and the Specialist Supportive Clinical Management were even recommended as first-line therapies by the two current guidelines from The Netherlands and the United Kingdom, based on recently published results [53▪▪,54▪▪]. Little agreement was found for psychodynamic therapy and interpersonal psychotherapy as alternative treatments, because of scant evidence for their use [55–57]. A need for further research on the psychological treatment of AN was noted for all ages [28,58].
Regarding pharmacotherapy of AN, recommendations varied widely – four guidelines, among them the medically oriented WFSBP guideline, made no specific recommendation for any medication, or advocated against their sole or primary use. The greatest level of consistency across four out of nine guidelines was found for the careful use of antipsychotics to reduce associated obsessional thinking in patients with AN, but it was inconsistent whether or not antipsychotics should be recommended for weight gain. In addition, three guidelines generally recommended antidepressants for the treatment of depressive symptoms, but a consistent recommendation for specific types of antidepressants (SSRIs, TCAs) could not be identified. Single guidelines’ recommendations emerged regarding other medications, for example, against the use of bupropion. Estrogen was with some consistency recommended to be offered only upon specific indication (see [59▪]). Overall, these inconsistent pharmacological recommendations for the treatment of AN may reflect the scarce evidence base for the pharmacological treatment of this disorder [13,28,60▪].
For the treatment of BN, all guidelines but the medically oriented WFSBP guideline issued recommendations on specific psychological interventions: The majority of them recommended cognitive-behavioral therapy as a first-line treatment for BN, reflecting the treatment literature [11,52]. In contrast, the United Kingdom guideline recommended offering cognitive-behavioral self-help treatment first, presumably because of an emphasis on cost-effectiveness , for which initial data are available . Interpersonal psychotherapy was recommended as an alternative to cognitive-behavioral therapy by the majority of guidelines, given its slower short-term efficacy, but equivalent long-term efficacy . Psychodynamic therapy was recommended by the German and guideline from the United States only, despite its limited evidence base [62,63], possibly because of particularities in healthcare systems. Family-based therapy was recommended mostly for younger patients by half of the guidelines, which is supported by recent clinical research . Most guidelines recommended self-help treatment, and the majority of these, especially the more recent guidelines, emphasized guided cognitive-behavioral self-help treatment, documented to be efficacious in the treatment of BN . A few recommendations with unclear rationale and/or sparse evidence base were issued for alternative treatments (e.g., a combination of psychodynamic and cognitive-behavioral therapies) and nutritional counseling.
Regarding the pharmacological treatment of BN, most guidelines recommended antidepressants for the treatment of BN, specifically the SSRI fluoxetine, albeit with several restrictions (e.g., combined use with psychotherapy only). Fluoxetine has approval for the treatment of adults with BN in several countries (e.g., the United States, Germany). However, only a few and often inconsistent recommendations were made for the use of TCAs and anticonvulsants, specifically topiramate, and against the use of MAOIs and lithium. Again, these singular and contradictory recommendations may mirror the overall paucity of research on pharmacological treatments of BN .
For the treatment of BED, all guidelines provided recommendations for specific psychological interventions (except the medically oriented WFSBP guideline). Cognitive-behavioral therapy was consistently recommended by all respective guidelines and mostly as a first-line treatment, given its comprehensive evidence base [10▪▪]. Cognitive-behavioral therapy was followed by cognitive-behavioral self-help treatment, with the majority of guidelines recommending a guided format, a treatment with an increasing evidence base . Of note, the guideline from the United Kingdom favored guided cognitive-behavioral self-help treatment as a first-line treatment, likely for economic reasons, as described for BN. Interpersonal psychotherapy was further recommended by the majority of the guidelines, based on a small number of studies . An explicit non-evidence-based recommendation for psychodynamic therapy was made by the German guideline only  reflecting healthcare system specificities, while family-based treatment was recommended for children and adolescents with BED by the Dutch guideline only, based on emerging evidence for family-based treatment of adolescents with BN . A recommendation for nutritional counseling was made by two guidelines, which may reflect findings of lower efficacy of this treatment regarding binge-eating outcome [67▪▪].
Regarding the pharmacological treatment of BED, the majority of guidelines made a recommendation for SSRIs, which is in line with current literature [10▪▪], while only the WFSBP guideline recommended TCAs, based on studies published before 1999. Three guidelines recommended the use of the anticonvulsant topiramate; however, the drug's side-effects, especially cognitive impairment, have been noted . Regarding antiobesity medications, two guidelines recommended orlistat for weight loss in BED and BN [69,70] and sibutramine for binge eating in BED, the latter being withdrawn from many markets because of adverse cardiovascular events. Combined psychological and pharmacological treatment was recommended by two guidelines; however, this is not supported by current evidence [71▪▪].
Overall, consistency across guidelines seemed to be the greatest for psychological treatments and for single medications with a larger evidence base, while for psychological and medical treatments with a smaller evidence base, recommendations varied considerably, and expert consensus played a greater role. Regarding the dissemination and implementation of evidence-based treatments into clinical practice, the guidelines thus do endorse main empirically validated treatment approaches with considerable agreement, but beyond this, the variability is greater in what recommendations evidence-based clinical guidelines subsume. A larger evidence base is critical in offering clinically reliable and consistent guidance in eating disorders, and many important areas of future clinical research have been identified for all eating disorders at different ages, given the treatment gap and the research-practice gap described at the outset of this article [15▪▪,22▪].
The available evidence is one reason for differences among guidelines. Among additional reasons, while several guidelines were issued within the past 3 years or are about to be published, the majority were 5 years and older. Especially for disorders such as BED with a large recent increase in clinical research, changes in recommendations over time are to be expected. Several recommendations were non-evidence-based and likely reflected particularities in healthcare systems, for example, the availability of outpatient, day patient, and inpatient settings or of therapists trained in a specific intervention. The guidelines differed as well in their scope, considering treatment in selected aspects (e.g., Denmark, France) or comprehensively (e.g., Germany, the United States). Some guidelines were created by one healthcare profession or one specialized professional organization only (e.g., the guidelines from the United States, WFSBP) and may thus reflect the view of this profession only. Most guidelines, however, pursued a multiprofessional approach in guideline development, and some of them noted the inclusion of other stakeholders as well. In fact, the current literature for guideline development advocates for broad stakeholder involvement of all relevant professions, healthcare providers, and patients (e.g., [25–27]) for optimal acceptance and implementation.
Another additional source for differences among guidelines may be how the evidence was examined, with guidelines based on meta-analyses (e.g., Germany, the United Kingdom), systematic reviews (e.g., Australia and New Zealand, the United States), or unsystematic reviews of the evidence (e.g., France). The transparency with which evidence was converted into specific recommendations further varied across guidelines; several guidelines explicitly evaluated the strength of evidence and provided clear rationale for a specific recommendation (e.g., Germany, the United Kingdom, WFSBP), while others did not (e.g., France), leaving the empirical foundation of a recommendation unclear. To develop a guideline, it has been recommended to use a systematic approach to evaluate the strength of evidence, for example the Grading of Recommendations Assessment, Development, and Evaluation , or the system of the Oxford Centre for Evidence-Based Medicine [26,73]. For some guidelines, only summary statements without the systematic review component were available in the review languages, making the empirical background of a recommendation difficult to understand (e.g., Denmark). Guidelines differed further in readability, with most guidelines providing clear or even standardized recommendations that were easily located (e.g., Germany, the United Kingdom), while others provided them in a more complex text format (e.g., the United States). Although these aspects are central to the quality of a guideline, it is notable that a systematic quality evaluation  of clinical eating disorder guidelines is currently lacking; this was considered to be beyond the scope of this treatment-oriented review but could help to systematically identify strengths and limitations of current eating disorder guidelines.
Strengths of this study were a systematic compilation of main treatment recommendations of current evidence-based eating disorders guidelines. Not within the scope of this review were: general setting-oriented recommendations (e.g., communication with the patient, therapeutic infrastructure, organization of transitions between different levels of care); methods for the identification, assessment, and diagnosis of eating disorders; and the practical applicability of the guidelines and their actual implementation in clinical settings. Several of these aspects warrant further investigation. One further limitation is that several guidelines had to be excluded from this review because of not meeting the language requirement. For further comparative research, it would be desirable to have guidelines published not only in the national language, but also in other languages for international reception.
The current systematic, international comparison demonstrated notable commonalities and differences among current evidence-based clinical guidelines for eating disorders. Currently, several evidence-based clinical guidelines for eating disorders are in progress (e.g., Germany, the United States). Because developing and updating clinical guidelines is time-consuming and complex, an international coordination of guideline development, for example, across the European Union, would be desirable. Collaborative efforts would need to carefully specify the goals and scope of a common ‘guideline trunc’ which should be based on an elaborated, quality-assuring developmental process, while accounting for different cultures and national requirements. European clinical studies on major research gaps could represent an important first step toward this end.
The authors are grateful to Jamie L. Manwaring, PhD and Lisa Opitz, BSc for her help in editing this article.
Financial support and sponsorship
A.H. and R.S. are funded by the German Federal Ministry of Education and Research (grant 01EO1501).
Conflicts of interest
There are no conflicts of interest.
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Keywords:Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
eating disorders; evidence-based; guideline; therapy; treatment