Pragmatic clinical trials to advance research in children and adolescents with eating disorders.

OBJECTIVE: To discuss the utility of pragmatic clinical trials (PCTs) to help advance research in eating disorders (EDs). METHODS: We describe challenges associated with traditional explanatory research trials and examine PCTs as an alternative, including a review of the PRECIS-2 tool. RESULTS: There are many challenges associated with the design and completion of traditional RCTs within the field of EDs. Pragmatic clinical trials are studies that closely align with conditions available in everyday practice and focus on outcomes that are relevant to patients and clinicians. Results of PCTS maximize applicability and generalizability to clinical settings. DISCUSSION: Available therapies established for the treatment of EDs provide remission rates that rarely exceed 50%, implying a need for additional research on new or adjunctive treatments. In addition to a general overview of PCTs, we draw upon published literature and our own experiences involving adjunctive olanzapine for the treatment of children and youth with anorexia nervosa to help highlight challenges associated with randomized controlled trial (RCT) design and implementation, and offer pragmatic suggestions that would allow patients greater choice in treatment trials, while at the same time capturing outcomes that are most likely to advance treatment efforts. CONCLUSIONS: Pragmatic clinical trials provide alternatives to RCT design that can help bolster research in EDs that aims to explore real-world effects of interventions. PUBLIC SIGNIFICANCE: Available therapies established for the treatment of eating disorders (EDs) in children and adolescents provide remission rates that rarely exceed 50%, implying a need for additional research on new or adjunctive treatments. In this article, we discuss the utility of pragmatic trials to help promote research that can help advance knowledge that is relevant to clinical care settings.

Approach to anorexia nervosa and atypical anorexia nervosa in adolescents.

OBJECTIVE: To address screening, diagnosis, and treatment of adolescents with anorexia nervosa and atypical anorexia nervosa in primary care. SOURCES OF INFORMATION: A literature search was conducted in PubMed using the subject headings anorexia nervosa, adolescents, COVID-19, review, guidelines, and primary care. Applicable articles were reviewed, with key recommendations summarized. Most evidence is level I. MAIN MESSAGE: Recent studies suggest that the global COVID-19 pandemic contributed to an increase in the incidence of eating disorders, particularly among teenagers. This has resulted in increasing responsibility for primary care providers regarding the assessment, diagnosis, and management of these disorders. Moreover, primary care providers are in ideal positions to identify adolescents at risk of eating disorders. Early intervention is of utmost importance for avoiding long-term health consequences. High rates of atypical anorexia nervosa indicate a need for providers to have awareness of weight biases and stigmas. Treatment primarily involves a combination of renourishment and psychotherapy, generally through family-based therapy, with pharmacotherapy playing a lesser role. CONCLUSION: Anorexia nervosa and atypical anorexia nervosa are serious, potentially life-threatening illnesses that are best addressed through early detection and treatment. Family physicians are in an optimal position to screen for, diagnose, and treat these illnesses.

Attitudes toward physical activity as a treatment component for adolescents with anorexia nervosa: An exploratory qualitative study of patient perceptions.

OBJECTIVE: Anorexia nervosa (AN) with compulsive exercise is associated with poor treatment outcomes. This study sought to understand the attitudes of adolescents with AN from various stages of treatment, toward physical activity research practices and physical activity as a component of treatment. METHOD: Seventeen adolescents 12-18 years old (15 female) with AN (10 with acknowledged history of compulsive exercise) were recruited from a Canadian Tertiary Care Hospital's Eating Disorder Program. Six inpatients, 5-day program patients, and six outpatients treated by either the inpatient and/or day treatment program in the past 2 years completed individual, semi-structured interviews that were audio-recorded and transcribed. Results were analyzed deductively using qualitative techniques. RESULTS: Participants recognized both benefits (psychological, sociological, and physiological) and risks (trigger negative thoughts, increase competitive behavior) of implementing physical activity into acute AN treatment. Patient characteristics, such as stage of treatment and exercise history, had an impact on participants' perceptions toward physical activity in AN. Participants suggested that the ideal physical activity program would be focused on fun, individualized and progressively integrated, group-based, and directly supported by staff. Although the majority of participants stated that they would wear an activity monitor for research purposes, concerns were voiced regarding compliance and the potential impact on eating disorder symptomatology. DISCUSSION: Participants overwhelmingly supported the careful implementation of structured physical activity and physical activity psychoeducation into the acute treatment of adolescents with AN. This study allows for the inclusion of patient voices in the conversation surrounding the role of physical activity in AN treatment.

Asceticism, perfectionism and overcontrol in youth with eating disorders.

PURPOSE: Personality traits such as perfectionism and asceticism, and combinations of these traits (i.e., overcontrol) have been related to eating disorder (ED) diagnosis, symptoms, and chronicity in adult patients with EDs. However, as limited evidence exists in adolescents, the aim of the present study was to examine these links in a clinical sample of adolescents with EDs. METHOD: A retrospective chart review was conducted on 178 adolescents (91% females; Mage = 15.73 years, SD = 1.31) receiving services at a tertiary care pediatric ED program. An examination of variability in mean levels of perfectionism, asceticism, and overcontrol across ED symptom groups (restrictive and binge/purge ED subtypes) was conducted to learn of diagnostic differences, while correlations were used to explore the association of these personality traits with comorbid anxiety and depressive symptoms. Hierarchical linear regression was used to assess whether overcontrol was related to length of stay (LOS) in an inpatient program. RESULTS: Results indicated that adolescents with binge-purge symptoms had higher levels of perfectionism, asceticism and overcontrol compared to those with restrictive symptoms, and that greater levels of perfectionism, asceticism and overcontrol were associated with elevated depression and anxiety symptoms. Additionally, overcontrol predicted greater LOS in the inpatient ED program. CONCLUSION: Results suggest the importance of assessing, monitoring and targeting overcontrol in treatment for adolescents with EDs given its impact on comorbid symptoms and LOS. LEVEL OF EVIDENCE: Level III, evidence obtained from case-control analytic studies.

Characteristics and clinical trajectories of patients meeting criteria for avoidant/restrictive food intake disorder that are subsequently reclassified as anorexia nervosa.

OBJECTIVE: To examine the initial assessment profiles and early treatment trajectories of youth meeting the criteria for avoidant/restrictive food intake disorder (ARFID) that were subsequently reclassified as anorexia nervosa (AN). METHOD: A retrospective cohort study of patients assessed and treated in a tertiary care eating disorders (ED) program was completed. RESULTS: Of the 77 included patients initially meeting criteria for ARFID, six were reclassified as having AN (7.8%) at a median rate of 71 days after the first assessment. Patients in this cohort presented at very low % treatment goal weight (median 71.6%), self-reported abbreviated length of illness (median 6 months), and exhibited low resting heart rates (median 46 beats per minute). Nutrition and feeding focused worries related more to general health as opposed to specific weight and shape concerns or fears at assessment in half of those reclassified with AN. Treatment at the 6-month mark varied among patients, but comprised family and individual therapy, as well as prescription of psychotropic medication. CONCLUSION: Prospective longitudinal research that utilizes ARFID-specific as well as traditional eating disorder diagnostic measures is required to better understand how patients with restrictive eating disorders that deny fear of weight gain can be differentiated and best treated.

Binge eating and social anxiety in treatment-seeking adolescents with eating disorders or severe obesity.

PURPOSE: Binge eating is a common behavior in children and adolescents who suffer from either eating disorders (EDs) or from severe obesity. The purpose of the current study was to explore the association between social anxiety and binge eating and compare prevalence rates of social anxiety between youth with severe obesity or EDs who did or did not engage in binge eating. METHODS: Retrospective data on treatment-seeking youth's (n = 490) eating behaviors and social anxiety at assessment were analyzed. RESULTS: Results indicate that those who engage in binge eating have higher rates of social anxiety; frequency of binges does not predict severity of social anxiety, though social anxiety predicts presence of binge eating. Adolescents with EDs had higher rates of social anxiety than those with obesity, and for both groups, rates of social anxiety were highest in those who binge. CONCLUSIONS: Clinicians who treat youth with EDs and with obesity should be aware of the relationship between binge eating and social anxiety and of the need for treatment to address both these disorders. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Bingeing, Purging, and Suicidal Ideation in Clinical and Non-Clinical Samples of Youth.

Suicidal ideation is a serious mental health concern reported by adolescents. Despite understanding of increased suicidal ideation in patients with eating disorders (EDs) and obesity, few studies have compared how disordered eating (bingeing, vomiting and over exercising) is associated with suicidal ideation in clinical and non-clinical samples of youth across the ED and weight spectrum. The present study aimed to 1) comparatively examine rates of suicidal ideation and disordered eating behaviors in clinical samples of youth with EDs, complex obesity, or from the community, and 2) examine whether disordered eating was associated with suicidal ideation above and beyond age, body mass index, diagnosis, treatment-seeking status, and depressive symptoms in large samples of males vs. females in an attempt to understand whether these behaviors should lead to concern regarding suicidal ideation. Data from charts on treatment-seeking adolescents diagnosed with either an ED (N = 315), severe complex obesity (N = 212), and from the community (N = 3036) were pooled together for comparative purposes. Results showed that suicidal ideation was higher in youth seeking treatment for an ED (50.2%) and obesity (23.7%) as compared to youth from the community (13%). Binary logistic regression analyses revealed that vomiting (OR = 1.73 for females, 8.17 for males) and over-exercising (OR = 1.47 for females, 1.68 for males) was significantly associated with suicidal ideation in both males and females. Findings underscore the importance of screening for suicidal ideation in youth who report vomiting or over-exercising despite diagnostic presentation, age, weight, or treatment setting.

Development of the Ottawa Disordered Eating Screen for Youth: The ODES-Y.

OBJECTIVE: To develop a concise screening tool that allows for early identification of disordered eating in youth. STUDY DESIGN: In this 2-step classification accuracy study, questions for the Ottawa Disordered Eating Screen-Youth, a 2-question screening tool (index test), were conceptualized by clinician-scientists from tertiary care pediatric eating disorder and weight-related clinics, and was validated using retrospective data (2004-2010) from a community-based study, the Research on Eating and Adolescent Lifestyles (REAL) study. RESULTS: Analyses of contrast between the index test and the reference standard using data from 2892 (1714 females) students between grade 7 and grade 12 revealed classification statistics of 67.1% for sensitivity, 85.9% for specificity, 4.7 for positive likelihood ratio, 0.38 for negative likelihood ratio, 50.6% for positive predictive value, and 92.4% for negative predictive value for females and 61.1% for sensitivity, 93.9% for specificity, and 9.9 for positive likelihood ratio, 0.41 for negative likelihood ratio, 32.3% for positive predictive value, and 98.0% for negative predictive value for males. CONCLUSIONS: Our findings suggest that the index test has utility as a short and accurate screening tool for earlier detection of disordered eating thoughts and behaviors in youth. Additional research is needed to best determine how the index test can be administered to youth across various health care, school, public health, and surveillance settings in clinically sensitive pragmatic ways.

Use of cyproheptadine to stimulate appetite and body weight gain: A systematic review.

OBJECTIVE: A systematic review identifying the use of cyproheptadine (CY) as an appetite stimulant was completed. METHOD: Studies of any design exploring the efficacy of CY as an appetite stimulant in all age groups and populations were included. Primary outcomes of studies included were weight gain, appetite stimulation, and/or caloric/nutritional intake increase. The review was completed in accordance with PRISMA standards. RESULTS: A total of 46 articles across 21 different treatment populations met criteria for the review, including 32 randomized controlled trials, 4 prospective cohort studies, 4 retrospective cohort studies, 4 case reports and 2 case series. Of these, 39 demonstrated that CY resulted in significant weight gain in the sample under study. Studies exploring the use of CY in those with malignant/progressive disease states, such as HIV and cancer, showed minimal to no benefit of the medication. Transient mild to moderate sedation was the most commonly reported side effect. Studies included were heterogeneous in terms of methods as well as study patient demographics, characteristics and concurrent medical conditions. Few studies provided objective measures of appetite change. DISCUSSION: CY appears to be a safe, generally well-tolerated medication that has utility in helping facilitate weight gain in patients drawn from a variety of underweight populations. Future prospective randomized controlled studies in low weight patients that include objective measures of appetite and intake are needed to better understand the mechanism by which CY augments weight gain.

Building evidence for the use of descriptive subtypes in youth with avoidant restrictive food intake disorder.

OBJECTIVE: To examine characteristics of patients with Avoidant/Restrictive Food Intake Disorder (ARFID) in an effort to identify and describe subtypes of the disorder. METHOD: A retrospective chart review was completed for patients aged 8-17 years assessed over a 17-year period. RESULTS: Seventy-seven patients were included in the study, the majority of whom were female (n = 56, 73%). The average age of patients was 13.7 years (SD = 2.4 years). Three specific subtypes of ARFID (aligning with example presentations outlined in the DSM-5) were identified: (a) those with weight loss and/or medical compromise as a consequence of apparent lack of interest in eating (n = 30, 39%); (b) restriction arising as a result of sensory sensitivity (n = 14, 18%); and (c) restriction based upon food avoidance and/or fear of aversive consequences of eating (n = 33, 43%). Clinical characteristics of patients varied depending on the assigned subtype. DISCUSSION: Our findings highlight the need for further research into the relative merit of subtype-assignment in patients with ARFID and whether such practice would aid in the recommended treatment. Further research is required to understand whether these categories are generalizable and applicable to other samples such as young children or adults with ARFID, and how treatment options might differ according to subtype.

Approche de l'anorexie mentale et de l'anorexie mentale atypique chez l'adolescent.

OBJECTIF: Aborder le dépistage, le diagnostic et le traitement de l'anorexie mentale et de l'anorexie mentale atypique chez les adolescents en soins primaires. SOURCES DE L'INFORMATION: Une recherche documentaire a été effectuée dans PubMed à l'aide des rubriques thématiques en anglais anorexia nervosa, adolescents, COVID-19, review, guidelines et primary care. Les articles pertinents ont été passés en revue et les principales recommandations ont été résumées. La plupart des données probantes sont de niveau I. MESSAGE PRINCIPAL: De récentes études font valoir que la pandémie mondiale de la COVID-19 a contribué à une augmentation de l'incidence des troubles du comportement alimentaire, en particulier chez les adolescents. Il s'ensuit de plus grandes responsabilités pour les professionnels des soins primaires concernant l'évaluation, le diagnostic et la prise en charge de ces troubles. En outre, les professionnels des soins primaires sont bien placés pour identifier les adolescents à risque de troubles du comportement alimentaire. Une intervention précoce revêt une importance capitale pour éviter les conséquences à long terme pour la santé. Des taux élevés d'anorexie mentale atypique indiquent la nécessité que les professionnels soient sensibilisés aux préjudices et à la stigmatisation entourant le poids. Le traitement comporte principalement une combinaison de renutrition et de psychothérapie, généralement au moyen d'une thérapie familiale, et la pharmacothérapie joue un rôle secondaire. CONCLUSION: L'anorexie mentale et l'anorexie mentale atypique sont des maladies graves et potentiellement mortelles, et leur prise en charge optimale comprend la détection et le traitement précoces. Les médecins de famille sont très bien placés pour dépister, diagnostiquer et traiter ces maladies.

A psycho-education intervention for parents of adolescents with eating disorders: a randomized controlled trial.

This study evaluated the efficacy of a 2-hour psycho-education session combined with bi-weekly telephone support in increasing parent/caregiver knowledge about eating disorders, increasing self-efficacy by empowering parents to support their child's recovery, and decreasing the impact of eating disorder symptoms on the family. The intervention was targeted at parents/caregivers whose child was waiting to be assessed for an eating disorder. Participants included 51 parents/caregivers and 36 youths. The brief intervention successfully increased parent/caregiver knowledge of the illness, feelings of self-efficacy, and help-seeking behaviors. These findings are clinically useful as waiting lists are common in Canada.

Exploring avoidant/restrictive food intake disorder in eating disordered patients: a descriptive study.

OBJECTIVE: To assess and compare clinical characteristics of patients with avoidant/restrictive food intake disorder (ARFID) to those with anorexia nervosa (AN). METHOD: A retrospective review of adolescent eating disorder (ED) patients assessed between 2000 and 2011 that qualified for a diagnosis of ARFID was completed. A matched AN sample was used to compare characteristics between groups. RESULTS: Two hundred and five patients met inclusion criteria and were reviewed in detail. Of these, 34 (5%) patients met criteria for ARFID. A matched sample of 36 patients with AN was used to draw comparisons. Patients with ARFID were younger than those with AN, more likely to present before age 12, and more likely to be male. Patients in both groups presented at low weights. Common eating-specific behaviors and symptoms in the ARFID group included food avoidance, loss of appetite, abdominal pain, and fear of vomiting. Rates of comorbid psychiatric diagnoses and medical morbidity were high in both groups. Almost 80% of AN patients and one-third of ARFID patients required hospital admission as a result of medical instability. Symptom profiles in 4/34 ARFID patients resulted in eventual reclassification to AN. DISCUSSION: This study supports the notion that a small percentage of adolescent patients presenting with restrictive eating disorders meet criteria for ARFID. Patients are younger than average, more likely to be male compared to adolescent AN samples, and have high rates of psychiatric and medical morbidity. The study also suggests that a proportion of patients evolve into AN as treatment progresses.

A family-based eating disorder day treatment program for youth: examining the clinical and statistical significance of short-term treatment outcomes.

This article describes an innovative family-based day treatment program (DTP) for youth with moderate to severe eating disorders. A sample of 65 youth completed a battery of psychological measures pre- and post-treatment and 6 months after program completion. Treatment outcomes were assessed in three main domains: (a) medical stabilization, (b) normalization of eating behavior, and (c) improved psychological functioning. Overall, patients demonstrated statistically significant and clinically meaningful improvements on all outcome measures. Findings indicate that a comprehensive DTP can successfully facilitate positive outcomes in youth with eating disorders and that these improvements can be maintained 6 months post-treatment.

A study protocol for implementing Canadian Practice Guidelines for Treating Children and Adolescents with Eating Disorders.

BACKGROUND: Eating disorders have one of the highest mortality rates among psychiatric illnesses. Timely intervention is crucial for effective treatment, as eating disorders tend to be chronic and difficult to manage if left untreated. Clinical practice guidelines play a vital role in improving healthcare delivery, aiming to minimize variations in care and bridge the gap between research and practice. However, research indicates an active guideline implementation approach is crucial to effective uptake. METHODS: Mixed methods will be used to inform and evaluate our guideline implementation approach. Semi-structured focus groups will be conducted in each of the eight provinces in Canada. Each focus group will comprise 8-10 key stakeholders, including clinicians, program administrators, and individuals with lived experience or caregivers. Qualitative data will be analyzed using conventional content analysis and the constant comparison technique and the results will be used to inform our implementation strategy. The study will then evaluate the effectiveness of our implementation approach through pre- and post-surveys, comparing changes in awareness, use, and impact of the guidelines in various stakeholder groups. DISCUSSION: Through a multifaceted implementation strategy, involving the co-creation of educational materials, tailored training, and context-specific strategies, this study intends to enhance guideline uptake and promote adherence to evidence-based practices. Our study will also contribute valuable information on the impact of our implementation strategies.

Growth trajectories of maintenance variables related to refractory eating disorders in youth.

Despite decades of eating disorder (ED) research, studies of factors involved in long-term EDs are still lacking. This longitudinal study investigated the role of maintenance variables in a transdiagnostic adolescent ED sample. Participants included 275 adolescents who underwent specialized ED treatment. Hierarchical linear modeling confirmed a significant growth pattern of maintenance factors, wherein there was initial increase, then a decline during treatment, followed by a slight rebound post-treatment. Refractory status did not predict the variability in maintenance curves, suggesting that although this growth pattern existed, requiring a second treatment encounter did not explain the differences found in these patterns.

Evidence-based pharmacotherapy of eating disorders.

The objective was to review scientific evidence for efficacy and safety of pharmacotherapy in adults or children with an eating disorder (ED). We conducted a computer search for all randomized controlled trials (RCTs) published between 1960 and May 2010 for treatment of anorexia nervosa (AN), bulimia nervosa (BN) or binge-eating disorder (BED). For drugs for which no RCT was found, open trials or case reports were retrieved. Clinically relevant RCTs in the treatment of AN have used atypical antipsychotics, selective serotonin reuptake inhibitors (SSRIs), and zinc supplementation. Olanzapine demonstrated an adjunctive effect for in-patient treatment of underweight AN patients, and fluoxetine helped prevent relapse in weight-restored AN patients in 1/2 studies. For treatment of BN, controlled studies have used SSRIs, other antidepressants, and mood stabilizers. In 9/11 studies, pharmacotherapy yielded a statistically significant although moderate reduction in binge/purge frequency, and some additional benefits. For BED, RCTs have been conducted using SSRIs and one serotonin norepinephrine reuptake inhibitor (SNRI), mood stabilizers, and anti-obesity medications. In 11/12 studies, there was a statistically significant albeit limited effect of medication. Meta-analyses on efficacy of pharmacotherapy for BN and BED support moderate effect sizes for medication, but generally low recovery rates. Treatment resistance is an inherent feature of AN, where treatment should focus on renourishment plus psychotherapy. For BN and BED, combined treatment with pharmacotherapy and cognitive behaviour therapy has been more effective than either alone. Data on the long-term efficacy of pharmacotherapy for EDs are scarce. Short- and long-term pharmacotherapy of EDs still remains a challenge for the clinician.

An examination of medical and psychological morbidity in adolescent males with eating disorders.

The objective of this study was to examine the clinical profile of adolescent male patients presenting for eating disorder (ED) assessment over a 17-year period. A retrospective cohort study was completed. A total of 52 patients (8% of the total sample) were included in the study. The average age of patients was 14.7 years and the most common diagnosis observed was Eating Disorder Not Otherwise Specified (EDNOS). Rates of concurrent depression and anxiety were very high, as were rates of medical co-morbidity, including osteoporosis. Our study supports findings documented in previously published reports of males with eating disorders and adds to the limited knowledge base which targets adolescents specifically. Multi-center controlled trials are required to further investigate male-specific ED symptomatology, treatment courses, and outcomes.

Classification of Children and Adolescents With Avoidant/Restrictive Food Intake Disorder.

BACKGROUND AND OBJECTIVES: Evidence suggests that children and adolescents with avoidant/restrictive food intake disorder (ARFID) have heterogeneous clinical presentations. To use latent class analysis (LCA) and determine the frequency of various classes in pediatric patients with ARFID drawn from a 2-year surveillance study. METHODS: Cases were ascertained using the Canadian Pediatric Surveillance Program methodology from January 1, 2016, to December 31, 2017. An exploratory LCA was undertaken with latent class models ranging from 1 to 5 classes. RESULTS: Based on fit statistics and class interpretability, a 3-class model had the best fit: Acute Medical (AM), Lack of Appetite (LOA), and Sensory (S). The probability of being classified as AM, LOA, and S was 52%, 40.7%, and 6.9%, respectively. The AM class was distinct for increased likelihood of weight loss (92%), a shorter length of illness (<12 months) (66%), medical hospitalization (56%), and heart rate <60 beats per minute (31%). The LOA class was distinct for failure to gain weight (97%) and faltering growth (68%). The S class was distinct for avoiding certain foods (100%) and refusing to eat because of sensory characteristics of the food (100%). Using posterior probability assignments, a mixed group AM/LOA (n = 30; 14.5%) had characteristics of both AM and LOA classes. CONCLUSIONS: This LCA suggests that ARFID is a heterogeneous diagnosis with 3 distinct classes corresponding to the 3 subtypes described in the literature: AM, LOA, and S. The AM/LOA group had a mixed clinical presentation. Clinicians need to be aware of these different ARFID presentations because clinical and treatment needs will vary.