Lisdexamfetamine maintenance treatment for binge-eating disorder following successful treatments: randomized double-blind placebo-controlled trial.

BACKGROUND: Controlled research examining maintenance treatments for responders to acute interventions for binge-eating disorder (BED) is limited. This study tested efficacy of lisdexamfetamine (LDX) maintenance treatment amongst acute responders. METHODS: This prospective randomized double-blind placebo-controlled single-site trial, conducted March 2019 to September 2023, tested LDX as maintenance treatment for responders to acute treatments with LDX-alone or with cognitive-behavioral therapy (CBT + LDX) for BED with obesity. Sixty-one (83.6% women, mean age 44.3, mean BMI 36.1 kg/m2) acute responders were randomized to LDX (N = 32) or placebo (N = 29) for 12 weeks; 95.1% completed posttreatment assessments. Mixed-models and generalized-estimating equations comparing maintenance LDX v. placebo included main/interactive effects of acute (LDX or CBT + LDX) treatments to examine their predictive/moderating effects. RESULTS: Relapse rates (to diagnosis-level binge-eating frequency) following maintenance treatments were 10.0% (N = 3/30) for LDX and 17.9% (N = 5/28) for placebo; intention-to-treat binge-eating remission rates were 59.4% (N = 19/32) and 65.5% (N = 19/29), respectively. Maintenance LDX and placebo did not differ significantly in binge-eating but differed in weight-loss and eating-disorder psychopathology. Maintenance LDX was associated with significant weight-loss (-2.3%) whereas placebo had significant weight-gain (+2.2%); LDX and placebo differed significantly in weight-change throughout treatment and at posttreatment. Eating-disorder psychopathology remained unchanged with LDX but increased significantly with placebo. Acute treatments did not significantly predict/moderate maintenance-treatment outcomes. CONCLUSIONS: Adults with BED/obesity who respond to acute lisdexamfetamine treatment (regardless of additionally receiving CBT) had good maintenance during subsequent 12-weeks. Maintenance lisdexamfetamine, relative to placebo, did not provide further benefit for binge-eating but was associated with significantly better eating-disorder psychopathology outcomes and greater weight-loss.

Exploring Dietary Restraint as a Mediator of Behavioral and Cognitive-Behavioral Treatments on Outcomes for Patients With Binge-Eating Disorder With Obesity.

OBJECTIVE: To explore dietary-restraint as a mediator of binge eating and weight-loss outcomes within a randomized controlled trial comparing cognitive-behavioral therapy (CBT) and behavioral weight loss (BWL) for binge-eating disorder (BED) with obesity. METHODS: Ninety participants were randomly assigned to CBT or BWL and assessed by evaluators blinded to conditions at pretreatment, throughout-, and post-treatment (6 months). Three dietary-restraint measures (Eating Disorder Examination-Questionnaire [EDE-Q]-Restraint, Three-Factor Flexible-Restraint and Rigid-Restraint) were administered at pretreatment and after 2 months of treatment. Regression models examined whether changes at 2-months in the restraint scales mediated the effects of treatment (CBT versus BWL) on binge eating and weight-loss outcomes at post-treatment. RESULTS: CBT and BWL had similar binge-eating outcomes and similar changes in EDE-Q-restraint and flexible-restraint. BWL had greater 2-month increases in rigid-restraint and greater weight-loss at posttreatment than CBT, with results suggesting 2-month changes in rigid-restraint mediated the greater difference (>7 pounds) in weight-loss. The observed mediation effect of 2.92 suggests 39% of total treatment-effect on weight-loss was mediated through 2-month increases in rigid-restraint. DISCUSSION: This secondary analysis within a trial comparing CBT and BWL for BED suggests early-change in rigid-restraint has a mediating effect of BWL on weight-loss. Findings indicate that BWL improves binge eating and challenge views that dietary-restraint might exacerbate binge eating in BED with obesity. Findings require confirmation using hypothesis-testing in future trials. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00537758 ("Treatment for Obesity and Binge Eating Disorder").

Overvaluation of shape/weight at posttreatment predicts relapse at 12-month follow-up after successful behaviorally-based treatment of binge-eating disorder.

OBJECTIVE: To test whether overvaluation of shape/weight at the end of treatment prospectively predicts relapse at 12-month follow-up in patients with binge-eating disorder (BED). METHOD: Participants were 129 patients with BED who achieved abstinence from binge eating after 6 months of behaviorally-based weight-loss treatments in a clinical trial. Independent assessments conducted at posttreatment and at 12-month follow-up included the Eating Disorder Examination interview, the Beck Depression Inventory, and weight measurements. RESULTS: Of the 129 participants who attained abstinence from binge-eating at posttreatment, 46 (36%) were categorized with clinical overvaluation and 83 (64%) with subclinical overvaluation; 115 (89%) were re-assessed at 12-month follow-up. Participants with overvaluation at posttreatment were significantly more likely than those without to relapse at 12-months to non-abstinence from binge eating (54% vs. 28%) and to diagnosis-level binge-eating frequency of once weekly or greater (31% vs. 13%). Overvaluation at posttreatment predicted significantly higher eating-disorder psychopathology and depression scores at 12-month follow-up but were unrelated to weight and weight changes. Treatment groups did not have main or interaction effects; posttreatment overvaluation effects were observed regardless of treatment and of covarying for posttreatment value of dependent variables. CONCLUSIONS: Our findings suggest that overvaluation of shape/weight at the end of treatment predicts relapse and heightened eating-disorder psychopathology and depression scores 1 year later in patients who achieved abstinence from binge eating with behaviorally-based treatments. Overvaluation of shape/weight has significant clinical implications and warrants consideration as a diagnostic specifier for BED as it provides important prospective prognostic information. PUBLIC SIGNIFICANCE: Although effective treatments are available for binge-eating disorder, relapse following successful treatments is not uncommon. Almost nothing is known about what predicts relapse following treatments for binge-eating disorder. Our study found that overvaluation of shape/weight (i.e., body image concerns that overly impact self-worth) at posttreatment prospectively predicted relapse and higher eating-disorder psychopathology and depression 1 year later in patients who achieved binge-eating abstinence with behaviorally based treatments. CLINICALTRIALS: gov registration: NCT00829283. (Treatment of obesity and binge eating: Behavioral weight loss vs. stepped care.).

The children of parents who receive treatment for binge-eating disorder experience improvements in disordered eating.

OBJECTIVE: Parental eating disorders are associated with disordered eating behaviors and psychopathology in their children, but it is not known whether parent treatment for binge-eating disorder (BED) is associated with changes in child disordered eating behaviors and weight. Benefits or the "ripple" effect of treatment on untreated family members has been described in the obesity literature but not for BED. METHOD: Participants evaluated for two randomized clinical trials for BED were screened for whether they had children. 76 parents completed baseline assessments about a school-aged child; 62 were randomized to treatment, of whom 41 completed end-of-treatment assessments about their child's eating behaviors and weight (which were not targeted in the parent treatments). RESULTS: Analyses revealed a significant effect of time on children's binge-eating frequency and perceived weight category and a significant effect of parent medication on perceived weight category. Parental change in binge eating was associated significantly with changes in child secretive eating and food hoarding. Parental change in weight was not associated significantly with change in age/sex-normed child BMI percentile, but had some associations with parent-perceived child weight category. CONCLUSIONS: Parent changes during their treatment were associated with changes in their children. Future longitudinal research is needed to examine when disordered eating emerges and clarify critical intervention timing related to children's age and parental BED. Further clinical research is also needed to assess the effectiveness of treating disordered eating at the family level. PUBLIC SIGNIFICANCE: Prior cross-sectional work has found that parents with BED are more likely to have children who engage in binge eating compared to parents without eating-disorder psychopathology. This study was an initial exploration of change in children when parents received treatment in randomized controlled trials for BED. In this study, parent changes in binge eating were associated with reduced child secretive eating and food hoarding.

Trauma-Focused Cognitive-Behavioral Therapy for Adolescents Bullied Because of Weight: A Feasibility Study.

OBJECTIVE: The objective of this study was to test the feasibility and acceptability of a treatment for weight bullying. METHOD: Participants who had experienced weight-related bullying and were currently experiencing traumatic stress were recruited and enrolled in a feasibility trial of trauma-focused cognitive behavioral therapy combined with cognitive-behavioral therapy for eating disorders (TF-CBT-WB). Thirty adolescents (aged 11-17) were determined eligible and 28 began treatment (12 weeks). RESULTS: This study demonstrated the treatment feasibility and acceptability of TF-CBT-WB for adolescents with traumatic stress following weight-bullying experiences. Overall retention and treatment satisfaction were good. Within-subjects improvements were observed for intrusion symptoms of traumatic stress, global eating-disorder severity, overvaluation of weight/shape, dissatisfaction with weight/shape, dietary restraint, and depression. Clinically-meaningful improvements were attained for several patient outcomes. Clinically-meaningful decreases in functional impairment were attained by more than half of the participants. CONCLUSIONS: Overall, this clinical trial testing TF-CBT-WB for adolescents experiencing traumatic stress following weight-bulling experiences demonstrated therapy feasibility, acceptability, and initial evidence that clinically-meaningful improvements in patient outcomes were feasible. However, some patient outcomes thought to be more central to how the youth viewed the world failed to show improvements, suggesting that additional content related to these constructs might yield greater benefit. TRIAL REGISTRATION: This pilot study was registered on clinicaltrials.gov: NCT04587752, Cognitive-Behavioral Therapy for Weight-related Bullying.

Neural Responses to Auditory Food Stimuli Following Cognitive Behavioral Therapy for Binge-Eating Disorder.

OBJECTIVE: Adults with binge-eating disorder (BED), compared with those without BED, demonstrate higher blood-oxygen-level-dependent (BOLD) response to food cues in reward-related regions of the brain. It is not known whether cognitive behavioral therapy (CBT) can reverse this reward system hyperactivation. This randomized controlled trial (RCT) assessed changes in BOLD response to binge-eating cues following CBT versus wait-list control (WLC). METHOD: Females with BED (N = 40) were randomized to CBT or WLC. Participants completed assessments at baseline and 16 weeks including measures of eating and appetite and functional magnetic resonance imaging (fMRI) to measure BOLD response while listening to personalized scripts of binge-eating and neutral-relaxing cues. Data were analyzed using general linear models with mixed effects. RESULTS: Overall retention rate was 87.5%. CBT achieved significantly greater reductions in binge-eating episodes than WLC (mean ± standard error decline of 14.6 ± 2.7 vs. 5.7 ± 2.8 episodes in the past 28 days, respectively; p = 0.03). CBT and WLC did not differ significantly in changes in neural responses to binge-eating stimuli during the fMRI sessions. Compared with WLC, CBT had significantly greater improvements in reward-based eating drive, disinhibition, and hunger as assessed by questionnaires (ps < 0.05). DISCUSSION: CBT was effective in reducing binge eating, but, contrary to our hypothesis, CBT did not improve BOLD response to auditory binge-eating stimuli in reward regions of the brain. Further studies are needed to assess mechanisms underlying improvements with CBT for BED. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03604172.

Treatment of Eating Disorders: Current Status, Challenges, and Future Directions.

Specific psychological treatments have demonstrated efficacy and represent the first-line approaches recommended for anorexia nervosa, bulimia nervosa, and binge-eating disorder. Unfortunately, many patients, particularly those with anorexia nervosa, do not derive sufficient benefit from existing treatments, and better or alternative treatments for eating disorders are needed. Less progress has been made in developing pharmacologic options for eating disorders. No medications approved for anorexia nervosa exist, and only one each exists for bulimia nervosa and for binge-eating disorder; available data indicate that most patients fail to benefit from available medications. Longer and combined treatments have generally not enhanced outcomes. This review presents emerging findings from more complex and clinically relevant adaptive treatment designs, as they offer some clinical guidance and may serve as models for future enhanced treatment research.

Change in impulsivity is prospectively associated with treatment outcomes for binge-eating disorder.

BACKGROUND: Impulsivity may be a process underlying binge-eating disorder (BED) psychopathology and its treatment. This study examined change in impulsivity during cognitive-behavioral therapy (CBT) and/or pharmacological treatment for BED and associations with treatment outcomes. METHODS: In total, 108 patients with BED (NFEMALE = 84) in a randomized placebo-controlled clinical trial evaluating the efficacy of CBT and/or fluoxetine were assessed before treatment, monthly throughout treatment, at post-treatment (16 weeks), and at 12-month follow-up after completing treatment. Patients completed established measures of impulsivity, eating-disorder psychopathology, and depression, and were measured for height and weight [to calculate body mass index (BMI)] during repeated assessments by trained/monitored doctoral research-clinicians. Mixed-effects models using all available data examined changes in impulsivity and the association of rapid and overall changes in impulsivity on treatment outcomes. Exploratory analyses examined whether baseline impulsivity predicted/moderated outcomes. RESULTS: Impulsivity declined significantly throughout treatment and follow-up across treatment groups. Rapid change in impulsivity and overall change in impulsivity during treatment were significantly associated with reductions in eating-disorder psychopathology, depression scores, and BMI during treatment and at post-treatment. Overall change in impulsivity during treatment was associated with subsequent reductions in depression scores at 12-month follow-up. Baseline impulsivity did not moderate/predict eating-disorder outcomes or BMI but did predict change in depression scores. CONCLUSIONS: Rapid and overall reductions in impulsivity during treatment were associated with improvements in specific eating-disorder psychopathology and associated general outcomes. These effects were found for both CBT and pharmacological treatment for BED. Change in impulsivity may be an important process prospectively related to treatment outcome.

Machine learning v. traditional regression models predicting treatment outcomes for binge-eating disorder from a randomized controlled trial.

BACKGROUND: While effective treatments exist for binge-eating disorder (BED), prediction of treatment outcomes has proven difficult, and few reliable predictors have been identified. Machine learning is a promising method for improving the accuracy of difficult-to-predict outcomes. We compared the accuracy of traditional and machine-learning approaches for predicting BED treatment outcomes. METHODS: Participants were 191 adults with BED in a randomized controlled trial testing 6-month behavioral and stepped-care treatments. Outcomes, determined by independent assessors, were binge-eating (% reduction, abstinence), eating-disorder psychopathology, and weight loss (% loss, ⩾5% loss). Predictors included treatment condition, demographic information, and baseline clinical characteristics. Traditional models were logistic/linear regressions. Machine-learning models were elastic net regressions and random forests. Predictive accuracy was indicated by the area under receiver operator characteristic curve (AUC), root mean square error (RMSE), and R2. Confidence intervals were used to compare accuracy across models. RESULTS: Across outcomes, AUC ranged from very poor to fair (0.49-0.73) for logistic regressions, elastic nets, and random forests, with few significant differences across model types. RMSE was significantly lower for elastic nets and random forests v. linear regressions but R2 values were low (0.01-0.23). CONCLUSIONS: Different analytic approaches revealed some predictors of key treatment outcomes, but accuracy was limited. Machine-learning models with unbiased resampling methods provided a minimal advantage over traditional models in predictive accuracy for treatment outcomes.

Naltrexone plus bupropion combination medication maintenance treatment for binge-eating disorder following successful acute treatments: randomized double-blind placebo-controlled trial.

BACKGROUND: Certain treatments have demonstrated acute efficacy for binge-eating disorder (BED) but there is a dearth of controlled research examining pharmacotherapies as maintenance treatments for responders to initial interventions. This gap in the literature is particularly critical for pharmacotherapy for BED which is associated with relapse following discontinuation. The current study tested the efficacy of naltrexone/bupropion maintenance treatment amongst responders to acute treatments for BED. METHODS: Prospective randomized double-blind placebo-controlled single-site trial, conducted August 2017-December 2021, tested naltrexone/bupropion as maintenance treatment for responders to acute treatments with naltrexone/bupropion and/or behavioral weight-loss therapy for BED with comorbid obesity. Sixty-six patients (84.8% women, mean age 46.9, mean BMI 34.9 kg/m2) who responded to acute treatments were re-randomized to placebo (N = 34) or naltrexone/bupropion (N = 32) for 16 weeks; 86.3% completed posttreatment assessments. Mixed models and generalized estimating equations comparing maintenance treatments (naltrexone/bupropion v. placebo) included main and interactive effects of acute treatments. RESULTS: Intention-to-treat binge-eating remission rates following maintenance treatments were 50.0% (N = 17/34) for placebo and 68.8% (N = 22/32) for naltrexone/bupropion. Placebo following response to acute treatment with naltrexone/bupropion was associated with significantly decreased probability of binge-eating remission, increased binge-eating frequency, and no weight loss. Naltrexone/bupropion following response to acute treatment with naltrexone/bupropion was associated with good maintenance of binge-eating remission, low binge-eating frequency, and significant additional weight loss. CONCLUSIONS: Adult patients with BED with co-occurring obesity who have good responses to acute treatment with naltrexone/bupropion should be offered maintenance treatment with naltrexone/bupropion.