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.

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.

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.

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.

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.

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.

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.

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.

Numerous theories posit different core features to borderline personality disorder (BPD). Recent advances in network analysis provide a method of examining the relative centrality of BPD symptoms, as well as examine the replicability of findings across samples. Additionally, despite the increase in research supporting the validity of BPD in adolescents, clinicians are reluctant to diagnose BPD in adolescents. Establishing the replicability of the syndrome across adolescents and adults informs clinical practice and research. This study examined the stability of BPD symptom networks and centrality of symptoms across samples varying in age and clinical characteristics.

Cross-sectional analyses of BPD symptoms from semi-structured diagnostic interviews from the Collaborative Longitudinal Study of Personality Disorders (CLPS), the Methods to Improve Diagnostic Assessment and Service (MIDAS) study, and an adolescent clinical sample. Network attributes, including edge (partial association) strength and node (symptom) expected influence, were compared.

The three networks were largely similar and strongly correlated. Affective instability and identity disturbance emerged as relatively central symptoms across the three samples, and relationship difficulties across adult networks. Differences in network attributes were more evident between networks varying both in age and in BPD symptom severity level.

Findings highlight the relative importance of affective, identity, and relationship symptoms, consistent with several leading theories of BPD. The network structure of BPD symptoms appears generally replicable across multiple large samples including adolescents and adults, providing further support for the validity of the diagnosis across these developmental phases.

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.

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.

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).

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.

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.

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.

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.

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.

Psychiatric comorbidity is common in binge-eating disorder (BED) but effects on treatment outcomes are unknown. The current study aimed to determine whether psychiatric comorbidity predicted or moderated BED treatment outcomes.

In total, 636 adults with BED in randomized-controlled trials (RCTs) were assessed prior, throughout, and posttreatment by doctoral research-clinicians using reliably-administered semi-structured interviews, self-report measures, and measured weight. Data were aggregated from RCTs testing cognitive-behavioral therapy, behavioral weight loss, multi-modal (combined pharmacological plus cognitive-behavioral/behavioral), and/or control conditions. Intent-to-treat analyses (all available data) tested comorbidity (mood, anxiety, ‘any disorder’ separately) as predictors and moderators of outcomes. Mixed-effects models tested comorbidity effects on binge-eating frequency, global eating-disorder psychopathology, and weight. Generalized estimating equation models tested binge-eating remission (zero binge-eating episodes during the past month; missing data imputed as failure).

Overall, 41% of patients had current psychiatric comorbidity; 22% had mood and 23% had anxiety disorders. Psychiatric comorbidity did not significantly moderate the outcomes of specific treatments. Psychiatric comorbidity predicted worse eating-disorder psychopathology and higher binge-eating frequency across all treatments and timepoints. Patients with mood comorbidity were significantly less likely to remit than those without mood disorders (30% v. 41%). Psychiatric comorbidity neither predicted nor moderated weight loss.

Psychiatric comorbidity was associated with more severe BED psychopathology throughout treatment but did not moderate outcomes. Findings highlight the need to improve treatments for BED with psychiatric comorbidities but challenge perspectives that combining existing psychological and pharmacological interventions is warranted. Treatment research must identify more effective interventions for BED overall and for patients with comorbidities.

The nature and significance of impulse-control difficulties in binge-eating disorder (BED) are uncertain. Most emerging research has focused on food-specific rather than general impulsivity. The current study examines the clinical presentation of patients with BED categorized with and without clinical levels of general impulsivity.

A total of 343 consecutive treatment-seeking patients with BED were categorized as having BED with general impulsivity (GI+; N = 73) or BED without general impulsivity (GI−: N = 270) based on structured diagnostic and clinical interviews. The groups were compared on demographic, developmental, and psychological features, and on rates of psychiatric and personality comorbidity.

Individuals with BED and general impulsivity (GI+) reported greater severity of eating-disorder psychopathology, greater depressive symptoms, and greater rates of comorbidity than those without general impulsivity (GI−).

A subtype of individuals with BED and general impulsivity may signal a more severe presentation of BED characterized by heightened and broader psychopathology. Future work should investigate whether these impulse-control difficulties relate to treatment outcomes.

Eating-disorder severity indicators should theoretically index symptom intensity, impairment, and level of needed treatment. Two severity indicators for binge-eating disorder (BED) have been proposed (categories of binge-eating frequency and shape/weight overvaluation) but have mixed empirical support including modest clinical utility. This project uses structural equation model (SEM) trees – a form of exploratory data mining – to empirically determine the precise levels of binge-eating frequency and/or shape/weight overvaluation that most significantly differentiate BED severities.

Participants were 788 adults with BED enrolled in BED treatment studies. Participants completed interviews and self-report measures assessing eating-disorder and comorbid symptoms. SEM Tree analyses were performed by specifying an outcome model of BED severity and then recursively partitioning the outcome model into subgroups. Subgroups were split based on empirically determined values of binge-eating frequency and/or shape/weight overvaluation. SEM Forests also quantified which variable contributed more improvement in model fit.

SEM Tree analyses yielded five subgroups, presented in ascending order of severity: overvaluation <1.25, overvaluation = 1.25–2.74, overvaluation = 2.75–4.24, overvaluation ⩾4.25 with weekly binge-eating frequency <4.875, and overvaluation ⩾4.25 with weekly binge-eating frequency ⩾4.875. SEM Forest analyses revealed that splits that occurred on shape/weight overvaluation resulted in much more improvement in model fit than splits that occurred on binge-eating frequency.

Shape/weight overvaluation differentiated BED severity more strongly than binge-eating frequency. Findings indicate a nuanced potential BED severity indicator scheme, based on a combination of cognitive and behavioral eating-disorder symptoms. These results inform BED classification and may allow for the provision of more specific and need-matched treatment formulations.

The aim of this fixed-dose study was to evaluate the efficacy and safety of dasotraline in the treatment of patients with binge-eating disorder (BED).

Patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for BED were randomized to 12 weeks of double-blind treatment with fixed doses of dasotraline (4 and 6 mg/d), or placebo. The primary efficacy endpoint was change in number of binge-eating (BE) days per week at week 12. Secondary efficacy endpoints included week 12 change on the BE CGI-Severity Scale (BE-CGI-S) and the Yale-Brown Obsessive–Compulsive Scale Modified for BE (YBOCS-BE).

At week 12, treatment with dasotraline was associated with significant improvement in number of BE days per week on the dose of 6 mg/d (N = 162) vs placebo (N = 162; −3.47 vs −2.92; P = .0045), but not 4 mg/d (N = 161; −3.21). Improvement vs placebo was observed for dasotraline 6 and 4 mg/d, respectively, on the BE-CGI-S (effect size [ES]: 0.37 and 0.27) and on the YBOCS-BE total score (ES: 0.43 and 0.29). The most common adverse events on dasotraline were insomnia, dry mouth, headache, decreased appetite, nausea, and anxiety. Changes in blood pressure and pulse were minimal.

Treatment with dasotraline 6 mg/d (but not 4 mg/d) was associated with significantly greater reduction in BE days per week. Both doses of dasotraline were generally safe and well-tolerated and resulted in global improvement on the BE-CGI-S, as well as improvement in BE related obsessional thoughts and compulsive behaviors on the YBOCS-BE. These results confirm the findings of a previous flexible dose study.

Dasotraline is a long-acting dopamine/norepinephrine reuptake inhibitor with a PK profile characterized by slow absorption and a t½ of 47-77 hours, permitting once-daily dosing. In a previous flexible dose study, dasotraline demonstrated significant efficacy in the treatment of binge-eating disorder (BED). The aim of this confirmatory fixed-dose study was to evaluate efficacy and safety of dasotraline in the treatment of patients with BED.

Patients meeting DSM-5 criteria for BED were randomized to 12 weeks of double-blind treatment with dasotraline (4 mg/d or 6 mg/d), or placebo. The primary efficacy endpoint was change in number of binge-eating days per week at week 12. Secondary efficacy endpoints included changes at Week 12 on the Binge Eating Clinical Global Impression of Severity Scale (BE-CGI-S), the Yale-Brown Obsessive-Compulsive Scale Modified for Binge Eating (Y-BOCS-BE), and the proportion of patients with 100% cessation of binge-eating episodes during the final 4 weeks of treatment. Efficacy was assessed using an MMRM analysis (and a logistic regression model for cessation) with a pre-specified sequential testing procedure used to control overall type I error rate.

A total of 486 were in the ITT population (dasotraline 6 mg/d (N=162), 4 mg/d (N=161), or placebo (N=163). At week 12, treatment with dasotraline was associated with significant reduction in number of binge-eating days per week in the 6 mg/d group vs. placebo (-3.5 vs. -2.9; P=0.0045), but non-significant improvement in the 4 mg/d group vs. placebo (-3.2; P=0.12). Greater improvement was observed vs. placebo for dasotraline 6 mg/d and 4 mg/d, respectively, on the BE-CGI-S (P<0.01 and P<0.03) and the Y-BOC-BE (P<0.001 and P<0.02; all P-values were nominal, not adjusted for multiplicity). The proportion of patients who achieved 4-week cessation of binge-eating episodes was only significant for the dasotraline 6 mg in the completer population (P<0.05; post-hoc analysis) but was not significant for either dose of dasotraline vs. placebo when drop-outs were included in the analysis. The most common adverse events on dasotraline 6 mg/d and 4 mg/d were combined insomnia (early, middle, late), dry mouth, headache, decreased appetite, nausea, and anxiety. Changes in systolic and diastolic blood pressure were minimal. Mean baseline to endpoint changes in supine pulse rate on dasotraline 6 mg/d and 4 mg/d vs. placebo was +6.2 bpm and +4.8 vs. +0.2 bpm.

In this 12-week, placebo-controlled, fixed-dose study, treatment with dasotraline 6 mg/d was associated with a significant reduction in frequency of binge-eating days per week; efficacy was not demonstrated for the 4 mg dose. Treatment with both doses of dasotraline resulted in improvement in the Y-BOCS-BE and the BE-CGI-S. Dasotraline was safe and generally well-tolerated at both doses; most common adverse events were insomnia, dry mouth and headache.

Clinicaltrials.gov: NCT03107026

Supported by funding from Sunovion Pharmaceuticals Inc.

Mental disorders may emerge as the result of interactions between observable symptoms. Such interactions can be analyzed using network analysis. Several recent studies have used network analysis to examine eating disorders, indicating a core role of overvaluation of weight and shape. However, no studies to date have applied network models to binge-eating disorder (BED), the most prevalent eating disorder.

We constructed a cross-sectional graphical LASSO network in a sample of 788 individuals with BED. Symptoms were assessed using the Eating Disorders Examination Interview. We identified core symptoms of BED using expected influence centrality.

Overvaluation of shape emerged as the symptom with the highest centrality. Dissatisfaction with weight and overvaluation of weight also emerged as highly central symptoms. On the other hand, behavioral symptoms such as binge eating, eating in secret, and dietary restraint/restriction were less central. The network was stable, allowing for reliable interpretations (centrality stability coefficient = 0.74).

Overvaluation of shape and weight emerged as core symptoms of BED. This trend is consistent with past network analyses of eating disorders more broadly, as well as literature that suggests a primary role of shape and weight concerns in BED. Although DSM-5 diagnostic criteria for BED does not currently include a cognitive criterion related to body image or shape/weight overvaluation, our results provide support for including shape/weight overvaluation as a diagnostic specifier.