lisdexamfetamine-dimesylate and Binge-Eating-Disorder

Eating disorders (EDs) are a non-heterogeneous group of illnesses with significant physical and mental comorbidity and mortality associated with maladaptive coping. With the exception of lisdexamfetamine (Vyvanse) for binge eating disorder, no medications have been effective for the core symptoms of ED. ED requires a multimodal approach. Complementary and integrative medicine (CIM) can be helpful as an adjunct. The most promising CIM interventions are traditional yoga, virtual reality, eye movement desensitization and reprocessing, Music Therapy, and biofeedback/neurofeedback.

Topics: Acupuncture Therapy; Adolescent; Anorexia Nervosa; Art Therapy; Binge-Eating Disorder; Bulimia Nervosa; Feeding and Eating Disorders; Humans; Integrative Medicine; Lisdexamfetamine Dimesylate; Neurofeedback; Phototherapy; Spirituality; Virtual Reality; Yoga

Many individuals with eating disorders remain symptomatic after a course of psychotherapy and pharmacotherapy; therefore, the development of innovative treatments is essential.. To learn more about the current evidence for treating eating disorders with stimulants, we searched for original articles and reviews published up to April 29, 2021 in PubMed and MEDLINE using the following search terms: eating disorders, anorexia, bulimia, binge eating, stimulants, amphetamine, lisdexamfetamine, methylphenidate, and phentermine.. We propose that stimulant medications represent a novel avenue for future research based on the following: (a) the relationship between eating disorders and attention deficit/hyperactivity disorder (ADHD); (b) a neurobiological rationale; and (c) the current (but limited) evidence for stimulants as treatments for some eating disorders. Despite the possible benefits of such medications, there are also risks to consider such as medication misuse, adverse cardiovascular events, and reduction of appetite and pathological weight loss. With those risks in mind, we propose several directions for future research including: (a) randomized controlled trials to study stimulant treatment in those with bulimia nervosa (with guidance on strategies to mitigate risk); (b) examining stimulant treatment in conjunction with psychotherapy; (c) investigating the impact of stimulants on "loss of control" eating in youth with ADHD; and (d) exploring relevant neurobiological mechanisms. We also propose specific directions for exploring mediators and moderators in future clinical trials.. Although this line of investigation may be viewed as controversial by some in the field, we believe that the topic warrants careful consideration for future research.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Binge-Eating Disorder; Bulimia Nervosa; Central Nervous System Stimulants; Humans; Lisdexamfetamine Dimesylate; Randomized Controlled Trials as Topic

Binge-eating disorder (BED) is a common psychiatric condition with adverse psychological and metabolic consequences. Lisdexamfetamine (LDX) is the only approved BED drug treatment. New drugs to treat BED are urgently needed.. A comprehensive review of published psychopathological, pharmacological and clinical findings.. The evidence supports the hypothesis that BED is an impulse control disorder with similarities to ADHD, including responsiveness to catecholaminergic drugs, for example LDX and dasotraline. The target product profile (TPP) of the ideal BED drug combines treating the psychopathological drivers of the disorder with an independent weight-loss effect. Drugs with proven efficacy in BED have a common pharmacology; they potentiate central noradrenergic and dopaminergic neurotransmission. Because of the overlap between pharmacotherapy in attention deficit hyperactivity disorder (ADHD) and BED, drug-candidates from diverse pharmacological classes, which have already failed in ADHD would also be predicted to fail if tested in BED. The failure in BED trials of drugs with diverse pharmacological mechanisms indicates many possible avenues for drug discovery can probably be discounted.. (1) The efficacy of drugs for BED is dependent on reducing its core psychopathologies of impulsivity, compulsivity and perseveration and by increasing cognitive control of eating. (2) The analysis revealed a large number of pharmacological mechanisms are unlikely to be productive in the search for effective new BED drugs. (3) The most promising areas for new treatments for BED are drugs, which augment noradrenergic and dopaminergic neurotransmission and/or those which are effective in ADHD.

Topics: Attention Deficit Disorder with Hyperactivity; Binge-Eating Disorder; Humans; Lisdexamfetamine Dimesylate; Neuropharmacology; Weight Loss

Binge-Eating Disorder (BED) is the most common eating disorder in the United States. Lisdexamfetamine (LDX) was approved in 2015 by the FDA for treatment of BED and is the only drug approved for treating the disorder. There has been no systematic evaluation of the published clinical and preclinical evidence for efficacy of LDX in treating BED and the mechanisms responsible for the therapeutic action of the drug. To address this gap, we conducted a systematic review and meta-analysis using PRISMA guidelines. Fourteen clinical and seven preclinical articles were included. There is consistent evidence from clinical studies that LDX is an effective treatment for BED and that the drug reduces the BED symptoms and body weight of patients with the disorder. There is also consistent evidence from preclinical studies that LDX reduces food intake but no consistent evidence for a preferential reduction of palatable food consumption by the drug in rodents. The evidence on mechanism of action is more limited and suggests LDX may reduce binge eating by a combination of effects on appetite/satiety, reward, and cognitive processes, including attention and impulsivity/inhibition, that are mediated by catecholamine and serotonin mechanisms in the brain. There is an urgent need for adequately powered, placebo-controlled, behavioural and neuroimaging studies with LDX (recruiting patients and/or individuals with subclinical BED symptoms) to further investigate the mechanism of action of the drug in treating BED. An improved understanding of the behavioural and neurochemical mechanisms of action of LDX could lead to the development of improved drug therapies to treat BED.

Topics: Binge-Eating Disorder; Body Weight; Central Nervous System Stimulants; Humans; Impulsive Behavior; Lisdexamfetamine Dimesylate; Treatment Outcome

Emerging evidence supports a prevalence overlap between ADHD and bulimia nervosa/binge eating disorder. A high degree of ADHD symptoms may have a negative impact on recovery in eating disorders with loss of control over the eating, bingeing and purging. Screening/diagnostic evaluation of ADHD in all persons with loss of control over the eating/bingeing/purging eating disorders is required. For patients diagnosed with ADHD, treatment with stimulants can be tested and evaluated for both eating disorders and ADHD symptoms. While there is evidence that lisdexamfetamine reduces symptoms of binge eating disorder, rigorous studies evaluating ADHD treatment, including medication, for bulimia nervosa are still missing.

Topics: Attention Deficit Disorder with Hyperactivity; Binge-Eating Disorder; Bulimia Nervosa; Central Nervous System Stimulants; Feeding and Eating Disorders; Humans; Lisdexamfetamine Dimesylate

Eating disorders are serious psychiatric illnesses with high rates of morbidity and mortality. Effective treatments have traditionally included behaviorally focused therapies as well as several medication strategies. Recent years have seen promising developments in these treatments, including additional support for family-based approaches for children and adolescents, new evidence for "third-wave" behavioral therapies, and new support for the use of lisdexamfetamine for binge eating disorder and olanzapine for anorexia nervosa. Case study and pilot data are beginning to show limited support for neuromodulatory interventions targeting brain regions thought to be involved in eating disorders. This review summarizes treatment developments over the last several years and points towards future directions for the field.

Topics: Adolescent; Anorexia Nervosa; Behavior Therapy; Binge-Eating Disorder; Central Nervous System Stimulants; Child; Feeding and Eating Disorders; Humans; Lisdexamfetamine Dimesylate

Binge eating disorder (BED) is the most common eating disorder and was newly recognized in 2013 in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). BED is frequently associated with obesity and the metabolic syndrome, as well as with other psychiatric diseases, such as mood (49%), anxiety (41%), and substance use (22%) disorders. BED is highly prevalent and carries a high burden of mental and physical illness and disability. However, BED is frequently under-recognized and under-treated.. This paper reviews the main pharmacological treatments for BED and provides an expert opinion based on the available evidence and on the authors' clinical experience with patients affected by BED.. Several medications have proven to be effective for the treatment of BED, including Lisdexamfetamine (LDX), topiramate as well as anti-anxiety and antidepressant medications. To date, LDX is the only FDA approved medication for BED. Consequently, as a general rule, the use of an FDA approved medication should always be preferred. However, when in the presence of concomitant psychiatric conditions such as anxiety or depression, other medications that have proven efficacy in those comorbid conditions can be used and may contextually provide a benefit for BED.

Topics: Antidepressive Agents; Binge-Eating Disorder; Humans; Lisdexamfetamine Dimesylate; Obesity; Topiramate

Medications are a useful adjunct to nutritional and psychotherapeutic treatments for eating disorders. Antidepressants are commonly used to treat bulimia nervosa; high-dose fluoxetine is a standard approach, but many other antidepressants can be used. Binge eating disorder can be treated with antidepressants, with medications that diminish appetite, or with lisdexamfetamine. Anorexia nervosa does not generally respond to medications, although recent evidence supports modest weight restoration benefits from olanzapine.

Topics: Anorexia Nervosa; Antidepressive Agents, Second-Generation; Binge-Eating Disorder; Bulimia Nervosa; Central Nervous System Stimulants; Fluoxetine; Humans; Lisdexamfetamine Dimesylate

Anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder (BED) are the primary eating disorders (EDs). The only psychopharmacological treatment options for EDs with approval in some countries include fluoxetine for BN and lisdexamfetamine for BED. Given the high comorbidity and genetic correlations with other psychiatric disorders, it seems possible that novel medications for these conditions might also be effective in EDs. Areas covered: The current scientific literature has increased our understanding of how medication could be beneficial for patients with EDs on a molecular, functional and behavioral level. On the basis of theoretical considerations about neurotransmitters, hormones and neural circuits, possible drug targets for the treatment of EDs may include signal molecules and receptors of the self-regulatory system such as serotonin, norepinephrine and glutamate, the hedonic system including opioids, cannabinoids and dopamine and the hypothalamic homeostatic system including histamine, ghrelin, leptin, insulin, and glucagon-like peptide-1. Expert commentary: The latest research points to an involvement of both the immune and the metabolic systems in the pathophysiology of EDs and highlights the importance of the microbiome. Therefore, the next few years may unveil drug targets for EDs not just inside and outside of the brain, but possibly even outside of the human body.

Topics: Animals; Anorexia Nervosa; Binge-Eating Disorder; Bulimia Nervosa; Drug Design; Fluoxetine; Humans; Lisdexamfetamine Dimesylate; Microbiota; Molecular Targeted Therapy

Binge-eating disorder (BED) and night-eating syndrome (NES) are two forms of disordered eating associated with overweight and obesity. While these disorders also occur in nonobese persons, they seem to be associated with weight gain over time and higher risk of diabetes and other metabolic dysfunction. BED and NES are also associated with higher risk of psychopathology, including mood, anxiety, and sleep problems, than those of similar weight status without disordered eating. Treatments are available, including cognitive behavior therapy (CBT), interpersonal psychotherapy, lisdexamfetamine, and selective serotonin reuptake inhibitors (SSRIs) for BED; and CBT, SSRIs, progressive muscle relaxation, and bright light therapy for NES.

Topics: Antidepressive Agents; Anxiety Disorders; Binge-Eating Disorder; Clinical Trials as Topic; Comorbidity; Feeding Behavior; Female; Humans; Hydrocortisone; Lisdexamfetamine Dimesylate; Male; Metabolic Syndrome; Models, Psychological; Mood Disorders; Night Eating Syndrome; Obesity; Phototherapy; Prevalence; Psychotherapy; Relaxation Therapy; Selective Serotonin Reuptake Inhibitors; Serotonin; Sex Distribution; Sleep Wake Disorders; Stress, Psychological

Eating disorders represent a set of psychiatric illnesses with lifelong complications and high relapse rates. Individuals with eating disorders are often stigmatized and clinicians have a limited set of treatments options. Pharmacotherapy has the potential to improve long term compliance and patient commitment to treatment for eating disorders.. This review will examine the efficacy and safety profile of the FDA-approved medications for the treatment of bulimia nervosa (BN) and binge eating disorder (BED). This will include the evaluation of fluoxetine for BN, and lisdexamfetamine for BED. Safety information will be review from randomized control trials (RCT), open label trials, and case reports.. Fluoxetine for BN and lisdexamfetamine for BED are relatively safe and well-tolerated. Despite these properties, these two medications represent a limited arsenal for the pharmacological treatment of eating disorders. Thus, more research-based strategies are needed to develop safe, effective, and more targeted therapies for eating disorders.

Topics: Binge-Eating Disorder; Bulimia Nervosa; Fluoxetine; Humans; Lisdexamfetamine Dimesylate; Medication Adherence; Randomized Controlled Trials as Topic

The indications for lisdexamfetamine (LDX), a central nervous system stimulant, were recently expanded to include treatment of moderate to severe binge eating disorder (BED). Areas covered: This review aims to describe the chemistry and pharmacology of LDX, as well as the clinical trials investigating the efficacy and safety of this medication for the management of BED. Expert opinion: LDX is the first medication with United States Food and Drug Administration approval for the treatment of BED. It is an inactive prodrug of d-amphetamine that extends the half-life of d-amphetamine to allow for once daily dosing. D-amphetamine acts primarily to increase the concentrations of synaptic dopamine and norepinephrine. Metabolism of LDX to d-amphetamine occurs when peptidases in red blood cells cleave the covalent bond between d-amphetamine and l-lysine. D-amphetamine is then further metabolized by CYP2D6. Excretion is primarily through renal mechanisms. In clinical trials, LDX demonstrated statistical and clinical superiority over placebo in reducing binge eating days per week at doses of 50 and 70 mg daily. Commonly reported side effects of LDX include dry mouth, insomnia, weight loss, and headache, and its use should be avoided in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia or coronary artery disease. As with all CNS stimulants, risk of abuse needs to be assessed prior to prescribing.

Topics: Animals; Binge-Eating Disorder; Central Nervous System Stimulants; Drug Administration Schedule; Half-Life; Humans; Lisdexamfetamine Dimesylate; Methyldopa; Norepinephrine; Prodrugs; Severity of Illness Index

Psychological and pharmacological interventions for binge-eating disorder have previously demonstrated efficacy (compared with placebo or waitlist control); thus, we aimed to expand that literature with a review of comparative effectiveness. We searched MEDLINE,® EMBASE,® Cochrane Library, Academic OneFile, CINAHL® for binge-eating disorder treatment articles and selected studies using predetermined inclusion and exclusion criteria. Data were sufficient for network meta-analysis comparing two pharmacological interventions; psychological interventions were analysed qualitatively. In all, 28 treatment comparisons were included in this review: one pharmacological comparison (second-generation antidepressants versus lisdexamfetamine) and 26 psychological comparisons. Only three statistically significant differences emerged: lisdexamfetamine was better at increasing binge abstinence than second-generation antidepressants; therapist-led cognitive behavioural therapy was better at reducing binge-eating frequency than behavioural weight loss, but behavioural weight loss was better at reducing weight. The majority of other treatment comparisons revealed few significant differences between groups. Thus, patients and clinicians can choose from several effective treatment options. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Topics: Antidepressive Agents, Second-Generation; Binge-Eating Disorder; Cognitive Behavioral Therapy; Humans; Lisdexamfetamine Dimesylate; Randomized Controlled Trials as Topic; Treatment Outcome

Binge eating disorder (BED) is the most common eating disorder and an important public health problem. Lifetime prevalence of BED in the United States is 2.6%. In contrast to other eating disorders, the female to male ratio in BED is more balanced. BED co-occurs with a plethora of psychiatric disorders, most commonly mood and anxiety disorders. BED is also associated with obesity and its numerous complications. Although BED is similar in men and women in presentation and treatment outcomes, there are some key neurobiological differences that should be taken in consideration when personalizing treatment.

Topics: Binge-Eating Disorder; Comorbidity; Humans; Lisdexamfetamine Dimesylate; Mental Disorders; Psychotherapy; Sex Characteristics

Topics: Administration, Oral; Binge-Eating Disorder; Central Nervous System Stimulants; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Interactions; Humans; Lisdexamfetamine Dimesylate; Treatment Outcome

Binge-eating disorder (BED) is the most common eating disorder and is associated with poor physical and mental health outcomes. Psychological and behavioral interventions have been a mainstay of treatment for BED, but as understanding of this disorder has grown, pharmacologic agents have become promising treatment options for some patients. At this time, only one drug-the stimulant prodrug lisdexamfetamine-is approved for the treatment of BED. Numerous classes of medications including antidepressants, anticonvulsants, and antiobesity drugs have been explored as off-label treatments for BED with variable success. Although not all patients with BED may be suitable candidates for pharmacotherapy, all patients should be considered for and educated about pharmacologic treatment options.

Topics: Adult; Binge-Eating Disorder; Cognitive Behavioral Therapy; Combined Modality Therapy; Humans; Lisdexamfetamine Dimesylate; Obesity; Off-Label Use; Patient Education as Topic; Psychotropic Drugs; Randomized Controlled Trials as Topic; Treatment Outcome

The best treatment options for binge-eating disorder are unclear.. To summarize evidence about the benefits and harms of psychological and pharmacologic therapies for adults with binge-eating disorder.. English-language publications in EMBASE, the Cochrane Library, Academic OneFile, CINAHL, and ClinicalTrials.gov through 18 November 2015, and in MEDLINE through 12 May 2016.. 9 waitlist-controlled psychological trials and 25 placebo-controlled trials that evaluated pharmacologic (n = 19) or combination (n = 6) treatment. All were randomized trials with low or medium risk of bias.. 2 reviewers independently extracted trial data, assessed risk of bias, and graded strength of evidence.. Therapist-led cognitive behavioral therapy, lisdexamfetamine, and second-generation antidepressants (SGAs) decreased binge-eating frequency and increased binge-eating abstinence (relative risk, 4.95 [95% CI, 3.06 to 8.00], 2.61 [CI, 2.04 to 3.33], and 1.67 [CI, 1.24 to 2.26], respectively). Lisdexamfetamine (mean difference [MD], -6.50 [CI, -8.82 to -4.18]) and SGAs (MD, -3.84 [CI, -6.55 to -1.13]) reduced binge-eating-related obsessions and compulsions, and SGAs reduced symptoms of depression (MD, -1.97 [CI, -3.67 to -0.28]). Headache, gastrointestinal upset, sleep disturbance, and sympathetic nervous system arousal occurred more frequently with lisdexamfetamine than placebo (relative risk range, 1.63 to 4.28). Other forms of cognitive behavioral therapy and topiramate also increased abstinence and reduced binge-eating frequency and related psychopathology. Topiramate reduced weight and increased sympathetic nervous system arousal, and lisdexamfetamine reduced weight and appetite.. Most study participants were overweight or obese white women aged 20 to 40 years. Many treatments were examined only in single studies. Outcomes were measured inconsistently across trials and rarely assessed beyond end of treatment.. Cognitive behavioral therapy, lisdexamfetamine, SGAs, and topiramate reduced binge eating and related psychopathology, and lisdexamfetamine and topiramate reduced weight in adults with binge-eating disorder.. Agency for Healthcare Research and Quality.

Topics: Adult; Anti-Obesity Agents; Antidepressive Agents, Second-Generation; Binge-Eating Disorder; Central Nervous System Stimulants; Cognitive Behavioral Therapy; Fructose; Humans; Lisdexamfetamine Dimesylate; Topiramate

To describe the efficacy and safety of lisdexamfetamine dimesylate (LDX) for the treatment of binge eating disorder (BED).. The pivotal registration trials were accessed by querying http://www.ncbi.nlm.nih.gov/pubmed/, http://www.clinicaltrials.gov and http://www.clinicaltrialsregister.eu for the search terms 'lisdexamfetamine' and 'binge', and by also querying the Web of Science (Thomson Reuters) and Embase (Elsevier) commercial databases, and by asking the manufacturer for copies of posters presented at congresses. Product labelling provided additional information.. All available clinical reports of studies were identified.. Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports and other sources of information.. LDX is a central nervous system stimulant indicated for the treatment of moderate to severe BED. The recommended dose range is 50-70 mg/day. Approval for the treatment of BED was based on a clinical development programme that included an 11-week Phase II proof-of-concept, placebo-controlled study, testing fixed doses of LDX 30, 50 and 70 mg/day, and two 12-week Phase III placebo-controlled studies examining LDX 50-70 mg/day. Statistically significant reductions in binge eating days/week, the primary outcome measure, were observed for LDX doses of 50 and 70 mg/day, with effect sizes in the Phase III trials ranging from 0.83 to 0.97. The pooled NNT for response across all trials (as defined by a Clinical Global Impressions-Improvement score of 'very much improved' or 'much improved') for LDX vs. placebo was 3 (95% CI 3-4), and NNT for remission (as defined by 4-week cessation of binge eating) for LDX vs. placebo was 4 (95% CI 4-6). Reductions in weight ranged between 5.2% and 6.25% for LDX 50 or 70 mg/day. Discontinuation rates because of adverse events (AEs) were low; NNH for discontinuation because of an AE for LDX vs. placebo was 44 (95% CI 23-1971). The most commonly encountered AEs (incidence ≥ 10% and greater than the rate for placebo) were dry mouth, decreased appetite, insomnia and headache, with NNH values vs. placebo of 4 (95% CI 3-5), 11 (95% CI 8-17), 11 (95% CI 8-18) and 19 (95% CI 11-75), respectively.. LDX is the first pharmacological agent that has received regulatory approval for the treatment of BED. LDX 50 or 70 mg/day significantly reduced BED symptoms as measured by the number of binge eating days per week. Effect sizes were highly robust. Pending clinical trials include a long-term study examining maintenance of efficacy.

Topics: Antipsychotic Agents; Binge-Eating Disorder; Central Nervous System Stimulants; Clinical Trials as Topic; Dopamine Uptake Inhibitors; Humans; Lisdexamfetamine Dimesylate; Numbers Needed To Treat

Topics: Animals; Binge-Eating Disorder; Central Nervous System Stimulants; Humans; Lisdexamfetamine Dimesylate; Randomized Controlled Trials as Topic

Psychopharmacologic treatment is playing a greater role in the management of patients with eating disorders. In this paper, we review randomized, placebo-controlled trials (RCTs) conducted in anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and other eating disorders over the past 3 years. Fluoxetine remains the only medication approved for an eating disorder, that being BN. RCTs of antipsychotics in AN have had mixed results; the only agent with some evidence of efficacy is olanzapine. One study suggests dronabinol may induce weight gain in AN. Preliminary studies suggest lack of efficacy of alprazolam, dehydroepiandrosterone, or physiologic estrogen replacement in AN; erythromycin in BN; and the opioid antagonist ALKS-33 in BED. In BED with obesity or overweight, bupropion may cause mild weight loss without seizures, and chromium may improve glucose regulation. Also in BED, three RCTs suggest the stimulant prodrug lisdexamfetamine may reduce binge eating episodes, and another RCT suggests intranasal naloxone may decrease time spent binge eating. There remains a disconnection between the size of eating disorders as a public health problem and the lack of pharmacotherapy research of these conditions.

Topics: Administration, Intranasal; Anorexia Nervosa; Anti-Obesity Agents; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Baclofen; Binge-Eating Disorder; Bulimia Nervosa; Bupropion; Central Nervous System Stimulants; Chromium Compounds; Humans; Lisdexamfetamine Dimesylate; Morphinans; Naloxone; Narcotic Antagonists; Obesity; Randomized Controlled Trials as Topic

This Phase II, placebo-controlled, double-blind study investigated the efficacy, safety, and tolerability of nivasorexant in the treatment of adults with moderate to severe binge-eating disorder (BED).. Adults meeting the DSM-5 BED criteria were randomized 1:1 to placebo or nivasorexant (100 mg b.i.d.). The primary endpoint was the change from baseline to Week 12 in the number of binge eating (BE) days per week. Exploratory efficacy endpoints included cessation of BE in the last 4 weeks of treatment; and change from baseline to Week 12 in the number of BE episodes/week, the clinician global impression (CGI) of change, the Yale-Brown Obsessive-Compulsive Scale modified for BE, and the Hamilton rating scale for depression (HAMD-17). Key safety outcomes included treatment-emergent adverse events (TEAEs) and adverse events of special interest (i.e., somnolence and fatigue).. Sixty-eight participants were randomized to each treatment arm. The change from baseline to Week 12 in the number of BE days/week was the same for placebo (least squares mean [LSM]: -2.93) and nivasorexant (LSM: -2.93), with no difference between the treatment groups (LSM difference = .000 [95% confidence interval (CI): -.69, .69], p = .9992). Furthermore, no differences between treatment groups were observed in the exploratory efficacy endpoints. Nivasorexant was well tolerated; the overall incidence of TEAEs was balanced between treatment groups, and the frequency of somnolence and fatigue in the nivasorexant group were similar to placebo.. In this proof-of-concept study, 100 mg b.i.d. nivasorexant did not improve BE in adults with moderate to severe BED.. The results of this Phase II study indicate that nivasorexant was well tolerated in adults with BED, but did not improve binge eating behavior over placebo. Further research is needed to improve our understanding of the role of the orexin-1 receptor in BED.

Topics: Adult; Binge-Eating Disorder; Bulimia; Double-Blind Method; Humans; Lisdexamfetamine Dimesylate; Sleepiness; Treatment Outcome

Lisdexamfetamine dimesylate (LDX) is the only drug currently approved by the FDA for the treatment of Binge-Eating Disorder (BED), but little is known about the behavioural mechanisms that underpin the efficacy of LDX in treating BED. We examined the behavioural and neural effects of an acute dose of LDX (50 mg) in 22 women with binge-eating symptomatology using a randomised, crossover, double-blind, placebo-controlled experimental medicine design. LDX reduced self-reported appetite ratings and intake of both a pasta meal and a palatable cookie snack. LDX also decreased the eating rate of pasta but not of cookies and reduced self-reported liking ratings for pasta at the end of the meal. When viewing food pictures during an fMRI scan, LDX reduced activity bilaterally in the thalamus. LDX enhanced sustained attention and reduced impulsive responding in a continuous performance task but had no effect on emotional bias or working memory. These results suggest the observed effects of LDX on food intake (and by implication the efficacy of LDX in treating BED) may be related to the actions of the drug to enhance satiety, reduce food-related reward responding when full and/or increase cognitive control. Novel pharmacotherapies for BED might be most effective if they have a broad spectrum of effects on appetite, reward and cognition.

Topics: Attention Deficit Disorder with Hyperactivity; Binge-Eating Disorder; Biomedical Research; Central Nervous System Stimulants; Cognition; Dextroamphetamine; Double-Blind Method; Feeding Behavior; Female; Humans; Lisdexamfetamine Dimesylate; Reward; Treatment Outcome

This study examined Sheehan Disability Scale (SDS) performance in binge eating disorder (BED) and explored relationships between SDS and BED outcomes using data from three placebo-controlled lisdexamfetamine (LDX) studies (two short-term, dose-optimized studies and one double-blind, randomized-withdrawal study) in adults with Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR)-defined BED.. Analyses evaluated the psychometric properties of the SDS.. Confirmatory factor analysis supported a unidimensional total score in the short-term studies, with internal consistency (Cronbach's α) being 0.878. Total score exhibited good construct validity, with moderate and statistically significant correlations observed with Yale-Brown Obsessive Compulsive Scale modified for binge eating, Binge Eating Scale (BES), and EuroQol Group 5-Dimension 5-Level health status index scores. Known-groups validity analysis for the short-term studies demonstrated a significantly lower total score at end of study in participants considered "not ill" versus "ill" based on Clinical Global Impressions-Severity scores. SDS total score changes in the short-term studies were greater in responders than nonresponders based on binge eating abstinence or BES score. In the randomized-withdrawal study, SDS scores increased relative to baseline to a greater extent in participants randomized to placebo than LDX.. These analyses support the reliability, validity, and responsiveness to change of the SDS in individuals with BED.

Topics: Adult; Binge-Eating Disorder; Double-Blind Method; Humans; Lisdexamfetamine Dimesylate; Psychometrics; Reproducibility of Results

To determine whether physical dependence developed during lisdexamfetamine dimesylate treatment, as evidenced by presence of withdrawal symptoms after treatment cessation in adults with binge-eating disorder (BED) treated for up to 38 weeks.. Three studies enrolled adults with DSM-IV-TR-defined BED. In two 12-week, randomized, double-blind, placebo-controlled studies conducted from November 2012 to September 2013, participants were treated with placebo or dose-optimized lisdexamfetamine (50 or 70 mg). In a double-blind, placebo-controlled, randomized-withdrawal maintenance-of-efficacy study conducted from January 2014 to April 2015, participants categorized as responders after 12 weeks of open-label lisdexamfetamine (50 or 70 mg) were randomized to continued lisdexamfetamine or placebo for 26 weeks. The Amphetamine Cessation Symptom Assessment (ACSA), a 16-item self-report instrument (total score: 0-64), assessed withdrawal experiences. Mean ± SD ACSA scores and medians are presented for study completers.. In the short-term efficacy studies, mean ± SD ACSA aggregate scores for placebo and lisdexamfetamine (pooled data) were 7.0 ± 7.60 (n = 275) and 4.9 ± 6.41 (n = 271), respectively, on the day of the last dose at week 12/early termination (ET) and 4.8 ± 6.82 (n = 234) and 5.5 ± 7.50 (n = 221) on day 7 after the last dose. In the maintenance-of-efficacy study, mean ± SD ACSA aggregate scores for placebo and lisdexamfetamine were 4.8 ± 6.67 (n = 44) and 4.7 ± 7.78 (n = 85) on the day of the last dose at week 38/ET and 3.9 ± 5.75 (n = 37) and 5.2 ± 7.93 (n = 71) on day 7 after the last dose.. Study results suggest that abrupt lisdexamfetamine termination was not associated with amphetamine withdrawal symptoms at the exposure durations and therapeutic doses analyzed.. Clinicaltrials.gov identifiers: NCT01718483, NCT01718509, and NCT02009163.

Topics: Adult; Amphetamine-Related Disorders; Binge-Eating Disorder; Dopamine Uptake Inhibitors; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Substance Withdrawal Syndrome

The Yale-Brown Obsessive Compulsive Scale modified for Binge Eating (Y-BOCS-BE) assesses the obsessiveness of binge eating thoughts and compulsiveness of binge eating behaviors. The findings of this study extend previously published Y-BOCS-BE psychometric evaluations in adults with binge eating disorder (BED).. Data from three phase 3 lisdexamfetamine dimesylate studies in adults with BED (two randomized, double-blind, placebo-controlled short-term efficacy studies; one double-blind, placebo-controlled, randomized-withdrawal maintenance-of-efficacy study) were used. Psychometric evaluations included assessment of Y-BOCS-BE dimensionality, internal consistency, convergent validity, test?retest reliability, and determinations of clinically meaningful improvement using distribution- and anchor-based methods.. Domain specification analyses determined that the Y-BOCS-BE possessed a bifactor structure composed of a general binge eating severity domain and three subdomains (obsessive/compulsive, restraint, and control). Y-BOCS-BE internal consistency was maximized at week 12 (Cronbach?s ?, 0.95) and test?retest reliability was maximized in the 8-week retest interval from week 4 to week 12 across all no-change anchors (r?=?0.74?0.90). Likewise, convergent validity of the Y-BOCS-BE across all validators was maximized at week 12 (all r???0.66). Meaningful improvement for Y-BOCS-BE total scores was estimated to require score reductions of 12 to 17 points depending on the anchor.. The Y-BOCS-BE is a valuable tool for assessing BED symptoms. Maximization of Y-BOCS-BE reliability and validity at later study time points may be related to both treatment effects and improved insight into BED by participants during the study.

Topics: Adult; Binge-Eating Disorder; Central Nervous System Stimulants; Conduct Disorder; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Obsessive-Compulsive Disorder; Psychometrics; Quality of Life; Reproducibility of Results; Surveys and Questionnaires; Young Adult

To describe clinical characteristics and lisdexamfetamine dimesylate (LDX) treatment effects, based on gender and age, in adults diagnosed with moderate to severe binge eating disorder (BED).. Adults diagnosed with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision-defined BED of moderate to severe severity were randomized to 12 weeks of dose-optimized LDX (50 or 70 mg) or placebo in 2 studies (conducted from November 26, 2012, to September 25, 2013 [study 1] and from November 26, 2012, to September 20, 2013 [study 2]). These post hoc analyses pooled data by gender (men vs women) and age (< 40 vs ≥ 40 years) across studies; reported P values are nominal (descriptive and unadjusted).. The pooled safety analysis and full analysis sets included 745 and 724 participants, respectively (men, n = 105 and n = 97; women, n = 640 and n = 627; < 40 years, n = 398 and n = 386; ≥ 40 years, n = 347 and n = 338). Across subgroups, most participants had a body mass index ≥ 30 kg/m² (63.0%-75.5%). The mean baseline number of binge eating days/wk was comparable across gender (4.6-4.7) and age (4.6-4.9), as was Yale-Brown Obsessive Compulsive Scale modified for Binge Eating (Y-BOCS-BE) total score (gender, 20.42-21.70; age, 21.40-21.63). Least squares mean (95% CI) treatment differences nominally favored LDX in all subgroups (all P < .001) for changes from baseline in binge eating days/wk at weeks 11-12 and in Y-BOCS-BE total score at week 12; no interactions by gender or age were reported. Consistent with the overall profile of LDX, across all subgroups LDX was associated with higher frequencies of treatment-emergent adverse events than placebo and with increases in blood pressure and pulse.. Across gender and age, participants exhibited comparable clinical characteristics and responses to dose-optimized LDX compared with placebo.. ClinicalTrials.gov identifiers: NCT01718483 and NCT01718509.

Topics: Adolescent; Adult; Age Factors; Binge-Eating Disorder; Central Nervous System Stimulants; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Sex Factors; Treatment Outcome; Young Adult

We examined the effects of lisdexamfetamine (LDX) treatment on ventral prefrontal cortex (VPFC) and striatal brain activation in binge eating disorder (BED). We hypothesized that participants with BED have an abnormal brain response to palatable food cues, and that VPFC and striatal regions would respond to such cues after LDX treatment. Twenty women with moderate to severe BED consented to a 12-week, open-label trial of LDX with fMRI before and after treatment. Twenty obese women without BED served as healthy controls and received one fMRI. LDX was started at 30 mg/d with a target of 70 mg/d at week 12. At baseline, women with BED showed greater activation in ventrolateral prefrontal cortex (VLPFC), striatum, and globus pallidus to food pictures and brain activation to food pictures predicted clinical outcome at 12 weeks. After 12 weeks of LDX treatment, BED women showed significant reductions in globus pallidus activation. Reductions in ventromedial prefrontal cortex (VMPFC) and thalamus activation specifically correlated with binge eating and obsessive-compulsive symptom reductions, respectively. Results suggest that BED is characterized by an abnormally large VPFC-subcortical brain response to palatable foods that LDX treatment helps modify. Moreover, VPFC-subcortical activation at baseline is a potential biomarker of LDX response.

Topics: Adult; Binge-Eating Disorder; Brain; Corpus Striatum; Dopamine Uptake Inhibitors; Female; Humans; Lisdexamfetamine Dimesylate; Middle Aged; Nerve Net; Obesity; Pilot Projects; Prefrontal Cortex; Treatment Outcome

A 12-month, open-label extension study assessed the long-term safety and tolerability of lisdexamfetamine dimesylate (LDX) in adults with binge eating disorder (BED).. Adults (aged 18-55 y) with BED who completed 1 of 3 antecedent studies were enrolled in a 52-week, open-label extension study (dose optimization, 4 weeks [initial titration dose, 30-mg LDX; target doses, 50- or 70-mg LDX]; dose maintenance, 48 weeks). Safety evaluations included the occurrence of treatment-emergent adverse events (TEAEs), vital sign and weight assessments, and Columbia-Suicide Severity Rating Scale responses.. Of the 604 enrolled participants, 599 (521 women and 78 men) comprised the safety analysis set, and 369 completed the study. Mean (SD) LDX exposure was 284.3 (118.84) days; cumulative LDX exposure duration was 12 months or longer in 344 participants (57.4%). A total of 506 participants (84.5%) reported TEAEs (TEAEs leading to treatment discontinuation, 54 [9.0%]; severe TEAEs, 42 [7.0%]; serious TEAEs, 17 [2.8%]). Treatment-emergent adverse events reported in greater than or equal to 10% of participants were dry mouth (27.2%), headache (13.2%), insomnia (12.4%), and upper respiratory tract infection (11.4%). Mean (SD) changes from antecedent study baseline in systolic and diastolic blood pressure, pulse, and weight at week 52/early termination (n = 597) were 2.19 (11.043) and 1.77 (7.848) mm Hg, 6.58 (10.572) beats per minute, and -7.04 (7.534) kg, respectively. On the Columbia-Suicide Severity Rating Scale, there were 2 positive responses for any active suicidal ideations; there were no positive responses for suicidal behavior or completed suicides.. In this 12-month, open-label, extension study, the long-term safety and tolerability of LDX in adults with BED were generally consistent with its established profile for attention-deficit/hyperactivity disorder.

Topics: Adolescent; Adult; Binge-Eating Disorder; Dopamine Uptake Inhibitors; Drug Administration Schedule; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Outcome Assessment, Health Care; Young Adult

This study examined the time course of efficacy-related endpoints for lisdexamfetamine dimesylate (LDX) versus placebo in adults with protocol-defined moderate to severe binge-eating disorder (BED).. In two 12-week, double-blind, placebo-controlled studies, adults meeting DSM-IV-TR BED criteria were randomized 1:1 to receive placebo or dose-optimized LDX (50 or 70 mg). Analyses across visits used mixed-effects models for repeated measures (binge eating days/week, binge eating episodes/week, Yale-Brown Obsessive Compulsive Scale modified for Binge Eating [Y-BOCS-BE] scores, percentage body weight change) and chi-square tests (Clinical Global Impressions-Improvement [CGI-I; from the perspective of BED symptoms] scale dichotomized as improved or not improved). These analyses were not part of the prespecified testing strategy, so reported p values are nominal (unadjusted and descriptive only).. Least squares mean treatment differences for change from baseline in both studies favored LDX over placebo (all nominal p values <  .001) starting at Week 1 for binge eating days/week, binge-eating episodes/week, and percentage weight change and at the first posttreatment assessment (Week 4) for Y-BOCS-BE total and domain scores. On the CGI-I, more participants on LDX than placebo were categorized as improved starting at Week 1 in both studies (both nominal p values <  .001). Across these efficacy-related endpoints, the superiority of LDX over placebo was maintained at each posttreatment assessment in both studies (all nominal p values <  .001).. In adults with BED, LDX treatment appeared to be associated with improvement on efficacy measures as early as 1 week, which was maintained throughout the 12-week studies.

Topics: Adult; Binge-Eating Disorder; Central Nervous System Stimulants; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Treatment Outcome

The ability of pharmacotherapies to prevent relapse and maintain efficacy with long-term treatment in psychiatric conditions is important.. To assess lisdexamfetamine dimesylate maintenance of efficacy in adults with moderate to severe binge-eating disorder.. A multinational, phase 3, double-blind, placebo-controlled, randomized withdrawal study including 418 participants was conducted at 49 clinical research study sites from January 27, 2014, to April 8, 2015. Eligible adults met DSM-IV-R binge-eating disorder criteria and had moderate to severe binge eating disorder (≥3 binge-eating days per week for 14 days before open-label baseline; Clinical Global Impressions-Severity [CGI-S] scores ≥4 [moderate severity] at screening and open-label baseline). Following a 12-week, open-label phase (dose optimization, 4 weeks [lisdexamfetamine dimesylate, 50 or 70 mg]; dose maintenance, 8 weeks), lisdexamfetamine responders (≤1 binge eating day per week for 4 consecutive weeks and CGI-S scores ≤2 at week 12) were randomized to placebo or continued lisdexamfetamine during a 26-week, double-blind, randomized withdrawal phase.. Lisdexamfetamine administration.. The primary outcome variable, time to relapse (≥2 binge-eating days per week for 2 consecutive weeks and ≥2-point CGI-S score increases from randomized withdrawal baseline), was analyzed using a log-rank test (primary analysis); the analysis was stratified for dichotomized 4-week cessation status. Safety assessments included treatment-emergent adverse events.. Of the 418 participants enrolled in the open-label phase of the study, 411 (358 [87.1%] women; mean [SD] age, 38.3 [10.4] years) were included in the safety analysis set. Of 275 randomized lisdexamfetamine responders (placebo, n = 138; lisdexamfetamine, n = 137), the observed proportions of participants meeting relapse criteria were 3.7% (5 of 136) for lisdexamfetamine and 32.1% (42 of 131) for placebo. Lisdexamfetamine demonstrated superiority over placebo on the log-rank test (χ21, 40.37; P < .001) for time to relapse; the hazard ratio, based on a Cox proportional hazards model for lisdexamfetamine vs placebo, was 0.09 (95% CI, 0.04-0.23). The treatment-emergent adverse events observed were generally consistent with the known profile of lisdexamfetamine.. Risk of binge-eating relapse over 6 months was lower in participants continuing lisdexamfetamine than in those randomized to placebo. The hazard for relapse was lower with lisdexamfetamine than placebo.. clinicaltrials.gov Identifier: NCT02009163.

Topics: Adult; Binge-Eating Disorder; Central Nervous System Stimulants; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Prodrugs; Recurrence; Treatment Outcome; Young Adult

The efficacy and safety of lisdexamfetamine dimesylate (LDX) vs placebo in binge eating disorder (BED) was evaluated in two multicenter, double-blind, placebo-controlled trials. Adults (study 1, n=383; study 2, n=390) meeting DSM-IV-TR BED criteria were randomized (1:1) to placebo or LDX (50 or 70 mg/day) dose titration; optimized doses were maintained to the end of double-blind treatment (week 12/early termination). Change from baseline in binge eating days/week at weeks 11-12 (primary efficacy endpoint) was assessed with mixed-effects models for repeated measures. Secondary endpoints related to binge eating and medical parameters, safety, and treatment compliance were also assessed. Least squares mean (95% CI) treatment differences for change from baseline binge eating days/week at weeks 11-12 significantly favored LDX (study 1: -1.35 [-1.70, -1.01]; study 2: -1.66 [-2.04, -1.28]; both P<0.001). In both studies, treatment-emergent adverse events (TEAEs) reported by ⩾10% of LDX participants were dry mouth, insomnia, and headache. Serious TEAEs occurred in two (1.1%) placebo participants in each study and in three (1.6%) and one (0.6%) LDX participants in study 1 and study 2, respectively. Across studies, mean increases from baseline at week 12/early termination with LDX for pulse and systolic and diastolic blood pressure ranged from 4.41-6.31 b.p.m. and 0.2-1.45 and 1.06-1.83 mm Hg, respectively. LDX (50 and 70 mg/day) was superior to placebo in decreasing binge eating days/week from baseline and improving binge eating-related key secondary endpoints. Safety results appear consistent with the known safety profile of LDX.

Topics: Adult; Binge-Eating Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Treatment Outcome

In a published 11-week, placebo-controlled trial, 50 and 70 mg/d lisdexamfetamine dimesylate (LDX), but not 30 mg/d LDX, significantly reduced binge eating days (primary endpoint) in adults with binge eating disorder (BED). This report provides descriptions of LDX effects on secondary endpoints (Binge Eating Scale [BES]; Three-Factor Eating Questionnaire [TFEQ]; Yale-Brown Obsessive Compulsive Scale modified for Binge Eating [Y-BOCS-BE]; and the Barratt Impulsiveness Scale, version 11 [BIS-11]) from that study. Week 11 least squares mean treatment differences favoured all LDX doses over placebo on the BES (p ≤ 0.03), TFEQ Disinhibition and Hunger subscales (all p < 0.05), and Y-BOCS-BE total, obsessive, and compulsive scales (all p ≤ 0.02) and on BIS-11 total score at 70 mg/d LDX (p = 0.015) and the TFEQ Cognitive Restraint subscale at 30 and 70 mg/d LDX (both p < 0.05). These findings indicate that LDX decreased global binge eating severity and obsessive-compulsive and impulsive features of BED in addition to binge eating days.

Topics: Adolescent; Adult; Binge-Eating Disorder; Bulimia; Compulsive Behavior; Double-Blind Method; Feeding Behavior; Female; Humans; Impulsive Behavior; Lisdexamfetamine Dimesylate; Male; Middle Aged; Obsessive Behavior; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome; Young Adult

To evaluate lisdexamfetamine dimesylate (LDX) in the treatment of binge eating disorder (BED).. Fifty participants with BED received LDX (20-70 mg/day) (n = 25) or placebo (n = 25) for up to 12 weeks in a single-center, randomized, double-blind, and flexible-dose trial. The primary outcome measure was binge eating (BE) days/week.. In the primary longitudinal analysis, compared with placebo, LDX was not associated with a significantly greater rate of reduction in BE days/week, as well as BE episodes/week, and scores on the Clinical Global Impression-Severity or Yale-Brown Obsessive-Compulsive Scale modified for binge eating scales. It was, however, associated with significantly decreased weight, body mass index, and fasting triglyceride level. In the secondary last observation carried forward analyses, LDX was associated with statistically significant reductions in BE days/week, BE episodes/week, weight, and BMI, as well as a statistically significant greater level of categorical response and global improvement. The mean (standard deviation) LDX daily dose at endpoint evaluation was 59.6 (14.9) mg. One participant discontinued LDX for a serious adverse cardiovascular event, which resolved fully.. Lisdexamfetamine dimesylate may have clinical utility for BED but further studies of its efficacy, tolerability, and safety in this population are needed. Copyright © 2016 John Wiley & Sons, Ltd.

Topics: Adult; Binge-Eating Disorder; Body Mass Index; Body Weight; Central Nervous System Stimulants; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Treatment Outcome

Binge-eating disorder (BED), a public health problem associated with psychopathological symptoms and obesity and possibly with metabolic syndrome, lacks approved pharmacotherapies.. To examine the efficacy and safety of lisdexamfetamine dimesylate, a dextroamphetamine prodrug, to treat moderate to severe BED.. We performed a randomized, double-blind, parallel-group, forced dose titration, placebo-controlled clinical trial at 30 sites from May 10, 2011, through January 30, 2012. Safety and intention-to-treat analyses included 259 and 255 adults with BED, respectively.. Lisdexamfetamine dimesylate at dosages of 30, 50, or 70 mg/d or placebo were provided to study participants (1:1:1:1). Dosages were titrated across 3 weeks and maintained for 8 weeks. We followed up participants for a mean (SD) of 7 (2) days after the last dose.. We assessed the change in binge-eating (BE) behaviors measured as days per week (baseline to week 11) with a mixed-effects model using transformed log (BE days per week) + 1. Secondary measures included BE cessation for 4 weeks. Safety assessments included treatment-emergent adverse events, vital signs, and change in weight.. At week 11, log-transformed BE days per week decreased with the 50-mg/d (least squares [LS] mean [SE] change, -1.49 [0.066]; P = .008) and 70-mg/d (LS mean [SE] change, -1.57 [0.067]; P < .001) treatment groups but not the 30-mg/d treatment group (LS mean [SE] change, -1.24 [0.067]; P = .88) compared with the placebo group. Nontransformed mean (SD) days per week decreased for placebo and the 30-, 50-, and 70-mg/d treatment groups by -3.3 (2.04), -3.5 (1.95), -4.1 (1.52), and -4.1 (1.57), respectively. The percentage of participants achieving 4-week BE cessation was lower with the placebo group (21.3%) compared with the 50-mg/d (42.2% [P = .01]) and 70-mg/d (50.0% [P < .001]) treatment groups. The incidence of any treatment-emergent adverse events was 58.7% for the placebo group and 84.7% for the combined treatment group. In the treatment groups, 1.5% of participants had serious treatment-emergent adverse effects. Events with a frequency of at least 5% and changes in heart rate were generally consistent with the known safety profile. The mean (SD) change in body weight was -0.1 (3.09), -3.1 (3.64), -4.9 (4.43), -4.9 (3.93), and -4.3 (4.09) kg for the placebo group, the 30-, 50-, and 70-mg/d treatment groups, and the combined treatment groups, respectively (P < .001 for each dose vs placebo group comparison in post hoc analysis).. The 50- and 70-mg/d treatment groups demonstrated efficacy compared with the placebo group in decreased BE days, BE cessation, and global improvement. The safety profile was generally consistent with previous findings in adults with attention-deficit/hyperactivity disorder. Further investigation of lisdexamfetamine in BED is ongoing.. clinicaltrials.gov Identifier: NCT01291173.

Topics: Adult; Binge-Eating Disorder; Dextroamphetamine; Dopamine Uptake Inhibitors; Double-Blind Method; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Severity of Illness Index; Treatment Outcome

In the Canadian healthcare setting, there is limited understanding of the pathways to diagnosis and treatment for patients with binge eating disorder (BED).. This retrospective chart review examined the clinical characteristics, diagnostic pathways, and treatment history of adult patients diagnosed with BED.. Overall, 202 charts from 57 healthcare providers (HCPs) were reviewed. Most patients were women (69%) and white (78%). Mean ± SD patient age was 37 ± 12.1 years. Comorbidities identified in > 20% of patients included obesity (50%), anxiety (49%), depression and/or major depressive disorder (46%), and dyslipidemia (26%). Discussions regarding a diagnosis of BED were typically initiated more often by HCPs than patients. Most patients (64%) received a diagnosis of BED ≥ 3 years after symptom onset. A numerically greater percentage of patients received (past or current) nonpharmacotherapy than pharmacotherapy (84% vs. 67%). The mean ± SD number of binge eating episodes/week numerically decreased from pretreatment to follow-up with lisdexamfetamine (5.4 ± 2.8 vs. 1.7 ± 1.2), off-label pharmacotherapy (4.7 ± 3.9 vs. 2.0 ± 1.13), and nonpharmacotherapy (6.3 ± 4.8 vs. 3.5 ±  6.0) Across pharmacotherapies and nonpharmacotherapies, most patients reported improvement in symptoms of BED (84-97%) and in overall well-being (80-96%).. These findings highlight the importance of timely diagnosis and treatment of BED. Although HCPs are initiating discussions about BED, earlier identification of BED symptoms is required. Furthermore, these data indicate that pharmacologic and nonpharmacologic treatment for BED is associated with decreased binge eating and improvements in overall well-being.. IV, chart review.

Topics: Adult; Binge-Eating Disorder; Canada; Depressive Disorder, Major; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Retrospective Studies; Young Adult

This study examined the feasibility, safety, and potential efficacy of lisdexamfetamine (LDX) as a treatment for adults with bulimia nervosa (BN).. An open-label 8-week feasibility study was conducted in participants with BN. Enrollment rate, dropout rate, safety outcomes, and eating disorder symptom change were examined.. Eighteen of 23 participants completed the study per protocol. There was no participant-initiated dropout due to adverse drug reactions and no severe and unexpected adverse drug reactions. An average increase in heart rate of 12.1 beats/min was observed. There was a mean weight reduction of 2.1 kg and one participant was withdrawn for clinically significant weight loss. In the intent-to-treat sample, there were reductions in objective binge episodes and compensatory behaviors from Baseline to Post/End-of-Treatment (mean difference = -29.83, 95% confidence interval: -43.38 to -16.27; and mean difference = -33.78, 95% confidence interval: -48.74 to -18.82, respectively).. Results of this study indicate that a randomized controlled trial would be feasible with close monitoring of certain safety parameters (especially over a longer time period as long-term safety is unknown). However, the results should not be used as evidence for clinicians to prescribe LDX to individuals with BN before its efficacy and safety are properly tested.. NCT03397446.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Binge-Eating Disorder; Bulimia Nervosa; Central Nervous System Stimulants; Double-Blind Method; Feasibility Studies; Humans; Lisdexamfetamine Dimesylate; Treatment Outcome

Diets high in sugar or fat are associated with multiple health conditions, including binge eating disorder (BED). BED affects approximately 2% of the US adult population, and occurs more frequently in females. It is important to develop animal models of palatable food consumption and food seeking that may have relevance for BED and other conditions associated with excessive food intake. The catecholamine uptake blocker and d-amphetamine prodrug lisdexamfetamine is used to treat BED. The present experiments studied the effect of lisdexamfetamine on food intake and food-reinforced effort-based choice in female Wistar rats. Three groups of rats received different food exposure conditions in the home cage randomly spread over several weeks: a chocolate exposure group (CE; brief access of chocolate and additional lab chow, n = 15), a lab chow exposure (LChE) group given additional access to lab chow (n = 8), and a third group given empty food dishes (n = 7). In tests of food intake under non-restricted conditions, lisdexamfetamine (0.1875-1.5 mg/kg IP) significantly reduced intake of both chocolate and chow in the CE group. In the LChE group, there was a trend towards reduced chow intake induced by lisdexamfetamine. All rats were trained on a Progressive Ratio/chow feeding choice task, in which they had a choice between working for high carbohydrate chocolate flavored pellets by lever pressing vs. approaching and consuming a concurrently available lab chow. The LChE group and the empty food dish group were combined to create one control group (n = 15). There was a significant overall dose-related suppressive effect of lisdexamfetamine on lever pressing but no group difference, and no dose x group interaction. Lisdexamfetamine significantly decreased chow intake in the CE group, but not in the control group. In conclusion, lisdexamfetamine affected both food intake and food-reinforced operant behavior, with larger effects seen in the group exposed to chocolate.

Topics: Animals; Binge-Eating Disorder; Body Weight; Bulimia; Chocolate; Conditioning, Operant; Consummatory Behavior; Disease Models, Animal; Eating; Feeding Behavior; Female; Food Preferences; Lisdexamfetamine Dimesylate; Prodrugs; Rats; Rats, Wistar; Reward; Treatment Outcome

Topics: Binge-Eating Disorder; Female; Humans; Lisdexamfetamine Dimesylate; Male; Weight Loss

Lisdexamfetamine dimesylate (LDX) demonstrated efficacy in terms of reduced binge eating days per week in adults with binge eating disorder (BED) in two randomized clinical trials (RCTs).. The objective of this study was to evaluate the cost effectiveness of LDX versus no pharmacotherapy (NPT) in adults with BED from a USA healthcare payer's perspective.. A decision-analytic Markov cohort model was developed using 1-week cycles and a 52-week time horizon. Markov health states were defined based upon the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria of BED. Model parameter estimates were obtained from RCTs, a survey, and literature. The primary outcome was incremental cost-effectiveness ratio (ICER). The analysis assumed a 12-week course of treatment, based upon RCTs' treatment duration. One-way deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of the results.. Patients on LDX therapy gained 0.006 quality-adjusted life years (QALY) compared to patients on the NPT arm, while the average total cost was US$175 higher for LDX therapy. The estimated ICER for LDX compared with NPT was US$27,618 per QALY, which was shown to be cost effective given a willingness-to-pay threshold of US$50,000.. Treatment of BED with LDX showed increase in QALYs at an acceptable cost and is considered to be cost effective at the commonly used willingness-to-pay threshold in the USA. Based on the available evidence, the current model focused on short-term benefits only. There is a need to generate additional scientific evidence supporting long-term benefits of LDX therapy for BED.

Topics: Adult; Appetite Depressants; Binge-Eating Disorder; Cohort Studies; Cost-Benefit Analysis; Diagnostic and Statistical Manual of Mental Disorders; Humans; Lisdexamfetamine Dimesylate; Markov Chains; Models, Statistical; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Treatment Outcome; United States

Compulsive and perseverative behaviour in binge-eating, female, Wistar rats was investigated in a novel food reward/punished responding conflict model. Rats were trained to perform the conditioned avoidance response task. When proficient, the paradigm was altered to a food-associated conflict test by placing a chocolate-filled jar (empty jar for controls) in one compartment of the shuttle box. Entry into the compartment with the jar triggered the conditioning stimulus after a variable interval, and foot-shock 10 seconds later if the rat did not leave. Residence in the 'safe' compartment with no jar did not initiate trials or foot-shocks. By frequently entering the chocolate-paired compartment, binge-eating rats completed their 10 trials more quickly than non-binge controls. Binge-eating rats spent a greater percentage of the session in the chocolate-paired compartment, received foot-shocks more frequently, and tolerated foot-shocks for longer periods; all consistent with compulsive and perseverative behaviour. The d-amphetamine prodrug, lisdexamfetamine, has recently received US approval for the treatment of moderate to severe binge-eating disorder in adults. Lisdexamfetamine (0.8 mg/kg po [d-amphetamine base]) decreased chocolate consumption by binge-eating rats by 55% and markedly reduced compulsive and perseverative responding in the model. These findings complement clinical results showing lisdexamfetamine reduced compulsiveness scores in subjects with binge-eating disorder.

Topics: Animals; Binge-Eating Disorder; Bulimia; Compulsive Behavior; Conditioning, Operant; Feeding Behavior; Female; Lisdexamfetamine Dimesylate; Rats; Rats, Wistar; Reward