Efficacy, safety, and tolerability of nivasorexant in adults with binge-eating disorder: A randomized, Phase II proof of concept trial.

OBJECTIVE: 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). METHODS: 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). RESULTS: 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. DISCUSSION: In this proof-of-concept study, 100 mg b.i.d. nivasorexant did not improve BE in adults with moderate to severe BED. PUBLIC SIGNIFICANCE: 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.

The potential role of stimulants in treating eating disorders.

BACKGROUND: Many individuals with eating disorders remain symptomatic after a course of psychotherapy and pharmacotherapy; therefore, the development of innovative treatments is essential. METHOD: 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. RESULTS: 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. DISCUSSION: 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.

Metformin abuse: A novel and dangerous purging behavior in anorexia nervosa.

OBJECTIVE: To report a case of severe multisystem illness, near death and permanent kidney failure in a woman with a history of anorexia nervosa-binge purge type due to abuse of prescription metformin, an approved oral diabetes medication obtained surreptitiously via the internet. METHOD: Psychiatric and medical records were reviewed from the medical care of this patient. A literature search was also performed on prescription medication abuse as a mode of purging. DISCUSSION: Metformin abuse in a patient with an eating disorder as a purging behavior is a rarely reported, albeit very dangerous entity. Clinicians treating eating disorders should increasingly be aware of the potential abuse of prescription medications, unapproved for weight loss but which have weight loss, as a reported side effect. This is particularly important as the ability to obtain prescription medications via the internet, without a prescription, becomes more ubiquitous.

d-Fenfluramine and lorcaserin inhibit the binge-like feeding induced by µ-opioid receptor stimulation of the nucleus accumbens in the rat.

Multiple laboratories have shown that the stimulation of µ-opioid receptors in the nucleus accumbens (NAcc) powerfully increases intake of palatable and high-fat diets. Separate studies have demonstrated that serotonin agonists advance satiety processes, and several serotonin-targeting agents have been prescribed to promote weight loss. However, it is unknown if serotonin signaling can modulate the increased feeding elicited by activation of NAcc µ-opioid receptors. These experiments assessed the effects of systemic treatments with the serotonin agonists d-fenfluramine and lorcaserin on the binge-like feeding induced by µ-opioid receptor stimulation of the NAcc in Sprague-Dawley rats. Consistent with previous reports, stimulation of NAcc µ-opioid receptors (with 0.025 µg/0.5 µl/side DAMGO) significantly increased consumption of high-fat vegetable shortening, and systemic treatment with d-fenfluramine and lorcaserin dose-dependently decreased intake. Interestingly, d-fenfluramine and lorcaserin reversed the binge-like feeding observed following stimulation of NAcc µ-opioid receptors. Both serotonergic drugs also attenuated the increases of ambulation observed following administration of DAMGO in the NAcc. These data demonstrate that serotonergic anorectics, in addition to their known role in advancing satiety processes during normal feeding, can also inhibit the binge-like feeding that is elicited by activation of µ-opioid receptors within the ventral striatum.

Reward sensitivity in Parkinson's patients with binge eating.

BACKGROUND: Parkinson's disease (PD) patients who are treated with dopamine replacement therapy are at risk of developing impulse control disorders (ICDs) (such as gambling, binge eating, and others). According to recent evidence, compulsive reward seeking in ICDs may arise from an excessive attribution of incentive salience (or 'wanting') to rewards. OBJECTIVES: In this study, we tested this hypothesis in patients with PD who developed binge eating (BE). METHODS: Patients with BE, patients without BE, and healthy controls performed different experimental tasks assessing food liking and wanting. Participants first rated the degree of liking and wanting for different foods using explicit self-report measures. They then performed an affective priming task that measured participants' affective reactions towards foods (liking), and a grip-force task that assessed their motivation for food rewards (wanting). All participants also completed several questionnaires assessing impulsivity, reward sensitivity, anxiety and depression, and underwent a neuropsychological evaluation. RESULTS: Patients with BE displayed an altered liking for sweet foods compared to controls but not to patients without BE. Furthermore, this difference emerged only when implicit measures were used. Importantly, an increased wanting was not associated with binge eating even if wanting, but not liking scores significantly correlated with LED levodopa, confirming the hypothesis of a distinction between the two components of rewards. Lastly, binge eating was associated with depression and lower working memory scores. CONCLUSIONS: Take together these results suggest that binge eating in PD is associated with cognitive abnormalities, and to lesser extent affective abnormalities, but not with an increased incentive salience.

Nonmedical prescription stimulant use for suppressing appetite and controlling body weight is uniquely associated with more severe eating disorder symptomatology.

OBJECTIVE: Nonmedical prescription stimulant use (NPS; i.e., use without a prescription or in ways other than prescribed) to suppress appetite or control weight appears to be associated with eating disorder (ED) symptomatology among college students. However, it remains unknown if this relationship is motive-specific and uniquely related to ED symptomatology. This research examined whether engaging in NPS specifically for appetite/weight-related purposes is associated with ED symptomatology and a unique indicator of more severe symptomatology. METHOD: A nonclinical sample of college students (N = 668; 79% female) reported eating disorder symptoms via the Eating Pathology Symptoms Inventory and Eating Disorder Examination-Questionnaire, and lifetime history of NPS and corresponding motives. RESULTS: Binge eating, body dissatisfaction, negative attitudes towards obesity, restricting, purging, and cognitive restraint were reported more frequently by students who endorsed NPS for weight/appetite-related purposes than by those who used for other purposes or denied lifetime NPS. Additionally, NPS for appetite/weight-related purposes was uniquely associated with ED symptomatology after adjusting for gender, lifetime NPS, and past-month binge eating and purging. DISCUSSION: Engaging in NPS for appetite/weight-related purposes is a unique indicator of ED symptomatology, highlighting the need to query for this behavior among individuals with an ED. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:813-816).

Pharmacological modulation of the endocannabinoid signalling alters binge-type eating behaviour in female rats.

BACKGROUND AND PURPOSE: Binge eating disorder (BED) is characterized by excessive food intake during short periods of time. Recent evidence suggests that alterations in the endocannabinoid signalling could be involved in the pathophysiology of BED. In this study, we investigated whether pharmacological manipulation of endocannabinoid transmission may be effective in modulating the aberrant eating behaviour present in a validated rat model of BED. EXPERIMENTAL APPROACH: Binge-type eating was induced in female rats by providing limited access to an optional source of dietary fat (margarine). Rats were divided into three groups, all with ad libitum access to chow and water: control (C), with no access to margarine; low restriction (LR), with 2 h margarine access 7 days a week; high restriction (HR), with 2 h margarine access 3 days a week. KEY RESULTS: Compared with the LR group, the HR group consumed more margarine and this was accompanied by an increase in body weight. The cannabinoid CB1/CB2 receptor agonist Δ9-tetrahydrocannabinol significantly increased margarine intake selectively in LR rats, while the fatty acid amide hydrolase inhibitor URB597 showed no effect. The CB1 receptor inverse agonist/antagonist rimonabant dose-dependently reduced margarine intake in HR rats. Notably, in HR rats, chronic treatment with a low dose of rimonabant induced a selective long-lasting reduction in margarine intake that did not develop tolerance, and a significant and persistent reduction in body weight. CONCLUSIONS AND IMPLICATIONS: Chronic pharmacological blockade of CB1 receptors reduces binge eating behaviour in female rats and may prove effective in treating BED, with an associated significant reduction in body weight.

[Extensive interactions between eating and weight disorder, major depression, pain, and sarcoidosis - case 5/2012]. / Komplexe Wechselwirkung von Ess- und Gewichtsstörung, Depression, Schmerzstörung und Sarkoidose - Fall 5/2012.

HISTORY AND ADMISSION FINDINGS: We report on a 41-year-old female patient suffering from obesity, binge eating more than twice a week with loss of control, eating rapidly and feeling guilty after eating, dyspnoea and chronic pain in the whole body, especially in her arms, legs and in both ankles. Furthermore, subdued mood, loss of interest and pleasure, fatigue and impaired concentration could be recognized. In the past, weight increase had been observed when corticosteroids were given against exacerbations of sarcoidosis. INVESTIGATIONS: In the case of our patient, the beginning of sarcoidosis and increase of weight and pain correlated with augmentation of depression and psychosocial stress. Dysfunctional behavioral features and multiple interactions between diseases could be observed. DIAGNOSIS, TREATMENT AND COURSE: We diagnosed obesity, binge eating disorder, major depression, chronic pain disease with somatic and psychical components and sarcoidosis. The patient was treated in a multimodal therapy program including psychotherapy, pharmacotherapy and psychopharmacotherapy, nutritionist advice and therapeutic exercise. A weight loss of 7.9 kg (5.9 %), well-balanced diet, reduction of binge eating and of pain intensity, mood stabilization as well as perception and expression of emotions and coping strategies in chronic diseases were achieved. CONCLUSION: Interdisciplinary treatment of patients suffering from psychosomatic, somatic and mental diseases is crucial for a good outcome.

Effect of 2-hydroxyestradiol on binge intake in rats.

One conundrum of binge eating is that women are more likely to suffer from binge-related disorders, even though estradiol decreases food intake. 2-hydroxyestradiol (2OHE2), an estrogen metabolite, may account for the contradiction, due to possible interference with DA signaling. We hypothesized that 2OHE2 would enhance bingeing in a rodent model. Two cohorts (1 male, 1 female) of 34 non-food-deprived rats were separated into daily control (D) (received an optional source of dietary fat for 20 min every day) or bingeing (INT) groups (received fat intermittently, i.e. 20 min on Mon, Weds, Fri). During the 5-week binge induction period, shortening intakes escalated significantly faster in females than in males, such that males consumed significantly less fat/kg body mass than did females after 5 weeks. This result is consistent with the idea that biological differences contribute to sex differences in bingeing. Rats were then injected with 2OHE2 (1.0, 3.0, and 10.0 µg/kg intraperitoneally), vehicle, or 2-methoxyestradiol (2ME2) immediately prior to fat access. Fat intake was significantly stimulated by 2OHE2 only in the INT rats (p<0.03). Furthermore, this effect seemed to be more subtle in females than in males. Thus, 2OHE2 appears to exacerbate binge size. These data suggest a novel biological mechanism for sex differences in the risk of eating disorders.

Impulse control disorders in Parkinson disease: a cross-sectional study of 3090 patients.

CONTEXT: An association between dopamine-replacement therapies and impulse control disorders (ICDs) in Parkinson disease (PD) has been suggested in preliminary studies. OBJECTIVES: To ascertain point prevalence estimates of 4 ICDs in PD and examine their associations with dopamine-replacement therapies and other clinical characteristics. DESIGN: Cross-sectional study using an a priori established sampling procedure for subject recruitment and raters blinded to PD medication status. PATIENTS: Three thousand ninety patients with treated idiopathic PD receiving routine clinical care at 46 movement disorder centers in the United States and Canada. MAIN OUTCOME MEASURES: The Massachusetts Gambling Screen score for current problem/pathological gambling, the Minnesota Impulsive Disorders Interview score for compulsive sexual behavior and buying, and Diagnostic and Statistical Manual of Mental Disorders research criteria for binge-eating disorder. RESULTS: An ICD was identified in 13.6% of patients (gambling in 5.0%, compulsive sexual behavior in 3.5%, compulsive buying in 5.7%, and binge-eating disorder in 4.3%), and 3.9% had 2 or more ICDs. Impulse control disorders were more common in patients treated with a dopamine agonist than in patients not taking a dopamine agonist (17.1% vs 6.9%; odds ratio [OR], 2.72; 95% confidence interval [CI], 2.08-3.54; P < .001). Impulse control disorder frequency was similar for pramipexole and ropinirole (17.7% vs 15.5%; OR, 1.22; 95% CI, 0.94-1.57; P = .14). Additional variables independently associated with ICDs were levodopa use, living in the United States, younger age, being unmarried, current cigarette smoking, and a family history of gambling problems. CONCLUSIONS: Dopamine agonist treatment in PD is associated with 2- to 3.5-fold increased odds of having an ICD. This association represents a drug class relationship across ICDs. The association of other demographic and clinical variables with ICDs suggests a complex relationship that requires additional investigation to optimize prevention and treatment strategies. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00617019.

Compulsive behaviors in patients with Parkinson's disease.

OBJECTIVE: Several impulse control disorders (ICDs) may develop in patients with Parkinson's disease (PD). We aimed to identify the frequency and phenomenology of ICDs in our PD population. METHODS: Among 554 PD patients examined in a 3-year period, we identified 33 patients with ICDs. Disease duration, gender, and age-matched 65 PD patients without ICDs were selected as controls. We noted age-at-onset, duration, and severity of PD, dose and types of dopaminergic treatment, as well as presence of motor complications in both groups. RESULTS: Of 554 patients, 33 (5.9%) had ICDs, of whom, 27 were men (81%), mean age-at onset of PD was 48 and disease duration 8 years. While all patients with ICDs were on dopamine agonist drugs (+/- an adjuvant), all but 2 of controls were on dopamine agonists. Punding was the most frequent behavioral problem (57%), 42% exhibited aggressive hypersexuality, 27% compulsive eating, 24% pathologic shopping, and 21% compulsive medication. Severity of PD, presence of l-Dopa-induced motor complications, l-Dopa equivalent doses of dopamine agonists administered were not statistically different between 2 groups. CONCLUSIONS: In this study performed in a tertiary clinic for movement disorders in Turkey, several ICDs occurred in a small group of PD patients, mostly in men with young-onset disease, similar to the previous reported series. However, in contrast to the Western series, the number of gamblers was quite low because gambling is illegal in our country. We did not find any association between ICDs and severity of PD as well as doses of dopaminergic agents.