Effect of non-invasive spinal cord stimulation in unmedicated adults with major depressive disorder: a pilot randomized controlled trial and induced current flow pattern.

Converging theoretical frameworks suggest a role and a therapeutic potential for spinal interoceptive pathways in major depressive disorder (MDD). Here, we aimed to evaluate the antidepressant effects and tolerability of transcutaneous spinal direct current stimulation (tsDCS) in MDD. This was a double-blind, randomized, sham-controlled, parallel group, pilot clinical trial in unmedicated adults with moderate MDD. Twenty participants were randomly allocated (1:1 ratio) to receive "active" 2.5 mA or "sham" anodal tsDCS sessions with a thoracic (anode; T10)/right shoulder (cathode) electrode montage 3 times/week for 8 weeks. Change in depression severity (MADRS) scores (prespecified primary outcome) and secondary clinical outcomes were analyzed with ANOVA models. An E-Field model was generated using the active tsDCS parameters. Compared to sham (n = 9), the active tsDCS group (n = 10) showed a greater baseline to endpoint decrease in MADRS score with a large effect size (-14.6 ± 2.5 vs. -21.7 ± 2.3, p = 0.040, d = 0.86). Additionally, compared to sham, active tsDCS induced a greater decrease in MADRS "reported sadness" item (-1.8 ± 0.4 vs. -3.2 ± 0.4, p = 0.012), and a greater cumulative decrease in pre/post tsDCS session diastolic blood pressure change from baseline to endpoint (group difference: 7.9 ± 3.7 mmHg, p = 0.039). Statistical trends in the same direction were observed for MADRS "pessimistic thoughts" item and week-8 CGI-I scores. No group differences were observed in adverse events (AEs) and no serious AEs occurred. The current flow simulation showed electric field at strength within the neuromodulation range (max. ~0.45 V/m) reaching the thoracic spinal gray matter. The results from this pilot study suggest that tsDCS is feasible, well-tolerated, and shows therapeutic potential in MDD. This work also provides the initial framework for the cautious exploration of non-invasive spinal cord neuromodulation in the context of mental health research and therapeutics. The underlying mechanisms warrant further investigation. Clinicaltrials.gov registration: NCT03433339 URL: https://clinicaltrials.gov/ct2/show/NCT03433339 .

Liraglutide in Obese or Overweight Individuals With Stable Bipolar Disorder.

BACKGROUND: Obesity is common among persons with bipolar disorder (BD). Liraglutide 3.0 mg/d subcutaneous injection is indicated for chronic weight management and associated with minimal adverse neuropsychiatric effects. This study evaluated whether liraglutide 3 mg/d reduced body weight, improved metabolic factors and eating psychopathology, and was safe and well tolerated in persons with stable BD who were obese (body mass index [BMI] >30 kg/m 2 ) or overweight (BMI ≥27 kg/m 2 ) with at least one weight-related comorbidity. METHODS: This was a 40-week, randomized (1:1 ratio), placebo-controlled, double-blind, parallel-group, 2-arm clinical trial of liraglutide targeted to 3.0 mg/d (in combination with a reduced-calorie diet and increased physical activity) in 60 participants with stable BD who were obese or overweight. Primary outcome was percent change in body weight from baseline to study end. Secondary outcomes included percentage of patients who lost ≥5% of baseline body weight, and changes in metabolic variables and measures of eating psychopathology. RESULTS: There were no significant baseline differences between the 29 liraglutide recipients and the 31 placebo recipients, except that liraglutide recipients had higher levels of binge eating and lower levels of high-density lipoprotein cholesterol. Compared with placebo, liraglutide was associated with significantly greater reductions in percent change in body weight, percentage of participants who lost at least 5% of body weight, and reductions in weight, BMI, hemoglobin A 1c levels, binge eating, and hunger. Liraglutide was well tolerated. CONCLUSIONS: Liraglutide 3 mg/d may be efficacious and safe for weight loss in individuals with stable BD and obesity or overweight. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03158805).

Lisdexamfetamine dimesylate in binge eating disorder: a placebo controlled trial.

OBJECTIVE: To evaluate lisdexamfetamine dimesylate (LDX) in the treatment of binge eating disorder (BED). METHOD: 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. RESULTS: 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. CONCLUSION: 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.

Sex differences in the risk of rapid cycling and other indicators of adverse illness course in patients with bipolar I and II disorder.

OBJECTIVES: To examine the independent effects of sex on the risk of rapid cycling and other indicators of adverse illness course in patients with bipolar I disorder (BP-I) or bipolar II disorder (BP-II). METHODS: We analyzed data from the first 1,225 patients enrolled in the Mayo Clinic Individualized Medicine Biobank for Bipolar Disorder. Demographic and clinical variables were ascertained using standardized questionnaires; height and weight were assessed to determine body mass index (BMI). Rates of rapid cycling, cycle acceleration, and increased severity of mood episodes over time were compared between women and men overall and within subgroups defined by bipolar disorder subtype (BP-I or BP-II). Multiple logistic regression analysis was used to assess the independent effect of sex on the risk of these indicators of adverse illness course. RESULTS: Women had significantly higher rates of rapid cycling than men. Overall rates of rapid cycling were higher in patients with BP-II than BP-I; and sex differences in the rate of rapid cycling were more pronounced in patients with BP-II than BP-I, although the power to detect statistically significant differences was reduced due to the lower sample size of subjects with BP-II. Female sex was a significant predictor of rapid cycling, cycle acceleration, and increased severity of mood episodes over time after adjusting for age, bipolar disorder subtype, BMI, having any comorbid psychiatric disorder, and current antidepressant use. CONCLUSIONS: Female sex was associated with significantly higher risk of rapid cycling, cycle acceleration, and increased severity of mood episodes over time in a sample of 1,225 patients with bipolar disorders.

Psychopharmacologic treatment of eating disorders: emerging findings.

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.

Overview of the treatment of binge eating disorder.

We performed a qualitative review of treatment studies of binge eating disorder (BED), focusing on randomized clinical trials (RCTs). Limited effectiveness has been demonstrated for self-help strategies, and substantial effectiveness has been shown for cognitive behavioral therapy (CBT) and interpersonal therapy (IPT). CBT and IPT may each be more effective than behavior weight loss therapy (BWLT) for reducing binge eating over the long term. The stimulant pro-drug lisdexamfetamine dimesylate (LDX) is the only drug approved by the FDA for the treatment of BED in adults based on 2 pivotal RCTs. Topiramate also decreases binge eating behavior, but its use is limited by its adverse event profile. Antidepressants may be modestly effective over the short term for reducing binge eating behavior and comorbid depressive symptoms, but are not associated with clinically significant weight loss. A RCT presented in abstract form suggests that intranasal naloxone may decrease time spent binge eating. There is no RCT of obesity surgery in BED, but many patients with BED seek and receive such surgery. While some studies suggest patients with BED and obesity do just as well as patients with obesity alone, other studies suggest that patients with BED have more post-operative complications, less weight loss, and more weight regain. This evidence suggests that patients with BED would benefit from receiving highly individualized treatment.

Placebo cessation in binge eating disorder: effect on anthropometric, cardiovascular, and metabolic variables.

OBJECTIVE: The aim of this study was to evaluate the effects of cessation of binge eating in response to placebo treatment in binge eating disorder (BED) on anthropometric, cardiovascular, and metabolic variables. METHOD: We pooled participant-level data from 10 randomized, double-blind, placebo-controlled trials of medication for BED. We then compared patients who stopped binge eating with those who did not on changes in weight, body mass index (BMI), systolic and diastolic blood pressure, pulse, and fasting lipids and glucose. RESULT: Of 234 participants receiving placebo, 60 (26%) attained cessation from binge eating. Patients attaining cessation showed modestly decreased diastolic blood pressure compared with patients who continued to binge eat. Weight and BMI remained stable in patients who stopped binge eating, but increased somewhat in those who continued to binge eat. DISCUSSION: Patients who stopped binge eating with placebo had greater reductions in diastolic blood pressure and gained less weight than patients who continued to binge eat. Self-report of eating pathology in BED may predict physiologic variables. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.

Clinical characterization of patients with bipolar disorder and a history of asthma: An exploratory study.

INTRODUCTION: Bipolar disorder (BD) and asthma are leading causes of morbidity in the US and frequently co-occur. OBJECTIVES: We evaluated the clinical features and comorbidities of patients with BD and a history of asthma. METHODS: In a cross-sectional analysis from the Mayo Clinic Bipolar Biobank, we explored the clinical characteristics of the BD and an asthma phenotype and fitted a multivariable regression model to identify risk factors for asthma. RESULTS: A total of 721 individuals with BD were included. From these, 140 (19%) had a history of asthma. In a multivariable model only sex and evening chronotype were significant predictors of asthma with the odds ratios and 95% confidence intervals being 1.65 (1.00, 2.72; p=0.05) and 1.99 (1.25, 3.17; p < 0.01), respectively. Individuals with asthma had higher odds of having other medical comorbidities after adjusting for age, sex, and site including hypertension (OR = 2.29 (95% CI 1.42, 3.71); p < 0.01), fibromyalgia (2.29 (1.16, 4.51); p=0.02), obstructive sleep apnea (2.03 (1.18, 3.50); p=0.01), migraine (1.98 (1.31, 3.00); p < 0.01), osteoarthritis (2.08 (1.20, 3.61); p < 0.01), and COPD (2.80 (1.14, 6.84); p=0.02). Finally, individuals currently on lithium were less likely to have a history of asthma (0.48 (0.32, 0.71); p < 0.01). CONCLUSION: A history of asthma is common among patients with BD and is associated with being female and having an evening chronotype, as well as with increased odds of having other medical comorbidities. A lower likelihood of a history of asthma among those currently on lithium is an intriguing finding with potential clinical implications that warrants further study.

A randomized, placebo-controlled study of zonisamide to prevent olanzapine-associated weight gain.

Weight gain is commonly observed with olanzapine treatment. Zonisamide is an antiepileptic drug associated with weight loss. This study examined the effectiveness of zonisamide in preventing weight gain in 42 patients beginning olanzapine for bipolar disorder or schizophrenia. Each patient had a body mass index of 22 mg/kg or greater and was randomized to taking olanzapine with either zonisamide (n = 20) or placebo (n = 22) for 16 weeks. The primary outcome measure was change in body weight in kilograms from baseline. In the primary analysis using longitudinal regression, patients who received zonisamide had a significantly slower rate of weight gain and increase in body mass index than those who received placebo. The patients treated with zonisamide gained a mean (SD) of 0.9 (3.3) kg, whereas those treated with placebo gained a mean (SD) of 5.0 (5.5) kg; P = 0.01. None of the patients in the zonisamide group, compared with 7 patients (33%) in the placebo group, gained 7% of body weight or greater from baseline (Fisher exact test, P = 0.009). The zonisamide group, however, reported significantly more cognitive impairment as an adverse event than the placebo group (25% vs 0, respectively; P = 0.02). Zonisamide was effective for mitigating weight gain in patients with bipolar disorder or schizophrenia initiating treatment with olanzapine but was associated with cognitive impairment as an adverse event.

Binge eating disorder in elderly individuals.

OBJECTIVE: To preliminarily describe the clinical features of elderly individuals with binge eating disorder (BED). METHOD: The psychological and general medical characteristics of 20 elderly individuals (65 years of age and older) who met DSM-IV-TR for BED were systematically evaluated. RESULTS: Elderly individuals with BED reported an average (SD) of 4.5 (2.9) binge eating episodes per week. Weight and shape concerns were of significant importance for participants' schema for self-evaluation. Mood disorders were the most frequent co-occurring psychiatric disorders. Despite having a mean (SD) body mass index of 36.4 (10.6), most participants presented in good general medical health. DISCUSSION: Regarding eating pathology, psychiatric comorbidity, and associated obesity, BED in this group of elderly individuals was similar to BED in younger adults. However, other than presenting with obesity, the participants reported good general medical health. BED might be a problem for a subset of physically healthy elderly individuals. Studies further examining psychiatric and medical presentation, including metabolic profile, of elderly individuals with BED may be warranted.

Duloxetine in the treatment of binge eating disorder with depressive disorders: a placebo-controlled trial.

OBJECTIVE: This study evaluated duloxetine in the treatment of binge eating disorder (BED) with comorbid current depressive disorders. METHOD: In this 12-week, double-blind, placebo-controlled trial, 40 patients with Diagnostic and Statistical Manual of Mental Disorders-IV-TR BED and a comorbid current depressive disorder received duloxetine (N = 20) or placebo (N = 20). The primary outcome measure was weekly binge eating day frequency. RESULTS: In the primary analysis, duloxetine (mean 78.7 mg/day) was superior to placebo in reducing weekly frequency of binge eating days (p = .04), binge eating episodes (p = .02), weight (p = .04), and Clinical Global Impression-Severity of Illness ratings for binge eating (p = .02) and depressive disorders (p = .01). Changes in body mass index and measures of eating pathology, depression, and anxiety did not differ between the two groups. DISCUSSION: Duloxetine may be effective for reducing binge eating, weight, and global severity of illness in BED with a comorbid current depressive disorder, but this finding needs confirmation in larger, placebo-controlled trials.

A matter of time: A systematic scoping review on a potential role of the circadian system in binge eating behavior.

Background: Emerging research suggests that food intake timing, eating behavior and food preference are associated with aspects of the circadian system function but the role that the circadian system may play in binge eating (BE) behavior in humans remains unclear. Objective: To systematically evaluate the evidence for circadian system involvement in BE behavior. Methods: Systematic searches of PubMed, EMBASE, and Scopus were performed for reports published from inception until May 2020 (PROSPERO Registration CRD42020186325). Searches were conducted by combining Medical Subject Headings related to the circadian system, BE behavior, and/or interventions. Observational and interventional studies in humans with BE behavior published in peer-review journals in the English language were included. Studies were assessed using quality and risk of bias tools (AXIS, ROB 2.0, or ROBINS). Results: The search produced 660 articles, 51 of which were included in this review. Of these articles, 46 were observational studies and 5 were interventional trials. Evidence from these studies suggests that individuals with BE behavior tend to have more food intake, more binge cravings, and more BE episodes later in the day. Hormonal and day/night locomotor activity rhythm disturbances may be associated with BE behavior. Furthermore, late diurnal preference ("eveningness") was associated with BE behavior and chronobiological interventions that shift the circadian clock earlier (e.g., morning bright light therapy) were found to possibly decrease BE behavior. Substantive clinical overlap exists between BE and night eating behavior. However, there is a significant knowledge gap regarding their potential relationship with the circadian system. Limitations include the lack of studies that use best-established techniques to assess the chronobiology of BE behavior, heterogeneity of participants, diagnostic criteria, and study design, which preclude a meta-analytic approach. Conclusion: Current evidence, although limited, suggests that the circadian system may play a role in the etiology of BE behavior. Further mechanistic studies are needed to fully characterize a potential role of the circadian system in BE behavior. A chronobiological approach to studying BE behavior may lead to identification of its neurobiological components and development of novel therapeutic interventions. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020186325], identifier [CRD42020186325].

Sodium oxybate in the treatment of binge eating disorder: an open-label, prospective study.

OBJECTIVE: To assess preliminarily the effectiveness of sodium oxybate in binge eating disorder. METHOD: This was an open-label, prospective, 16-week, flexible dose study of sodium oxybate in binge eating disorder. The primary outcome was binge eating episode frequency. RESULTS: Twelve individuals received sodium oxybate, 10 completed at least one postbaseline evaluation, and five completed the study. Mean dose at endpoint was 7.1 (2.0) g/day. Sodium oxybate was associated with significant reductions in frequency of binge days and binge episodes, as well as measures of clinical severity, eating pathology, obsessive-compulsive symptoms, food cravings, body mass index, and body weight. Nine participants had remission of binge eating and five lost ≥5% of their baseline weight; all five of the latter participants had remission of binge eating. DISCUSSION: In this open-label trial, sodium oxybate was effective in binge eating disorder, but associated with high a discontinuation rate.

Acamprosate in the treatment of binge eating disorder: a placebo-controlled trial.

OBJECTIVE: To assess preliminarily the effectiveness of acamprosate in binge eating disorder (BED). METHOD: In this 10-week, randomized, placebo-controlled, flexible dose trial, 40 outpatients with BED received acamprosate (N = 20) or placebo (N = 20). The primary outcome measure was binge eating episode frequency. RESULTS: While acamprosate was not associated with a significantly greater rate of reduction in binge eating episode frequency or any other measure in the primary longitudinal analysis, in the endpoint analysis it was associated with statistically significant improvements in binge day frequency and measures of obsessive-compulsiveness of binge eating, food craving, and quality of life. Among completers, weight and BMI decreased slightly in the acamprosate group but increased in the placebo group. DISCUSSION: Although acamprosate did not separate from placebo on any outcome variable in the longitudinal analysis, results of the endpoint and completer analyses suggest the drug may have some utility in BED.

Study protocol and rationale for a randomized, placebo-controlled trial of solriamfetol to treat binge eating disorder.

INTRODUCTION: Binge eating disorder (BED) is an important public health problem associated with severe psychosocial and medical consequences for which treatment options are limited. The objective of this study is to evaluate the efficacy and tolerability of the novel dopamine and norepinephrine reuptake inhibitor (DNRI) solriamfetol in the treatment of BED. METHODS: This study is a 12-week, randomized (1:1 ratio), placebo-controlled, double-blind, parallel-group, 2-arm clinical trial of solriamfetol in 64 outpatients with BED. The primary outcome is binge-eating day frequency as assessed by take-home patient-completed binge eating diaries. Secondary outcomes include binge-eating episode frequency and scores on The Yale-Brown Obsessive Compulsive Scale for Binge Eating (YBOCS-BE) and Clinical Global Severity (CGIS) scale. DISCUSSION: To our knowledge this is the first randomized, double-blind protocol investigating the safety and efficacy of solriamfetol in BED. We highlight the background and rationale for this study, including a discussion on using DNRIs in BED. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov, identifier NCT04602936, on Oct 26, 2020 https://www.clinicaltrials.gov/ct2/show/NCT04602936.

Revisiting the bipolar disorder with migraine phenotype: Clinical features and comorbidity.

INTRODUCTION: To evaluate the prevalence and clinical correlates of lifetime migraine among patients with bipolar disorder (BD). METHODS: In a cross-sectional study, we evaluated 721 adults with BD from the Mayo Clinic Bipolar Disorder Biobank and compared clinical correlates of those with and without a lifetime history of migraine. A structured clinical interview (DSM-IV) and a clinician-assessed questionnaire were utilized to establish a BD diagnosis, lifetime history of migraine, and clinical correlates. RESULTS: Two hundred and seven (29%) BD patients had a lifetime history of migraine. BD patients with migraine were younger and more likely to be female as compared to those without migraine (p values <0.01). In a multivariate logistic regression model, younger age (OR=0.98, p<0.01), female sex (OR=2.02, p<0.01), higher shape/weight concern (OR=1.04, p=0.02), greater anxiety disorder comorbidities (OR=1.24, p<0.01), and evening chronotype (OR=1.65, p=0.03) were associated with migraine. In separate regression models for each general medical comorbidity (controlled for age, sex, and site), migraines were significantly associated with fibromyalgia (OR=3.17, p<0.01), psoriasis (OR=2.65, p=0.03), and asthma (OR=2.0, p<0.01). Participants with migraine were receiving ADHD medication (OR=1.53, p=0.05) or compounds associated with weight loss (OR=1.53, p=0.02) at higher rates compared to those without migraine. LIMITATIONS: Study design precludes determination of causality. Migraine subtypes and features were not assessed. CONCLUSIONS: Migraine prevalence is high in BD and is associated with a more severe clinical burden that includes increased comorbidity with pain and inflammatory conditions. Further study of the BD-migraine phenotype may provide insight into common underlying neurobiological mechanisms.

Update on Binge Eating Disorder.

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.

Progress in Developing Pharmacologic Agents to Treat Bulimia Nervosa.

This paper reviews past and current progress in developing pharmacologic agents for the treatment of individuals with bulimia nervosa (BN). We searched the literature and clinical trial registries for compounds studied in BN, the related condition, binge eating disorder (BED), and preclinical models of binge-eating behavior. Drug classes evaluated included antidepressants, antiepileptic drugs, stimulants and other medications for attention-deficit/hyperactivity disorder, opioid antagonists, and weight loss agents, among others. The only available drugs with established efficacy in BN at this time include antidepressants (especially selective serotonin reuptake inhibitors [SSRIs]) and the antiepileptic topiramate, though the efficacy of these compounds is modest at best. The only medications we found currently receiving empirical study in people with BN were fluoxetine, other serotonergic antidepressants, intranasal naloxone, lisdexamfetamine dimesylate, phentermine-topiramate combination, the antiandrogenic oral contraceptive ethinyl estradiol plus drospirenone, and prazosin. Preclinical models suggest that nociceptin receptor antagonists, the selective serotonin 5-HT2C receptor agonist lorcaserin, monoamine stabilizers, and selective orexin-1 receptor antagonists might be helpful. We found no evidence of a drug developed specifically for the treatment of individuals with BN. Future areas for research in the pharmacotherapy of BN are suggested. Importantly, until drugs are developed specifically for eating disorders, drugs developed for other conditions that are centrally acting and associated with beneficial psychotropic effects and/or reduced appetite or weight loss might be considered for repurposing in BN.

Lisdexamfetamine in Pediatric Binge Eating Disorder: A Retrospective Chart Review.

OBJECTIVES: The purpose of this retrospective chart review was to evaluate lisdexamfetamine dimesylate (LDX) in the treatment of pediatric binge eating disorder (BED). METHODS: We examined the clinical records of 25 patients, 12 to 19 years of age, who were prescribed LDX and had a diagnosis of BED between 2014 and 2017. RESULTS: Binge eating disorder in adolescents was highly comorbid with attention deficit hyperactivity disorder, mood and anxiety disorders, and severe obesity. Fifteen participants reported some level of improvement of their BED symptoms with LDX treatment. Posttreatment body mass index (BMI) percentile was not significantly reduced, and all but 2 participants remained in their same BMI classification. Lisdexamfetamine dimesylate treatment duration was not associated with change in BMI percentile, and the medication was well tolerated. CONCLUSIONS: Lisdexamfetamine dimesylate may have clinical utility for BED in adolescents, but randomized, placebo-controlled studies of its efficacy, tolerability, and safety in this population are needed.

Effect of lisdexamfetamine on emotional network brain dysfunction in binge eating disorder.

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.