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Abstract

Objective: This study examined the feasibility, safety, and potential efficacy of lisdexamfetamine (LDX) as a treatment for adults with bulimia nervosa (BN). Method: 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. Results: 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 There was a mean weight reduction of 2.1 kg and one participant was withdrawn for clinically significant weight loss.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). Discussion: 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. Trial registration number: NCT03397446.

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... When considering the use of stimulants for individuals with BN, there is a heightened potential of cardiovascular complications (compared to those with ADHD or BED) secondary to purging-related dehydration and electrolyte imbalances (Mehler & Rylander, 2015). In the feasibility trial conducted by A. R. Keshen et al. (2021), an increase in blood pressure and heart rate was observed. The increase in blood primarily because of the potential to misuse the drug for appetite suppression and weight loss (Herzog et al., 2006). ...
... Compared to BED populations, BN populations demonstrate higher rates of restrictive eating, which could be exacerbated by stimulants or other medications (e.g., topiramate; Hoopes et al., 2003) and become problematic if weight loss or rebound binge/purge behavior occur (Elran- Barak et al., 2015). In the feasibility trial by A. R. Keshen et al. (2021), one of the 23 participants was withdrawn due to rapid weight loss (>5% weight loss in a 1 month), but no participants were withdrawn due to BMI decreasing below 20 kg/ m 2 . An average weight reduction of 2.1 kg was observed during the trial, comparable to that reported in the fluoxetine trials that led to regulatory approval for fluoxetine as a treatment for BN (i.e., 1.6 kg during the 8-week study; Wood, 1993). ...
... Most importantly, the recent feasibility study of treating BN with LDX showed improvements in binge/purge behaviors (associated with large effect sizes) and did not raise any significant safety concerns, albeit within the context of a study with strict eligibility criteria and a small sample size (A. R. Keshen et al., 2021). ...
Article
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.
... Lisdexamfetamine dimesylate (LDX) has been approved for the treatment of ADHD in adults and children and for BED in adults. A Health Canada approved open-label feasibility study examining LDX (50-70 mg/day) as a treatment for adults with BN concluded that, over an 8-week period, there were reductions in objective binge episodes and compensatory behaviors (N ¼ 23; Keshen et al. 2021). There was a clinically significant mean increase in heart rate observed and a decrease in BMI (which could be problematic if BN patients lose weight due to increased restriction from appetite suppression). ...
... Of the medications in an experimental phase (see McElroy et al. 2019 for a description of medications in clinical trial phases), stimulants offer an interesting route for further exploration. In their review paper, Keshen et al. (2022) present a rationale for further stimulant-based research based on neurobiology, the relationship between ADHD and BN, and the preliminary evidence from a recent feasibility study (Keshen et al. 2021). The authors also summarize the potential risks of treating BN with stimulants, and based on those risks, do not currently recommend stimulants as a treatment for BN, but rather propose specific avenues for future research. ...
Article
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Background: The efficacy and safety of Lisdexamfetamine dimesylate (LDX) in the treatment of moderate to severe binge eating disorder (BED) has been demonstrated in multiple randomised clinical trials. Despite this, little is known about how LDX acts to improve binge eating symptoms. This study aims to provide a comprehensive understanding of the neural mechanisms by which LDX improves symptoms of BED. We hypothesise that LDX will act by normalising connectivity within neural circuits responsible for reward and impulse control, and that this normalisation will correlate with reduced binge eating episodes. Methods: This is an open-label Phase 4 clinical trial of LDX in adults with moderate to severe BED. Enrolment will include 40 adults with moderate to severe BED aged 18-40 years and Body Mass Index (BMI) of 20-45 kg/m2, and 22 healthy controls matched for age, gender and BMI. Clinical interview and validated scales are used to confirm diagnosis and screen for exclusion criteria, which include comorbid anorexia nervosa or bulimia nervosa, use of psychostimulants within the past 6 months, and current use of antipsychotics or noradrenaline reuptake inhibitors. Baseline assessments include clinical symptoms, multimodal neuroimaging, cognitive assessment of reward sensitivity and behavioural inhibition, and an (optional) genetic sample. A subset of these assessments are repeated after eight weeks of treatment with LDX titrated to either 50 or 70 mg. The primary outcome measures are resting-state intrinsic connectivity and the number of binge eating episodes. Analyses will be applied to resting-state fMRI data to characterise pharmacological effects across the functional connectome, and assess correlations with symptom measure changes. Comparison of neural measures between controls and those with BED post-treatment will also be performed to determine whether LDX normalises brain function. Discussion: First enrolment was in May 2018, and is ongoing. This study is the first comprehensive investigation of the neurobiological changes that occur with LDX treatment in adults with moderate to severe BED. Trial registration: ACTRN12618000623291, Australian and New Zealand Clinical Trials Registry URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374913&isReview=true. Date of Registration: 20 April 2018.
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Background 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). Methods 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. Results 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. Conclusions 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.
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The efficacy and safety of lisdexamfetamine dimesylate (LDX) versus 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/d) 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 2 (1.1%) placebo participants in each study and in 3 (1.6%) and 1 (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 bpm and 0.2-1.45 and 1.06-1.83 mm Hg, respectively. LDX (50 and 70 mg/d) 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.Neuropsychopharmacology accepted article preview online, 07 September 2015. doi:10.1038/npp.2015.275.
Article
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To compare dietary restriction behaviors among adults with eating disorders involving binge eating, including anorexia nervosa-binge/purge subtype (AN-BE/P), bulimia nervosa (BN), and binge eating disorder (BED), and to examine whether dietary restriction behaviors impact binge eating frequency across diagnoses. Participants included 845 treatment seeking adults (M=30.42+10.76years) who met criteria for DSM-5 AN-BE/P (7.3%;n=62), BN (59.7%;n=504), and BED (33.0%;n=279). All participants self-reported their past and current eating disorder symptoms on the Eating Disorder Questionnaire. Adults with AN-BE/P and BN reported significantly more dietary restriction behaviors (e.g. eating fewer meals per day, higher frequency of fasting, consuming small and low calorie meals) in comparison to adults with BED. Adults with AN-BE/P and BN who reported restricting food intake via eating fewer meals per day had more frequent binge eating episodes. However, adults with BN who reported restricting food intake via eating small meals and low calorie meals had less frequent binge eating episodes. This study provides mixed support for the restraint model by suggesting that not all dietary restriction behaviors are associated with higher levels of binge eating. It may be that adults with BN who report a higher frequency of eating small and low calorie meals display more control over their eating in general, and therefore also have lower frequency of binge eating. Clinicians should assess for dietary restriction behaviors at the start of treatment prior to assuming that all forms of strict dieting and weight control behaviors similarly impact binge eating. Copyright © 2015. Published by Elsevier Ltd.
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As with anorexia nervosa, there are many medical complications associated with bulimia nervosa. In bulimia nervosa, these complications are a direct result of both the mode and the frequency of purging behaviours. For the purposes of this article, we will review in detail the many complications of the two major modes of purging, namely, self-induced vomiting and laxative abuse; these two account for more than 90% of purging behaviours in bulimia nervosa. Some of these complications are potentially extremely dangerous and need to be well understood to effectively treat patients with bulimia nervosa. Other methods of purging, such as diuretic abuse, are much less frequently utilized and will only be mentioned briefly. In a subsequent article, the treatments of these medical complications will be presented.
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Research on suicide prevention and interventions requires a standard method for assessing both suicidal ideation and behavior to identify those at risk and to track treatment response. The Columbia-Suicide Severity Rating Scale (C-SSRS) was designed to quantify the severity of suicidal ideation and behavior. The authors examined the psychometric properties of the scale. The C-SSRS's validity relative to other measures of suicidal ideation and behavior and the internal consistency of its intensity of ideation subscale were analyzed in three multisite studies: a treatment study of adolescent suicide attempters (N=124); a medication efficacy trial with depressed adolescents (N=312); and a study of adults presenting to an emergency department for psychiatric reasons (N=237). The C-SSRS demonstrated good convergent and divergent validity with other multi-informant suicidal ideation and behavior scales and had high sensitivity and specificity for suicidal behavior classifications compared with another behavior scale and an independent suicide evaluation board. Both the ideation and behavior subscales were sensitive to change over time. The intensity of ideation subscale demonstrated moderate to strong internal consistency. In the adolescent suicide attempters study, worst-point lifetime suicidal ideation on the C-SSRS predicted suicide attempts during the study, whereas the Scale for Suicide Ideation did not. Participants with the two highest levels of ideation severity (intent or intent with plan) at baseline had higher odds for attempting suicide during the study. These findings suggest that the C-SSRS is suitable for assessment of suicidal ideation and behavior in clinical and research settings.
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Up to 1% of young women may have bulimia nervosa, characterised by an intense preoccupation with body weight, uncontrolled binge-eating episodes, and use of extreme measures to counteract the feared effects of overeating. People with bulimia nervosa may be of normal weight, making it difficult to diagnose. After 10 years, about half of people with bulimia nervosa will have recovered fully, one third will have made a partial recovery, and 10% to 20% will still have symptoms. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for bulimia nervosa in adults? What are the effects of discontinuing treatment in people with bulimia nervosa in remission? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 27 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: cognitive behavioural therapy (CBT; alone or plus exposure/response prevention enhancement), cognitive orientation therapy, dialectical behavioural therapy, discontinuing fluoxetine in people with remission, guided self-help cognitive behavioural therapy, hypnobehavioural therapy, interpersonal psychotherapy, mirtazapine, monoamine oxidase inhibitors (MAOIs), motivational enhancement therapy, pharmacotherapy plus psychotherapy, pure or unguided self-help cognitive behavioural therapy, reboxetine, selective serotonin reuptake inhibitors (SSRIs), topiramate, tricyclic antidepressants (TCAs), and venlafaxine.
Article
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.
Article
Importance The ability of pharmacotherapies to prevent relapse and maintain efficacy with long-term treatment in psychiatric conditions is important. Objective To assess lisdexamfetamine dimesylate maintenance of efficacy in adults with moderate to severe binge-eating disorder. Design, Setting, and Participants 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. Interventions Lisdexamfetamine administration. Main Outcomes and Measures 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. Results 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. Conclusions and Relevance 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. Trial Registration clinicaltrials.gov Identifier: NCT02009163
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Psychostimulants have been assessed in bulimia nervosa patients with comorbid attention deficit/hyperactivity disorder (ADHD), but few studies have examined the impact of psychostimulants on bulimia nervosa patients without comorbid ADHD. The aim of this study was to examine psychostimulants as a potential treatment for bulimia nervosa and to assess the concern of weight loss, given the medication's appetite-suppressing effects. This retrospective study describes 6 case reports of outpatients who were prescribed a psychostimulant specifically for their bulimia nervosa. The number of binge/purge days per months and body mass index were assessed. All patients demonstrated reductions in the number of binge/purge days per month, and 1 patient experienced total remission of bulimic symptoms. Minor fluctuations in weight were observed, but no clinically significant reductions in weight were noted. These findings support the need for clinical trials to examine the efficacy and safety of this potential treatment.
Article
Bulimia nervosa represents a serious public health problem in the United States. We performed an 8-week, double-blind trial comparing fluoxetine hydrochloride (60 and 20 mg/d) with placebo in 387 bulimic women treated on an outpatient basis. Fluoxetine at 60 mg/d proved superior to placebo in decreasing the frequency of weekly binge-eating and vomiting episodes at end point. Fluoxetine at 20 mg/d produced an effect between that of the 60mg/d dosage and that of placebo. Depression, carbohydrate craving, and pathologic eating attitudes and behaviors also improved significantly with fluoxetine, with the higher dosage again showing a more robust effect than the lower dosage. Several adverse events (ie, insomnia, nausea, asthenia, and tremor) occurred significantly more frequently with fluoxetine (60 or 20 mg/d) than with placebo. However, there was no statistically significant difference among treatment groups in the proportion of patients discontinuing the study because of adverse events.
Article
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.
Article
There is increasing literature suggesting a link between attention-deficit hyperactivity disorder (ADHD) and eating disorders (EDs), especially bulimia nervosa. ADHD is under-diagnosed in girls and children of high intelligence are typically missed. We identified a case of a 23-year-old woman suffering from severe bulimia nervosa and previously unsuspected ADHD in adulthood; we diagnosed and treated her with extended-release methylphenidate. We performed a literature review on the ADHD and bulimia nervosa comorbidity. We discuss the reasons why her ADHD remained undiagnosed and the difficulties in diagnosing ADHD in patients with EDs. We suggest that identifying comorbid ADHD is crucial for these patients and argue for the use of a structured interview, collateral history and investigation of onset of symptoms to establish a diagnosis of ADHD in adults with bulimia nervosa. Comorbidities and overlap of symptomatology need to be taken into account. © 2013 Wiley Periodicals, Inc. (Int J Eat Disord 2013).
Article
Compared to children, adults with ADHD are at greater risk for developing adverse cardiovascular related outcomes and, if treated, may be likely to carry a greater burden of exposure to stimulant medications. The goal of this report is to critically review the available literature relevant to the cardiovascular safety of CNS stimulants for adult ADHD (aADHD). Twenty potential clinical trials of a CNS stimulant for aADHD have been published between 1979 and 2012. Of these, ten presented sufficient data to estimate the relative change in various cardiovascular parameters associated with ADHD treatment modalities. These trials were predominantly focused on long-acting stimulant preparations for acute symptom reduction (median duration=6 weeks, range: 4-24 weeks) and enrolled relatively young subjects (median age=36 years, range: 22-40). Using random effects meta-analysis, we found that subjects randomized to CNS stimulant treatment demonstrated a statistically significant increased resting heart rate [+5.7bpm (3.6, 7.8), p<0.001] and systolic blood pressure findings [+2.0mmHg (0.8, 3.2), p=0.005] compared with subjects randomized to placebo. There was a statistically significant increased risk for a resting heart rate >90bpm [4.2% (n=50) vs. 1.7% (n=8), OR=2.75 (1.3, 6.7), p=0.006] associated with CNS stimulant treatment. In light of prognostic value of resting heart rate with regard to cardiovascular morbidity in epidemiological studies, future research of adults with ADHD should focus on the potential clinical impact of the increase in heart rate observed in this meta-analysis.
Article
Methylphenidate (MPT) was prescribed four days after an uncomplicated appendectomy in a 27 year old woman who had suffered from bulimia nervosa (BN) for at least nine years. Before the onset of appendicitis, her bingeing and self-induced vomiting had occurred several times daily. With MPT the patient reported a calm emotional state and an absence of temptation to binge or to induce vomiting. Previously published reports of treatment of BN with MPT could not be found. This may be the first. Vulnerability to surgical disorders and to postoperative complications as well as the safety and efficacy of MPT in patients suffering from BN deserve further study.
Article
We first establish the association between binge eating and dieting and present sequence data indicating that dieting usually precedes binging, chronologically. We propose that dieting causes binging by promoting the adoption of a cognitively regulated eating style, which is necessary if the physiological defense of body weight is to be overcome. The defense of body weight entails various metabolic adjustments that assist energy conservation, but the behavioral reaction of binge eating is best understood in cognitive, not physiological, terms. By supplanting physiological regulatory controls with cognitive controls, dieting makes the dieter vulnerable to disinhibition and consequent overeating. Implications for therapy are discussed, as are the societal consequences of regarding dieting as a "solution" to the problem of binging.
Article
Eight patients with bulimia nervosa were given methylamphetamine or placebo intravenously under double blind controlled conditions. In every patient, methylamphetamine reduced self-ratings of hunger and amount of food eaten as measured under laboratory conditions. This shows that the food intake of patients with bulimia nervosa can be modified by experimental drugs. The symptom of bulimia (rapid, excessive and distressing eating) which may be followed by self-induced vomiting or purgation was seen in four patients after receiving placebo but in none after receiving methylamphetamine. These findings suggest that the severe symptom of bulimia may be amenable to drug treatment. Further studies are needed to explore the mechanism by which methylamphetamine appears to prevent bulimia.
Article
The goals of the current study were to compare the relapse rates obtained when definitions of both remission and relapse were systematically varied and to propose some consensus definitions related to relapse in bulimia nervosa (BN). This was an uncontrolled, prospective follow-up study based on 46 women who met criteria for BN (based on criteria in the 3rd Rev. ed. of the Diagnostic and Statistical Manual of Mental Disorders [Washington, DC: American Psychiatric Association]) before treatment and were abstinent or had low frequency symptoms after treatment. Assessments were conducted every 3 months for up to 19 months. Data were analyzed with Kaplan-Meier survival analysis. Relapse rates at 19 months ranged from 21% to 55% depending on the definitions of remission and relapse applied. Relapse rates are strongly influenced by definitions of remission and relapse. We propose that partial remission, defined as a maximum of two symptom episodes per month for 2 months, should constitute eligibility for relapse and relapse should be defined as meeting full diagnostic criteria for 3 months.
Article
Drug abuse in women with eating disorders has received relatively little attention. The frequency of drug use disorder (DUD) by specific drug type was examined in the current longitudinal study. In a prospective study, women diagnosed with either anorexia nervosa (AN; n = 136) or bulimia nervosa (BN; n = 110), were interviewed and assessed for research diagnostic criteria (RDC) DUD every 6-12 months over 8.6 years. Forty-two (17%) women in the current longitudinal study had a lifetime history of DUD, with 19 prospective onsets over the course of the study (9 AN and 10 BN). The most commonly abused illicit drugs were amphetamines, cocaine, and marijuana, and rates of DUD did not differ between intake diagnoses of AN and BN. Drug abuse in women with eating disorders is an area of clinical concern and should be monitored routinely throughout the treatment process.
Article
Recent research has raised important questions about the relationships between weight suppression (WS) (discrepancy between highest-ever and current weight), dietary restraint, and binge eating in bulimia nervosa (BN). In the current study, these variables were studied cross-sectionally through secondary analyses of baseline data collected in a multi-site treatment study. Participants (N = 182) were treatment-seeking women diagnosed with BN. Dietary restraint and binge eating were measured via the Eating Disorders Examination. WS was directly and dietary restraint was inversely related to frequency of binge eating. The inverse relationship between dietary restraint and binge eating may be explained in part by the fact that the most restrained patients with BN had the greatest desire to lose weight. Implications of these findings for future research on the perpetuation and treatment of BN are discussed.
Methylphenidate treatment for bulimia nervosa associated with a cluster B personality disorder
  • M S Sokol
  • N S Gray
  • A Goldstein
  • W H Kaye
Sokol, M. S., Gray, N. S., Goldstein, A., & Kaye, W. H. (1999). Methylphenidate treatment for bulimia nervosa associated with a cluster B personality disorder. International Journal of Eating Disorders, 25(2), 233-237. https://doi.org/10.1002/(SICI)1098-108X(199903)25:2<233::AID-EAT14>3.0.CO;2-2
Structured clinical interview for DSM‐5—Research version (SCID‐5 for DSM‐5, research version; SCID‐5‐RV)
  • M. B. First
  • J. B. W. Williams
  • R. S. Karg
  • R. L. Spitzer