Handout for the Neuroscience Education Institute (NEI) online activity: Eating Disorders

Transcription

1 Handout for the Neuroscience Education Institute (NEI) online activity: Eating Disorders

2 Learning Objectives Identify the diagnostic criteria for binge-eating disorder, bulimia nervosa, and anorexia nervosa Implement evidence-based treatment in the management of patients with eating disorders, including binge-eating disorder

3 Pretest Question 1 A 23-year-old woman presents in great distress, stating that she thinks she has binge eating disorder. For the past 3 months, she has had weekly episodes of eating large amounts of food and is unable to stop herself until she has consumed an entire container of ice cream or a bag of potato chips. On a few occasions, these episodes have occurred more than once per week. These episodes typically occur at night. She has never induced vomiting but does take laxatives and exercises for hours after one of these eating episodes. Her body mass index (BMI) is Does this patient meet the diagnostic criteria for binge eating disorder? 1. No, because her BMI is normal 2. No, because her episodes are not frequent enough 3. No, because she engages in inappropriate compensatory behavior 4. Yes

4 Pretest Question 2 What is the common denominator between anorexia nervosa and bulimia? 1. Absence of menses 2. Binge eating 3. Fear of obesity 4. Distorted body image 5. Nausea

5 Pretest Question 3 Lisdexamfetamine is approved for: 1. Moderate to sever binge eating disorder 2. Weight loss associated with binge eating disorder 3. 1 and 2

6 Eating Disorders Can Affect All Organ Systems Presenting complaints are quite varied Neurologic presentations Cardiac presentations Endocrine presentations Gastrointestinal complaints Opportunistic Infections Psychiatric complications Renal presentations Metabolic or electrolyte abnormalities Gynecologic and Obstetric complaints Hematological presentations

7 Eating Disorders: Lifetime Prevalence 5 4 Prevalence (%) Anorexia nervosa Bulimia nervosa Binge eating disorder Hudson JI et al. Biol Psychiatry 2007;61(3):

8 + + Biological predisposition Easily acquired, energy dense food Reduced energy expenditure Obesity epidemic

9 DSM-5 Diagnostic Categories Anorexia (AN) Bulimia nervosa (BN) Binge Eating Disorder (BED) Avoidant/restrictive food intake disorder Other specified feeding or eating disorders Association AP. Diagnostic and Statistical Manual of Mental Disorders, DSM-V

10 DSM-5 Diagnostic Characteristics Diagnosis Anorexia (AN) Bulimia nervosa (BN) Binge Eating Disorder (BED) Major Criteria Significantly low body weight, significant weight and shape concerns Recurrent binge eating and compensatory behaviors (e.g., purging, laxative use); significant weight and shape concerns Recurrent binge eating; at least 3 of 5 additional criteria related to binge eating (e.g., eating large amounts when not physically hungry, eating alone due to embarrassment); significant distress

11 Risk Factors Predict Future Onset of Eating Disorders AN BN BED PD Thin ideal internalization Positive thinness expectancy Denial of thin-ideal costs Body dissatisfaction Weight control behaviors Dieting Negative affect Overeating Fasting Excessive exercise Functional impairment Mental health care Body Mass Index AN: Anorexia disorder BN: Bulimia disorder BED: Binge Eating Disorder PD: Purging Disorder Stice E et al. J Abnorm Psychol. 2017;126(1):38-51.

12 Anorexia Nervosa (AN) DSM-5 Diagnostic Criteria Restriction of energy intake relative to requirements Intense fear of gaining weight or becoming overweight, even though underweight Disturbance in how one's body weight or shape is experienced Subtypes Restricting AN Binge-eating/purging AN Association AP. Diagnostic and Statistical Manual of Mental Disorders, DSM-V

13 Anorexia Severity Rating Mild anorexia = BMI between Moderate anorexia = BMI between Severe anorexia = BMI between Extreme anorexia = BMI < 15 Extreme Severe Moderate Mild Obesity Morbid Obesity Anorexia Normal Overweight BMI = Body Mass Index Association AP. Diagnostic and Statistical Manual of Mental Disorders, DSM-V

14 Bulimia Nervosa DSM-5 Diagnostic Criteria Recurrent episodes of binge eating characterized by BOTH of the following: Eating in a discrete amount of time (within a 2 hour period) large amounts of food Sense of lack of control over eating during an episode Frequent episodes of binge eating followed by inappropriate behaviors to avoid weight gain (e.g., selfinduced vomiting) Association AP. Diagnostic and Statistical Manual of Mental Disorders, DSM-V

15 Bulimia Nervosa DSM-5 Diagnostic Criteria, cont d The binge eating and inappropriate compensatory behaviors both occur, on average, at least once a week for 3 months Self-evaluation is unduly influenced by body shape and weight The disturbance does not occur exclusively during episodes of anorexia nervosa Association AP. Diagnostic and Statistical Manual of Mental Disorders, DSM-V

16 Bulimia Severity Rating Mild Bulimia Moderate Bulimia Severe Bulimia Extreme Bulimia 1-3 episodes / week 4-7 episodes / week 8-14 episodes / week > 14 episodes / week Association AP. Diagnostic and Statistical Manual of Mental Disorders, DSM-V

17 Binge Eating Disorder DSM-5 Diagnostic Criteria Recurrent binge eating episodes Occur during discrete periods of time Consumption of more food than is typical for most people Associated with feelings of impaired control over eating Episodes must occur at least once a week for a minimum of 3 months Feeling of loss of control during eating episodes Association AP. Diagnostic and Statistical Manual of Mental Disorders, DSM-V

18 Binge Eating Severity Rating Mild Binge Eating Moderate Binge Eating Severe Binge Eating Extreme Binge Eating 1-3 episodes / week 4-7 episodes / week 8-13 episodes / week 14 episodes / week The minimum level of severity is based on the number of weekly binge eating episodes Severity level can be increased to reflect other symptoms and functional disability Association AP. Diagnostic and Statistical Manual of Mental Disorders, DSM-V

19 Psychiatric Comorbidities Anorexia nervosa 33-50% of anorexia patients have a comorbid mood disorder, such as depression Mood disorders are more common in the binge/purge subtype than in the restrictive subtype Bulimia nervosa Nearly half of bulimia patients have a comorbid mood disorder More than half of bulimia patients have comorbid anxiety disorders Nearly 1 in 10 bulimia patients have a comorbid substance abuse disorder, usually alcohol use Ulfvebrand S et al. Psychiatry Res. 2015;230(2):294-9.

20 BED and Psychiatric Comorbidities Anxiety disorders 64.1% Substance use disorders 23.3% BED Mood disorders 46.4% Impulse-control disorders 43.4% Hudson JI et al. Biol Psychiatry 2007;61(3):

21 Mortality Rate Eating disorders may have the highest mortality rate of all psychiatric disorders The biggest risk is unintentional death due to the effects of starvation or purging 1 in 5 anorexia deaths is by suicide Comprehensive evaluation of individuals with eating disorder should include assessment of suicide-related ideation and behaviors as well as other risk factors for suicide, including a history of suicide attempts Arcelus J et al. Arch Gen Psychiatry. 2011;68(7):724-31; Forcano L et al. Compr Psychiatry. 2011;52(4):352-8.

22 Screening for Comorbidities Assessment of Mood Disorders Patient Health Questionnaire-9 (PHQ-9) Hamilton Depression Rating Scale (HAM-D) Assessment of self-harm and suicide risk Assessment of substance abuse disorders Assessment of anxiety and OCD

23 Screening Tools for Eating Disorders Eating Disorder Examination (EDE) 1 41-item measure assessing the key behavioral features and associated psychopathology of eating disorders Eating Disorder Examination Questionnaire (EDE-Q) 2 relies on self-report, may generate higher scores than EDE interview Eating Attitudes Test (EAT) 3,4 Identifies abnormal eating attitudes and behaviours Eating Loss of Control Scale 5 1 Fairburn CG, Beglin SJ. Int J Eat Disord. 1994;16: ; 2 Mond JM et al. Behav Res Ther. 2006;44(1):53-62; 3 Garner DM, Garfinkel PE. Psychol Med. 1979;9(2):273-9; 4 Garner DM et al. Psychol Med. 1982;12(4):871-8; 5 Blomquist KK et al. Psychol Assess. 2014;26(1):77-89;

24 Screening Tools for Eating Disorders SCOFF screen for abnormal eating behaviors high sensitivity and specificity for AN and BN S C O F F Do you make yourself feel sick when you feel full? Are you concerned that you have lost control over how much you are consuming? Have you lost more than 14 pounds in a 3-month period? Do you believe yourself to be fat or obese even when others feel you are too thin? Does obsession with food intake control your life? Note: One point is given for every yes answer; a score of 2 indicates the patient likely has anorexia nervosa or bulimia nervosa. Adapted from Morgan JF et al., BMJ. 1999;319(7223):

25 Screening Tool for Binge Eating Binge eating may not be revealed unless the clinician makes a direct inquiry regarding eating behaviors Binge Eating Disorder Screener-7 (BEDS-7) 1. First question: During the last 3 months, did you have any episodes of excessive overeating (i.e., eating significantly more than what most people would eat in a similar period of time)? If the answer is no, the remaining 6 questions do not apply. Herman BK et al. Poster presented at American Psychiatric Association 168th Annual Meeting; May 16 20,2015; Toronto, ON.

26 Differential Diagnosis of Binge Eating Disorder BED (vs. bulimia nervosa) No inappropriate compensatory behavior No marked or sustained dietary restriction BED without obesity (vs. BED with obesity) Less overvaluation of body weight and shape Less psychiatric comorbidity

27 The Eating Continuum Hypothesis Homeostatic eating Intermittent "loss of control" eating Passive overeating Binge eating episodes Binge eating disorder with food addiction Davis C. ISRN Obes 2013:

28 "Addictive" Foods Highly processed foods and drugs of abuse are both associated with: Compulsive overuse, even in the face of severe adverse consequences Loss of control over intake Inability to cut down Davis C. ISRN Obes 2013:

29 Brain Activation to Images of Food Differs in Binge Eating Disorders vs. Overweight Controls BED>BN, C-NW, C-OW: Medial OFC (right hemisphere) BED>BN: Lateral OFC (right hemisphere) No differences detected in ventral striatum BN>BED, C-NW, C-OW: ACC (right hemisphere) BN>BED, C-OW: ACC (left hemisphere) BED: binge eating disorder. BN: bulimia nervosa. C-NW: control, normal weight. C-OW: control, overweight. OFC: orbitofrontal cortex. ACC: anterior cingulate cortex. Schienle A et al. Biol Psychiatry 2009;65:

30 Brain Activation to Images of Food Can Distinguish Between Binge Eating Disorder and Controls BED vs. C-NW: right insula 1 Also left lateral OFC BED vs. C-OW: right ventral striatum 2 Also left insula, medial OFC, right ACC BED vs. BN: left ventral striatum 3 Also left and right insula, right ACC 1 86% accuracy, P<10-5, corr., 82% sensitivity, 90% specificity 2 71% accuracy, P=0.013, uncorr., 59% sensitivity, 82% specificity 3 84% accuracy, P<10-3, corr., 82% sensitivity, 86% specificity BED: binge eating disorder. BN: bulimia nervosa. C-NW: control, normal weight. C-OW: control, overweight. OFC: orbitofrontal cortex. ACC: anterior cingulate cortex. Weygandt M et al. Hum Brain Mapping 2012;33:

31 When Is Binge Eating an Impulsive-Compulsive Disorder? Enhanced motivation and drive to consume food Increasing amounts of food to maintain satiety, tolerance Lack of control over eating; eating too rapidly or too much when not hungry or even when full Great deal of time spent eating Habits and conditioning to food and food cues Distress and dysphoria when dieting Eating alone; feeling disgusted with oneself, guilty, or depressed Overeating maintained despite knowledge of adverse physical and psychological consequences

32 TREATMENT OF EATING DISORDERS

33 Devaluation of a Reward Can Turn Goal-Directed Behavior Into Stimulus-Directed Behavior Salient Stimulus novel exciting palatable Reward Evaluation How beneficial is the outcome? Is there any risk? Engaging in the behavior would lead to a positive result Very little to no risk is required to achieve the reward Favorable Outcome Unfavorable Outcome Engaging in the behavior would lead to a negative result A high degree of risk is required to achieve the reward Goal-directed behavior Action-outcome learning Behavior Stimulus-directed behavior Stimulus-response learning Everitt BJ, Robbins TW. Nat Neurosci 2005;8(11):

34 Habit Formation Ventral striatum: evaluation can still occur Dorsal striatum: no evaluation (binge eating, gambling addiction, drug addiction)

35 Maladaptations of the Reward Pathway Can Shift Behavior From Normal to Impulsive to Compulsive NORMAL IMPULSIVITY COMPULSIVITY Salient Stimulus Salient Stimulus Stimulus Favorable Outcome Pleasurable Reward Favorable Outcome Pleasurable Reward Favorable Behavior Outcome Pleasurable Reward Learning "Liking" Knowing & anticipating "Wanting" Binge Absence Habits Opioids Dopamine Anticipation Wyvell CL, Berridge KC. J Neurosci 2000;20(21): ; Stahl SM. Stahl's Essential Psychopharmacology. 4th ed

36 Normal Reward-Seeking Behavior in Response to a Salient Stimulus Cortical Inhibitory Control Striatum Goal-Directed Behavior Stimulus-Directed Behavior Behavior Salient Stimulus Dopaminergic Neurons Everitt BJ, Robbins TW. Neurosci Biobehav Rev 2013;37:

37 Abnormal Reward-Seeking Behavior in Response to a Salient Stimulus Cortical Inhibitory Control Goal-Directed Behavior Striatum Stimulus-Directed Behavior Behavior Salient Stimulus Dopaminergic Neurons Everitt BJ, Robbins TW. Neurosci Biobehav Rev 2013;37:

38 Maladaptations in the Reward Circuitry That Potentially Underlie Binge Eating Disorder Normal Impulsive Trait Cortical Inhibitory Control Reduced Cortical Inhibitory Control Risky behavior Inappropriate behavior Inability to stop actions Poor decision making Impatience Subcortical Reward Center Goal-Directed Behavior Stimulus-Directed Behavior Normal Eating Behavior Subcortical Reward Center Goal-Directed Behavior Stimulus-Directed Behavior Abnormal Compulsive Eating Behavior Excitatory Inputs Modulating Behavior Increased Excitatory Inputs Modulating Behavior May lead to compulsive behavior, actions that persist inappropriately

39 Reward-Seeking Behavior Is Tightly Regulated on Multiple Levels The firing state of dopaminergic neurons can differentially regulate reward-seeking behavior Tonic firing produces a low level of basal activity Phasic firing results in the rapid activation of dopaminergic signaling, which drives behavior The organization of the striatum is such that the activity of the ventral striatum influences the activity of the dorsal striatum Compulsive behavior is theorized to result from the disruption of this regulation Reward-seeking behavior is under a high degree of regulation from different areas of the frontal cortex

40 Treatment of Eating Disorders Psychotherapy Multidimensional Medications Nutritional Rehabilitation

41 Anorexia Nervosa (AN) Treatment Treatment of comorbid psychiatric conditions such as anxiety and depression should be held until it is clear that symptoms are not caused by starvation alone Effect of all antidepressants has generally been disappointing Meta-analysis of 8 studies of antipsychotics for the treatment of AN failed to demonstrate efficacy for body weight and related outcomes in women Kishi T et al. J Clin Psychiatry 2012;73(6):e

42 Role of Oxytocin in AN Low dose antipsychotic may be useful in reducing anxiety and obsessive thinking Animal data suggest that oxytocin is a satiety hormone Higher oxytocin levels were associated with the severity of disordered eating psychopathology in AN Treatment implications?

43 Bulimia Nervosa (BN) Reduce the frequency of binging and purging in both depressed and non-depressed persons with bulimia SRI SSRI SRI SNRI NRI 1 H1 NA+ TCA SRI NOT RECOMMENDED MAOI M1 NRI Walsh BT. J Clin Psychiatry 1991;52(suppl):34-8.

44 Bulimia Nervosa (BN) Treatment Fluoxetine One and only treatment for any eating disorder authorized by regulatory authorities 8-week, double-blind trial comparing 20 and 60 mg/day with placebo in 387 women Fluoxetine 60 mg/day superior to placebo Insomnia, nausea, asthenia, and tremor more common with fluoxetine Arch Gen Psychiatry 1992;49(2):

45 Treatment Reduced binge eating behavior Weight loss SSRIs, high dose ++ Not clinically significant TCAs +/- +/- Duloxetine + + Orlistat +/- + Topiramate Zonisamide + + Naltrexone, high dose + + Lisdexamfetamine Opioid antagonists +/- CBT ++ Interpersonal therapy ++ Dialectical behavior therapy ++ Self-help ++ Behavioral weight loss + ++ Bariatric surgery Approved by FDA First line First line McElroy SL. Ther Clin Risk Manage 2012;8:

46 Psychotherapy: Shows Positive Posttreatment Recovery Results in Binge Eating Patients CBT: Cognitive Behavioral Therapy IPT: Interpersonal Psychotherapy Posttreatment: 82% Posttreatment: 74% 12-month follow-up: 71% 12-month follow-up: 62% Wilfley DE et al. Arch Gen Psychiatry 2002;59(8):

47 DAT NET VMAT lysine Lisdexamfetamine DAT NET VMAT lysine Approved for binge eating disorder; not approved for weight loss Dose range: mg/day Trials: 1 Phase II (11 weeks), 2 Phase III (12 weeks) Significant reductions in binge eating days per week (primary outcome) Effect sizes: Pooled NNT: 3 (response), 4 (remission) Most common AEs: dry mouth, decreased appetite, insomnia, headache Citrome L. Int J Clin Pract 2015;69(4):410-21; McElroy SL et al. JAMA Psychiatry 2015;72(3):

48 Meta-analysis: Treatment of BED Pharmacological treatment or combination psychological/pharmacological treatment was evaluated in 34 studies Demographics: overweight/obese Caucasian women years old Therapist-led cognitive behavioral therapy, lisdexamfetamine, topiramate, and second-generation antidepressants (SGAs) decreased binge eating frequency Reduced related psychopathology (susceptibility to hunger, cognitive control over eating, concerns about weight) Lisdexamfetamine and topiramate reduced weight in adults with BED Brownley KA et al. Ann Intern Med doi: /m

49 Hypothesized Mechanism of Lisdexamfetamine in Binge Eating Disorder Lisdexamfetamine (LDX) (hypothesized) Cortical Inhibitory Control Striatum Goal-Directed Behavior Stimulus-Directed Behavior Behavior Salient Stimulus Dopaminergic Neurons Lisdexamfetamine (LDX) (hypothesized) Everitt BJ, Robbins TW. Neurosci Biobehav Rev 2013;37:

50 Hypothesized Mechanism of Lisdexamfetamine in Binge Eating Disorder Controlled-Release Stimulants as Treatments Slow and Sustained Drug Delivery Immediate-Release Stimulants as Drugs of Abuse Rapid and Pulsatile Drug Delivery Drug Concentration Drug Concentration Net Effect Time Dose Slow-rising steady state drug level Increase in tonic dopamine firing Not at the mercy of fluctuating dopamine levels Net Effect Time Dose Dose Dose Transient and high drug level Increase in phasic dopamine firing Highly reinforcing, pleasurable effects of drugs of abuse Stahl SM. Stahl's Essential Psychopharmacology. 4th ed

51 Hypothesized Mechanism of Lisdexamfetamine in Binge Eating Disorder Striatum Increases tonic firing Blunts the effect of phasic firing Restores the balance of dopaminergic signaling Hypothalamus Decreases the desire for food intake (immediate) May play a role in relapse prevention once striatal balance is restored (long-lasting) Prefrontal Cortex Tunes the signals Reduces impulsivity and compulsivity drives Similar to proposed MOA in ADHD

52 Peptides Regulate Appetite in the Hypothalamus MC4R appetite NPY AgRP MSH appetite stimulating appetite suppressing AgRP NPY POMC NPY: neuropeptide Y. AgRP: agouti-related peptide. MC4R: melanocortin 4 receptor. POMC: proopiomelanocortin. Stahl SM. Stahl's Essential Psychopharmacology. 4th ed

53 Lisdexamfetamine Actions: Enhance POMC MC4R appetite NPY AgRP MSH appetite stimulating appetite suppressing AgRP NPY DA POMC NE lisdexamfetamine Stahl SM. Stahl's Essential Psychopharmacology. 4th ed

54 Other Medications Topiramate Wide spectrum of actions Anti-binge eating and anti-purging actions Promotes weight loss First study: McElroy et al week, multicenter, randomized controlled trial with 407 patients Marked reduction in the frequency of binge eating episodes with significant weight loss Atomoxetine Significantly greater reduction in binge eating episode frequency, body weight, and scores on rating scales than placebo Efficacious and fairly well tolerated Mean daily dose: 106 mg Final average dose: 300 mg/day McElroy SL et al. J Clin Psychiatry 2007;68(3):390-8; Milano W et al. Adv Ther 2005;22(1):25-31.

55 Summary Physical and psychiatric comorbidities are common in patients with an eating disorder Effective treatment of eating disorders are multidimensional and include pharmacologic approaches, psychotherapy, and nutritional rehabilitation At present, lisdexamfetamine is the only medication approved by the FDA for binge eating disorder