The purpose of this study is to explore the effect of Lisdexamfetamine on Prefrontal Brain Dysfunction in Binge Eating Disorder

12-week, open-label LDX trial for BED including fMRI assessments to test the following specific predictions:

1. At baseline, patients with BED will show greater ventral prefrontal, striatal, and amygdala brain activation to high-calorie food pictures (reward) than matched healthy comparison subjects.
2. After 12 weeks of LDX treatment, BED will exhibit reduced ventral prefrontal, striatal and amygdala brain activation to food cues compared to baseline.
3. BED patients who display cessation of binge eating and those who demonstrate clinical improvement after 12 weeks of LDX treatment will show greater reductions in ventral prefrontal, striatal, and amygdala brain activation to food pictures than patients who do not stop binge eating and those who do not improve, respectively.

Inclusion Criteria: Criteria for entering this study will include all of the following:

1. Subjects will meet the DSM-IV-TR criteria for a diagnosis of binge eating disorder (BED) for at least the last 6 months.
2. Subjects will report at least 3 binge eating (BE) days per week for the two weeks prior to LDX initiation prospectively documented in take-home binge diaries.
3. Women, through the ages of 18 and 55 years, inclusive.
4. Willingness to receive open-label LDX treatment for 12 weeks.
5. Willingness to receive an fMRI before and after 12 weeks of LDX treatment.

Exclusion Criteria:

Criteria for exclusion from this study will include all of the following:

1. Have concurrent symptoms of bulimia nervosa or anorexia nervosa.
2. Women who are pregnant, lactating, or of childbearing potential who are not using adequate contraceptive measures. The following are considered to be adequate methods of birth control: 1. intrauterine device (IUD); 2. barrier protection; 3. a contraceptive implantation system (Norplant); 4. oral contraceptive pills; 5. a surgically sterile patient; and 6. abstinence. All female subjects will have a negative pregnancy test prior to randomization.
3. Subjects who are displaying suicidal ideation on the Columbia-Suicide Severity Scale (C-SSRS) (21), or a suicide attempt within the last year as defined by the C-SSRS, or homicidality.
4. Subjects who are receiving a psychological (e.g., supportive psychotherapy, cognitive behavior therapy, interpersonal therapy) or weight loss (e.g., Weight Watchers) intervention for BED that was begun within the 3 months before study entry. Subjects who are receiving psychotherapy that was initiated prior to 3 months of the beginning of the study will be allowed to continue to receive their psychotherapy during the trial only if they agree to not make any changes to the frequency or nature of their psychotherapy during the course of the drug trial.
5. A DSM-IV-TR diagnosis of substance abuse or dependence (except nicotine abuse or dependence) within the 6 months prior to randomization.
6. Subjects who have used psychostimulants to facilitate fasting or dieting as a part of their eating disorder within the past 6 months; patients who have misused psychostimulants within the past 6 months; and patients who have a drug screen at the screening visit positive for psychostimulants.
7. A lifetime DSM-IV-TR history of ADHD, psychosis, mania or hypomania, or dementia.
8. History of any psychiatric disorder which might interfere with a diagnostic assessment, treatment, or compliance, or a current Montgomery Asberg Depression Scale (MADRS) (22) score ≥ 18.
9. Clinically unstable medical disease, including cardiovascular, hepatic, renal, gastrointestinal, pulmonary, metabolic, endocrine or other systemic disease; clinically significant abnormalities on physical exam; or clinically significant laboratory abnormalities. Subjects should be biochemically euthyroid to enter the study.
10. Have a history of a structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormality, coronary artery disease, stroke, or other serious cardiovascular problem.
11. History of seizures, including clinically significant febrile seizures in childhood.
12. Have uncontrolled hypertension (>160/100) or tachycardia (heart rate >110). m. Have an ECG with significant arrhythmias or conduction abnormalities, which in the opinion of the physician investigator preclude study participation.
13. Have clinically relevant abnormal laboratory results, specifically including hypokalemia.
14. Have a specific medical condition where LDX use is contraindicated, such as narrow angle glaucoma or Tourette's syndrome.
15. Subjects requiring treatment with any drug which might interact adversely with or obscure the action of the study medication. This includes warfarin, anticonvulsants, clonidine, theophylline, and pseudoephedrine.
16. Subjects who have received any psychotropic medications (other than hypnotics) within two weeks prior to LDX initiation, including monoamine oxidase inhibitors, tricyclics, selective serotonin reuptake inhibitors, antipsychotics, mood stabilizers, or psychostimulants.
17. Subjects who have received investigational medications or depot neuroleptics within three months prior to LDX initiation.
18. Subjects who have a known allergy to LDX or its constituents
19. An MRI scan is contraindicated in the subject for safety reasons, claustrophobia, or if the patient exceeds the weight limit of MRI scanner, ~350 pounds.

Study will be published in a peer-reviewed journal