1. Introduction

2. Methods

3. Pharmacotherapy trials in BN

and BED: designs utilized and

medications evaluated

4. Antidepressants

5. Antiepileptic drugs

6. Antiobesity agents

7. Drugs for ADHD

8. Anti-addiction

(or anti-craving) drugs

9. Hormonal treatments

10. 5HT3 antagonists

11. Lithium

12. Other agents

13. Expert opinion

Review

Current pharmacotherapy optionsfor bulimia nervosa and bingeeating disorderSusan L McElroy, Anna I Guerdjikova, Nicole Mori & Anne M O’Melia†Lindner Center of HOPE, Mason, OH, USA

Introduction: Growing evidence indicates binge eating, defined as the con-

sumption of an abnormally large amount of food accompanied by a sense of

loss of control, is an important public health problem. Althoughpsychotherapy

may be effective, not all patients respond adequately.

Areas covered: This article provides an overview of bulimia nervosa (BN) and

binge eating disorder (BED), the two conditions characterized by recurrent

binge eating as a core feature, and reviews studies of specific medications

in treating patients with BN or BED, focusing on randomized controlled

trials (RCTs).

Expert opinion: Although the evidence base is small, growing data indicate

pharmacotherapy may be helpful for some patients with BN or BED. Anti-

depressants, especially selective serotonin reuptake inhibitors (SSRIs), are

modestly effective for reducing binge eating over the short term in BN and

BED. SSRIs may be modestly effective in BN over the long term. Topiramate

has consistently been shown to decrease binge eating in BED and BN, but

side effects may limit its usefulness. Single RCTs suggest zonisamide and atom-

oxetine may be effective in BED. Combination therapy may be required for

optimal outcomes. It is not yet known whether the binge eating of BN and

BED respond similarly to pharmacotherapy.

Keywords: binge eating, bulimia nervosa, medication management, pharmacotherapy

Expert Opin. Pharmacother. (2012) 13(14):2015-2026

1. Introduction

Binge eating is broadly defined as the consumption of an abnormally large amountof food accompanied by a sense of lack of control [1]. Two eating disorders, bulimianervosa (BN) and binge eating disorder (BED), require binge eating as core definingfeatures. BN is further defined by inappropriate compensatory weight loss behaviorsand excessive concern for shape and weight. By contrast, for BED, binge eatingmust be associated with other indicators of loss of control and distress, but notwith the inappropriate compensatory weight loss behaviors of BN [1-3]. Althoughnot a defining feature, BED, like BN, is also associated with excessive weight andshape concerns. For the upcoming DSM-5, it has been proposed that BED beelevated from an example of eating disorder not otherwise specified (NOS) to adiagnosis in its own right along with BN in the category, “Feeding and EatingDisorders” [4]. It has also been proposed that the frequency and chronicity criteriafor binge eating (at least once/week for at least three months) be the same for BNand BED. Of note, binge eating also occurs in anorexia nervosa, but is not requiredfor its diagnosis.

Binge eating is an important public health problem. BED is the most commoneating disorder in the United States, with a lifetime prevalence of 2.8% in adults [5]

and 1.6% in adolescents [6]. BN occurs with a lifetime prevalence of 1.0% in adults [5]

10.1517/14656566.2012.721781 © 2012 Informa UK, Ltd. ISSN 1465-6566 2015All rights reserved: reproduction in whole or in part not permitted

Exp

ert O

pin.

Pha

rmac

othe

r. D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y H

INA

RI

on 0

9/26

/12

For

pers

onal

use

onl

y.

and 0.9% in adolescents [6]. Both BN and BED are morecommon in females, often chronic, and associated with psychi-atric and medical comorbidity and disability [2,3,5-8]. Ascompared to BN, BED is more common in males, has a laterage of onset in adult cohorts, and is more often associatedwith obesity, including severe obesity [5]. Binge eating episodesmay be larger in BN than in BED [9]. Dieting often precedesbinge eating in BN, whereas sporadic weight control attemptsoccur after binge eating in BED [3]. Studies are beginning toelucidate the psychobiology of binge eating behavior. Thisresearch suggests binge eating may be associated with abnor-malities in homeostatic feeding, reward function, higher levelself regulating processes, and neurotransmitter systems suchas dopamine [2,10,11].Specialized psychotherapies, in particular cognitive beha-

vior therapy [CBT] and interpersonal therapy [IPT], andself-help strategies are effective for reducing binge eating in

BN and BED, but not all patients respond adequately [12-14].Moreover, these treatments are generally not effective forsome of the common comorbidities of binge eating, such asbipolar disorder or obesity. An increasing number ofreviews [15-20] and guidelines [21-23] have recently discussedthe role pharmacotherapy might play in treating patientswith BN or BED. Only one drug, however, has beenapproved by the United States Food and Drug Admini-stration (FDA) or any other regulatory agency for the treat-ment of binge eating, that being fluoxetine for BN. No drugis yet approved for the treatment of BED or binge eatingbehavior in general.

In this paper, we first review the data supporting theeffectiveness of specific medications or medication classes intreating BN and BED. We conclude by summarizing thesedata and discussing the role pharmacotherapy might play inthe treatment of binge eating. We also suggest future areasfor research in the pharmacotherapy for binge eating.

2. Methods

A PubMed search of all English-language articles pub-lished through May 2012 was conducted. The key searchterms were: pharmacotherapy; antidepressants; antiepileptics;anti-obesity; antipsychotics; mood stabilizers; opioid antago-nists; randomized control trial (RCT); and stimulants. Theseterms were paired with binge eating, binge eating disorder(BED), and bulimia nervosa (BN). We also paired the latterterms with the following individual medications: acampro-sate, amphetamine, atomoxetine, exenatide, fenfluramine,lamotrigine, liraglutide, methylphenidate, naltrexone, pram-lintide, sibutramine, topiramate, and zonisamide. We supple-mented our search by review of reference lists of relevantarticles. In evaluating the effectiveness of medications forbinge eating, only placebo-controlled, randomized clinical tri-als (RCTs) involving ‡ 20 subjects (or ‡ 8 subjects for cross-over designs), or meta-analyses of such trials, were reviewed. IfRCTs were not available, the largest open-label studies of adrug were evaluated.

3. Pharmacotherapy trials in BN and BED:designs utilized and medications evaluated

Two primary pharmacotherapy RCT designs have been uti-lized to evaluate medications in BN: short-term studies ofpatients who are actively binge eating and purging and long-term maintenance studies of patients whose bulimic symp-toms have responded to an acute intervention. By contrast,most RCTs of BED have been short-term trials in activelybinge eating patients. Monotherapy trials, in which medica-tion alone is compared with placebo or a psychological treat-ment, and combination therapy trials, where medication plusa psychological treatment is compared with the psychologicaltreatment alone and/or the medication alone, have been donein both conditions. Primary outcomes in the acute BN trials

Article highlights.

. Bulimia nervosa (BN) and binge eating disorder (BED) areprevalent conditions that do not always respond topsychotherapy. Growing clinical research shows thatpharmacotherapy may have a role in the treatment ofBN and BED, including in patients who respondinadequately to psychotherapy, patients with comorbidmedical or psychiatric disorders, and those with chronicor intractable illness.

. Fluoxetine has regulatory approval for BN. No drug hasregulatory approval for BED.

. Medication classes receiving the most study in BN orBED are antidepressants, antiepileptics, anti-obesitydrugs, drugs for attention-deficit hyperactivitydisorder (ADHD), and anti-addiction (or anti-craving)agents.

. Antidepressants appear modestly effective for BN andBED over the short term. Fluvoxamine and fluoxetinemay be modestly effective for BN over the long term.

. Data regarding the efficacy of topiramate in thetreatment of BED, and to a lesser extent BN, areconsistently positive, but use of the drug is limited by itsadverse event profile.

. Medications with one published positive randomizedclinical trial for binge eating populations includeondansetron for BN and zonisamide and atomoxetinefor BED. Preliminary results from Phase-II studies suggestlisdexamfetamine and intranasal naloxone may behelpful for BED.

. Combination therapy is sometimes required for optimaloutcomes. More research is needed to determine whichspecific agents, including combinations of agents, mightbe most useful for which patient subgroups.

. Pharmacotherapy should be considered a therapeuticoption for most patients with BN or BED, includingthose naı̈ve to treatment, and when psychotherapyresponse has been inadequate.

. More research is needed to determine what placepharmacotherapy will fill in the therapeuticarmamentarium for BN and BED.

This box summarizes key points contained in the article.

S. L. McElroy et al.

2016 Expert Opin. Pharmacother. (2012) 13(14)

Exp

ert O

pin.

Pha

rmac

othe

r. D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y H

INA

RI

on 0

9/26

/12

For

pers

onal

use

onl

y.

have usually been measures of the frequency of binge eatingepisodes and/or inappropriate compensatory behaviors (e.g.,vomiting), or rates of remission or response of bulimicsymptoms. Primary outcomes in the maintenance trials haveusually been time to relapse or rate of relapse. Primary out-comes in BED trials have typically been the frequency ofbinge eating episodes (binge frequency) or binge days (a dayduring which at least one binge eating episode occurs; bingeday frequency), the rate of remission or response of bingeeating behavior, and less frequently, weight loss. Secondaryoutcomes for both conditions have been measures of globaleating disorder pathology, mood symptoms, global clinicalimprovement, laboratory measures, and treatment adherence.Most studies excluded patients with serious or unstablecomorbid psychiatric or medical disorders such as bipolar dis-order, substance use disorders, diabetes, and hypertension orother forms of cardiovascular disease.

The three major classes of drugs studied thus far in BNand BED in RCTs have been antidepressants, antiepileptics,and anti-obesity agents. Drug classes that have receivedless study include medications for attention-deficit hyper-activity disorder (ADHD), anti-addiction (or anti-craving)agents, 5HT3 antagonists, hormonal agents, and lithium.The individual studies are reviewed below according todrug class.

4. Antidepressants

4.1 Short-term RCTsAntidepressants are presently the most extensively studieddrug class in BN and BED. A meta-analysis of 10 RCTs ofantidepressants in patients with BN found the pooled relativerisk (RR) for remission of binge episodes was 0.88 (95% con-fidence intervals [CI] = 0.82, 0.93; p < 0.001), favoring anti-depressants over placebo [24]. In the meta-analysis, there wasno evidence of statistically significant differences in efficacyamong different classes of antidepressants, which included tri-cyclics, monoamine oxidase inhibitors [MAOIs], fluoxetine,miansain, trazodone, and bupropion [24]. However, patientstreated with antidepressants were more likely to discontinueprematurely due to adverse events. Patients receiving tricyclicsdropped out due to any cause more frequently than thosereceiving placebo, though the opposite was found for fluoxe-tine. Subsequent small RCTs of sertraline and fluvoxaminefound these drugs were also superior to placebo for reducingbinge eating and purging in BN [25,26].

In BED, at least nine RCTs have evaluated antidepres-sants [18]. A meta-analysis of seven of these studies (1 with atricyclic, 6 with selective serotonin reuptake inhibitors[SSRIs]) showed significantly higher binge eating remissionrates for the antidepressant group compared with the placebogroup: 40.5 vs. 22.2% (RR = 0.77 [95% CI = 0.65, 0.92;p = .003]) [27]. Antidepressants were also superior for reducingdepressive symptoms. No differences between groups at theend of treatment were found in the mean frequency of binge

eating episodes, in BMI, or in treatment discontinuation forany reason.

Dose response studies have not yet been done for BED.However, in the largest study of an antidepressant in BN(N = 387), fluoxetine 60 mg/d was superior to placebofor reducing binge eating and vomiting episodes, while20 mg/d was shown to have an intermediate effect [28]. Flu-oxetine 60 mg/d was also superior to placebo in reducingdepression, carbohydrate craving, and pathological eatingattitudes and behaviors. Fluoxetine has been shown effica-cious in BN patients inadequately response to psycho-therapy [29] and in BN patients treated in the primary caresetting [30]. Post-hoc analyses suggest lack of early reductionin binge eating or vomiting predicts nonresponse for BN,while early response predicts remission for BED [31,32].A RCT in BED patients with co-occurring depressive disor-ders found the serotonin-norepinephrine reuptake inhibitor(SNRI) duloxetine decreased binge eating, body weight,and global measures of BED and depression [33]. Thougheffective in BN, bupropion was associated with an increasedrisk for seizures, and is contraindicated for the treatment ofBN and anorexia nervosa [34]. A RCT of bupropion in BEDwith obesity (NCT00414167) is ongoing, and a retrospec-tive analysis found that bupropion may be associated withgreater weight loss than sertraline for BED patients [35].No placebo-controlled RCTs comparing antidepressantswith different mechanisms of action have been conductedin BN or BED.

4.2 Maintenance RCTsAt least two relapse-prevention RCTs have been done withantidepressants in BN. In the first, 72 patients with DSM-III-R BN successfully treated with intensive inpatient psycho-therapy were randomized to receive fluvoxamine (N = 33) orplacebo (N = 39) as outpatients for 12 weeks [36]. At endpoint,the fluvoxamine group had significantly more patients report-ing no binges in the past week than the placebo group(p < .05). Premature termination rates were high; 38% forfluvoxamine recipients compared with 14% for placebo reci-pients. In the second study, 150 outpatients with DSM-IV BN, purging type responding to treatment with fluoxetine60 mg/d for 8 weeks were randomly assigned to continue flu-oxetine 60 mg/d (n = 76) or switch to placebo (n = 74) for52 weeks [37]. Fluoxetine-treated patients exhibited a signifi-cantly longer time to relapse (defined as a return to baselinevomiting frequency that persisted for 2 weeks) than placebo-treated patients (c2 = 5.79, af = 1, p < 0.02). At endpoint,fluoxetine was also superior for vomiting episodes, binge eat-ing episodes, obsessive-compulsive symptoms, and clinicalglobal outcome. The attrition rate, however, was very high,with 83% of fluoxetine recipients and 92% of placebo reci-pients discontinuing prematurely. Comparable relapse pre-vention RCTs of antidepressant monotherapy in BED havenot yet been conducted, but preliminary data has suggestedthat some patients with BED who initially respond to SSRIs

Current pharmacotherapy options for bulimia nervosa and binge eating disorder

Expert Opin. Pharmacother. (2012) 13(14) 2017

Exp

ert O

pin.

Pha

rmac

othe

r. D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y H

INA

RI

on 0

9/26

/12

For

pers

onal

use

onl

y.

with decreased binge eating and weight loss may maintainthese benefits for up to 6 months with continuation of theSSRI [38].

4.3 RCTs of combination treatmentIn 2001, Bacaltchuk et al. published a Cochrane review ofRCTs comparing antidepressants with psychological treat-ments or their combination for reducing symptoms inBN [39]. Remission rates for antidepressant monotherapywere 20 vs. 39% for psychological treatment alone(RR = 1.28; 95% CI = 0.98, 1.67). Dropout rates were higherfor antidepressants alone than psychological treatments alone(RR = 2.18; 95% CI = 1.09, 4.35). Remission rates forthe combination of antidepressants plus psychological treat-ments were 42 vs. 23% for antidepressant monotherapy(RR = 1.38; 95% CI = 0.98, 1.93). Remission rates forpsychological treatments alone were 36 vs. 49% for the com-bination (RR = 1.21; 95% CI = 1.02, 1.45). Dropout rateswere higher for the combination compared with psychologicaltreatments alone (RR = .57; 95% CI = .38, .88). The only sta-tistically significant difference was that combination therapywas superior to psychological treatment alone. The authorsconcluded that combined antidepressant -- psychologicalapproaches were more effective than psychotherapy alone,but that there may have been an insufficient number of trialsto show combination therapy or psychotherapy alone superiorto antidepressants alone. They also concluded that psychother-apy was more acceptable to patients and that the addition ofantidepressants to psychotherapy reduced its acceptability.The few controlled combination therapy RCTs in BED

had contrasting results. In one, diet counseling with psycho-logical support plus imipramine was superior to diet counsel-ing and psychological support plus placebo for 8 weeks indecreasing binge eating (p < .01) and weight (p < .001) [40].Benefits were maintained at 8 month follow up despite dis-continuation of imipramine. In another study, 16 weeks ofcognitive behavior therapy (CBT) with placebo or CBTwith fluoxetine were both superior to fluoxetine alone andplacebo alone for decreasing binge eating [41]. There was noadditive effect for the combination of fluoxetine plus CBTover CBT alone for decreasing binge eating, and no singleor combined treatment was effective for weight loss. In a thirdstudy, 116 BED patients receiving group behavioral weightcontrol treatment for 20 weeks were randomized twice toadjunctive CBT or no CBT and to fluoxetine (40 -- 80 mgdaily) or placebo [42]. CBT, but not adjunctive fluoxetine,was effective for reducing binge eating. Fluoxetine, however,was effective for decreasing depressive symptoms. NeitherCBT alone, fluoxetine alone, nor their combination wereeffective for weight loss.

4.4 Other antidepressantsOpen-label data suggest milnacipran, reboxetine, and duloxe-tine may be effective in BN, including in treatment resistantcases [18], and that venlafaxine may be effective for reducing

binge eating and body weight in BED patients withobesity [43].

5. Antiepileptic drugs

The antiepileptic drugs studied thus far in binge eatingpopulations in RCTs include carbamazepine, lamotrigine,topiramate, phenytoin, and zonisamide [44].

5.1 CarbamazepineAmong 16 patients with DSM-III BN participating in a cross-over RCT for 12 -- 18 weeks, no significant difference inresponse was seen between carbamazepine and placebo [45].The one patient who had a remission in her BN symptomswhile receiving carbamazepine had comorbid cyclothymicdisorder; her mood symptoms also respond to carbamazepine.

5.2 TopiramateFive placebo-controlled RCTs of topiramate have been pub-lished to date in binge eating populations, two in BN [46-48]

and three in BED [49-51]. In all five studies, comprising 670patients, topiramate was superior to placebo for reducing bingeeating. The details of these studies are summarized below.

The first study of topiramate in BN was a 10-week trial in69 patients [46,47]. Topiramate (median dose 100 mg/d) wassuperior to placebo in reducing the frequency of binge andpurge days (days during which at least one binge eating orpurging episode occurred; p = .004); other measures of eatingdisorder symptomatology; and body weight. Significantlymore topiramate recipients (52%) than placebo recipients(24%) achieved ‡ 50% reduction in the number of bingeand/or purge days (p = .012). Numerically, more topiramaterecipients (63%) than placebo-recipients (53%) finishedthe trial. The most common side effects associated withtopiramate were fatigue, flu-like symptoms, and parasthesia.

In the second RCT in BN, 60 patients received topiramate(titrated to 250 mg/d by the sixth week with the dosage thenheld constant) or placebo for 10 weeks [48]. Topiramate wasassociated with significant decreases in the frequency of bing-ing/purging, body weight, and all scales on the SF 36 HealthSurvey (all ps < .001). Comparable numbers of patients in thetwo groups completed the trial, and all patients toleratedtopiramate well.

In the first RCT in BED, 61 patients with obesity receivedtopiramate (median dose 212 mg/d) or placebo for14 weeks [49]. Topiramate was significantly superior to pla-cebo in reducing binge frequency, as well as obsessive-compulsive features of binge eating, global severity of illness,body weight, and BMI. Dropout rate, however, was highwith 14 (47%) topiramate recipients and 12 (39%) placeborecipients failing to complete the trial. Paresthesia, dry mouth,headache, and dyspepsia were the most common side effectsassociated with topiramate.

The second RCT in BED was a multicenter trial inwhich 407 patients were randomized to receive topiramate

S. L. McElroy et al.

2018 Expert Opin. Pharmacother. (2012) 13(14)

Exp

ert O

pin.

Pha

rmac

othe

r. D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y H

INA

RI

on 0

9/26

/12

For

pers

onal

use

onl

y.

(median final dose 300 mg/d) or placebo for 16 weeks [50].Compared with placebo, topiramate significantly reducedweekly binge day frequency, binge frequency, weight, andBMI (all ps < 0.001). Topiramate also significantly decreasedobsessive-compulsive features of BED; trait impulsivity; othermeasures of eating disorder psychopathology; and disability.Significantly more topiramate-treated patients (58%) achievedremission compared with placebo-treated patients (29%;p < 0.001). Discontinuation rates were 30% in each group.Paresthesia, upper respiratory tract infection, somnolence,and nausea were the most frequent topiramate side effects.

The third RCT of topiramate in BED was a 3-center studyin which 73 obese patients were randomized to 19 sessions ofCBT in conjunction with topiramate (mean final dose206 mg/d) or placebo for 21 weeks [51]. Compared withpatients receiving placebo, patients receiving topiramateshowed a significantly greater rate of weight reduction (theprimary outcome measure) over the course of treatment(p < .001), as well as a significantly greater mean weight loss(--6.8 kg vs. --0.9 kg for placebo). A significantly higher rateof topiramate-treated patients (84%) attained remission ofbinge eating as compared to placebo-treated patients (61%;p = .03). There was no difference between groups in comp-letion rates. Paresthesia and taste perversion were more fre-quent with topiramate, whereas insomnia was more frequentwith placebo.

Topiramate has also been reported to reduce BN or BEDsymptoms in patients with treatment-resistant illness, includ-ing those with comorbid depressive or bipolar disorders, trau-matic brain injury or epilepsy, those receiving the drugadjunctively with antidepressants and/or mood stabilizers,and those with binge eating symptoms after bariatricsurgery [44,52,53]. On the other hand, there are reports oftopiramate misuse in eating disorder patients [44].

5.3 ZonisamideIn the only placebo-controlled RCT of zonisamide publishedto date in a binge eating sample, 60 patients with DSM-IV BED and obesity received zonisamide (mean [SD] endpointdose 436 159 mg/d) or placebo for 12 weeks [54]. Zonisamidewas superior to placebo for reducing binge frequency, bodyweight, BMI, and measures of global severity, disinihibitionof eating, and obsessive-compulsive features of binge eating.Attrition, however, was high, with 60% of zonisamide-treated patients and 40% of placebo-treated patients failingto complete the 12-week treatment period. Eight zonisamiderecipients discontinued for adverse events. The most commonside effects observed with zonisamide were dry mouth,somnolence, headache, nausea, nervousness, and altered taste.

5.4 LamotrigineIn the only RCT in a binge eating population, lamotrigine andplacebo had similarly high rates of reduction of weekly bingeeating frequency in 51 patients with BED and obesity [55].Lamotrigine, however, was associated with a numerically

greater amount of weight loss (1.17 kg for lamotrigine vs.0.15 kg for placebo) and statistically significant reductions infasting levels of glucose, insulin, and triglycerides.

5.5 PhenytoinIn a crossover RCT, 19 of 20 women with “binge eating syn-drome” completed six weeks each of phenytoin and placebo ina counter-balanced design [56]. Patients given phenytoin firstexperienced a 37% decrease in binge frequency (p < .01),but showed no change in binge frequency when switched toplacbo. Patients given placebo first experienced no change inbinge frequency, and did experience a 39% decrease afterswitching to phenytoin (p < .01). The significantly fewerbinges found in the phenytoin-first group than in theplacebo-first group (p < .02) indicated a carryover effect forthe phenytoin-first sequence.

5.6 Long-term and other studiesNo long-term placebo-controlled RCTs of antiepileptic drugsin BN or BED have been published. An open-label extensionstudy suggested that the anti-binge eating and weight losseffects of topiramate were maintained up to 1 year in BEDpatients, but treatment termination was common, includingfor adverse effects [57]. Another open-label study found thatzonisamide with CBT was superior to CBT alone for mainte-nance of binge eating response and weight loss in BEDpatients receiving treatment for 1 year [58].

5.7 Other antiepilepticsIn patients with comorbid bipolar disorder, valproate hasbeen reported to improve binge-purge symptoms in BN [59],but to worsen binge eating and enhance weight gain inBED [52]. A case series of 9 obese patients with BED treatedwith oxcarbazepine had inconsistent findings [60].

6. Antiobesity agents

The antiobesity agents studied thus far in BN or BED inRCTs have been the serotonin releasing agent D-fenflur-amine, the serotonin and norepinephrine reuptake inhibitorsibutramine, and the gastrointestinal lipase inhibitor orlistat.Although D-fenfluramine may reduce binge eating in BNand BED [18,61], and sibutramine reduces binge eating andbody weight in BED [62-64], both compounds have beenremoved from the worldwide market for safety concerns,and will not be reviewed in detail.

6.1 OrlistatOrlistat has been shown to reduce binge eating symptoms andenhance weight loss in twoRCTs in patients with BED and obe-sity [65,66]. In the first study, 50 patients were randomized toreceive individual CBT delivered by guided self help (CBTgsh)in combination with orlistat 120 mg three times daily orCBTgsh in combination with placebo for 12 weeks, andevaluated again at 3-month follow-up [65]. Binge eating

Current pharmacotherapy options for bulimia nervosa and binge eating disorder

Expert Opin. Pharmacother. (2012) 13(14) 2019

Exp

ert O

pin.

Pha

rmac

othe

r. D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y H

INA

RI

on 0

9/26

/12

For

pers

onal

use

onl

y.

remission rates were significantly higher for orlistat than placeboat posttreatment (64 vs. 36%) but not at 3-month follow-up (52% in both groups). Rates for achieving at least 5% weightloss were significantly higher for the orlistat group at both post-treatment (36 vs. 8%) and 3-month follow-up (32 vs. 8%). Inthe second study, 89 patients were randomized to orlistat120 mg three times daily or placebo in combination with amildly hypocaloric diet for 24 weeks [66]. Mean percentageweight loss (the primary outcome) was significantly greater fororlistat-recipients than for placebo-recipients (--7.4 vs. --2.3%;p = .0001). Waist circumference, hip circumference, total per-centage body fat, total cholesterol level, diastolic blood pressure,and insulin level were also significantly improved with orlistat.Although the mean number of binge eating episodes per weekwas numerically but not significantly decreased for orlistat-treated patients, Eating Disorder Inventory scores at week24 were significantly lower for orlistat than placebo (p = .011).More patients in the placebo group (29%) than the orlistatgroup (11%) discontinued prematurely.Orlistat has not been evaluated in BN. Moreover, orlistat

misuse has been reported in patients with BN [67] and BED [68].

6.2 Other anti-obesity agentsPhentermine, the most commonly prescribed medication forobesity in the US, is currently under evaluation as a componentin combination with topiramate (Qnexa) and with pramlintidefor weight loss in obesity [69-71]. There are no published RCTsof phentermine, alone or in combination with topiramate orpramlintide, in BN or BED.Open-label trials evaluating phen-termine in combination with fenfluramine [72] or fluoxetine [73]

in BED patients had mixed results.

7. Drugs for ADHD

Placebo-controlled RCTs of the selective norepinephrinereuptake inhibitor atomoxetine and the stimulants lisdexam-fetamine and methylamphetamine have been done in bingeeating samples.

7.1 AtomoxetineIn the one study of atomoxetine, 40 BED patients were ran-domized to receive flexibly dosed drug (mean endpoint dose106 mg/d) or placebo for 10 weeks [74]. Atomoxetine wassuperior to placebo in decreasing binge eating, global severityof BED, obsessive features of BED, hunger, and body weight.Fifteen patients (6 receiving atomoxetine) did not completethe trial. The most common atomoxetine side effectswere dry mouth, nausea, nervousness, insomnia, headache,constipation, and sweating.

7.2 StimulantsIn a crossover RCT, 8 patients with BN received methylam-phetamine or placebo intravenously followed by a testmeal [75]. Significantly fewer mean (SD) calories wereconsumed after methylamphetamine (224 ± 111) than after

placebo (943 ± 222; p < .02). Additionally, “the frequencyof bulimia” was significantly lower after methylamphetamine(0 of 8 patients) than after placebo (4 of 8 patients; p < .05).Preliminary results from a recently completed fixed-dosePhase-III study of lisdexamfetamine in 270 BED patients sug-gested it may be superior to placebo for reducing binge eat-ing [76]. A smaller flexible-dose RCT of lisdexamfetamine inBED (NCT01090713) is ongoing.

8. Anti-addiction (or anti-craving) drugs

A growing number of “anti-craving” medications [77] havebeen systematically evaluated in binge eating populations,but with mixed results.

8.1 Opioid antagonistsTwo placebo-controlled RCTs of naltrexone at standard dosesin binge eating populations, one in BN and the other in BED,were largely negative [78,79]. Similarly, a recently completed6-week RCT of the novel opioid antagonist ALKS 33,10 mg/d, in 68 patients with BED found no outcome differ-ences between drug and placebo [80]. Other studies, however,have suggested that naltrexone administered in supratherapeu-tic doses (200-400 mg/day) or in conjunction with an antide-pressant may decrease binge eating, including in patients withtreatment-resistant illness or comorbid diabetes [81-85]. Prelim-inary results of a six month Phase-II study of intranasal nalox-one in 129 patients with BED suggested this agent may besuperior to placebo in reducing time spent binge eating [86].A large program sponsored by Orexigen showing that naltrex-one in combination with bupropion (Contrave) is associatedwith more weight loss in obesity than either drug alone [70,71]

suggests this combination may have utility for BED, especiallysince the combination improved control over eating [87].

8.2 AcamprosateIn the only study of acamprosate in a binge eating population,40 patients with BED received drug (mean endpoint dailydose 2597 mg/d) or placebo for 10 weeks [88]. Acamprosatewas not associated with a significantly greater decrease inbinge frequency or any other outcome measure in the primarylongitudinal analysis. However, in the secondary endpointanalysis, the drug was associated with statistically significantimprovement in binge day frequency and in measures ofobsessive-compulsive symptoms of binge eating, food craving,and quality of life. Among completers, BMI decreased signif-icantly more for acamprosate-recipients than placebo-recipients (p = .04). In addition, the drug was well toleratedwith a significantly higher completion (79%) rate than forplacebo (45%, p = .05). Diarrhea was the more commonside effect.

8.3 Other anti-addiction agentsThe g-amminobutyric acid (GABA) B-receptor agonistbaclofen, which may reduce alcohol intake in alcohol

S. L. McElroy et al.

2020 Expert Opin. Pharmacother. (2012) 13(14)

Exp

ert O

pin.

Pha

rmac

othe

r. D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y H

INA

RI

on 0

9/26

/12

For

pers

onal

use

onl

y.

dependence, was reported to decrease binge eating in BN andBED in a 10-week open-label trial when given at 60 mg/d [89].

9. Hormonal treatments

Two placebo-controlled RCTs have assessed hormonal agentswith antiandrogenic properties in BN patients with mixedresults. In the first study, 46 women were randomized to thetestosterone receptor antagonist flutamide (n = 9), citalopram(n = 15), flutamide plus citalopram (n = 10), or placebo(n = 12) for 3 months [90]. Final flutamide and citaprolamdoses were 500mg/d and 40mg/d, respectively. Binge eatingwas significantly reduced compared with placebo only in thegroup receiving the combination (p = .04). Vomiting wasnot significantly decreased in any group. Two patients discon-tinued flutamide for increases in serum transaminase levelswhich resolved upon drug discontinuation. In the secondstudy, treatment with spironolactone, an aldosterone antago-nist with antiandrogenic properties marketed as a diuretic,for 56 days had no effects on binge eating or vomitingcompared with placebo in 93 patients with BN [91].

10. 5HT3 antagonists

One 4-week placebo-controlled RCT of ondansetron has beenconducted in 26 women with severe BN, defined as the occur-rence of at least 7 binge/vomit episodes per week [92]. Ondan-setron, self-administered in 4 mg capsules up to 6/d upon theurge to binge or vomit, was associated with a significantlygreater decrease in binge/vomit frequencies, a significantdecrease in the time spent engaging in bulimic behaviors, andwith a significant increase in normal meals consumed com-pared with placebo. However, at study endpoint, participantsreceiving ondansetron continued to display over a mean of5 binge/vomit episodes per week. Moreover, reports of QTinterval prolongation with ondansetron prompted the FDAto advise that ondanestron not be used in patients with congen-ital long QT syndrome, and that ECG monitoring be con-ducted when using the drug in certain clinical situations,including in patients with electrolyte abnormalities [93]. Therehave been no studies of 5-HT3 antagonists in BED.

11. Lithium

A placebo-controlled RCT in 91 patients with BN found lith-ium (mean level. 62 mEq/l) was not superior to placebo indecreasing binge eating episodes, except possibly in depressedpatients [94]. However, case reports have described the success-ful treatment with lithium of patients with BN or BED andcomorbid bipolar disorder [18,53].

12. Other agents

The glutamate modulating agent memantine has been reportedto reduce binge eating in BED in two open-label trials [95,96]. In

an open-label trial in 12 patients with BED, the sodium salt ofg hydroxybutyrate, sodium oxybate (mean endpoint dose 7.1[2.0] g/d), was associated with significant reductions in bingeeating and body weight [97]. Placebo-controlled RCTs of thewakefulness-promoting agent armodafinil (NCT01010789)and the dietary supplement chromium (NCT00904306) inBED are ongoing.

There are no published controlled studies of antipsychoticsin BN or BED. Rather, second generation antipsychotics havebeen reported to induce or exacerbate binge eating in patientswith eating disorders [98], as well as in patients with psychoticdisorders [99].

13. Expert opinion

Pharmacotherapy research of BN and BED is in its early stages.Fluoxetine is the only medication with regulatory approval inBN, and no medication has approval for use in BED. Manyof the available pharmacotherapy studies in BN and BED arelimited by small sample size, high placebo response and drop-out rates, and unclear generalizability of findings to real worldclinical situations. Very few placebo-controlled maintenancetrials in patients whose binge eating was in remission havebeen published. There has only been one placebo-controlledpharmacotherapy study in BN patients who were inadequatelyresponsive to psychotherapy; comparable studies have not beendone for BED. There have been no controlled pharmacother-apy studies in adolescents or older adults with BN or BED,or in children with loss of control eating. Except for obesityand major depressive disorder in BED, there has been no phar-macotherapy study of patients with BN or BED and a specifiedpsychiatric or medical comorbidity. Moreover, it is not yetknown whether the binge eating in BN and BED respondsimilarly to pharmacotherapy.

Yet many individuals with binge eating receive pharmaco-therapy [14], and several conclusions regarding the pharmaco-therapy of BN and BED from extant research can be reached(Table 1). Substantial evidence indicates antidepressants aremodestly efficacious for binge eating in both BN and BEDover the short-term [15,17-19,23,24]. A smaller body of datasuggests they may be modestly effective as maintenanceagents in BN [36,37]. Antidepressants, including the SNRIduloxetine, may also be useful for the depressive symptomsand/or syndromes that may accompany BN and BED. Theydo not, however, appear to have clinically significant benefitson body weight in BED, and their long-term efficacy in BEDis not known. Antidepressants may enhance the anti-bingeeating effects of CBT in BN or BED, but available data aremixed [39-42]. It is unknown whether these findings wouldgeneralize to antidepressants with different pharmacodynamicprofiles, such as bupropion or vilazodone.

Considerable double-blind, placebo-controlled data showthat topiramate is effective for the binge eating of BN andBED [46-51]. Topiramate also may be effective for othercorrelates of binge eating, such as purging in BN, and for

Current pharmacotherapy options for bulimia nervosa and binge eating disorder

Expert Opin. Pharmacother. (2012) 13(14) 2021

Exp

ert O

pin.

Pha

rmac

othe

r. D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y H

INA

RI

on 0

9/26

/12

For

pers

onal

use

onl

y.

weight loss in BEDwith obesity. One RCT showed topiramatemay enhance the effectiveness of CBT in BED [51], while anopen-label study found topiramate’s anti-binge-eating andweight loss effects in BED may persist for up to one year(though drug discontinuation rates were high, in part due toadverse events) [57]. Orlistat, when used in combination withCBT or dietary therapy, leads to enhanced weight loss and pos-sibly reduced binge eating in BED [65,66]. Drugs shown effica-cious in one published RCT include ondansetron for BN [92],and zonisamide and atomoxetine for BED [54,74]. Preliminaryreports from Phase-II studies suggest lisdexamfetamine andintranasal naloxone may be helpful for BED [76,86].In light of the nascent status of pharmacotherapy research

in binge eating, some authorities suggest psychotherapyshould be the first-line treatment of BN and BED [13,17,21].However, this recommendation needs to account for a num-ber of factors. These include patient preference; the incom-plete effectiveness and availability of psychotherapy; thepotential lack of generalizability of psychotherapy study find-ings; and the fact that pharmacotherapy can be combinedwith or added to psychotherapy. Moreover, both BN andBED are most likely each heterogeneous conditions [100].Thus, while some patients respond to psychotherapy alone,others respond optimally only with pharmacotherapy,

including combinations of medications [101]. Identificationof factors predicting requirement of pharmacotherapy, alongwith the particular medications most likely to be effective,will help realize personalized treatment of BN and BED.

Despite the preliminary status of the knowledge base, phar-macotherapy should be considered a therapeutic option formost BN and BED patients, including those naı̈ve to treat-ment, but especially when psychotherapy response has beeninadequate. Patients with binge eating should be educatedabout psychological and medical options, including the viewthat psychotherapy is considered a treatment of choice forBN and BED, but that the knowledge base for pharmacother-apy is growing. For patients who decline psychotherapy, orhave an inadequate response, fluoxetine (or another SSRI)should be offered as a first-line option for BN; for BED, top-iramate or an antidepressant should be offered. Thoughbupropion is contraindicated for BN, it has been used inBED, in part due to its weight loss effects. Zonisamide maybe considered in patients unable to tolerate topiramate, espe-cially if they responded to the drug. Some patients with BN orBED may require combination pharmacotherapy for optimalresults [14,101,102].

Pharmacotherapy of BN and BED should also be guided byco-occurring conditions. Although empirical data are largelylacking, antidepressants may be helpful for BN or BEDpatients with a depressive or anxiety disorder; topiramateor zonisamide for those with comorbid obesity and/or anobesity-related complication; atomoxetine or stimulants forthose with comorbid ADHD; and anti-addiction or anti-craving drugs for those with co-occurring substance use disor-ders. Similarly, no empirical data are available for treatingBN or BED patients with bipolar disorder. In such patientswith obesity or fear of taking a mood stabilizer because ofpossible weight gain, agents effective in mania or bipolardepression that have minimal effects on weight may beconsidered, such as the second generation antipsychotics aripi-prazole, lurasidone, or ziprasidone for predominantly manicpresentations, and lamotrigine or lurasidone for predomi-nantly depressive presentations. For patients with BN orBED who have mood-stabilizing responses but continue tohave binge eating, augmentation with topiramate or antide-pressants may be considered. Electrolyte disturbances mustbe monitored for in patients with purging behavior who aretreated with lithium.

When treating BN or BED patients with pharmacotherapy,it is important that psychological strategies be pursued andoptimized. This includes strongly recommending psychother-apy to patients who have an inadequate response to pharma-cotherapy, including those who initially refuse psychotherapy.

In summary, pharmacotherapy has an important role in themanagement of BN and BED, including in patients inade-quately responsive to psychotherapy, patients with comorbidpsychiatric or medical disorders, and those with chronic orintractable illness. However, the available pharmacotherapeuticarmamentarium for both conditions and its supporting evidence

Table 1. Pharmacological treatment of bulimia nervosa

and binge eating disorder: summary of evidence.

Drug/Class Bulimia

Nervosa

Binge eating

disorder

Antidepressants (acute)SSRIs +++ +++Tricyclics +++ +++SNRIs + ++MAOIs +++ NDAntidepressants (long term) +++ +/-

AntiepilepticsLamotrigine ND +/-Phenytoin +/- +/-Topiramate +++ +++Zonisamide ND ++

Anti-Obesity DrugsOrlistat ND +++

Anti-ADHD drugsAtomoxetine ND ++Stimulants + ++

Anti-Addiction DrugsAcamprosate ND +/-Opioid Antagonists - +/-Opioid Antagonists (high dose) + +

+++: At least 2 positive placebo-controlled RCTs; ++: 1 positive placebo-

controlled RCT with no negative RCTs; +: Positive open studies; +/-: Mixed

results; -: Placebo-controlled RCT data mostly negative; MAOIs: Monoamine

oxidase inhibitors; ND: No data; RCT: Randomized placebo-controlled trial;

SSRIs: Selective serotonin reuptake inhibitors; SNRIs: Selective serotonin

norepinephrine reuptake inhibitor.

S. L. McElroy et al.

2022 Expert Opin. Pharmacother. (2012) 13(14)

Exp

ert O

pin.

Pha

rmac

othe

r. D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y H

INA

RI

on 0

9/26

/12

For

pers

onal

use

onl

y.

base is far from adequate. Further study is needed to clarifywhich specific agents, and combinations of agents, might bemost useful for which patient subgroups, as well as to delineatethe larger role of pharmacotherapy in relationship to other treat-ments. Novel medical treatments for binge eating are neededand rational drug discovery devoted to binge eating needs tooccur. In the meantime, current and future medications withpsychotropic benefits and/or favorable effects on appetite andweight might be considered as potential therapeutic agents forBN and BED.

Declaration of interest

This study has been supported by the Lindner Centre ofHope, and the University of Cincinnati. S McElroy is a

consultant to or member of the scientific advisory boardsof: Alkermes, Corcept, MedAvante, Shire, and Teva; She isa principal or co-investigator on studies sponsored by: theAgency for Healthcare Research & Quality (AHRQ),Alkermes, AstraZeneca, Cephalon, Eli Lilly and Company,Marriott Foundation, National Institute of Mental Health,Orexigen Therapeutics, Inc., Shire, Takeda Pharmaceu-tical Company Ltd., and Transcept Pharmaceutical, Inc;She is also an inventor on United States Patent No.6,323,236 B2, Use of Sulfamate Derivatives for TreatingImpulse Control Disorders, and along with the patient’sassignee, University of Cincinnati, Cincinnati, Ohio, hasreceived payments from Johnson & Johnson, which hasexclusive rights under the patent. All other authors declareno conflict of interest.

BibliographyPapers of special note have been highlighted as

either of interest (�) or of considerable interest(��) to readers.

1. A.P.A. Diagnostic and statistical manual

of mental disorders. 4th edition.

Text Revision American Psychiatric

Association; Washington, DC: 2000

2. Treasure J, Claudino AM, Zucker N.

Eating disorders. Lancet

2010;375(9714):583-93.. Excellent general overiew of current

research on eating disorders.

3. Wonderlich SA, Gordon KH,

Mitchell JE, et al. The validity and

clinical utility of binge eating disorder.

Int J Eat Disord 2009;42(8):687-705.. Excellent overview of evidence

indicating binge eating disorder is a

discrete diagnostic entity.

4. A.P.A. DSM-5: feeding and Eating

Disorders. Available from: http://www.

dsm5.org/proposedrevision/Pages/

FeedingandEatingDisorders.aspx [Last

accesed 2012 July 5]

5. Hudson JI, Hiripi E, Pope HG Jr, et al.

The prevalence and correlates of eating

disorders in the National Comorbidity

Survey Replication. Biol Psychiatry

2007;61(3):348-58. Important study of the epidemiology

of eating disorders in adults.

6. Swanson SA, Crow SJ, Le Grange D,

et al. Prevalence and correlates of eating

disorders in adolescents: results from the

national comorbidity survey replication

adolescent supplement. Arch Gen

Psychiatry 2011;68:714-23. Important study of the epidemiology

of eating disorders in adolescents.

7. Mitchell JE, Crow SJ. Medical

comorbidities of eating disorders. In:

Agras WS, editor. The Oxford handbook

of eating disorders. Oxford University

Press; New York: 2010. p. 259

8. Hudson JI, Lalonde JK, Coit CE, et al.

Longitudinal study of the diagnosis of

components of the metabolic syndrome

in individuals with binge eating disorder.

Am J Clin Nutrition

2010;91(6):1568-73

9. Walsh BT, Boudreau G. Laboratory

studies of binge eating disorder. Int J

Eat Disord 2003;34(Suppl):S30-8

10. Berner LA, Bocarsly ME, Hoebel BG,

et al. Pharmacological interventions for

binge eating: lessons from animal

models, current treatments, and future

directions. Curr Pharm Des

2011;17(12):1180-7

11. Wang G-J, Geliebter A, Volkow ND,

et al. Enhanced striatal dopamine release

during food stimulation in binge eating

disorder. Obesity (Silver Spring)

2011;19:1601-8

12. Hay PP, Bacaltchuk J, Stefano S, et al.

Psychological treatments for bulimia

nervosa and binging. Cochrane Database

Syst Rev 2009(4):CD000562

13. Wilson GT. Treatment of binge eating

disorder. Psychiatr Clin North Am

2011;34(4):773-83

14. Yager J. Management of patients with

chronic, intractable eating disorders. In:

Yager J, Powers PS, editors. Clinical

manual of eating disorders. American

Psychiatric Publishin, Washington, DC;

2007. p. 407-39

15. Berkman ND, Bulik CM, Brownley KA,

et al. Management of eating disorders.

Evid Rep Technol Assess (Full Rep)

2006;Apr(135):1-166

16. Hay PJ, Bacaltchuk J. Bulimia nervosa.

Clin Evid (Online) 2008;2008:1009

17. Reas DL, Grilo CM. Review and

meta-analysis of pharmacotherapy for

binge-eating disorder.

Obesity (Silver Spring)

2008;16(9):2024-38

18. McElroy SL, Guerdjikova A,

O’Melia AM, et al. Pharmacotherapy of

the eating disorders. In: Agras S, editor.

Oxford Handbook of Eating Disorders.

Oxford University Press, Inc; New York,

NY: 2010. p. 417-51

19. Flament MF, Bissada H, Spettigue W.

Evidence-based pharmacotherapy of

eating disorders.

Int J Neuropsychopharmacol

2012;15(2):189-207

20. McElroy SL, Guerdjikova AI, Mori N,

et al. Pharmacolgical management of

binge eating disorder: current and

emerging treatment options.

Therapeutics and Clinical

Risk Management 2012;8:219-41

21. NICE. Eating disorders. Core

interventions in the treatment and

managment of anorexia nervosa, bulimia

nervosa and related eating disorders.

Clinical guideline no 9. London January

2004

22. A.P.A. Treatment of patients with eating

disorders, third edition. American

Psychiatric Association. Am J Psychiatry

2006;163(7 Suppl):4-54

Current pharmacotherapy options for bulimia nervosa and binge eating disorder

Expert Opin. Pharmacother. (2012) 13(14) 2023

Exp

ert O

pin.

Pha

rmac

othe

r. D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y H

INA

RI

on 0

9/26

/12

For

pers

onal

use

onl

y.

23. Aigner M, Treasure J, Kaye W, et al.

World Federation of Societies of

Biological Psychiatry (WFSBP) guidelines

for the pharmacological treatment of

eating disorders. World J Biol Psychiatry

2011;12(6):400-43

24. Bacaltchuk J, Hay PPJ. Antidepressants

versus placebo for people with bulimia

nervosa. Cochrane Database Syst Rev

2003(4):CD003391.. Important review showing

antidepressants are modestly effective

for bulimia nervosa.

25. Milano W, Petrella C, Sabatino C, et al.

Treatment of bulimia nervosa with

sertraline: a randomized controlled trial.

Adv Ther 2004;21(4):232-7

26. Milano W, Siano C, Putrella C, et al.

Treatment of bulimia nervosa with

fluvoxamine: a randomized controlled

trial. Adv Ther 2005;22(3):278-83

27. Stefano SC, Bacaltchuk J, Blay SL, et al.

Antidepressants in short-term treatment

of binge eating disorder: systematic

review and meta-analysis. Eat Behav

2008;9(2):129-36

28. FBNCSG. Fluoxetine in the treatment of

bulimia nervosa. A multicenter,

placebo-controlled, double-blind trial.

Arch Gen Psychiatry 1992;49:139-47.. Largest randomized, placebo-controlled

pharmacotherapy trial in bulimia

nervosa to date.

29. Walsh BT, Agras WS, Devlin MJ, et al.

Fluoxetine for bulimia nervosa following

poor response to psychotherapy.

Am J Psychiatry 2000;157(8):1332-4

30. Walsh BT, Fairburn CG, Mickley D,

et al. Treatment of bulimia nervosa in a

primary care setting. Am J Psychiatry

2004;161(3):556-61

31. Sysko R, Sha N, Wang Y, et al. Early

response to antidepressant treatment in

bulimia nervosa. Psychol Med

2010;40(6):999-1005

32. Grilo CM, Masheb RM, Wilson GT.

Rapid response to treatment for binge

eating disorder. J Consult Clin Psychol

2006;74(3):602-13

33. Guerdjikova AI, McElroy SL,

Winstanley EL, et al. Duloxetine in the

treatment of binge eating disorder with

depressive disorders: a placebo-controlled

trial. Int J Eat Disord 2012;45:281-9

34. Horne RL, Ferguson JM, Pope HG Jr,

et al. Treatment of bulimia with

bupropion: a multicenter controlled trial.

J Clin Psychiatry 1988;49(7):262-6

35. Calandra C, Russo RG, Luca M.

Bupropion versus sertraline in the

treatment of depressive patients with

binge eating disorder: Retrospective

cohort study. Psychiatr Q 2011;

83(2):177-85

36. Fichter MM, Kruger R, Rief W, et al.

Fluvoxamine in prevention of relapse in

bulimia nervosa: effects on eating-specific

psychopathology.

J Clin Psychopharmacol 1996;16(1):9-18

37. Romano SJ, Halmi KA, Sarkar NP, et al.

A placebo-controlled study of fluoxetine

in continued treatment of bulimia

nervosa after successful acute fluoxetine

treatment. Am J Psychiatry

2002;159(1):96-102. Largest randomized, placebo-controlled

maintenance pharmacotherapy trial in

bulimia nervosa to date.

38. Leombruni P, Piero A, Lavagnino L,

et al. A randomized, double-blind trial

comparing sertraline and fluoxetine

6-month treatment in obese patients with

binge eating disorder.

Prog Neuropsychopharmacol

Biol Psychiatry 2008;32(6):1599-605

39. Bacaltchuk J, Hay P, Trefiglio R.

Antidepressants versus psychological

treatments and their combination for

bulimia nervosa. Cochrane Database

Syst Rev 2001(4):CD003385

40. Laederach-Hofmann K, Graf C,

Horber F, et al. Imipramine and diet

counseling with psychological support in

the treatment of obese binge eaters:

a randomized, placebo-controlled double-

blind study. Int J Eat Disord

1999;26(3):231-44

41. Grilo CM, Masheb RM, Wilson GT.

Efficacy of cognitive behavioral therapy

and fluoxetine for the treatment of binge

eating disorder: a randomized

double-blind placebo-controlled

comparison. Biol Psychiatry

2005;57(3):301-9

42. Devlin MJ, Goldfein JA, Petkova E,

et al. Cognitive behavioral therapy

and fluoxetine as adjuncts to group

behavioral therapy for binge

eating disorder. Obes Res

2005;13(6):1077-88

43. Malhotra S, King KH, Welge JA, et al.

Venlafaxine treatment of binge-eating

disorder associated with obesity: a series

of 35 patients. J Clin Psychiatry

2002;63(9):802-6

44. McElroy SL, Guerdjikova AI, Martens B,

et al. Role of antiepileptic drugs in the

management of eating disorders.

CNS Drugs 2009;23(2):139-56

45. Kaplan AS, Garfinkel PE, Darby PL,

et al. Carbamazepine in the treatment of

bulimia. Am J Psychiatry

1983;140(9):1225-6

46. Hoopes SP, Reimherr FW, Hedges DW,

et al. Treatment of bulimia nervosa with

topiramate in a randomized,

double-blind, placebo-controlled trial,

part 1: improvement in binge and purge

measures. J Clin Psychiatry

2003;64(11):1335-41

47. Hedges DW, Reimherr FW, Hoopes SP,

et al. Treatment of bulimia nervosa with

topiramate in a randomized,

double-blind, placebo-controlled trial,

part 2: improvement in psychiatric

measures. J Clin Psychiatry

2003;64(12):1449-54

48. Nickel C, Tritt K, Muehlbacher M, et al.

Topiramate treatment in bulimia nervosa

patients: a randomized, double-blind,

placebo-controlled trial. Int J Eat Disord

2005;38(4):295-300

49. McElroy SL, Arnold LM, Shapira NA,

et al. Topiramate in the treatment of

binge eating disorder associated with

obesity: a randomized, placebo-controlled

trial. Am J Psychiatry

2003;160(2):255-61

50. McElroy SL, Hudson JI, Capece JA,

et al. Topiramate for the treatment of

binge eating disorder associated with

obesity: a placebo-controlled study.

Biol Psychiatry 2007;61(9):1039-48. Largest randomized, placebo-controlled

pharmacotherapy trial in binge eating

disorder to date.

51. Claudino AM, de Oliveira IR,

Appolinario JC, et al. Double-blind,

randomized, placebo-controlled trial of

topiramate plus cognitive-behavior

therapy in binge-eating disorder.

J Clin Psychiatry 2007;68(9):1324-32. Important study showing topiramate

plus CBT is superior to placebo plus

CBT for weight reduction and

remission of binge eating in binge

eating disorder.

52. Shapira NA, Goldsmith TD,

McElroy SL. Treatment of binge-eating

disorder with topiramate: a clinical case

S. L. McElroy et al.

2024 Expert Opin. Pharmacother. (2012) 13(14)

Exp

ert O

pin.

Pha

rmac

othe

r. D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y H

INA

RI

on 0

9/26

/12

For

pers

onal

use

onl

y.

series. J Clin Psychiatry

2000;61(5):368-72

53. Kotwal R, Guerdjikova A, McElroy SL,

et al. Lithium augmentation of

topiramate for bipolar disorder with

comorbid binge eating disorder and

obesity. Hum Psychopharmacol

2006;21(7):425-31

54. McElroy SL, Kotwal R, Guerdjikova AI,

et al. Zonisamide in the treatment of

binge eating disorder with obesity:

a randomized controlled trial.

J Clin Psychiatry 2006;67(12):1897-906

55. Guerdjikova AI, McElroy SL, Welge JA,

et al. Lamotrigine in the treatment of

binge-eating disorder with obesity:

a randomized, placebo-controlled

monotherapy trial. Int Clin

Psychopharmacol 2009;24(3):150-8

56. Wermuth BM, Davis KL, Hollister LE,

et al. Phenytoin treatment of the

binge-eating syndrome. Am J Psychiatry

1977;134(11):1249-53

57. McElroy SL, Shapira NA, Arnold LM,

et al. Topiramate in the long-term

treatment of binge-eating disorder

associated with obesity. J Clin Psychiatry

2004;65(11):1463-9

58. Ricca V, Castellini G, Lo Sauro C, et al.

Zonisamide combined with cognitive

behavioral therapy in binge eating

disorder: a one-year follow-up study.

Psychiatry (Edgmont) 2009;6(11):23-8

59. Herridge PL, Pope HG, Jr. Treatment of

bulimia and rapid-cycling bipolar

disorder with sodium valproate: a case

report. J Clin Psychopharmacol

1985;5(4):229-30

60. Leombruni P, Gastaldi F, Lavagnino L,

et al. Oxcarbazepine for the treatment of

binge eating disorder: a case series.

Adv Ther 2008;25(7):718-24

61. Stunkard A, Berkowitz R, Tanrikut C,

et al. D-fenfluramine treatment of binge

eating disorder. Am J Psychiatry

1996;153(11):1455-9

62. Appolinario JC, Bacaltchuk J, Sichieri R,

et al. A randomized, double-blind,

placebo-controlled study of sibutramine

in the treatment of binge-eating disorder.

Arch Gen Psychiatry

2003;60(11):1109-16

63. Milano W, Petrella C, Casella A, et al.

Use of sibutramine, an inhibitor of the

reuptake of serotonin and noradrenaline,

in the treatment of binge eating disorder:

a placebo-controlled study. Adv Ther

2005;22(1):25-31

64. Wilfley DE, Crow SJ, Hudson JI, et al.

Efficacy of sibutramine for the treatment

of binge eating disorder: a randomized

multicenter placebo-controlled

double-blind study. Am J Psychiatry

2008;165(1):51-8

65. Grilo CM, Masheb RM, Salant SL.

Cognitive behavioral therapy guided

self-help and orlistat for the treatment of

binge eating disorder: a randomized,

double-blind, placebo-controlled trial.

Biol Psychiatry 2005;57(10):1193-201

66. Golay A, Laurent-Jaccard A, Habicht F,

et al. Effect of orlistat in obese patients

with binge eating disorder. Obes Res

2005;13(10):1701-8

67. Fernandez-Aranda F, Amor A,

Jimenez-Murcia S, et al. Bulimia nervosa

and misuse of orlistat: two case reports.

Int J Eat Disord 2001;30(4):458-61

68. Hagler Robinson A. Orlistat misuse as

purging in a patient with binge-eating

disorder. Psychosomatics

2009;50(2):177-8

69. Aronne LJ, Halseth AE, Burns CM,

et al. Enhanced weight loss following

coadministration of pramlintide with

sibutramine or phentermine in a

multicenter trial. Obesity (Silver Spring)

2010;18(9):1739-46

70. Aronne LJ, Powell AG, Apovian CM.

Emerging pharmacotherapy for obesity.

Expert Opin Emerg Drugs

2011;16(3):587-96

71. Ioannides-Demos LL, Piccenna L,

McNeil JJ. Pharmacotherapies for

obesity: past, current, and future

therapies. J Obes 2011;2011:179674

72. Alger SA, Malone M, Cerulli J, et al.

Beneficial effects of pharmacotherapy on

weight loss, depressive symptoms, and

eating patterns in obese binge eaters and

non-binge eaters. Obes Res

1999;7(5):469-76

73. Devlin MJ, Goldfein JA, Carino JS,

et al. Open treatment of overweight

binge eaters with phentermine and

fluoxetine as an adjunct to

cognitive-behavioral therapy. Int J

Eat Disord 2000;28(3):325-32

74. McElroy SL, Guerdjikova A, Kotwal R,

et al. Atomoxetine in the treatment of

binge-eating disorder: a randomized

placebo-controlled trial. J Clin Psychiatry

2007;68(3):390-8

75. Ong YL, Checkley SA, Russell GF.

Suppression of bulimic symptoms with

methylamphetamine. Br J Psychiatry

1983;143:288-93

76. Shire. Shire Reports Positive

Phase 2 Study Met Primary End Point

for Investigative Use of Vyvanse

(lisdexamfetamine dimesylate)

Capsules, (CII) in Adults with

Binge Eating Disorder. 2012.

Available from: http://www.shire.com/

shireplc/en/media/shirenews/?id=593

[Last accessed 14 June 2012]

77. O’Brien CP. Anticraving medications

for relapse prevention: a possible

new class of psychoactive medications.

Am J Psychiatry 2005;162(8):1423-31

78. Mitchell JE, Christenson G, Jennings J,

et al. A placebo-controlled, double-blind

crossover study of naltrexone

hydrochloride in outpatients with normal

weight bulimia. J Clin Psychopharmacol

1989;9(2):94-7

79. Alger SA, Schwalberg MD,

Bigaouette JM, et al. Effect of a tricyclic

antidepressant and opiate antagonist on

binge-eating behavior in normoweight

bulimic and obese, binge-eating subjects.

Am J Clin Nutr 1991;53(4):865-71

80. Alkermes. Alkermes Announces Results

from Phase 2 Study of ALKS 33 for

Treatment of Binge Eating Disorder.

2011.Available from: http://investor.

alkermes.com/phoenix.zhtml?

c=92211&p=irol-newsArticle&

ID=1582921&highlight [Last accessed

14 June 2012]

81. Marrazzi MA, Bacon JP, Kinzie J, et al.

Naltrexone use in the treatment of

anorexia nervosa and bulimia nervosa.

Int Clin Psychopharmacol

1995;10(3):163-72

82. Jonas JM, Gold MS. The use of opiate

antagonists in treating bulimia: a study

of low-dose versus high-dose naltrexone.

Psychiatry Res 1988;24(2):195-9

83. Raingeard I, Courtet P, Renard E, et al.

Naltrexone improves blood glucose

control in type 1 diabetic women with

severe and chronic eating disorders.

Diabetes Care 2004;27(3):847-8

84. Marrazzi MA, Markham KM, Kinzie J,

et al. Binge eating disorder: response to

naltrexone. Int J Obes Relat

Metab Disord 1995;19(2):143-5

85. Neumeister A, Winkler A,

Wober-Bingol C. Addition of naltrexone

Current pharmacotherapy options for bulimia nervosa and binge eating disorder

Expert Opin. Pharmacother. (2012) 13(14) 2025

Exp

ert O

pin.

Pha

rmac

othe

r. D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y H

INA

RI

on 0

9/26

/12

For

pers

onal

use

onl

y.

to fluoxetine in the treatment of binge

eating disorder. Am J Psychiatry

1999;156(5):797

86. Lightlake Therapeutics Inc. Lightlake

Therapeutics Inc. Announces Positive

Preliminary Phase II Clinical Trial

Results of Binge Eating Disorder

Treatment. 2012. Available

from: http://www.prnewswire.com/news-

releases/lightlake-therapeutics-inc-

announces-positive-preliminary-phase-ii-

clinical-trial-results-of-binge-eating-

disorder-treatment-149993255.html [Last

accessed 6 July 2012]

87. Greenway FL, Fujioka K,

Plodkowski RA, et al. Effect of

naltrexone plus bupropion on weight loss

in overweight and obese adults (COR-I):

a multicentre, randomised, double-blind,

placebo-controlled, phase 3 trial. Lancet

2010;376(9741):595-605

88. McElroy SL, Guerdjikova AI,

Winstanley EL, et al. Acamprosate in the

treatment of binge eating disorder:

a placebo-controlled trial. Int J

Eat Disord 2011;44(1):81-90

89. Broft AI, Spanos A, Corwin RL, et al.

Baclofen for binge eating: an open-label

trial. Int J Eat Disord 2007;40(8):687-91

90. Sundblad C, Landen M, Eriksson T,

et al. Effects of the androgen antagonist

flutamide and the serotonin reuptake

inhibitor citalopram in bulimia nervosa:

a placebo-controlled pilot study.

J Clin Psychopharmacol 2005;25(1):85-8

91. von Wietersheim J, Muler-Bock V,

Rauh S, et al. No effect of

spironolactone on bulimia nervosa

symptoms. J Clin Psychopharmacol

2008;28(2):258-60

92. Faris PL, Kim SW, Meller WH, et al.

Effect of decreasing afferent vagal activity

with ondansetron on symptoms of

bulimia nervosa: a randomised,

double-blind trial. Lancet

2000;Mar4355(9206):792-7

93. FDA. FDA Drug Safety

Communication: abnormal heart

rhythms may be associated with use of

Zofran (ondanestron). 2011.

Available from: http://www.fda.gov/

Drugs/DrugSafety/ucm271913.htm [Last

accessed 10 July 2012]

94. Hsu LK, Clement L, Santhouse R, et al.

Treatment of bulimia nervosa with

lithium carbonate. A controlled study.

J Nerv Ment Dis 1991;179(6):351-5

95. Hermanussen M, Tresguerres JA. A new

anti-obesity drug treatment: first clinical

evidence that, antagonising

glutamate-gated Ca2+ ion channels with

memantine normalises binge-eating

disorders. Econ Hum Biol

2005;3(2):329-37

96. Brennan BP, Roberts JL, Fogarty KV,

et al. Memantine in the treatment of

binge eating disorder: an open-label,

prospective trial. Int J Eat Disord

2008;41(6):520-6

97. McElroy SL, Guerdjikova AI,

Winstanley EL, et al. Sodium oxybate in

the treatment of binge eating disorder:

an open-label, prospective study. Int J

Eat Disord 2011;44(3):262-8

98. Gebhardt S, Haberhausen M, Krieg JC,

et al. Clozapine/olanzapine-induced

recurrence or deterioration of binge

eating-related eating disorders.

J Neural Transm 2007;114(8):1091-5

99. Theisen FM, Linden A, Konig IR, et al.

Spectrum of binge eating

symptomatology in patients treated with

clozapine and olanzapine.

J Neural Transm 2003;110(1):111-21

100. Sysko R, Hildebrandt T, Wilson GT,

et al. Heterogeneity moderates treatment

response among patients with binge

eating disorder. J Consult Clin Psychol

2010;78(5):681-90

101. Brambilla F, Samek L, Company M,

et al. Multivariate therapeutic approach

to binge-eating disorder: combined

nutritional, psychological and

pharmacological treatment.

Int Clin Psychopharmacol

2009;24(6):312-17

102. Marilov VV, Sologub MB. Comparative

effectiveness of mood stabilizers in the

complex therapy of bulimia nervosa.

Zh Nevrol Psikhiatr Im S S Korsakova

2010;110(1):59-61

AffiliationSusan L McElroy1,2,3 MD,

Anna I Guerdjikova1,2,4 PhD,

Nicole Mori1,2,5 RN MSN &

Anne M O’Melia1,2,6 MD1Lindner Center of HOPE,

4075 Old Western Row Road,

Mason, OH 45040, USA2University of Cincinnati College of Medicine,

Psychiatry & Behavioral Neuroscience,

260 Stetson St.,

Cincinnati OH 45219, USA3Chief Research Officer,

Lindner Center of HOPE,

4075 Old Western Row Road,

Mason, OH 45040, USA

Tel: +1 513 536 0700;

Fax: +1 513 536 0709;

E-mail: susan.mcelroy@lindnercenter.org4Associate Research Director,

Harold C. Schott Eating Disorders Program,

Lindner Center of HOPE,

4075 Old Western Row Road,

Mason, OH 45040, USA5Nurse Practitioner,

Lindner Center of HOPE,

4075 Old Western Row Road,

Mason, OH 45040, USA6Medical Director,

Harold C. Schott Eating Disorders Program,

Lindner Center of HOPE,

4075 Old Western Row Road,

Mason, OH 45040, USA

S. L. McElroy et al.

2026 Expert Opin. Pharmacother. (2012) 13(14)

Exp

ert O

pin.

Pha

rmac

othe

r. D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y H

INA

RI

on 0

9/26

/12

For

pers

onal

use

onl

y.