Curr Psychiatry Rep (2016) 18: 55

DOI 10.1007/s11920-016-0696-z

EATING DISORDERS (C GRILO, SECTION EDITOR)

Combining Pharmacological and Psychological Treatments

for Binge Eating Disorder: Current Status, Limitations,
and Future Directions
Carlos M. Grilo 1 & Deborah L. Reas 2,3 & James E. Mitchell 4,5

Published online: 16 April 2016

# Springer Science+Business Media New York 2016

Abstract Binge eating disorder (BED) is characterized by behavioral therapy (CBT) or behavioral weight loss (BWL)
recurrent binge eating and marked distress about binge eating interventions produces superior outcomes to pharmacotherapy
without the extreme compensatory behaviors for weight con- only but does not substantially improve outcomes achieved
trol that characterize other eating disorders. BED is prevalent, with CBT/BWL only. One medication (orlistat) has improved
associated strongly with obesity, and is associated with height- weight losses with CBT/BWL albeit minimally, and only one
ened levels of psychological, psychiatric, and medical con- medication (topiramate) has enhanced reductions achieved
cerns. This article provides an overview of randomized con- with CBT in both binge eating and weight. Implications for
trolled treatments for combined psychological and pharmaco- future research are discussed.
logical treatment of BED to inform current clinical practice
and future treatment research. In contrast to the prevalence Keywords Binge eating disorder . Obesity . Cognitive
and significance of BED, to date, limited research has been behavioral therapy . Behavioral weight loss . Medication .
performed on combining psychological and pharmacological Pharmacotherapy
treatments for BED to enhance outcomes. Our review here
found that combining certain medications with cognitive
Introduction

Binge eating disorder (BED) is defined in the fifth edi-

This article is part of the Topical Collection on Eating Disorders
tion of the Diagnostic and Statistical Manual of Mental
Disorders (DSM-5) [1] by recurrent binge eating (i.e.,
* Carlos M. Grilo
[email protected] discrete overeating episodes while experiencing a sub-
jective loss of control during the eating), marked dis-
Deborah L. Reas tress about binge eating, and the absence of inappropri-
[email protected] ate weight compensatory behaviors (e.g., self-induced
James E. Mitchell vomiting, laxative misuse, extreme exercise, or extreme
[email protected] food restriction) that characterize bulimia nervosa. BED
is the most prevalent formal eating disorder diagnosis in
1
Department of Psychiatry, School of Medicine, Yale University, New both the USA and worldwide [2, 3]. BED, unlike the
Haven, CT, USA two other formal eating disorders usually presenting in
2
Regional Department for Eating Disorders, Division of Mental adolescence or young adults (anorexia nervosa and bu-
Health and Addiction, Oslo University Hospital, Oslo, Norway limia nervosa), is common in both men and women,
3
Department of Psychology, Faculty of Social Sciences, University of shows comparable distribution across racial/ethnic
Oslo, Oslo, Norway groups, and is distributed broadly across the adult
4
Neuropsychiatric Research Institute, Fargo, ND, USA lifespan [2, 4]. BED is associated strongly with severity
5
Department of Clinical Neuroscience, School of Medicine and of obesity and with a significantly elevated risk for
Health Sciences, University of North Dakota, Fargo, ND, USA major forms of psychiatric and medical comorbidity as
55 Page 2 of 11 Curr Psychiatry Rep (2016) 18: 55

well as psychosocial impairment [2, 3]. Although BED Methods

shares some features with the other eating disorders and
obesity (a medical, not psychiatric diagnosis), research The present narrative review summarizes randomized con-
has demonstrated its clinical distinctiveness and validity trolled treatments (RCTs) for combined psychological and
as a diagnostic entity [5, 6]. pharmacological treatment of BED to inform current clinical
The inclusion of BED as a research category in the fourth practice and future treatment research. We aim to provide a
edition of the Diagnostic and Statistical Manual of Mental brief state-of-the-art review of the major and recent findings,
Disorders (DSM-IV) [7] stimulated considerable research with an emphasis on developments over the past 3 years. An
adapting, refining, and testing treatment methods for BED. electronic search was performed for all English language arti-
As research better characterized the needs of patients with cles using MEDLINE via PubMed, the Cochrane Library, and
BED, it soon became evident that effective treatments needed Google Scholar published through February 1, 2015.
to address binge eating, associated eating disorder psychopa- Registered and ongoing clinical trials for binge eating disorder
thology (e.g., body image concerns), depressive psychopathol- were identified via the US National Institutes of Health web-
ogy, and often excess weight (i.e., obesity) and associated met- based registry of private and publicly supported clinical stud-
abolic problems [8]. Treatment studies, however, have varied ies (ClinicalTrials.gov). All randomized controlled trials
greatly in their designs, methods, and consideration of outcome (RCTs) investigating the effects pharmacotherapy in
variables with most studies (as will be detailed in the following combination with psychological-behavioral interventions
section) focusing primarily on binge eating and weight. were considered. Exclusion criteria were the following: (1)
Critical reviews and meta-analyses of the treatment lit- phase I trials (open-label, case series, retrospective cohort de-
erature have generally converged in suggesting that a spe- signs); (2) non-English language; (3) studies pertaining to
cific specialized psychological treatment—cognitive be- non-purging bulimia nervosa, mixed eating disorder samples,
havioral therapy (CBT)—is the best-established treatment atypical eating disorders, or the ICD 10 category overeating
[9–11]. The National Institute of Clinical Excellence associated with psychological disturbances; and (4) RCTs in-
(NICE) guidelines [9] identified CBT as the treatment of vestigating either monotherapy psychopharmacological treat-
choice for BED with a methodological grade BA.^ ment or psychological treatment delivered alone.
Reviews have also suggested that other specialized psy-
chological treatments, notably interpersonal therapy (IPT)
and, to a lesser extent, guided self-help versions of CBT Results
(gsh-CBT) [12] and forms of dialectic behavior therapy
(DBT) are effective for reducing binge eating and associ- Table 1 lists 14 RCTs, of which 11 have been published, that
ated depressive and eating disorder psychopathology [10, have tested combination treatments for BED. Table 1 also lists
11]. Importantly, CBT and IPT have demonstrated that three additional RCTs registered on clinicaltrials.gov that are
their benefits are quite durable with follow-up studies testing various additive/combination approaches; outcome find-
reporting good maintenance through 24 months [13] and ings are presently unavailable for these three studies, yet we
up to 48 months [14]. Despite the robust improvements in opted to include them so that interested readers become aware
binge eating and pathology associated with these special- of this work. Inspection of Table 1 reveals that the 11 RCTs are
ist treatments, weight loss generally does not occur [13, quite diverse in their designs, methods, and treatments evaluat-
15]. Recent randomized controlled trials (RCTs) have ed. In contrast to the prevalence and public significance of BED
found that behavioral weight loss (BWL) treatment at [2], strikingly few studies have tested the clinically important
least initially is comparable to CBT and IPT for reducing question of whether combination treatment methods are effec-
binge eating but has the advantage of also producing tive for BED. Moreover, only two RCTs testing combination
modest weight loss [13, 15]. The effects of BWL appear treatments have been published since 2013 [31••, 32] and one of
durable through 12 months but less so than those for CBT these [32] included an anti-obesity medication (i.e., sibutramine)
and IPT at 24-month follow-up [13]. that subsequently was withdrawn from the market in 2010 be-
Critical reviews and meta-analyses of the effectiveness of cause of safety concerns.
pharmacotherapy for BED have generally converged in sug- As summarized in Table 1, the 11 published RCTs testing
gesting that certain medications have short-term efficacy rel- combination treatments for BED have ranged from 8- to 36-
ative to placebo for BED [16–19]. However, relative to the week interventions; all but two studies [25, 29••] reported
psychological treatment literature, the status of pharmacolog- follow-up data ranging 3 to 24 months after completing treat-
ical approaches is less clear; most notably, RCTs testing ments. Overall, the studies have been small, with sample sizes
pharmacology-only methods for BED have not reported ranging from 52 to 116, and enrolled primarily white women
follow-up data and very few medications have been studied with average age of roughly 40 years and average body mass
in confirmatory RCTs [16, 19]. index (BMI) of roughly 38. Also evident from Table 1 is the
Table 1 Study characteristics of published and ongoing RCTS investigating combined psychotherapy and pharmacotherapy for BED

Study Number % F % W Age BMI Trial FUP Treatment conditions Dose Psychiatric comorbidity
(week) (month)

Agras et al. (1994) 108 100 NA 45.0 38.6 36 3 (a) BWL only (a) 9 months (30 sessions) NA
[20] (b) CBT/BWL (b) 3 months (12 sessions) + 6 months (18 sessions)
(c) CBT/BWL + desipramine (c) 3 + 6 months + drug (mean dose 285 mg/day)
Laederach-Hoffman 31 87 NA (a) 35.7 39.5 8 6 (a) Diet (a) Bi-weekly (30 min) diet counseling + bi-weekly NA
et al. (1999) [21] (b) 40.7 counseling + supportive (15–25 min) supportive therapy + monthly sessions
therapy of group (90 min) behavior therapy
Curr Psychiatry Rep (2016) 18: 55

(b) Imipramine (b) Fixed dosage of 25 mg 3 times daily

Ricca et al. (2001) 108 59 NA 25.9 32.3 24 12 (a) CBT (a) 22 individual sessions DSM-III-R (current) MDD = 6.4 %
[22] (b) CBT + fluoxetine (b) CBT + 60 mg/day Dysthymia = 5.5 %
(c) CBT + fluvoxamine (c) CBT + 300 mg/day Adjustment disorder with depressed
(d) Fluoxetine only (d) Drug only, as (b) above mood = 3.6 %
(e) Fluvoxamine only (e) Drug only, as (c) above OCD = 1.8 %
Panic disorder = 1.8 %
Devlin et al. (2005, 116 78 77 43.0 40.9 20 24 (a) Fluoxetine (a) Flexible dosage of 60 mg/day Current MDD = 12 %
2007) [23, 24] (b) Placebo (b) Placebo Past MDD = 39 %
(c) CBT + placebo (c) 20 individual CBT sessions Other axis I = <10 %
(d) CBT + fluoxetine (d) As above, (a) + (c)
All of the above given in Maintenance treatment included double-blind
combo with group BWL medication for 18/24 months and monthly BWL
(16 sessions for 5 months) groups
Golay et al. (2005) 89 91 97 (a) 41 (a) 35.7 24 None (a) Orlistat + hypocaloric diet (a) Fixed dosage of 120 mg 3 times daily + hypocaloric Current GAD = 52 %
[25] (b) 41 (b) 37.3 (b) Placebo + hypocaloric diet (600 kcal/day subtracted from daily energy Current MDD = 18 %
diet expenditure)
(b) Placebo + hypocaloric diet
Grilo et al. (2005) 50 88 88 47 36.0 12 3 (a) Orlistat + gsh-CBT (a) Fixed dosage of 120 mg 3 times daily + gsh-CBT Lifetime DSM-IV:
[26] (b) Placebo + gsh-CBT (CBT self-help manual, plus 6 15–20 min individual Any axis I = 60 %
meetings over 12 weeks) MDD = 42 %
(b) Placebo + gsh-CBT Anxiety = 24 %
Substance use = 10 %
Grilo et al. (2005, 108 78 89 44 36.3 16 6, 12 (a) Fluoxetine only (a) Fixed dosage of 60 mg/day Lifetime DSM-IV:
2012) [27, 28••] (b) Placebo (b) Placebo Any Axis I = 73 %
(c) CBT + placebo (c) 16 individual weekly (60 min) sessions MDD = 50 %
(d) CBT + fluoxetine (d) As above, (a) + (c) Anxiety = 37 %
Alcohol use = 24 %
Any axis II = 31 %
Claudino et al. 73 96 58 (a) 35 (a) 37.4 21 None (a) CBT + placebo (a) 19 group sessions of CBT History of MDD = 35.6 %
(2007) [29••] (b) 41 (b) 37.4 (b) CBT + topiramate (b) CBT + flexible dosage of 200 mg/day
Ricca et al. (2009) 52 83 NA (a) 35 (a) 39.2 24 12 (a) CBT (a) 22 individual sessions of CBT for 24 weeks Current DSM-IV
[30] (b) 36 (b) 38.4 (b) CBT + zonisamide (b) CBT + zonisamide 25 mg/day for 7 days, increased MDD = 21.5 %
as tolerated by 50 mg/day every week to a max of Panic = 13.4 %
100 mg/day for BMI < 35 kg/m2 or 150 mg/day for GAD = 17.3 %
BMI > 35 kg/m2 OCD = 5.7 %
Grilo and White 40† 78 0 (a) 46 (a) 37.2 16 6 (a) BWL + placebo (a) 16 weekly sessions of a culturally enhanced Lifetime DSM-IV:
(2013) [31••] (b) 46 (b) 39.0 (b) BWL + orlistat adaptation of the Diabetes Prevention Program Any axis I = 88 %
(b) Fixed dosage of 120 mg 3 times daily + BWL Mood disorder = 83 %
Page 3 of 11 55
Table 1 (continued)

Study Number % F % W Age BMI Trial FUP Treatment conditions Dose Psychiatric comorbidity
(week) (month)
55 Page 4 of 11

Anxiety disorder = 48 %
Substance use = 30 %
Current axis I = 75 %
Grilo et al. (2014) 104 73 45 44 38.3 16 6, 12 (a) Sibutramine (a) Fixed dosage of 15 mg/day Current DSM-IV:
[32] (b) Placebo (b) Placebo Mood disorder = 46 %
(c) gsh-CBT + sibutramine (c) Self-help CBT + sibutramine (15 mg/day) Anxiety disorder = 36 %
(d) gsh-CBT + placebo (d) Self-help CBT + placebo Substance use = 22 %
NCT00601354a [33] 17 88 NR NA NA 12 None (a) Orlistat/BWL + guided (a) Orlistat (60 mg 3 times/day)/BWL + 12 weekly NA
P.I. Deb Safer self-help group therapy (2 h) sessions of gsh (emotion regulation)
(b) Orlistat/BWL (b) Orlistat (60 mg 3 times/day)/BWL
NCT01921582 [34] 56 100 NA NA NA 12 3 (a) Methylphenidate (a) Start dose of 18 mg/day increasing to 72 mg/day NA
P.I. Allan Kaplan (b) CBT (b) CBT delivered in 12 individual 50-min sessions
NCT00829283 [35] 191 71 79 48 39 24 6, 12 (a) Stepped care (a) BWL (1 month) followed by stratification by NA
P.I. Carlos Grilo (b) Standard treatment response:
Rapid responders:
(1a) BWL + Med (5 months)
(1b) BWL + placebo (5 months)
Non-rapid responders:
(2a) gsh-CBT + Med (5 months)
(2b) gsh-CBT + placebo (5 months)
(b) BWL (6 months)

BED binge eating disorder, FUP follow-up, RCT randomized controlled trial, BWL behavioral weight loss, CBT cognitive behavior therapy, gsh guided self-help, MDD major depressive disorder, GAD
generalized anxiety disorder, OCD obsessive-compulsive disorder, NA data not available
†
An additional N = 39 obese patients without BED were also randomized to the treatments. The reader is referred to the publication for findings which notably included BED status as a significant predictor
and moderator of outcomes [31••]
a
Study results are posted, yet indicate no statistical analyses were applied due to limitations of the study, such as early termination leading to small numbers of participants (N = 17) and technical problems
with measurement leading to unreliable or uninterpretable data
Curr Psychiatry Rep (2016) 18: 55
Curr Psychiatry Rep (2016) 18: 55 Page 5 of 11 55

striking diversity in psychiatric comorbidity patterns across 9 abstinence rates, binge eating reductions, weight loss, or eat-
of the 11 studies reporting such data. Although some studies ing disorder pathology, but did produce greater reduction in
[22, 23, 29••] reported relatively low rates of psychiatric co- depression scores. In contrast, the addition of CBT to BWL
morbidity, others tended to report high rates of both current significantly enhanced binge eating abstinence rates (62 vs
and past additional psychiatric disorders [26, 27, 31••, 32]. 33 %) and binge eating reductions. Devlin et al. [24], in a
Designs and medications tested have included unblinded ad- 24-month follow-up after initial treatments, reported that the
dition of medication—i.e., desipramine [20], imipramine [21], addition of CBT to BWL—but not fluoxetine—was associat-
fluoxetine and fluvoxamine [22], and zonisamide [30]—and ed with significantly greater binge eating abstinence rates and
double-blind blinded addition of various medications (fluox- reductions; neither CBT nor fluoxetine enhanced BWL
etine in two studies [23, 27], orlistat in three studies [25, 26, weight losses whereas fluoxetine enhanced depression out-
31••], topiramate [29••], and sibutramine [32] to either CBT or comes. Grilo and colleagues [27] reported that the addition
BWL methods. of fluoxetine did not significantly enhance CBT on any out-
Table 2 summarizes outcomes reported by the 11 published come measure, whereas CBT with either fluoxetine or placebo
RCTs that have tested combination treatments for BED. were significantly superior to both fluoxetine and placebo
Table 2 summarizes outcomes reported for the following out- (which did not differ from each other) on binge eating absti-
come variables: binge eating abstinence rates, binge eating nence (i.e., 50 and 61 % vs 29 and 30 %), binge eating reduc-
frequency, weight loss, depression scores, and eating disorder tions, and reductions in eating disorder psychopathology and
psychology scores. Inspection of Table 2 reveals that, overall, depression; weight loss was minimal and did not differ across
the studies varied considerably in their designs, treatment set- any treatment condition. Grilo and colleagues [28••], in a 12-
tings, assessment methods, statistical approaches, and month follow-up after initial treatments, reported that CBT
outcomes. plus fluoxetine and CBT plus placebo did not differ yet both
were significantly superior to fluoxetine only on most clinical
variables, except for weight loss. Binge eating abstinence rates
Discussion at 12-month follow-up were 27 % for CBT + fluoxetine, 36 %
for CBT + placebo, and 4 % for fluoxetine; collectively, these
Antidepressant Medications findings indicate the significantly superior specific durability
of CBT relative to fluoxetine and that fluoxetine does not
The evidence base suggests no advantage for adding antide- enhance CBT outcomes after treatment completion [28••].
pressant medications to either CBT or BWL. In the first additive
study for BED, Agras and colleagues [20] reported that the Anti-obesity Medications
addition of the antidepressant desipramine (open-label
unblinded method) during the last 6 months of a sequential Findings from double-blind RCTs generally suggests little ad-
treatment (involving CBT followed by behavioral weight loss) vantage for adding anti-obesity medications to either CBT or
did not significantly enhance binge eating outcomes although a BWL for BED although some findings suggest certain medi-
statistically significant (clinically meaningless) weight loss was cations may facilitate weight loss in this patient group, albeit
observed. Ricca and colleagues [22] reported that, in addition to rather modestly. These RCTs have examined orlistat [25, 26,
the lack of efficacy for monotherapy with either (open-label 31••], which is FDA-approved, an agent that acts locally in the
unblinded) fluoxetine or fluvoxamine, neither SSRI antidepres- gut and blocks some of the fat absorption but has no CNS
sant significantly enhanced CBT outcomes, while CBT alone effects, and sibutramine, a centrally acting agent, previously
was significantly superior to either medication alone. FDA-approved but withdrawn from the market.
Double-blind RCTs have provided further strong evidence Golay and colleagues [25], in an RCT with 89 obese pa-
indicating little advantage for adding antidepressant medica- tients clinically diagnosed with BED, compared the addition
tions to either CBT or BWL. Laederach-Hoffmann and col- of orlistat to a reduced-calorie diet (the diet seemed to be
leagues [21], in a small study of 31 patients with BED, report- prescribed with some guidance but would not be viewed as
ed the addition of imipramine to diet and supportive counsel- a behavioral (or lifestyle) weight loss intervention). Golay
ing failed to enhance binge eating outcomes but was associat- et al. [25] reported that orlistat + diet and placebo + diet did
ed with statistically significantly greater weight loss than pla- not differ significantly on percentage of patients no longer
cebo (−2.2 vs +0.2 kg). The two RCTs testing fluoxetine with meeting BED criteria (77 vs 71 %, respectively) nor on the
double-blind designs in combination approaches converged in frequency of binge eating (which was reduced substantially in
showing that this SSRI antidepressant did not significantly both conditions). The addition of orlistat to diet was associated
improve outcomes produced by either CBT [27] or BWL with significantly greater weight loss than the addition of pla-
[23]. Devlin et al. [23] reported that the addition of fluoxetine cebo (−7.4 vs −2.3 % mean weight loss, respectively) during
to BWL failed to significantly enhance binge eating 24-month treatments. Golay et al. [25] also reported that the
Table 2 Outcome for RCTS investigating combined psychotherapy and pharmacotherapy for binge eating disorder

Study Treatment Attrition % abstinent = (post- Binge eating frequency Weight loss Depression Eating pathology
condition (%) tx, FUP)
55 Page 6 of 11

Agras et al. (1994) Binge days, weekly Weight loss (kg) BDI TFEQ disinhibition
[20] (a) BWL only 27 19, 14 (a) 4.5 to 1.5 to 2.0 (a) 3.7 to 4.2 (a) 12.9 to 11.6 to 11.3 CBT/BWL-D > BWL only at week 24
(b) CBT/BWL 17 37, 28 (b) 4.4 to 1.2 to 1.7 (b) 1.6 to 0a (b) 13.5 to 12.7 to 8.9
(c) CBT/BWL-D 23 41, 32 (c) 5.1 to 0.9 to 1.5 (c) 6.0 to 4.8b (c) 13.7 to 10.8 to 7.8
Laederach-Hoffman Binge episodes, weekly Weight loss (kg) HAM-D NA
et al. (1999) [21] (a) Counseling 6 NA (a) 7.1 to 5.3 to 7.2 (a) +0.2 to +2.2 (a) 21.3 to 16.0 to 19.2
(b) Imipramine 7 (b) 7.1 to 2.5 to 4.1 (b) 2.2 to 5.1a (b) 22.6 to 9.8a to 12.6a
Ricca et al. (2001) [22] Binge episodes, monthly BMI BDI EDE
(a) CBT 15 NA (a) 18 to 8.0 to 8.0d,e Significantly reduced at (a) 22 to 14 to 14 (a) 3.8 to 3.4 to 3.3d,e
(b) CBT + FLX 27 (b) 17 to 6.0 to 7.0d,e post-tx and FUP for (b) 17 to 11 to 11 (b) 3.8 to 2.7 to 2.7d,e
(c) CBT + FLV 22 (c) 18.0 to 8.0 to 8.0d,e CBT, CBT + FLX, and (c) 22 to 10 to 10 (c) 4.0 to 2.7 to 2.6d,e
(d) FLX only 24 (d) 20.0 to 19.0 to 21.0 CBT + FLV, but not for(d) 20 to 15 to 16 (d) 3.4 to 3.8 to 3.9
(e) FLV only 27 (e) 20.0 to 18.0 to 18.0 the FLX and FLV (e) 21 to 14 to 14 (e) 3.8 to 3.8 to 3.8
groups Note: scores were Note: significantly reduced EDE total
significantly lower at post- for CBT, CBT-FLX and CBT-FLV
tx for all groups, with no but not FLX and FLV groups.
significant group Greatest reduction for CBT-FLV.
differences. No additional No additional improvement at FUP
improvement at FUP
Devlin et al. (2005, Main effect for CBT Monthly, pre-post Wt (kg) at pre-post BDI, pre-post At post-tx, no significant treatment
2007) [23, 24] (a) FLX 31 assignment: (a) 16.4 to 4.9 (a) 113.8 to 111.9 (a) 14.5 to 7.5 effects for TFEQ, BES, or BSQ.
(b) Placebo 48 62 vs 33 %** (b) 15.4 to 6.0 (b) 113.5 to 111.1 (b) 15.6 to 10.6 At FUP, FLX showed advantage to
(c) CBT 40 No main effect for (c) 17.1 to 3.7 (c) 116.5 to 114.6 (c) 13.9 to 8.4 placebo for TFEQ restraint
(d) CBT + FLX 25 FLX assignment: (d) 16.1 to 2.2 (d) 116.9 to 112.8 (d) 16.9 to 6.3 (p = .03).
All given in 52 vs 41 % Note: At post-tx and 2-year FUP, the Note: At post-tx and FUP, Note: At post-tx and FUP,
addition to No CBTxFLX addition of CBT to BWL significantly no significant main advantage to FLX vs.
group BWL interaction enhanced reduction in binge eating effects for either CBT placebo (p < .05)
frequency (p < .001) and binge or medication
remission relative to BWL without assignment
CBT
Golay et al. (2005) Binge episodes, weekly: % loss, IBW: BDI EDI total:
[25] (a) Orlistat/diet 11 77 (a) 5.4 to 1.0 (a) 7.4 % loss (a) 10.8 to 8.2 (a) 68.0 to 50.0
(b) Placebo/diet 29 71 (b) 6.2 to 1.7 (b) 2.3 % lossa (b) 13.6 to 11.6a (b) 64.9 to 58.4a
Note: % no longer
meeting BED
criteria
Grilo et al. (2005) [25] Binge episodes, monthly % achieving 5 % loss BDI EDE-interview global
(a) Orlistat + gsh- 24 64, 52 (a) 16.4 to 3.2 to 3.4 (a) 36 %, 32 % (a) 17.1 to 10.1 to 9.9 (a) 3.2 to 2.1 to 2.2
CBT
(b) Placebo + gsh- 20 36a, 52 (b) 13.5 to 3.6 to 2.8 (b) 8 %a, 8 %a (b) 20.6 to 14.7 to 14.6 (b) 3.2 to 2.4 to 2.3
CBT
Grilo et al. (2005, Binge episodes, monthly EDE-Q: Wt loss (lbs) at post-tx BDI EDE global
2012) [27, 28••] and FUP
(a) FLX only 22 22, 4 (a) 17.9 to 10.4 to 10.4 (a) 4.8 to 1.5 (a) 16.9 to 12.6 to 12.9 (a) 3.9 to 3.1 to 3.3
(b) Placebo‡ 15 26, NA (b) 13.2 to 7.2 (b) 5.0 to 9.8 (b) 18.7 to 11.7 (b) 3.5 to 2.6
Curr Psychiatry Rep (2016) 18: 55
Table 2 (continued)

Study Treatment Attrition % abstinent = (post- Binge eating frequency Weight loss Depression Eating pathology
condition (%) tx, FUP)

(c) CBT + placebo 21 61a,b, 36a (c) 16.6 to 2.3 to 4.6a,b (c) 5.6 to 4.1 (c) 16.5 to 7.4a to 11.4 (c) 3.8 to 2.1 to 2.7a,b
(d) CBT + FLX 23 50a,b, 27a (d) 16.5 to 4.3 to 4.6a,b (d) 20.2 to 8.3 to 11.2 (d) 4.0 to 2.2 to 2.4a,b
Claudino et al. (2007) Binge episodes, weekly Wt loss (kg) BDI BES
[29••] (a) CBT+ 19 84 (a) 4.2 to 0.0 (a) 6.8 kg (a) 16.8 to 10.9 (a) 27.2 to 7.5
topiramate
(b) CBT + placebo 28 61a (b) 3.4 to 0.3 (b) 0.9 kga (b) 15.9 to 9.2 (b) 26.5 to 8.6
Curr Psychiatry Rep (2016) 18: 55

Ricca et al. (2009) Binge episodes, monthly BMI BDI EDE-Q global
(a) CBT 33 NA (a) 5.0 to 2.0 to 3.0 (a) 39.2 to 38.4 to 38.9 (a) 19.5 to 14.5 to 17.5 (a) 2.8 to 2.6 to 2.7
(b) 50 (b) 5.0 to 2.0 to 2.0a (b) 38.4 to 36.7 a to 36.5a (b) 20 to 16 to 16.0 (b) 2.8 to 2.1a to 2.2a
CBT + zonisa-
mide
Grilo and White NA BMI BDI EDE global
‡
(2013) [31••] (a) BWL + orlistat 30 60, 50 (a) 39.0 to 37.9 to 37.6 (a) 22.9 to 11.4 to 10.3 (a) 2.5 to 1.6 to 1.5
(b) 25 70, 50 (b) 37.2 to 36.0 to 36.7a (b) 25.7 to 17.1 to 20.9 (b) 2.7 to 2.0 to 1.9
BWL + placebo
Grilo et al. (2014) [32] Binge episodes, monthly BMI BDI EDE global
(a) Sibutramine 27 39, 19, 19 (a) 22.4 to 5.0 to 4.9 to 5.8 (a) 39.4 to 38.4c,d to 38.7 (a) 12.8 to 7.9 to 9.7 to 10.1 (a) 2.4 to 1.7 to 1.9 to 1.8
to 39.3
(b) Placebo 15 30, 41, 37 (b) 21.1 to 5.3 to 5.7 to 6.7 (b) 39.3 to 39.6c,d to 38.8 (b) 13.6 to 9.6 to 8.7 to 7.5 (b) 2.6 to 2.1 to 1.8 to 1.8
to 39.5
a,b
(c) gsh- 12 24, 40, 40 (c) 14.6 to 6.4 to 3.6 to 4.9 (c) 36.5 to 35.9a,b to 35.3 (c) 17.0 to 9.8 to 10.3 to 10.5 (c) 2.5 to 1.7 to 1.7 to 1.6
CBT + placebo to 35.4
(d) gsh- 16 23, 50, 42 (d) 16.9 to 3.6 to 3.9 to 3.0 (d) 37.8 to 35.6a,b to 36.0 (d) 14.0 to 9.3 to 9.8 to 10.3 (d) 2.5 to 1.8 to 1.6 to 1.6
CBT + sibutra- to 36.5
mine

Superscripts denote significant group differences between treatment conditions

BED binge eating disorder, FUP follow-up, RCT randomized controlled trial, BWL behavioral weight loss, CBT cognitive behavior therapy, gsh guided self-help, NA data not available
*p < .05; **p < .001
†
Placebo group was offered treatment at the end of 2 × 2 trial and were not included in the 12-month FUP
‡
An additional N = 39 obese patients without BED were also randomized to the treatments. The reader is referred to the publication for findings which notably included BED status as a significant predictor
and moderator of outcomes [31••]
Page 7 of 11 55
55 Page 8 of 11 Curr Psychiatry Rep (2016) 18: 55

addition of orlistat was associated with lower eating disorder the major findings as they demonstrate several important
scores on a general self-report inventory at post-treatment. methodological issues. This study was performed in order to
Overall, these findings suggest that orlistat may enhance ascertain whether these specific treatments with reported effi-
weight loss in BED achieved with hypocaloric diets. cacy in research clinics (e.g., [12, 36] can be effectively de-
Grilo and colleagues [26], in an RCT with 50 obese patients livered in primary care settings to racially/ethnically diverse
with BED, reported that the addition of orlistat to CBT patients with BED by generalist clinicians. This study was
(delivered using guided self-help) was associated with signif- also designed to examine longer-term outcomes 12 months
icantly greater binge eating remission rates than placebo at after treatment completion to extend previous
post-treatment (64 vs 36 %, respectively) but not at 3-month pharmacotherapy-only RCTs testing this medication [36] or
follow-up after completing treatments (52 vs 52 %, respective- other medications (see [19]) which reported only post-
ly). The addition of orlistat was associated with greater rates of treatment outcomes for BED. Overall, binge eating abstinence
achieving 5 % weight loss at post-treatment (36 vs 8 %, re- rates were not significantly different across treatments and the
spectively) and the significant advantage persisted at 3-month treatments also differed little in terms of binge eating frequen-
follow-ups (32 vs 8 %, respectively). These findings suggest cy, eating disorder psychopathology, or depression.
that adding orlistat to gsh-CBT may enhance weight loss in Sibutramine was associated with significantly greater weight
obese patients with BED [26]. loss at post-treatment; however, after treatment completion
Grilo and White [31••], in an RCT with 89 obese patients and medication discontinuation, weight regain occurred in
(40 with BED and 39 without BED), tested the addition of patients who had received sibutramine and by 6- and 12-
orlistat to BWL. In this double-blind study, performed at a month follow-ups, percent weight loss was no longer differed
community mental health center serving economically/ significantly across groups. Demographic factors (age, sex,
educationally disadvantaged Hispanic patients, a culturally race, and education) did not predict nor moderate these treat-
enhanced BWL was delivered with either orlistat or placebo ment outcomes achieved in this generalist setting. The non-
for 4 months with follow-up 6 months after completing and significant effects on binge eating are at odds with the positive
discontinuing treatments. This study reported outcomes for findings reported for sibutramine monotherapy in a larger
BWL plus orlistat/placebo approximating findings in the effi- multi-site study [36]. Importantly, while the significant weight
cacy treatment literature for obesity and BED with much more losses associated with sibutramine over the short-term repli-
restrictive exclusion criteria. In this disadvantaged and psychi- cate the sibutramine monotherapy RCT [36], the observed
atrically complex patient group, treatment completion rates weight regain following medication discontinuation in the
were high (78 %) and did not differ significantly by either study by Grilo and colleagues [32] suggest that anti-obesity
medication assignment or BED status. Overall, treatments medications may need to be continued to sustain weight loss
were associated with significant improvements in eating dis- (i.e., following the Bchronic^ treatment model for obesity ver-
order psychopathology, depression, and weight loss (albeit sus the Bacute^ treatment model in the pharmacotherapy liter-
modest). Overall, the addition of orlistat to BWL did not en- ature for BED). Finally, these findings suggest that two treat-
hance outcomes compared to the addition of placebo; howev- ments with some demonstrated efficacy in research or special-
er, BED significantly moderated weight loss outcomes, ist settings (sibutramine and self-help CBT) may perform dif-
adding orlistat to BWL-enhanced weight loss in obese patients ferently when delivered by generalist clinicians in diverse pri-
without BED but not among those with BED. Patients with mary care settings. We note a similar pattern in studies with
BED achieved binge eating abstinence rates of 65 % at post- bulimia nervosa—CBT methods and fluoxetine treatments
treatment and 50 % at 6-month follow-up after completing with demonstrated efficacy in specialist settings [37] had
treatments. Although these obesity treatments (BWL plus minimal-to-no benefit when delivered by generalist clinicians
orlistat/placebo) benefitted obese patients with BED (compa- in primary care [38].
rable to rates of BWL in specialist centers [15]), BED was a
negative prognostic indicator for weight loss during treatment Anti-epileptic Medications
and for psychosocial outcomes following treatment.
Nonetheless, these findings suggest that structured BWL can Two RCTs have tested anti-epiletic medications (given their
be effectively delivered to patients with BED in community- observed appetite suppression effects) in combination with
based settings, although the addition of orlistat does not ap- CBT for BED [29••, 30]. Ricca and colleagues [30], in a study
pear to enhance weight loss outcomes. with 52 subthreshold and threshold BED patients, reported
Grilo and colleagues [32], in an RCT performed in a gen- that the addition of the zonisamide (open-label, unblinded)
eralist primary care setting with 104 obese patients with BED, to CBT for 24 weeks was associated with significantly greater
tested the effectiveness of self-help form of CBT and reductions than CBT-alone at post-treatment in eating disorder
sibutramine, alone and in combination. Although sibutramine psychopathology, depression, and BMI. At 12-month follow-
has been withdrawn from the market, this review summarizes up, patients treated with both CBT and zonisamide had
Curr Psychiatry Rep (2016) 18: 55 Page 9 of 11 55

significantly greater reductions than those treated with CBT in effects of pharmacotherapy for BED and the few such reports
binge eating frequency, in one of six measures of eating dis- indicate poor outcomes [28••, 32].
order psychopathology, and anxiety (but not depression) One especially noteworthy recent development in the status
scores. Ricca et al. [30], based on paired-samples Wilcoxon of pharmacotherapy for BED occurred in January 2015 when
tests comparing variables for each group at different times the FDA-approved lisdexamfetamine dimesylate (LDX) spe-
(with last observation carried forward), reported that both cifically for moderate-to-severe BED. This approval followed
groups had significant reductions in BMI at post-treatment an initial large phase II RCT [40••] and two phase III RCTs
and the CBT group but not the CBT + zonisamide group [41••] documenting that LDX (50–70 mg/day dosing) was
regained weight during the 12-month follow-up. significantly superior to placebo. McElroy et al. [41••] report-
Claudino and colleagues [29••], in an RCT with 73 patients ed binge eating abstinence rates of LDX versus placebo (study
with BED, tested the addition of topiramate versus placebo 1, 40 vs 14 %; study 2, 36 vs 13 %) at the end of the 11-week
with 21-weeks of CBT. Analyses revealed that topiramate, treatment; no longer-term follow-up is presently available.
relative to placebo, produced significantly greater binge eating With this new FDA approval, clinicians and patients have an
abstinence rates (84 vs 61 %, respectively, based on 1 week additional treatment option and one that is seemingly more
end-point analysis) and resulted in significantly (and clinically readily available or disseminated than some specialized psy-
meaningful) greater weight loss (−6.8 vs −0.9 kg). The addi- chological treatments. We note, however, three important fac-
tion of topiramate to CBT was not, however, associated with tors for readers to consider. First, while no study has yet di-
significantly greater reductions in binge eating frequency, eat- rectly compared LDX (FDA approved) and CBT (treatment of
ing disorder pathology, or depression. This study did not pro- choice in critical guidelines such as NICE [9]), reported binge
vide follow-up data and it is important to note that clinical use eating abstinence rates for CBT (generally at 50 % or greater)
of topiramate is challenging and may be limited by high rates that are durable over time [13] exceed those reported for LDX
of adverse events and treatment discontinuation. Although the (36–40 %) over the short term [41••]. Second, product label-
Claudino et al. [29••] RCT had low attrition (roughly 19 %) ing for LDX includes a BLimitation of Use^ specifically indi-
perhaps suggesting that CBT assists with medication tolerance cating that it is not indicated for weight loss and its effects on
or adherence, the sole longer-term maintenance study of obesity are unknown while noting that similar classes of med-
(open-label) topiramate reported 68 % of patients ication have been associated with cardiovascular adverse
discontinued topiramate, which appeared due to high rates of events. Third, LDX is classified as a DEA-controlled sub-
adverse events and difficulties tolerating the medication [39]. stance and product labeling includes a BWarning^ that CNS
stimulants have high potential for abuse/dependence.
Since a sizeable minority of patients do not benefit sufficient-
ly from the available monotherapies, the present review evalu-
Conclusion and Future Directions ated RCT testing combined psychological and pharmacological
treatment of BED to inform current clinical practice and future
The empirical base regarding treatment for BED remains lim- treatment research. The very limited number of such RCTs,
ited. Certain specific psychological treatments, most notably especially in recent years, is at odds with the substantial preva-
CBT—tested in methodologically rigorous studies as graded lence and public health impact characteristic of BED. Overall,
by critical guidelines such as the NICE [9]—have been docu- our review suggests that there is little support for combining
mented to produce robust improvements in binge eating, as- antidepressants with either CBT or BWL for patients with
sociated eating disorder psychopathology, and depression that BED; however, some studies have found that the addition of
have been shown to be durable through 4-year follow-ups antidepressant medication may enhance outcomes in terms of
after treatment [14]. CBT, and other effective specialist psy- lower depressive symptoms at post-treatment [21, 23] and
chological treatments, however, fail to produce weight loss in follow-up [24]. The Bclinically-logical^ strategy of adding
BED which is often accompanied by obesity, and are not anti-obesity medications in an attempt to enhance outcomes,
widely disseminated [12]. Certain forms of CBT delivered especially weight losses, has received some albeit limited sup-
by guided self-help [see 12], which have also demonstrated port with the medication orlistat. Four anti-obesity medications
effectiveness and longer-term durability [13], have much po- or medication combinations (phentermine/topiramate,
tential for broader dissemination. BWL, a widely available lorcaserin, naltrexone/bupropion, and liraglutide) have recently
non-specialist intervention, has also been found to be effective received FDA approval for treating obesity but none has been
for BED with the added advantage of producing weight loss tested for BED either alone or in combination with CBT/BWL.
over the short to intermediate term [15]. The pharmacotherapy The limitations noted earlier for LDX (including contraindica-
literature is also limited, with available evidence suggesting tion for obesity and weight loss) potentially limit its relevance as
that certain medications have efficacy over the short term [see a viable combination or additive strategy to enhance psycholog-
19]; almost no data are available regarding the longer-term ical treatments for BED. Our review revealed some initial
55 Page 10 of 11 Curr Psychiatry Rep (2016) 18: 55

support for combining anti-epiletic medication topiramate with Dr. James E. Mitchell reports grants from the National Institutes of
Health and book royalties from Guilford Press, Routledge Press, and
CBT [29••]. Topiramate significantly enhanced CBT outcomes
American Psychiatric Press.
for binge eating and weight loss in one study [29••]; these find-
ings require replication and need to be considered cautiously in Human and Animal Rights and Informed Consent This article does
light of the well-known unfavorable adverse event profile asso- not contain any studies with human or animal subjects performed by any
of the authors.
ciated with topiramate and high rates of discontinuation [39].
In summary, this review has evaluated the limited research Funding Preparation of this paper was supported, in part, by National
performed to date on combining psychological and pharma- Institutes of Health (NIH) Grant K24 DK070052 (Grilo). The NIH had no
cological treatments for BED. Our review here found that role or influence on the content of the paper nor does the content reflect
the views of the NIH.
combining certain medications with CBT/BWL interventions
produces superior outcomes to pharmacotherapy only but
does not substantially improve outcomes achieved with
CBT/BWL only. One medication (orlistat) has improved
weight losses albeit minimally and only one medication References
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•• Of major importance
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weight loss outcomes in patients with BED at post-treatment. data supported FDA approval of this medication for BED.
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31.•• Grilo CM, White MA. Orlistat with behavioral weight loss for obesity 906. Important methodological paper demonstrating analyses of
with versus without binge eating disorder: randomized placebo- predictors/moderators of treatment outcomes. Findings suggested
controlled trial at a community mental health center serving educa- that overvaluation of shape/weight and negative affect are signif-
tionally and economically disadvantaged Latino/as. Behav Res Ther. icant moderators of treatment outcome; patients with these char-
2013;51:167–75. RCT performed in a community-based setting acteristics fare better in CBT and in fluoxetine treatments.