Kimberly A. Brownley, PhD; Nancy D. Berkman, PhD; Christine M. Peat, PhD; Kathleen N. Lohr, PhD; Katherine E. Cullen, BA; Carla M. Bann, PhD; Cynthia M. Bulik, PhD
Acknowledgment: The authors thank Lauren Breithaupt and Margaret Sala for their assistance with abstract reviews. They acknowledge Isabelle Lanser, Michela Quaranta, Loraine Monroe, Laura Morgan, and Morgan Walker for their assistance with table development and manuscript preparation for this review. For their assistance with the report from which this manuscript was based, the authors also thank Meera Viswanathan, PhD; Ina F. Wallace, PhD; and Lynn Whitener, DrPH, MSLS.
Grant Support: By contract 290-2012-00008-U from AHRQ (all authors) and VR Dnr 538-2013-8864 from the Swedish Research Council (Dr. Bulik).
Disclosures: Dr. Brownley reports grants from the Agency for Healthcare Research and Quality during the conduct of the study, and personal fees from Shire and Sunovion Pharmaceuticals outside the submitted work. Dr. Lohr was an employee of RTI International–University of North Carolina Evidence-Based Practice Center during the conduct of the study; received consulting fees from ECRI Institute outside the submitted work; and is vice president (unpaid) for PROMIS (Patient Reported Outcomes Measurement Information System), a 501(c)(3) foundation to support development and dissemination of patient-reported outcomes measurement systems. Dr. Bulik reports grants from Shire, personal fees from Ironshore, and textbook royalties from Pearson, outside the submitted work. Dr. Peat reports grants from Shire and membership on the BED advisory board of Sunovion Pharmaceuticals. Authors not named here have disclosed no conflicts of interest. Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-2455.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.
Reproducible Research Statement:Study protocol: Available at www.effectivehealthcare.ahrq.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=1942. Statistical code and data set: In Methods and Results sections, respectively; full report is available at www.effective healthcare.ahrq.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=2157.
Requests for Single Reprints: Kimberly A. Brownley, PhD, Department of Psychiatry, University of North Carolina, CB #7175, Chapel Hill, NC 27599; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Brownley: Department of Psychiatry, University of North Carolina, CB #7175, Chapel Hill, NC 27599.
Drs. Berkman, Lohr, and Bann and Ms. Cullen: RTI International, PO Box 12194, Research Triangle Park, NC 27709.
Drs. Peat and Bulik: Department of Psychiatry, University of North Carolina, CB #7160, Chapel Hill, NC 27599.
Author Contributions: Conception and design: N.D. Berkman, C.M. Peat, K.E. Cullen, C.M. Bulik.
Analysis and interpretation of the data: K.A. Brownley, N.D. Berkman, C.M. Peat, K.N. Lohr, C.M. Bann, C.M. Bulik.
Drafting of the article: K.A. Brownley, N.D. Berkman, C.M. Peat, K.N. Lohr, K.E. Cullen, C.M. Bann.
Critical revision for important intellectual content: K.A. Brownley, N.D. Berkman, C.M. Peat, K.N. Lohr, C.M. Bulik.
Final approval of the article: K.A. Brownley, N.D. Berkman, C.M. Peat, K.N. Lohr, K.E. Cullen, C.M. Bann, C.M. Bulik.
Statistical expertise: C.M. Bann.
Obtaining of funding: K.A. Brownley, N.D. Berkman, C.M. Peat, K.N. Lohr, C.M. Bulik.
Administrative, technical, or logistic support: N.D. Berkman, K.N. Lohr, K.E. Cullen.
Collection and assembly of data: K.A. Brownley, N.D. Berkman, C.M. Peat, K.E. Cullen, C.M. Bulik.
The best treatment options for binge-eating disorder are unclear.
To summarize evidence about the benefits and harms of psychological and pharmacologic therapies for adults with binge-eating disorder.
English-language publications in EMBASE, the Cochrane Library, Academic OneFile, CINAHL, and ClinicalTrials.gov through 18 November 2015, and in MEDLINE through 12 May 2016.
9 waitlist-controlled psychological trials and 25 placebo-controlled trials that evaluated pharmacologic (n = 19) or combination (n = 6) treatment. All were randomized trials with low or medium risk of bias.
2 reviewers independently extracted trial data, assessed risk of bias, and graded strength of evidence.
Therapist-led cognitive behavioral therapy, lisdexamfetamine, and second-generation antidepressants (SGAs) decreased binge-eating frequency and increased binge-eating abstinence (relative risk, 4.95 [95% CI, 3.06 to 8.00], 2.61 [CI, 2.04 to 3.33], and 1.67 [CI, 1.24 to 2.26], respectively). Lisdexamfetamine (mean difference [MD], −6.50 [CI, −8.82 to −4.18]) and SGAs (MD, −3.84 [CI, −6.55 to −1.13]) reduced binge-eating–related obsessions and compulsions, and SGAs reduced symptoms of depression (MD, −1.97 [CI, −3.67 to −0.28]). Headache, gastrointestinal upset, sleep disturbance, and sympathetic nervous system arousal occurred more frequently with lisdexamfetamine than placebo (relative risk range, 1.63 to 4.28). Other forms of cognitive behavioral therapy and topiramate also increased abstinence and reduced binge-eating frequency and related psychopathology. Topiramate reduced weight and increased sympathetic nervous system arousal, and lisdexamfetamine reduced weight and appetite.
Most study participants were overweight or obese white women aged 20 to 40 years. Many treatments were examined only in single studies. Outcomes were measured inconsistently across trials and rarely assessed beyond end of treatment.
Cognitive behavioral therapy, lisdexamfetamine, SGAs, and topiramate reduced binge eating and related psychopathology, and lisdexamfetamine and topiramate reduced weight in adults with binge-eating disorder.
Agency for Healthcare Research and Quality.
Appendix Table 1. DSM-5 Diagnostic Criteria for Binge-Eating Disorder
Table 1. Interventions Commonly Used in Treating Patients With Binge-Eating Disorder
Analytic framework for treatment effectiveness and harms.
BMI = body mass index; GERD = gastroesophageal reflux disease; KQ = key question.
* Effectiveness of treatment.
† Differences between subgroups.
Appendix Table 2. Inclusion and Exclusion Criteria*
AHRQ = Agency for Healthcare Research and Quality.
* The figure was adapted from a larger report. Not all studies assessed for risk of bias are accounted for at the bottom of the figure because some populations are not included in the analysis in this article.
† Three studies (3 articles) also are included for binge-eating disorder treatment (key questions 1, 2, and 3) synthesis.
Appendix Table 3. Baseline Characteristics of the Included BED Treatment Effectiveness Trials (n = 34)
Table 2. Treatment Effectiveness for Binge-Eating Disorder: Qualitative Synthesis Results
Effect of therapist-led cognitive behavioral therapy on abstinence from binge eating.
RR = risk ratio.
Effect of lisdexamfetamine, 50 or 70 mg/d (top), and second-generation antidepressants (bottom) on abstinence from binge eating.
Appendix Table 4. Harms Associated With Treatments for Binge-Eating Disorder: Qualitative Synthesis Results*
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Per Sodersten, Cecilia Bergh, Michael Leon
October 11, 2016
Conflict of Interest:
I think that complete openness concerning financial arrangements is a good idea. <br/>Our research is carried out at the Karolinska Institute (KI), I am a professor at KI. The research is translated clinically by Mando Group AB, a company started by Södersten and Bergh, who have 47.5% of the stock each. Professor Michael Leon has 5%. Mando Group AB contracts with the County Council of Stockholm every fifth year to treat patients with eating disorders. Mando Groups AB signed its first contract in 1997 with the County Council of Stockholm and, since then, its treatment is one standard of care offered to the citizens of Stockholm. This arrangement is the same as when the County Council of Stockholm contracts with its own clinics to treat patients with all kinds of disease, including eating disorders. That is to say, the County Council of Stockholm provides eating disorders services to the citizens of Stockholm both through a clinic of its own and through Mando Group AB. There is a third provider of care for patients with eating disorders in Stockholm, which is a private clinic. All health care in Sweden is funded through the tax system, private pay is extremely uncommon. However, patients can pay privately for treatment by Mando Group AB and patients from Australia have done that because insurers in Australia have denied reimbursement. <br/>I would like to add, firstly, that we are in compliance with the recommendation of the International Committee of Medical Journal Editors on “Author Responsibilities-Conflicts of Interest” http://www.icmje.org/recommendations/browse/roles-and-responsibilities/author-responsibilities--conflicts-of-interest.html.<br/>Secondly, I would like to say that all profit that Mando Group AB has made has been re-invested in research and development and that there have been no dividends to stock owners. We do not intend to change this policy. We declare all of this in each manuscript submission and so far, journals have judged it necessary to publish only some of the details.<br/>It seems to me that the potential ethical problem when scientists translate their research findings into the clinic in a company is not unlike that which arises when any scientist, in an academic setting, is developing a theory and needs further economic funding for her/his work and may receive recognition and financial benefits for the work. The incentive is, in part, economic in this case as well and the ethical “problem” is similar in both cases. <br/>However, the more important incentive for us is the improvement of the treatment of patients with eating disorders. We are researchers working in an academic setting and like many other medical research institutes today, the KI encourages scientists to translate their research into the clinic in companies that aim to generate financial profits to be used for research and development (see: http://ki.se/sites/default/files/summary_strategy2018.pdf). <br/>
The Effect of CBT in the Treatment of BED
In an interesting article on the treatment of patients with Binge Eating Disorder (BED), Brownley and colleagues reviewed five studies on the outcomes of cognitive behavior therapy (CBT) (1). Because binge eating should occur at least once/week over three months for a diagnosis of BED (1, Appendix, Table 1), the criterion for the remission from BED should be abstinence of binge eating for three months. However, the studies that Brownley and colleagues reviewed used “self-monitoring … characterized as the number of days during a 14-day period in which patients reported at least one episode of binge eating” as a measure of outcome or 28 days without binge eating as the criterion for absence of that diagnosis (2). One study used a mere seven days without bingeing as the criterion for abstinence. Moreover, the follow-up assessment at 12 months after discharge was done by telephone and there also was no control group (3). Typically, there was a 20% dropout rate in these studies and although the patients who completed treatment improved, the number of patients in remission was not reported; several patients continued to binge eat both at discharge and after 12 months, which was the longest period of follow-up. However, one of the studies reported that only 20% among the patients that the authors intended to treat had abstained from binge eating 12 months after CBT therapy and 50% of those who completed the treatment did. More than 50% of the patients in this study were lost to follow-up and the controls were not followed-up (2). While Brownley and colleagues concluded that these studies provide “… strong support for therapist-led CBT … in helping patients with BED reduce binge-eating frequency and achieve abstinence” (1), we think that the studies supporting that conclusion need to be stronger before the effectiveness of CBT for BED can be evaluated. Almost 30 years ago, it was reported that behavioral methods are more effective in treating the binge eating associated with bulimia nervosa than CBT (4). We have confirmed this result by developing techniques to treat eating behavior directly. Thus, using three months of abstinence of binge eating as the criterion of remission, we have reported a 75% rate of remission and a 10% rate of relapse over five years of follow-up in 249 bulimic patients (5). We suggest that adding treating the disordered eating behavior directly will improve outcomes of CBT. 1. Brownley KA, Berkman ND, Peat CM, Lohr KN, Cullen KE, Bann CM, Bulik CM. Binge-Eating Disorder in adults: a systematic review and meta-analysis. Ann Intern Med. 2016;165:409-420. doi: 10.7326/M15-2455.2. Peterson CB, Mitchell JE, Crow SJ, Crosby RD, Wonderlich SA. The efficacy of self-help group treatment and therapist-led group treatment for binge eating disorder. Am J Psychiatry. 2009;166:1347-54.doi: 10.1176/appi.ajp.2009.09030345.3. Tasca G, Ritchie K, Conrad G, Balfour L, Gayton J, Lybanon V, et al. Attachment scales predict outcome in a randomized controlled trial of two group therapies for binge eating disorder: an aptitude by treatment interaction. Psychother Res. 2006;16:106-21. doi: 10.1080/10503300500090928.4. Freeman, CPL, Barry F, Dunkeld-Turnbull J, Henderson A. Controlled trial of psychotherapy for bulimia nervosa. BMJ 1988;296:521-5. doi: http://dx.doi.org/10.1136/bmj.296.6621.521.5. Bergh C, Callmar M, Danemar S, Hölcke M, Isberg S, Leon M, et al. Effective treatment of eating disorders: Results at multiple sites. Behav Neurosci. 2013;127:878-89. doi: 10.1037/a0034921.
Denise E. Wilfley, Ellen E. Fitzsimmons-Craft, & Dawn M. Eichen
Washington University School of Medicine
October 18, 2016
Conflict of Interest:
Dr. Wilfley is a consultant for Shire Pharmaceuticals and was an investigator on the two NIH-funded trials of interpersonal psychotherapy cited in the comment below.
Why We Recommend Specialist Psychological Treatments for Binge Eating Disorder
Brownley et al.’s (1) meta-analysis of treatment for binge eating disorder (BED) recommends therapist-led cognitive-behavioral therapy (CBT), lisdexamfetamine, and second-generation antidepressants (SGAs) as the most well-supported options. However, there are several factors that require consideration when interpreting these conclusions. First is the lack of attention to durability of effects. There are no data on response to pharmacotherapy after medication is stopped presented in the meta-analysis, and the active treatment periods have been very short (6-16 weeks). In contrast, large-scale NIH-funded randomized controlled trials of CBT and interpersonal psychotherapy (IPT) have demonstrated robust outcomes up to 2 years after treatment has been discontinued. Indeed, BED is chronic and debilitating, necessitating a focus on treatment response durability. Second, there is concern regarding the findings’ ability to generalize to the entire population of individuals with BED, as the pharmacological studies enrolled extremely restricted samples without psychiatric or medical comorbidities that may not translate to routine practice. Up to 43% of patients with BED have a current psychiatric comorbidity (2) and up to 60% of individuals with obesity who have BED meet criteria for the metabolic syndrome (3); therefore, there is an extremely large proportion of individuals with BED for whom pharmacotherapy may not be appropriate. Third, pharmacotherapy options for BED have many negative side effects (e.g., sleep disturbances, sympathetic nervous system arousal), and lisdexamfetamine has a high risk of abuse and dependence—these cannot be ignored when treating this vulnerable population. In contrast, there is minimal risk associated with psychological treatment (1). Finally, it is important to keep in mind that the conclusions of the report are dependent on its methodology. For example, the authors opted not to pool evidence from psychological treatments delivered in different formats (e.g., individual and group for IPT) but did aggregate information on medication dose. This decision led to the exclusion of IPT, which has been rigorously evaluated in two NIH-funded trials, is highly acceptable to patients, and is associated with low dropout (4-5). Due to concerns regarding durability, generalizability, and side effects of pharmacotherapy, we recommend specialist psychological treatments, such as CBT, which was recommended by Brownley et al. (1), and IPT, for BED, as they produce marked and sustained outcomes. Before pharmacotherapy could be recommended as a first-line option, both long-term outcome data and studies using more generalizable samples, with head-to-head evaluation with specialized psychological treatments, are required. Until such data are available, providers should prioritize specialist psychological treatment for BED.References1. Brownley KA, Berkman ND, Peat CM, Lohr KN, Cullen KE, Bann CM, Bulik CM. Binge-eating disorder in adults. Ann Intern Med 2016;165:409-420. 2. Grilo CM, White MA, Masheb RM. DSM‐IV psychiatric disorder comorbidity and its correlates in binge eating disorder. Int J Eat Disord 2009;42:228-234. 3. Mitchell JE. Medical comorbidity and medical complications associated with binge‐eating disorder. Int J Eat Disord 2016;49:319-323.4. Wilfley DE, Welch RR, Stein RI, Spurrell EB, Cohen LR, Saelens BE, et al. A randomized comparison of group cognitive-behavioral therapy and group interpersonal psychotherapy for the treatment of overweight individuals with binge-eating disorder. Arch Gen Psychiatry 2002;59:713-721.5. Wilson GT, Wilfley DE, Agras WS, Bryson SW. Psychological treatments of binge eating disorder. Arch Gen Psychiatry 2010;67:94-101.
Brownley KA, Berkman ND, Peat CM, Lohr KN, Cullen KE, Bann CM, et al. Binge-Eating Disorder in Adults: A Systematic Review and Meta-analysis. Ann Intern Med. 2016;165:409-420. doi: 10.7326/M15-2455
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Published: Ann Intern Med. 2016;165(6):409-420.
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