Current and Emerging Directions in the Treatment of Eating Disorders
====================================================================

Eating disorders are debilitating syndromes characterized by aberrant eating patterns and pervasive problems with body image. Recent lifetime prevalence estimates in women are 0.9% for anorexia nervosa (AN), 1.5% for bulimia nervosa (BN), and 3.5% for binge eating disorder (BED).[@b1-sart-6-2012-033] These disorders represent a significant public health problem because they are associated with distress, disability, and increased risk of death.[@b2-sart-6-2012-033] Additionally, eating disorders have high comorbidity with mood, anxiety, and substance use disorders.[@b1-sart-6-2012-033] Thus, clinicians may encounter patients with eating disorders while treating other conditions. While significant advances in identifying maintenance factors for these disorders, including thin-ideal internalization, body dissatisfaction, perfectionism, and negative affect,[@b3-sart-6-2012-033] have contributed to advances in treatment development, definitively efficacious treatments remain largely unidentified. The purpose of this review is to identify for those outside the field of eating disorders what treatments currently work best as well as emerging directions in the treatment of eating disorders.

While several reviews have been published summarizing current treatments for AN,[@b4-sart-6-2012-033] BN,[@b5-sart-6-2012-033] and BED,[@b6-sart-6-2012-033] the scope of these papers was limited to articles published during or prior to 2005. Given the treatment field's continual growth over the past five years, particularly for BED, the present review extends and updates previous reviews by incorporating studies published through 2010. Further, to our knowledge, no study has systematically examined the effect of current treatments on primary outcomes (e.g., those related to the eating disorder) and secondary outcomes (e.g., those not directly related to the eating disorder, such as depression or anxiety) separately for each disorder. Given that second wave treatments were originally designed to treat depression and anxiety and clinicians not specializing in eating disorders may be most familiar with these treatments and outcomes in these domains, it would be clinically informative to assess whether treatments help alleviate these symptoms when the eating disorder is the focus of treatment. Finally, our review examines how current treatment findings are informing future treatment directions and describes several treatment trials that are currently underway in the field.

Methods
=======

Journal articles were identified through searching PubMed and PsychINFO databases for articles published during or after 2000 using the following search terms: medication, atypical antipsychotics, antidepressants, selective serotonin reuptake inhibitors, randomized controlled trial (RCT), treatment, therapy, cognitive behavioral therapy, dialectical behavior therapy, interpersonal psychotherapy, psychodynamic, family therapy, behavioral weight loss, combined interventions, anorexia nervosa, bulimia nervosa, binge eating disorder, and eating disorder. Additional articles for the search period were identified by reviewing the reference lists of relevant articles. Articles spanning psychopharmacological interventions, psychosocial interventions, and combined psychopharmacological and psychosocial interventions were included to extend previous reviews within the field and to provide a comprehensive picture of treatment outcome.[@b5-sart-6-2012-033],[@b6-sart-6-2012-033] The first author identified articles for inclusion from electronic searches, and the second author reviewed the list for inclusion and provided additions based on her prior reviews of this literature. Inclusion criteria for the current directions section were broad and included any controlled trials published in peer-reviewed journals from 2000 to 2010, inclusive. Exclusion criteria for current directions included: articles published prior to 2000, open label medication trials, and non-randomized trials. Importantly, seminal articles published prior to 2000 are described in the text for historical context but are not included in tables. Trials included in the emerging directions section were identified through searching ongoing clinical trials from the International Standard Randomised Controlled Trial Registry, the Australian New Zealand Clinical Trials Registry, as well as reviewing abstracts presented at recent international conferences on eating disorders, including the International Conference on Eating Disorders (Austria, 2010 and Miami, 2011) and the Eating Disorders Research Society Meeting (Cambridge, 2010 and Edinburgh, 2011).

Our search identified 43 articles, 13 of which described treatment for AN, 13 for BN, and 17 for BED. Information regarding sample size, proportion of female participants, recruitment source, diagnostic/inclusion criteria, exclusion criteria, duration and setting of treatment conditions, primary outcomes, secondary outcomes, and results for primary and secondary outcomes, are summarized in [Tables 1](#t1-sart-6-2012-033){ref-type="table"}--[3](#t3-sart-6-2012-033){ref-type="table"}. To allow comparisons across articles, primary and secondary outcomes were identified *a priori* and uniformly applied across articles. Primary outcomes included any measures directly related to the central symptoms and diagnostic criteria for AN, BN, and BED within the Diagnostic and Statistical Manual (DSM-IV-TR)[@b7-sart-6-2012-033] as these would be used to determine presence versus remission from the eating disorder. Primary outcomes for AN included weight restoration or weight gain (depending upon the methods used to assess weight outcome), and concerns about weight, shape, and eating. Those for BN included binge and purge frequency and weight and shape concerns, and those for BED included binge frequency and associated eating disorder cognitions. Secondary outcomes for all disorders included features often associated with each disorder, but not related directly to eating disorder diagnosis, including depressive and anxiety symptoms,[@b8-sart-6-2012-033] psychosocial functioning,[@b1-sart-6-2012-033],[@b9-sart-6-2012-033] and, for BN and BED, changes in weight.

Current Directions
==================

Anorexia Nervosa
----------------

### Psychopharmacological Interventions

Given the medical severity and complications occurring in low weight AN patients, five out of the six studies reviewed examined medication as an adjunct to inpatient, day treatment, or outpatient programs. Thus, it is important to note that the standard for testing treatment efficacy is typically more rigorous for AN than for other eating disorders, as the question is not whether medication improves outcome compared to placebo, but whether medication improves outcome beyond treatment as usual (TAU). While several classes of medication have been evaluated in AN, few trials have found positive results.[@b10-sart-6-2012-033]

### Antidepressants

Given that AN has been associated with serotonin dysregulation and is often comorbid with depression and obsessive-compulsive disorder,[@b8-sart-6-2012-033] several studies have examined the efficacy of Selective Serotonin Reuptake Inhibitors (SSRIs), which have the advantage over tricyclics of being generally well-tolerated.[@b11-sart-6-2012-033]--[@b13-sart-6-2012-033] Results have provided little evidence for the usefulness of SSRIs in weight gain or in reducing anxiety or depression.[@b11-sart-6-2012-033],[@b14-sart-6-2012-033] Other studies have examined whether fluoxetine may help prevent relapse. Kaye and colleagues[@b12-sart-6-2012-033] conducted a 52-week trial (n = 39) and found that 20 mg fluoxetine was more likely to prevent relapse compared to placebo after inpatient hospital treatment. Further, fluoxetine was associated with improved weight, eating-related cognitions, anxiety, and obsessive-compulsive symptoms in this trial. However, results from this trial were not replicated. In a 52-week RCT of 93 patients, Walsh and colleagues[@b15-sart-6-2012-033] found no advantage for 20 mg fluoxetine in preventing relapse after weight restoration. Overall, antidepressants have not been effective in improving the primary outcome for AN: weight. Further, there is limited evidence for whether antidepressants are effective in improving secondary outcomes, such as anxiety and depression, in underweight patients with AN.

### Atypical Antipsychotics

Atypical antipsychotics help reduce anxiety, agitation, psychosis, and have the side effect of weight gain in the treatment of psychotic disorders,[@b16-sart-6-2012-033] suggesting that this class of drugs may be useful in the treatment of AN. Olanzapine has been the most systematically studied atypical antipsychotic and provides the most promise in the pharmacological treatment of adult AN. A growing body of evidence has found that olanzapine improves weight-related outcomes over placebo.[@b17-sart-6-2012-033]--[@b19-sart-6-2012-033] One study found that this effect may depend on diagnostic subtype. Brambilla et al[@b18-sart-6-2012-033] reported no differences between olanzapine and placebo for 30 AN patients after 3 months; however, when patients were stratified by subtype, olanzapine significantly increased body mass index (BMI) for individuals with the binge-purge subtype (ANbp), but not the restricting subtype (ANr). Olanzapine also has demonstrated benefits in improving secondary outcomes including reductions in obsessional thinking and rumination,[@b17-sart-6-2012-033],[@b20-sart-6-2012-033] compulsive rituals, and depression.[@b18-sart-6-2012-033] Further, olanzapine has been generally well-tolerated, with the most common side effect being mild drowsiness.[@b17-sart-6-2012-033],[@b18-sart-6-2012-033],[@b20-sart-6-2012-033] Atypical antipsychotics also have been recently examined in adolescents with AN, but studies have not supported its efficacy in adolescents.[@b21-sart-6-2012-033]--[@b23-sart-6-2012-033]

Psychosocial Interventions
--------------------------

### Psychodynamic Psychotherapy

Psychodynamic therapy has been examined in AN due to the interpretation that AN developed as an effort to exert control over one's environment in the context of dysfunctional family/interpersonal relationships. [@b24-sart-6-2012-033] However, studies have not supported its efficacy compared to other active treatments.[@b24-sart-6-2012-033]--[@b27-sart-6-2012-033] One study of 84 patients found that a 1-year, time-limited, focal psychoanalytic therapy produced better weight outcome compared to TAU, but did not differ from family therapy. [@b26-sart-6-2012-033] Studies examining Cognitive Analytic Therapy (CAT), a combination psychoanalytic and cognitive behavioral therapy, have failed to find differences in weight gain between CAT and TAU,[@b26-sart-6-2012-033] and a more traditional form of behavior therapy.[@b25-sart-6-2012-033]

### Cognitive Behavioral Therapy (CBT)

CBT for AN has focused on dysfunctional beliefs about food, body image, and the influence of weight/shape on self-evaluation, along with the influence of these thoughts on restricted food intake. The American Psychological Association (APA) task force[@b28-sart-6-2012-033] concluded only "modest/controversial support" exists for the use of CBT in AN. CBT has been superior to nutrition-based interventions in improving eating attitudes and weight outcomes[@b29-sart-6-2012-033] and reducing relapse.[@b30-sart-6-2012-033] However, these studies have been criticized because dietary interventions do not provide a demanding comparison group for AN treatment.[@b31-sart-6-2012-033] Supporting this criticism, other studies have failed to find differences between CBT and TAU[@b32-sart-6-2012-033] or alternative treatments, such as interpersonal psychotherapy or nonspecific supportive clinical management.[@b33-sart-6-2012-033] Thus, there has been limited support for the efficacy of CBT in adults with AN. This limited support may reflect the extreme cognitive rigidity associated with patients with AN,[@b34-sart-6-2012-033] which may impede progress with the cognitive component of treatment.

### Interpersonal Psychotherapy (IPT)

Only one RCT has investigated the efficacy of IPT in AN. McIntosh et al.[@b33-sart-6-2012-033] compared 20 sessions of IPT to CBT and nonspecific supportive clinical management in 56 patients, and found that clinical management was superior to IPT on global outcome (a 1--4 severity rating scale with 1 being in remission and 4 meeting full criteria for AN). IPT did not differ from the clinical management group on weight gain, and scores on restraint favored clinical management. IPT and CBT did not differ on global outcome or weight gain, and IPT was associated with worse restraint scores and a lower proportion of individuals rated as "significantly improved" compared to CBT. At five-year follow-up, no differences were found on any outcome measures between clinical management, CBT, and IPT.[@b35-sart-6-2012-033] Thus, although individuals treated with IPT may continue to improve after treatment completion, there is no evidence that IPT has been superior to alternative treatments or TAU for AN.

### Family Based Therapy

Family based therapy has been shown to be the most effective psychosocial treatment for children and adolescents with AN and has been rated as having "strong research support" by the APA task force.[@b28-sart-6-2012-033] Indeed, studies have found that family based therapy was associated with improvements in BMI and eating attitudes compared to TAU[@b26-sart-6-2012-033] and active, alternative treatments.[@b24-sart-6-2012-033],[@b36-sart-6-2012-033],[@b37-sart-6-2012-033] Family based treatment may succeed because it balances the benefits of a controlled environment for producing weight gain with the external validity of achieving these gains within the home environment. The effectiveness of family based therapy is specific to younger patients.[@b36-sart-6-2012-033] A follow-up study found that the superiority of family based therapy over individual therapy persisted after 5-years.[@b38-sart-6-2012-033] Further, in 86 outpatients, short-term family based therapy (10 sessions over 6 months) was as effective as long-term family based therapy (20 sessions over 12 months).[@b39-sart-6-2012-033] However, the two largest family based therapy studies (n = 84[@b26-sart-6-2012-033] and n = 121[@b37-sart-6-2012-033]), establishing improvements in weight over alternative treatments, have utilized the 12-month intervention.[@b26-sart-6-2012-033],[@b37-sart-6-2012-033] While strong evidence has supported familial involvement in the treatment of adolescent AN, the level of family involvement may depend on parental characteristics. When 40 families of adolescents with AN were stratified for level of maternal criticism, patients with high maternal criticism had significantly better outcome in separated family therapy compared to conjoint family therapy, while no differences were found for patients with low maternal criticism.[@b40-sart-6-2012-033] In sum, family based therapy represents a first line treatment for children/younger adolescents with AN.

Psychopharmacological and Psychosocial Interventions
----------------------------------------------------

To our knowledge, no studies have systematically compared medication alone, psychosocial treatment alone, and their combination to test whether combined treatments have advantages over single treatments in AN. This is likely due to the poor evidence base for psychopharmacological and psychosocial treatments in AN and ethical constraints on examining psychopharmacological intervention of unknown efficacy alone. Despite this limitation, some hypotheses may be developed based upon results from adjunctive medication trials and psychosocial treatments. Although the original aim of Pike et al.[@b30-sart-6-2012-033] was not to investigate the additional effects of medication on psychosocial treatment, they found differential responses to medication between CBT and nutritional counseling. Within the CBT condition, 7/8 individuals who met criteria for "good outcome" were prescribed an antidepressant, compared to 4/10 individuals who did not met criteria for "good outcome." In contrast, medication was unassociated with outcome for those randomized to nutritional counseling. Due to a lack of studies systematically comparing combination and single treatments, there is no conclusive evidence that combination treatments are associated with better outcome than psychosocial treatment alone.

Summary
-------

To date the most effective treatments for AN have included the use of olanzapine as an adjunct to treatment for adults with AN, and family based therapy for adolescents with AN. For olanzapine administered in an inpatient setting, 87% of patients achieved weight restoration compared to 56% of the placebo group.[@b17-sart-6-2012-033] However, less is known about how well olanzapine works on an outpatient basis. For adolescent outpatients, approximately 41% achieved weight restoration with family based therapy.[@b37-sart-6-2012-033],[@b40-sart-6-2012-033] These results highlight the need for novel psychosocial treatments for adults and better knowledge about the outpatient efficacy of olanzapine.

Bulimia Nervosa
===============

Psychopharmacological Interventions
-----------------------------------

### Antidepressants

Given that affective disturbances have been commonly associated with BN,[@b41-sart-6-2012-033] early pharmacological treatments focused on tricyclic antidepressants, and showed efficacy in decreasing binge episodes compared to placebo.[@b42-sart-6-2012-033],[@b43-sart-6-2012-033] However, these medications were associated with adverse side effects. Thus, current psychopharmacological research has focused on SSRIs. While fluvoxamine[@b44-sart-6-2012-033],[@b45-sart-6-2012-033] and sertraline[@b46-sart-6-2012-033] have been shown to be superior to placebo for reducing binge/purge frequency, relatively few studies have focused on these SSRIs. In contrast, several studies have examined the efficacy of fluoxetine. Overall, 60 mg of fluoxetine has been successful in reducing binge/purge frequency as well as eating disorder cognitions including weight concern, food preoccupation, restraint, and drive for thinness,[@b47-sart-6-2012-033]--[@b50-sart-6-2012-033] and has been well-tolerated.[@b49-sart-6-2012-033] 60 mg fluoxetine also has been shown to be superior to 20 mg of fluoxetine in reducing binge/purge frequency.[@b47-sart-6-2012-033] There has been mixed support for fluoxetine's efficacy in reducing depressive symptoms in patients with BN, with some studies finding no differences between fluoxetine and placebo[@b48-sart-6-2012-033],[@b50-sart-6-2012-033] and others favoring fluoxetine.[@b47-sart-6-2012-033]

One study examined the efficacy of fluoxetine in preventing relapse in 150 patients with BN after successful outpatient fluoxetine treatment.[@b49-sart-6-2012-033] The authors found that 52 weeks of 60 mg fluoxetine significantly reduced relapse rate compared to placebo (33% vs. 51%, respectively) and increased time to relapse (i.e., was associated with sustained remission). Those treated with fluoxetine also showed greater improvements in eating-related preoccupations and rituals. Thus, fluoxetine has been effective in reducing binge/purge frequency and eating-related symptoms in BN, but may not be efficacious for reducing depressive symptoms.

Psychosocial Interventions
--------------------------

### Cognitive Behavioral Therapy

There has been strong support for CBT in reducing binge/purge behaviors both compared to control conditions[@b51-sart-6-2012-033] and other active treatments including psychodynamic therapy,[@b52-sart-6-2012-033],[@b53-sart-6-2012-033] IPT,[@b54-sart-6-2012-033],[@b55-sart-6-2012-033] and family therapy. [@b56-sart-6-2012-033] Further, a meta-analysis of treatments in BN found that CBT had larger effect sizes than medication for reducing binge frequency (CBT = 1.28, medication = 0.66), purge frequency (CBT = 1.22, medication = 0.39), disordered eating attitudes (CBT = 1.35, medication = 0.71), and depression (CBT = 1.31, medication = 0.73).[@b57-sart-6-2012-033] CBT, delivered in 16--20 sessions over 4--5 months, has received an "A" grade by the National Institute for Clinical Excellence (NICE) in the UK.[@b58-sart-6-2012-033] CBT has been effectively delivered in group and guided self-help formats.[@b56-sart-6-2012-033],[@b59-sart-6-2012-033] The efficacy of CBT may be due to the well-developed symptom maintenance models for BN. Within the CBT model, binge eating and subsequent purging are consequences of extreme dietary restraint; thus, reducing dietary restraint by regularizing the patient's meal pattern results in reductions in binge/purge frequency. [@b60-sart-6-2012-033] However, there is less support for CBT improving secondary symptoms such as depression, social adjustment, self-esteem, interpersonal problems, and global psychiatric symptoms, beyond alternative treatments,[@b54-sart-6-2012-033],[@b59-sart-6-2012-033],[@b61-sart-6-2012-033] likely because CBT for BN focuses specifically on cognitions and behaviors related to the eating disorder.

Dialectical Behavior Therapy (DBT), a combination of CBT and mindfulness-based techniques, has been investigated for the treatment of BN, due to a strong association between BN and interpersonal problems,[@b62-sart-6-2012-033] impulsivity,[@b63-sart-6-2012-033] and affective dysregulation. [@b64-sart-6-2012-033] Safer and colleagues[@b65-sart-6-2012-033] compared 20 sessions of DBT adapted for BN to a waitlist condition in 31 patients and found that DBT significantly decreased binge/purge frequency; however, DBT was not associated with any improvements in affect regulation or self-esteem compared to the waitlist condition. In addition, it remains unclear whether DBT is superior to standard CBT for BN.

### Interpersonal Psychotherapy

Interest in IPT as a treatment for BN emerged as a consequence of early comparisons of CBT and psychodynamic psychotherapy. IPT, a short-term form of psychodynamic therapy focused on current relationships, was initially used as a control treatment to highlight the specific efficacy of CBT.[@b55-sart-6-2012-033] However, results showed that IPT was also associated with improvements in remission compared to behavioral therapy without a cognitive component. [@b55-sart-6-2012-033] This led to further investigation of IPT as a viable treatment option for BN. IPT has been shown to be superior to waitlist in reducing binge episode frequency;[@b66-sart-6-2012-033] however, IPT has been associated with inferior remission rates compared to CBT at end of treatment. [@b54-sart-6-2012-033],[@b55-sart-6-2012-033] At 1-year[@b54-sart-6-2012-033],[@b55-sart-6-2012-033] and 5-year follow up,[@b67-sart-6-2012-033] IPT was as effective as CBT in facilitating remission and ameliorating secondary symptoms, including general psychiatric symptoms, social adjustment, and depressive symptoms.[@b54-sart-6-2012-033],[@b55-sart-6-2012-033] Thus, IPT and CBT appear to be equally effective for achieving remission long-term, but CBT facilitates remission more rapidly. Given that patients with BN have poor psychosocial functioning, [@b9-sart-6-2012-033] improving interpersonal functioning may eventually help the patient to cope with life stressors more effectively instead of relying on maladaptive coping mechanisms, such as dietary restriction, bingeing, and purging.

### Family Based Interventions

In contrast to strong evidence for the efficacy of family based interventions for adolescents with AN, mixed evidence has emerged for the role of family based therapy in the treatment of adolescent BN.[@b56-sart-6-2012-033],[@b68-sart-6-2012-033] Having parents take control of or monitor their child's binge/purge behaviors may be difficult given the secretive nature of these behaviors as well as their tendency to emerge at an older age. Despite these challenges, Le Grange et al.[@b68-sart-6-2012-033] found 20 sessions of family based therapy was superior to supportive psychotherapy on remission rates, and reductions in compensatory behaviors, dietary restraint, and eating, weight, and shape concerns in a sample of 80 patients with BN and related EDNOS. However, in a similar sized sample, Schmidt and colleagues[@b56-sart-6-2012-033] found that 13 weeks of family therapy was inferior to CBT on abstinence from binge eating at 6-month follow-up, and no differences in binge frequency were found between treatments at 12-month follow-up. Thus, further research is needed to elucidate the effectiveness of family based therapy in adolescent BN.

Psychopharmacological and Psychosocial Interventions
----------------------------------------------------

Given the efficacy of CBT and fluoxetine in the treatment of BN, several studies have examined combined treatments to determine whether the use of medication as an adjunct to CBT provides any further improvement over CBT alone. Overall, no differences have emerged between combined treatments and CBT alone for reducing binge/purge frequency.[@b69-sart-6-2012-033]--[@b72-sart-6-2012-033] However, there has been some evidence that the addition of antidepressant medication may improve depressive symptoms above CBT alone.[@b72-sart-6-2012-033],[@b73-sart-6-2012-033] Walsh and colleagues[@b72-sart-6-2012-033] compared 16 weeks of CBT guided self-help with placebo, CBT guided self-help with fluoxetine, fluoxetine alone, and placebo alone in 91 patients. CBT plus placebo, CBT plus fluoxetine, and fluoxetine alone were equivalent in reducing binge/purge frequency, but interventions with fluoxetine showed greater improvements in depressive symptoms compared to placebo interventions. Importantly, in this and other trials, CBT was designed to address symptoms of BN rather than depression. Thus, it is unclear whether findings would hold if CBT for depression were offered for those with comorbid mood disorders. Within the depression literature, antidepressant medication has been found to enhance reductions in depression associated with CBT, particularly for more complex cases;[@b74-sart-6-2012-033] thus, it is likely that the addition of fluoxetine to treatment for patients with BN and comorbid mood disorders would be efficacious even if they were treated with CBT for depression. Overall, results from these studies support the use of CBT as a first line treatment for BN.

Summary
-------

The most effective current treatments for BN include CBT and 60 mg fluoxetine. However, even with the strong evidence base for the superiority of both fluoxetine and CBT over alternative treatments, remission rates have remained low. For fluoxetine approximately 20% of patients achieved remission,[@b48-sart-6-2012-033],[@b50-sart-6-2012-033] while 40% achieved remission with CBT across trials.[@b51-sart-6-2012-033],[@b54-sart-6-2012-033],[@b55-sart-6-2012-033],[@b59-sart-6-2012-033],[@b75-sart-6-2012-033] These results highlight the continued need for treatment refinement and implementation within this group.

Binge Eating Disorder
=====================

Psychopharmacological Interventions
-----------------------------------

### Antidepressants

Similar to results in BN, SSRIs reduce binge frequency in BED compared to placebo.[@b76-sart-6-2012-033]--[@b78-sart-6-2012-033] Positive findings have emerged across a range of different medications (i.e., fluoxetine, fluvoxamine, citalopram, sertraline) with limited focus on replication of positive findings for specific formulations. Thus, more studies replicating findings for specific medications are needed. Mixed results have emerged for the usefulness of SSRIs in decreasing weight or BMI for obese binge eaters, with some studies finding positive results[@b76-sart-6-2012-033]--[@b78-sart-6-2012-033] and others reporting no difference between SSRIs and placebo.[@b79-sart-6-2012-033] None of the reviewed studies found evidence that SSRIs were superior to placebo in reducing depressive symptoms in BED.[@b76-sart-6-2012-033]--[@b79-sart-6-2012-033]

Several other medications have shown promise in the treatment of BED. Two studies of 61[@b80-sart-6-2012-033] and 394[@b81-sart-6-2012-033] patients with BED found positive results for topiramate in reducing binge frequency, binge days, and weight.[@b80-sart-6-2012-033],[@b81-sart-6-2012-033] However, approximately 15%--20% of the treatment groups withdrew due to adverse side effects[@b80-sart-6-2012-033],[@b81-sart-6-2012-033] including problems with memory and depression.[@b81-sart-6-2012-033] Studies examining sibutramine, an appetite suppressant, showed promise in early trials.[@b82-sart-6-2012-033]--[@b84-sart-6-2012-033] Appolinario and colleagues[@b82-sart-6-2012-033] found that 12 weeks of sibutramine produced significant decreases in binge frequency compared to placebo in 60 outpatients; further, individuals on medication had significant reductions in weight, while the placebo group experienced increased weight. Of note, in October 2010, the US Food and Drug Administration (FDA) recommended against the prescription of sibutramine due to evidence of serious cardiovascular adverse events.[@b85-sart-6-2012-033] Thus, the current state of psychopharmacological directions in the treatment of BED remains focused on serotonergic agents.

Psychosocial Interventions
--------------------------

### Cognitive Behavioral Therapy

CBT has been shown to improve binge abstinence rates compared to no treatment[@b86-sart-6-2012-033],[@b87-sart-6-2012-033] and self-monitoring control.[@b88-sart-6-2012-033] However, there has been mixed evidence for the efficacy of CBT in reducing binge frequency compared to alternative treatments.[@b88-sart-6-2012-033],[@b89-sart-6-2012-033] One study found that CBT led to greater reductions in binge frequency, greater remission rates, and reduced hunger compared to behavioral weight loss (BWL) treatment.[@b88-sart-6-2012-033] However, CBT does not differ from IPT in reducing binge eating or increasing remission.[@b89-sart-6-2012-033],[@b90-sart-6-2012-033] These results appear to mirror similarities in remission rates between CBT and IPT for BN, and may be a function of similar models of factors maintaining binge eating in both BN and BED. Two studies[@b86-sart-6-2012-033],[@b87-sart-6-2012-033] examined the comparative efficacy of guided self-help (self-help manual plus weekly meetings with a therapist), pure self-help (self-help manual only), and traditional therapist-led CBT. Supporting the efficacy of alternative forms of treatment delivery, no differences in binge frequency were found between guided self-help, pure self-help, and traditional CBT.[@b86-sart-6-2012-033],[@b87-sart-6-2012-033] Thus, CBT appears to have efficacy for reducing binge frequency but does not appear to contribute to weight loss in BED.[@b90-sart-6-2012-033],[@b91-sart-6-2012-033] Further, CBT contributes to similar levels of improvement in other secondary outcomes, including depressive symptoms, self-esteem, and social adjustment, compared to alternative treatments.[@b88-sart-6-2012-033],[@b90-sart-6-2012-033],[@b91-sart-6-2012-033]

To date, only one study[@b92-sart-6-2012-033] of 44 patients has investigated the efficacy of DBT compared to waitlist control for the treatment for BED. Twenty weeks of DBT was successful in decreasing binge days, binge frequency, EDE weight, shape, and eating concerns, as well as emotional eating in response to anger compared to no treatment. However, DBT did not produce greater improvement than waitlist on secondary outcomes including weight loss, depressive symptoms, and negative affect regulation. While results show promise in improving primary outcomes, comparisons against active interventions are needed.

### Weight Loss Treatment

BWL treatments have been investigated as a means of helping patients with BED gain control over their food intake and reduce their weight. These programs have helped facilitate weight reduction but have mixed results for reducing binge eating, probably due to the more direct focus on weight loss as opposed to binge eating. Indeed, BWL did not differ from a self-monitoring control condition[@b88-sart-6-2012-033] in producing binge abstinence and has been found to be inferior to CBT at treatment end[@b88-sart-6-2012-033] and 2-year follow-up.[@b90-sart-6-2012-033] Although CBT outperforms BWL in reducing binge frequency, BWL has been shown to be superior to both CBT and IPT in reducing BMI and weight[@b90-sart-6-2012-033] and superior to CBT in increasing dietary restraint, which may help facilitate weight loss for obese binge eaters.[@b88-sart-6-2012-033],[@b90-sart-6-2012-033] In contrast, BWL does not appear to differ from alternative treatments on depressive symptoms, self-esteem, or social adjustment.[@b88-sart-6-2012-033],[@b90-sart-6-2012-033]

### Interpersonal Psychotherapy

IPT has produced similar reductions in binge eating compared to alternative treatments.[@b89-sart-6-2012-033],[@b90-sart-6-2012-033] Wilfley et al[@b89-sart-6-2012-033] found no differences in binge abstinence, binge days, or binge frequency between 20 sessions of group IPT and group CBT in a sample of 162 outpatients, both at end of treatment and 1-year follow-up. Similarly, Wilson and colleagues[@b90-sart-6-2012-033] compared 208 patients and found no differences in frequency of binge days between 24 weeks of IPT, CBT, and BWL at end of treatment or 1-year follow-up. However, at 2-year follow-up both IPT and CBT were superior to BWL. Thus, support exists for IPT's efficacy in the treatment of BED, and IPT appears to produce equivalent outcomes to those found for CBT.

Psychopharmacological and Psychosocial Interventions
----------------------------------------------------

In terms of combined treatments, studies investigating CBT and antidepressant medications have found no evidence for increased efficacy over CBT alone.[@b93-sart-6-2012-033],[@b94-sart-6-2012-033] Indeed, Grilo and colleagues[@b93-sart-6-2012-033] studied 108 individuals with BED and found that after 16 weeks, CBT plus fluoxetine and CBT plus placebo did not differ in producing remission from binge eating, and both were superior to fluoxetine or placebo alone. Further, CBT plus fluoxetine did not have additional benefits in ameliorating secondary outcomes, including depression or BMI, compared to CBT alone. One study of 50 patients found that 12 weeks of guided self-help CBT combined with the weight loss drug orlistat was associated with significantly greater remission rates and weight loss than CBT plus placebo,[@b95-sart-6-2012-033] highlighting a potential future direction for intervention.

Summary
-------

The best treatments to date for BED have included CBT and IPT. Remission rates from BED for each of these treatments have been higher than remission rates for AN or BN. Within studies that have compared CBT and IPT, approximately 82% of individuals treated with CBT and 80% of those treated with IPT achieved remission.[@b89-sart-6-2012-033],[@b90-sart-6-2012-033] While these remission rates appear high, it is notable that other studies that have examined CBT alone or compared with other treatments have produced lower estimates of remission.[@b88-sart-6-2012-033],[@b91-sart-6-2012-033],[@b96-sart-6-2012-033]

Emerging Directions
===================

[Table 4](#t4-sart-6-2012-033){ref-type="table"} provides a list of clinical trials that are currently underway or only recently completed. This table includes 13 studies focused on AN, 7 focused on BN, and 9 focused on BED. Across studies, 6 of 29 (21%) are trials focused on psychopharmacological interventions, representing one-sixth of the trials for AN, approximately half of the trials for BED, and none of the trials for BN.

Anorexia Nervosa
================

Emerging directions in the treatment of AN center mostly on expanding our knowledge regarding the usefulness of atypical antipsychotics and developing more efficacious psychosocial treatments for adults with AN, including those aimed at relapse prevention (see [Table 4](#t4-sart-6-2012-033){ref-type="table"}). Given the promising findings from trials involving olanzapine in increasing weight and improving cognitive symptoms of AN in adults, a 16-week, multi-site, double-blind, placebo-controlled outpatient trial of 160 adults with AN is currently underway to examine the effectiveness of olanzapine (2.5--10 mg) vs. placebo. This collaboration will increase knowledge about the outpatient efficacy of olanzapine, address limitations of small samples in previous studies (i.e., n = 15--34),[@b17-sart-6-2012-033]--[@b20-sart-6-2012-033] and help identify the best dose.[@b97-sart-6-2012-033]

Given the paucity of efficacious psychosocial treatments for adults with AN, the National Institute of Mental Health established a request for applications that funded the development and evaluation of four novel treatments. These treatments were designed to target specific vulnerabilities for AN in older adolescents and adults.[@b98-sart-6-2012-033]--[@b101-sart-6-2012-033] They include a couples-based treatment (UCAN),[@b100-sart-6-2012-033],[@b102-sart-6-2012-033],[@b103-sart-6-2012-033] cognitive remediation therapy (CRT),[@b98-sart-6-2012-033],[@b104-sart-6-2012-033] emotion acceptance behavior therapy (EABT),[@b99-sart-6-2012-033] and food exposure and response prevention therapy (AN-EXRP).[@b101-sart-6-2012-033],[@b105-sart-6-2012-033] While these trials are ongoing at the time of this review, preliminary results appear encouraging.

Uniting couples in the treatment of AN (UCAN) focuses on the patient in her interpersonal/social context, with the aim of maximizing social support and addressing issues of martial adjustment, communication, and sexual functioning.[@b106-sart-6-2012-033] Given the strong support for family based therapy in children/young adolescents with AN, this treatment functions as a developmentally appropriate extension for adults with AN through a focus on couple, rather than family, functioning. Two integral aspects of family based therapies for adolescents have been the focus on engaging caregivers in the support and reinforcement of the refeeding process and improvement of overall family functioning. Within family based therapy, improved communication and family functioning serves to increase support within the environment and help the adolescent stay healthy, and improvement on the part of the patient contributes to improved family relationships. This sense of teamwork and focus on improved communication translates well to couples approaches, and is an important part of UCAN. Preliminary findings[@b102-sart-6-2012-033],[@b103-sart-6-2012-033] indicated impressive outcomes associated with both UCAN and the supportive couples' therapy control condition. Although there was no significant difference between treatment conditions, retention, weight recovery, and remission exceeded levels observed in prior RCTs for outpatient treatment in adult patients with AN, suggesting partner involvement was beneficial.

CRT stems from neuropsychological research showing that individuals with AN exhibit weak central coherence, cognitive rigidity, and deficits in set shifting. These deficits are associated with an overly detail-oriented focus, which both maintains the disorder and interferes with traditional treatments, as patients often have difficulty grasping the therapeutic "big picture".[@b34-sart-6-2012-033] CRT targets these deficits through the use of cognitive exercises to improve thinking process skills and cognitive flexibility. This not only helps improve core cognitive symptoms of the disorder, but also enhances patients' ability to engage in and benefit from therapies that directly target the eating disorder. Preliminary results[@b104-sart-6-2012-033] support the acceptability of the treatment and improved performance on cognitive tasks for patients randomly assigned to receive CRT. The effects of improved cognitive processes on treatment engagement or outcome have not yet been reported.

EABT focuses on the role anorectic symptoms play in facilitating emotional avoidance. The treatment draws influence from several "third wave" treatments including acceptance and commitment therapy, DBT, and mindfulness-based cognitive therapy.[@b107-sart-6-2012-033] EABT focuses on techniques to enhance emotional awareness and increase important relationships and activities for the patient outside of the eating disorder.[@b107-sart-6-2012-033] In a recent case series, 3 of the 4 patients enrolled showed modest improvements in weight gain in an outpatient setting and additional improvements in anxiety, depression, and emotional avoidance were observed.[@b107-sart-6-2012-033]

AN-EXRP draws from similarities between AN and obsessive-compulsive disorder, including irrational fear/avoidance of food and extreme behaviors to manage these fears. Under this model, Steinglass and colleagues[@b105-sart-6-2012-033] developed a treatment to confront patients' anxiety around eating-related situations. These sessions begin with psychoeducation about the treatment and focus on developing an individualized hierarchy of feared foods, eating situations, and ritualized behaviors. Patients are then exposed slowly over time to each feared food situation, starting with the least feared item. Subjective ratings of anxiety are assessed immediately before, during, and after each exposure. The key aspect of exposure is the patient's direct experience of, and habituation to, the anxiety as well as the disconfirmation of her feared consequences regarding eating. Steinglass and colleagues[@b105-sart-6-2012-033] conducted a 4-week open series of AN-EXRP as an adjunct to inpatient treatment and found that decreases in anxiety over course of treatment were significantly associated with greater caloric intake in the post-treatment meal. However, change in weight was not reported, likely due to the inpatient setting of the study and success of normalizing weight in all participants.

In addition to trials conducted with the US, a German group[@b108-sart-6-2012-033] has developed an internet-based relapse prevention program for AN. The program allows patients to receive daily information regarding healthy behaviors and pitfalls to avoid, report their symptoms, receive feedback about progress, and encouragement to contact their counselor for additional support if symptoms increase. Preliminary findings[@b108-sart-6-2012-033] indicate that the interactive program was both successful in reducing relapse and contributed to further weight gain, suggesting its possible efficacy as an active treatment, compared to TAU.

Given the role that extreme exercise plays in maintaining the cognitive symptoms of AN, the Loughborough Eating Disorders Activity Therapy (LEAP)[@b109-sart-6-2012-033] was developed as an adjunct to CBT to promote healthy attitudes toward exercise behavior. The program is structured around four core themes of psychoeducation about "healthy/non-excessive" exercise, guided discovery, cognitive skills, and relapse prevention. Preliminary data from 19 patients showed that 8 sessions of LEAP as an augment to inpatient treatment were successful in reducing anxiety, depression, extreme exercise and extreme beliefs about exercise. A double-blind international RCT is currently underway to examine the efficacy of LEAP enhanced CBT in the outpatient treatment of AN.[@b110-sart-6-2012-033]

In addition to treatments focused on adults, given the success of family based therapy for adolescents,[@b37-sart-6-2012-033] two large trials are examining the cost-effectiveness of family based therapy modalities. Gowers and colleagues[@b111-sart-6-2012-033] conducted a cost-effectiveness study in 167 patients and found that specialized outpatient family treatment was more cost-effective than general outpatient and inpatient treatment. Eisler and colleagues[@b112-sart-6-2012-033] are currently conducting a large-scale, 12-month trial (n = 400) of multi-family day treatment compared to individual inpatient and outpatient family therapy. Multi-family day treatment is more intensive than outpatient treatment and is administered in group format. Group formats have advantages over single-family formats, including increased cost-effectiveness and increased opportunities for families to share their experiences with one another. Pragmatic studies such as these provide useful clinical information, given the often high cost of eating disorder treatment.[@b111-sart-6-2012-033]

Bulimia Nervosa
===============

Despite the strong body of evidence supporting the efficacy of CBT in the treatment of BN, most individuals who suffer from BN do not receive CBT.[@b113-sart-6-2012-033] This partly reflects challenges in training adequate numbers of therapists to provide CBT as well as therapists' concerns regarding the utility of CBT for the patients they treat. Despite attempts from initiatives to increase dissemination of CBT for anxiety and depression (i.e., Improving Access to Psychological Therapies (IAPT) in the UK;[@b114-sart-6-2012-033] Increasing Access to CBT in Canada),[@b115-sart-6-2012-033] these organizations do not provide services for eating disorders. Thus, emerging treatments are focusing on modalities that will allow CBT to reach a broader proportion of individuals with BN, and therapy content that will address a broader range of patient concerns. These include treatments using innovative technology and those incorporating affective components (see [Table 4](#t4-sart-6-2012-033){ref-type="table"}).

The efficacy of CBT delivered through alternative modes, including telemedicine, internet-based therapy, and the use of text messages, is being studied to increase dissemination. Mitchell and colleagues[@b116-sart-6-2012-033] found that CBT delivered over the phone was equivalent to CBT delivered face-to-face for producing abstinence from bingeing and purging, and both conditions were well-accepted by patients. Another study of 76 patients with BN examined the efficacy of internet-based CBT compared to waitlist and found greater improvements within the treatment group on binge-eating frequency, dietary restraint, weight, shape, and eating concerns, anxiety, and depression. [@b117-sart-6-2012-033] A recent study examined the feasibility of using text messages as a self-monitoring tool within group CBT and found that participants' adherence to the text self-monitoring was high (86%) and the text message self-monitoring received more favorable ratings compared to other forms of self-monitoring (e.g., paper and pencil diaries).[@b118-sart-6-2012-033]

Given that Safer and colleagues[@b65-sart-6-2012-033] found initial support for the use of DBT in BN, emerging treatment directions also focus on affective regulation and interpersonal functioning. Integrative Cognitive Affective Therapy (ICAT)[@b119-sart-6-2012-033] combines emotion-focused and interpersonal elements with traditional CBT. An initial pilot study of 21 patients with threshold or subthreshold BN found significant reductions in number of binge and purge episodes per week, with 70% of the sample achieving abstinence from bingeing and 65% achieving abstinence from purging. A recent enhanced version of CBT, CBT-E,[@b120-sart-6-2012-033] also incorporates modules on mood intolerance, clinical perfectionism, low self-esteem, and interpersonal difficulties that can be flexibly implemented based on the symptom configuration of the patient. Initial results have shown nearly identical remission rates between CBT-E and CBT overall. However, more complex cases with greater psychiatric comorbidity had lower global eating pathology in CBT-E, as compared to traditional CBT, while the reverse was true for less complex cases.

Emerging directions in combined treatments for BN focus on creating individualized treatment plans using a stepped--care approach. This approach layers treatments and medications in a triage method, based on response to previous treatment. Mitchell and colleagues[@b121-sart-6-2012-033] compared CBT to a stepped-care approach. Both treatments added fluoxetine after 6 sessions for predicted non-responders. The stepped-care approach began with supervised self-help, which helps increase accountability and adherence beyond traditional self-help, but still increases feasibility by reducing therapist workload. Supervised self-help was followed with CBT with a therapist for individuals who did not achieve abstinence from bingeing and purging using self-help. Results showed that while remission did not differ between groups at treatment end, the stepped-care approach had larger reductions in binge and compensatory episodes, depressive symptoms, and eating-related obsessions and compulsions at 1-year follow-up compared to the CBT only group. Studies utilizing stepped-care provide an important avenue for creating more individualized treatments that can improve global outcome for a greater number of patients at a lower cost.

Binge Eating Disorder
=====================

BED is associated with high rates of comorbid psychopathology, particularly mood and Cluster B personality disorders.[@b122-sart-6-2012-033] BED is also associated with obesity and many patients are motivated to seek treatment to control their eating and to lose weight. However, current treatments either reduce binge eating or weight, but not both. Thus, emerging directions largely focus on investigating treatments that incorporate affect regulation skills and novel medications[@b123-sart-6-2012-033]--[@b125-sart-6-2012-033] or treatments (bariatric surgery) that decrease appetite or promote weight loss (see [Table 4](#t4-sart-6-2012-033){ref-type="table"}).

Given the promising results for the potential efficacy of DBT in BED,[@b92-sart-6-2012-033] Chen and colleagues[@b126-sart-6-2012-033] conducted a preliminary trial of DBT in a mixed sample of 3 BN and 5 BED outpatients with comorbid borderline personality disorder. They found that DBT produced large effect sizes in decreasing binge frequency (Cohen's d = 1.07), Eating Disorder Examination scores (d = 1.66), and increasing global adjustment (d = 0.92) compared to waitlist. This study, along with similar trials currently underway, provides an encouraging direction for more direct incorporation of associated personality features in the treatment of BED.

Mechanical interventions to reduce gastric capacity, including bariatric surgery, are being examined in obese individuals with BED to evaluate the effect of surgery on both weight and binge eating. A recent non-randomized study compared BED participants who received bariatric weight loss surgery to a lifestyle modification program similar to BWL.[@b127-sart-6-2012-033] The authors found that both groups had significant and equivalent reductions in binge frequency, and the bariatric surgery group had a larger reduction in body weight 1-year post treatment (22.1% vs. 10.3%, respectively). However, it is important to note that one recent study found that 12% of individuals with premorbid eating pathology who underwent bariatric surgery developed self-induced vomiting post-surgery. [@b128-sart-6-2012-033] Thus, bariatric surgery represents a possible avenue for treatment of obese binge eaters; however, RCTs are needed to accurately compare treatment efficacy and safety.

Similarities between BED and addictive disorders also have led to the recent investigation of acamprosate, a glutamate antagonist used in the treatment of alcohol dependence. McElroy and colleagues[@b129-sart-6-2012-033] found that patients receiving acamprosate reduced the number of binge days per week, BMI, food cravings, and obsessive-compulsive symptoms related to binge eating, compared to placebo.

Emerging directions in the use of combined interventions for BED involve using a stepped-care approach, similar to BN. These approaches have developed in response to research showing that CBT has been effective for treating binge eating, but not weight loss, while BWL has been effective in reducing weight, with less clear outcomes for binge eating. A current study by Grilo and colleagues[@b130-sart-6-2012-033] is underway comparing BWL to a stepped-care approach. The stepped-care intervention will begin with BWL and then follow a decision tree based on early response with possible additions of CBT guided self-help and an appetite suppressant. Regardless of the outcome, results will help clarify more efficient and individualized treatment options for both early responders and treatment-resistant patients.

Conclusions
===========

In summary, strong research support exists for family based therapies in the treatment of adolescent AN, while for adults, initial research supports the use of olanzapine in increasing weight and reducing anorectic cognitions. For BN, both 60 mg fluoxetine and CBT have a large empirical evidence base in reducing binge and purge episode frequency. Currently, treatments for BED have had difficulty in improving *both* binge eating and weight loss, with CBT and IPT producing similar positive results. Disappointingly, the most efficacious treatments are not available to most patients seeking treatment. Further, many patients who receive these treatments do not respond, and relapse occurs in a substantial minority of treatment responders. While several gaps in the current treatment literature exist, the field is making substantial efforts to develop novel interventions to address these limitations. However, treatment development and evaluation remain lengthy and slow processes. For example, there was a substantial time lapse between the original 1987 report of the efficacy of family based therapy for adolescents with AN[@b36-sart-6-2012-033] and the recent large-scale RCT confirming this result in 2010.[@b37-sart-6-2012-033] Understanding these and similar trends can better help us evaluate progress and move the field forward. An exciting avenue for progress is the use of technology to increase dissemination of eating disorder-specific interventions as these might be most accessible for clinicians encountering eating disorders in patients with mood, anxiety, or substance use disorders.

**Author Contributions**

Conceived and designed the experiments: TAB, PKK. Analysed the data: TAB. Wrote the first draft of the manuscript: TAB. Contributed to the writing of the manuscript: TAB, PKK. Agree with manuscript results and conclusions: TAB, PKK. Jointly developed the structure and arguments for the paper: TAB, PKK. Made critical revisions and approved final version: PKK. All authors reviewed and approved of the final manuscript.

**Funding**

Author's institution receiving funding from National Institute of Mental Health, R01MH061836.

**Disclosures and Ethics**

As a requirement of publication author(s) have provided to the publisher signed confirmation of compliance with legal and ethical obligations including but not limited to the following: authorship and contributorship, conflicts of interest, privacy and confidentiality and (where applicable) protection of human and animal research subjects. The authors have read and confirmed their agreement with the ICMJE authorship and conflict of interest criteria. The authors have also confirmed that this article is unique and not under consideration or published in any other publication, and that they have permission from rights holders to reproduce any copyrighted material. Any disclosures are made in this section. The external blind peer reviewers report no conflicts of interest. Provenance: the authors were invited to submit this paper.

###### 

Interventions for Anorexia Nervosa.

  ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
  **Author**                                               **N (% female)**   **Recruitment source**                        **Diagnostic/inclusion criteria**                                            **Exclusion criteria**                                                 **Tx conditions (duration and setting)**                           **Primary outcome assessed**                            **Secondary outcome assessed**                     **Primary results**                                                                                                               **Secondary results**
  -------------------------------------------------------- ------------------ --------------------------------------------- ---------------------------------------------------------------------------- ---------------------------------------------------------------------- ------------------------------------------------------------------ ------------------------------------------------------- -------------------------------------------------- --------------------------------------------------------------------------------------------------------------------------------- -----------------------------------------------------------------------
  **Psychopharmacological Interventions**                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       

  Antidepressants                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               

  *Fluoxetine*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  

  Kaye et al.[@b12-sart-6-2012-033]                        39 (100)           Inpatient ED Program responders               DSM-IV ANr                                                                                                                                          52 weeks\                                                          Weight change for relapse prevention, YBOCS-EDS         HRSD, YBOCS, HARS                                  FLX had significant change in weight, Y-BOCS-ED from pre-post tx, PL did not greater tx completion for FLX vs. PL (63% vs. 16%)   FLX had significant change in HARS, HRSD from pre-post tx, PL did not
                                                                                                                                                                                                                                                                                Outpatient\                                                                                                                                                                                                                                                                                                     
                                                                                                                                                                                                                                                                                20 mg\                                                                                                                                                                                                                                                                                                          
                                                                                                                                                                                                                                                                                -- FLX-- PL                                                                                                                                                                                                                                                                                                     

  Walsh et al.[@b15-sart-6-2012-033]                       93 (100)           Weight restored patients with AN              DSM-IV AN (w/o amenorrhea), 16--45 years old, BMI \> 19                                                                                             52 weeks\                                                          Time to relapse                                                                                            FLX = PL                                                                                                                          
                                                                                                                                                                                                                                                                                Outpatient\                                                                                                                                                                                                                                                                                                     
                                                                                                                                                                                                                                                                                20--80 mg -- FLX + CBT-- PL + CBT                                                                                                                                                                                                                                                                               

  Antipsychotics                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                

  *Olanzapine*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  

  Mondraty et al.[@b20-sart-6-2012-033]                    15 (--)            Inpatient psychiatric unit                    DSM-IV AN                                                                                                                                           Inpatient -- 46 ± 31 days OLZ (10 mg)-- 53 ± 31 days CPZ (20 mg)   Anorectic rumination (Padua inventory), weight                                                             OLZ \> CPZ                                                                                                                        

  Brambilla et al.[@b18-sart-6-2012-033]                   30 (100)           ED center referrals                           DSM-IV AN \>18 years old                                                     Serious psychiatric or medical condition                               3 months\                                                          BMI, EDI, YBC-EDS                                       HRSD, TCI, Buss-Durkee rating scale (aggression)   OLZ \> PL on YBC-ED compulsions, on BMI for ANbp only                                                                             OLZ \> PL on HRSD, TCI-persistence
                                                                                                                                                                                                                                                                                Outpatient -- CBT + OLZ (2.5--5 mg)-- CBT + PL                                                                                                                                                                                                                                                                  

  Bissada et al.[@b17-sart-6-2012-033]                     34 (100)           ED tx center referrals                        DSM-IV AN (w/o amenorrhea), BMI \< 17.5                                      Serious psychiatric or medical condition, suicidality, concurrent tx   10 weeks\                                                          BMI                                                     PAI, YBOCS                                         OLZ \> PL                                                                                                                         OLZ \> PL on YBOCS obsessions
                                                                                                                                                                                                                                                                                Day hospital -- OLZ (2.5--10 mg)-- PL                                                                                                                                                                                                                                                                           

  Attia et al.[@b19-sart-6-2012-033]                       23 (96)            Community recruitment                         DSM-IV AN w/o amenorrhea, \>16 years old, 19 \> BMI \>14                     Severe medical or psychiatric problem                                  8 weeks\                                                           BMI, EDI, YCB-EDS, BSQ                                  BAI, BDI                                           OLZ \> PL on BMI                                                                                                                  OLZ = PL
                                                                                                                                                                                                                                                                                Outpatient\                                                                                                                                                                                                                                                                                                     
                                                                                                                                                                                                                                                                                -- OLZ (mean:7.95 mg)-- PL (mean:8.75 mg)                                                                                                                                                                                                                                                                       

  **Psychosocial Interventions**                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                

  *Psychodynamic*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               

  Dare et al.[@b26-sart-6-2012-033]                        84 (74)            Community referrals                           DSM-IV AN, \> 18 years old                                                   Serious psychiatric or medical condition                               1 year\                                                            M-R scales, weight                                                                                         FOC, FT \> TAU\                                                                                                                   
                                                                                                                                                                                                                                                                                Outpatient -- FOC-- CAT-- FT-- TAU                                                                                                                                            CAT = TAU on weight                                                                                                               

  *Cognitive Behavioral Therapy*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                

  Pike et al.[@b30-sart-6-2012-033]                        33 (100)           Inpatient tx responders                       DSM-IV ANr, 18--45 years old, \>90% IBW                                      Severe comorbid psychopathology                                        50 sessions\                                                       Relapse rate, time to relapse, M-R scales                                                                  CBT \> NUT                                                                                                                        
                                                                                                                                                                                                                                                                                Outpatient -- CBT-- NUT                                                                                                                                                                                                                                                                                         

  McIntosh et al.[@b33-sart-6-2012-033]                    56 (100)           Community referrals                           DSM-IV AN, 17--40 years old, BMI \< 19                                       Severe psychiatric or medical condition                                20 sessions\                                                       Global anorexia nervosa rating, BMI, weight, EDE, EDI   GAF                                                CBT = IPT\                                                                                                                        NST \> IPT = CBT
                                                                                                                                                                                                                                                                                Outpatient -- CBT-- IPT-- NST                                                                                                                                                 CBT = NST\                                                                                                                        
                                                                                                                                                                                                                                                                                                                                                                                                                                                              On global rating CBT = NST \> IPT on EDE restraint                                                                                

  *Interpersonal Psychotherapy*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 

  McIntosh et al.[@b33-sart-6-2012-033]                    56 (100)           Community referrals                           DSM-IV AN, 17--40 years old, BMI \< 19                                       Severe psychiatric or medical condition                                20 sessions\                                                       Global anorexia nervosa rating, BMI, weight, EDE, EDI   GAF                                                CBT = IPT\                                                                                                                        NST \> IPT = CBT
                                                                                                                                                                                                                                                                                Outpatient -- CBT-- IPT-- NST                                                                                                                                                 NST \> IPT\                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                              On global rating CBT = NST \> IPT on EDE restraint                                                                                

  *Family Based Therapy*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        

  Eisler et al.[@b40-sart-6-2012-033]                      40 (98)            Community referrals                           DSM-IV or ICD-10 AN                                                                                                                                 Mean of 16 sessions (flexible dose)\                               M-R scales, EDI, EAT                                    RSES, SMFQ, MOCI                                   SFT \> CFT for families with high EE CFT \> SFT on EDI                                                                            CFT \> SFT on MOCI, SMFQ
                                                                                                                                                                                                                                                                                Outpatient -- CFT-- SFT                                                                                                                                                                                                                                                                                         

  Geist et al.[@b131-sart-6-2012-033]                      61 (100)           Community referrals to specialist tx center   DSM-IV AN \< 90% IBW, 12--17 years old                                       Suicide risk, serious psychiatric or medical condition                 8 sessions\                                                        Weight, EDI                                             CDI, BSI, FAM-III                                  FT = FGP                                                                                                                          FT = FGP
                                                                                                                                                                                                                                                                                Outpatient -- FT-- FGP                                                                                                                                                                                                                                                                                          

  Dare et al.[@b26-sart-6-2012-033]                        84 (74)            Community referrals                           DSM-IV AN, \> 18 years old                                                   Serious psychiatric or medical condition                               1 year\                                                            M-R scales, weight                                                                                         FOC, FT \> TAU on weight                                                                                                          
                                                                                                                                                                                                                                                                                Outpatient -- FOC-- CAT-- FT-- TAU                                                                                                                                                                                                                                                                              

  Lock et al.[@b39-sart-6-2012-033]                        86 (90)            Pediatric referrals                           DSM-IV AN (≥1 menstrual cycle missed), 12--18 years old                      Serious psychiatric or medical condition, additional tx                Outpatient -- STFT (10 sessions)-- LTFT (20 sessions)              EDE, BMI, YBC-EDS                                       KSADS, CBCL, family functioning scale              STFT = LFT                                                                                                                        STFT = LFT

  Lock et al.[@b37-sart-6-2012-033]                        121 (91)           Community clinic referrals                    DSM-IV AN w/o amenorrhea, 12--18 years old, living with family, IBW \< 86%   Serious psychiatric or medical condition, previous FT, AFT tx          24 sessions\                                                       Remission rate, BMI percentile                                                                             FT = AFT on remission rate FT \> AFT on BMI\                                                                                      
                                                                                                                                                                                                                                                                                Outpatient -- FT-- AFT 6 and 12 month follow-up                                                                                                                               At follow-up: FT \> AFT on remission rate FT = AFT on BMI                                                                         

  **Psychopharmacological + Psychosocial Interventions**                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        

  Walsh et al.[@b15-sart-6-2012-033]                       93 (100)           Weight restored patients with AN              DSM-IV AN (w/o amenorrhea) 16--45 years old, BMI \> 19                                                                                              52 weeks\                                                          Time to relapse                                                                                            FLX + CBT = PL + CBT                                                                                                              
                                                                                                                                                                                                                                                                                Outpatient\                                                                                                                                                                                                                                                                                                     
                                                                                                                                                                                                                                                                                20--80 mg -- FLX + CBT-- PL + CBT                                                                                                                                                                                                                                                                               

  Brambilla et al.[@b18-sart-6-2012-033]                   30 (100)           ED center referrals                           DSM-IV AN \>18 years old                                                     Serious psychiatric or medical condition                               3 months\                                                          BMI, EDI, YBC-EDS                                       HRSD, TCI, Buss-Durkee rating scale (aggression)   CBT + OLZ \> CBT + PL on eating disorder compulsions, on BMI for ANbp only                                                        CBT + OLZ \> CBT+ PL HRSD, TCI-persistence
                                                                                                                                                                                                                                                                                Outpatient -- CBT + OLZ (2.5--5 mg)-- CBT + PL                                                                                                                                                                                                                                                                  
  ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

**Note:** Greater than symbol (\>) refers to significantly better outcome.

**Abbreviations:** AFT, Adolescent Focused Therapy; AN, Anorexia Nervosa; BDI, Beck Depression Inventory; BED, Binge Eating Disorder; BMI, Body Mass Index; BN, Bulimia Nervosa; BSI, Brief Symptom Inventory; CBCL, Child Behavior Checklist; CBT, Cognitive Behavioral Therapy; CDI, Children's Depression Inventory; CFT, Conjoint Family Therapy; CGI, Clinical Global Impression; EAT, Eating Attitudes Test; ED, Eating Disorder; EDI, Eating Disorders Inventory; EDE, Eating Disorders Examination; FAM-II, Family Assessment Measure; FGP, Family Group Psychoeducation; FLX, Fluoxetine; FLV, Fluvoxamine; FT, Family-Based Therapy; FOC, Focal therapy; g, Group Therapy; GAF, Global Assessment of Functioning; HRSD, Hamilton Rating Scale for Depression; IPT, Interpersonal Psychotherapy; K-SADS, Kiddie Schedule of Affective Disorders; LTFT, Long Term Family Therapy; MOCI, Maudsley Obsessive Compulsive Index; M-R, Morgan-Russell Outcome; NST, Nonspecific Supportive Therapy; NUT, Nutritional Counseling; PAI, Personality Assessment Inventory; PL, Placebo; RSES, Rosenberg Self Esteem Scale; SFT, Separated Family Therapy; SMFQ, Short Mood and Feelings Questionnaire; STFT, Short Term Family Therapy; TFEQ, Three Factor Eating Questionnaire; TOP, Topiramate; WL, Wait List Control; YCB-EDS, Yale Cornell Brown ED Scale.

###### 

Interventions for Bulimia Nervosa.

  -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
  **Author**                                               **N (% female)**   **Recruitment source**                     **Diagnostic/inclusion criteria**                                               **Exclusion criteria**                                                          **Tx conditions (duration and setting)**              **Primary outcome assessed**                                **Secondary outcome assessed**                                     **Primary results**                                                                                                                            **Secondary results**
  -------------------------------------------------------- ------------------ ------------------------------------------ ------------------------------------------------------------------------------- ------------------------------------------------------------------------------- ----------------------------------------------------- ----------------------------------------------------------- ------------------------------------------------------------------ ---------------------------------------------------------------------------------------------------------------------------------------------- ----------------------------------------------------------------------
  **Psychopharmacological Interventions**                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    

  Antidepressants                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            

  *Fluoxetine*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               

  Walsh et al.[@b50-sart-6-2012-033]                       22 (100)           Poor responders to outpatient CBT or IPT   DSM-III-R BNp                                                                                                                                                   8 weeks\                                              Binge, purge episodes in last month, EDE, TFEQ              RSES, BMI, BDI                                                     FLX \> PL                                                                                                                                      FLX = PL
                                                                                                                                                                                                                                                                                         Outpatient\                                                                                                                                                                                                                                                                                                                         
                                                                                                                                                                                                                                                                                         60 mg -- FLX-- PL                                                                                                                                                                                                                                                                                                                   

  Romano et al.[@b49-sart-6-2012-033]                      150 (98)           Outpatient FLX treatment responders        DSM-IV BNp \> 18                                                                Serious psychiatric condition, previous external treatment \>4 weeks            52 weeks\                                             Time to relapse, binge/purge frequency, YCB-EDS             CGI, PGI                                                           FLX \> PL                                                                                                                                      FLX \> PL
                                                                                                                                                                                                                                                                                         outpatient relapse prevention\                                                                                                                                                                                                                                                                                                      
                                                                                                                                                                                                                                                                                         60 mg -- FLX-- PL                                                                                                                                                                                                                                                                                                                   

  *Fluvoxamine*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              

  Milano et al.[@b44-sart-6-2012-033]                      12 (100)                                                      DSM-IV BN                                                                                                                                                       12 weeks\                                             Binge/purge episodes                                        Body weight                                                        FLV \> PL                                                                                                                                      FLV \> PL
                                                                                                                                                                                                                                                                                         Outpatient\                                                                                                                                                                                                                                                                                                                         
                                                                                                                                                                                                                                                                                         200 mg -- FLV-- PL                                                                                                                                                                                                                                                                                                                  

  *Sertraline*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               

  Milano et al.[@b46-sart-6-2012-033]                      20 (100)           Outpatient                                 DSM-IV BNp 24--36 years old                                                                                                                                     12 weeks\                                             Binge/purge episodes                                        \% body weight reduction                                           SER \> PL                                                                                                                                      SER \> PL
                                                                                                                                                                                                                                                                                         Outpatient\                                                                                                                                                                                                                                                                                                                         
                                                                                                                                                                                                                                                                                         100 mg -- SER-- PL                                                                                                                                                                                                                                                                                                                  

  **Psychosocial Interventions**                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             

  *Interpersonal Psychotherapy*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              

  Agras et al.[@b54-sart-6-2012-033]                       220 (--)           Outpatient                                 DSM-III-R BNp, \>18 years old                                                   Severe psychical or psychiatric condition, current AN, current tx, pregnancy    19 sessions\                                          Recovery and remission rate, binge/purge frequency, EDE     SCL-90-R, RSES, IIP, SAS                                           CBT \> IPT on % remitted and recovered, binge/purge frequency, dietary restraint At follow-up: CBT= IPT                                        CBT = IPT\
                                                                                                                                                                                                                                                                                         Outpatient -- CBT-- IPT\                                                                                                                                                                                                                                                                                                            At follow-up: CBT = IPT
                                                                                                                                                                                                                                                                                         1 year follow-up                                                                                                                                                                                                                                                                                                                    

  *Cognitive Behavioral Therapy*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             

  Agras et al.[@b54-sart-6-2012-033]                       220 (--)           Outpatient                                 DSM-III-R BNp, \>18 years old                                                   Severe psychical or psychiatric condition, current AN, current tx, pregnancy    19 sessions\                                          Recovery and remission rate, binge/purge frequency, EDE     SCL-90-R, RSES, IIP, SAS                                           CBT \> IPT on % remitted and recovered, binge/purge frequency, dietary restraint At follow-up: CBT = IPT                                       CBT = IPT\
                                                                                                                                                                                                                                                                                         Outpatient -- CBT-- IPT\                                                                                                                                                                                                                                                                                                            At follow-up: CBT = IPT
                                                                                                                                                                                                                                                                                         1 year follow-up                                                                                                                                                                                                                                                                                                                    

  Carter et al.[@b61-sart-6-2012-033]                      85 (100)           Waitlist for tx at hospital-based clinic   DSM-IV BNp (≥1 episode/week)                                                    \<17 years old, pregnant, medical illness, current psychosocial tx, BMI \<18    8 weeks -- CBTsh-- NSTsh-- WL                         Frequency of binge and compensatory behaviors, EDI, EDE     RSES, BDI, IIP                                                     CBTsh = NSTsh = WL Simple time effects: CBTsh and NSTsh both had significant decreases in binge/compensatory behaviors over time; WL did not   CBTsh = NSTsh = WL

  Bailer et al.[@b59-sart-6-2012-033]                      81 (--)            Community outpatient                       DSM-IV BNp \>17 years old                                                       Medical instability, severe suicidality                                         18 weeks\                                             Monthly frequency of binge/purge episodes, EDI              BDI                                                                gCBT = GSH\                                                                                                                                    gCBT= GSH
                                                                                                                                                                                                                                                                                         Outpatient -- gCBT-- GSH\                                                                                                                                                            At follow-up: Guided self-help \> gCBT in remission rate                                                                                       
                                                                                                                                                                                                                                                                                         1 year follow-up                                                                                                                                                                                                                                                                                                                    

  Schmidt et al.[@b56-sart-6-2012-033]                     85 (--)            Community referrals                        DSM-IV BN or EDNOS (\<2 episodes per week; or purging only), 13--20 years old   BMI \< 10th percentile, substance dependence, severe mental illness             13 weeks\                                             Abstinence from binge eating, vomiting, EATATE, EDE, ORFI   Health costs                                                       CBTgsh \> FT on abstinence of binge eating at 6 months CBTgsh = FT on abstinence of binge eating at 12 months, purging at 6, 12 months         CBTgsh = FT
                                                                                                                                                                                                                                                                                         Outpatient -- Family Therapy (FT)-- CBTgsh                                                                                                                                                                                                                                                                                          

  *Dialectical Behavior Therapy*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             

  Safer et al.[@b65-sart-6-2012-033]                       31 (100)           Community                                  Adapted DSM-IV BNp (≥1 episode/week), 18--65 years old                          BMI \< 17.5, psychosis, suicidality, active drug/alcohol abuse, concurrent tx   20 sessions\                                          Frequency of binge/purge episodes                           BDI, NMRS, EES, multi-dimensional personality scale, PANAS, RSES   DBT \> WL                                                                                                                                      DBT = WL
                                                                                                                                                                                                                                                                                         Outpatient -- DBT-- WL                                                                                                                                                                                                                                                                                                              

  *Weight Loss Treatment*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    

  Burton and Stice[@b132-sart-6-2012-033]                  85 (100)           University and community outpatient        Adapted DSM-IV BN (≥1 episode/week), 18--55 years old                           Treatment in past month, BMI \< 19, serious medical or psychiatric condition    Outpatient\                                           Remission status, binge/compensatory episodes (EDE)         BMI, SAS, health care utilization scale                            HDI \> WL                                                                                                                                      HDI \> WL for reduction in BMI, health care utilization
                                                                                                                                                                                                                                                                                         6 sessions -- HDI-- WL                                                                                                                                                                                                                                                                                                              

  *Family Based Therapy*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

  LeGrange et al.[@b68-sart-6-2012-033]                    80 (--)            Community and outpatient referrals         DSM-IV BN (≥1 episode/week) for 6 months, 12--19 years old                      Substance dependence, BMI \< 17.5                                               20 sessions\                                          Remission rate (EDE)                                        K-SADS, BDI, RSES, tx suitability                                  FT \> SPT                                                                                                                                      FT\> SPT on vomiting, compensatory behavior frequency, EDE subscales
                                                                                                                                                                                                                                                                                         outpatient -- FBT-- Supportive Psychotherapy (SPT)                                                                                                                                                                                                                                                                                  

  Schmidt et al.[@b56-sart-6-2012-033]                     85 (--)            Community referrals                        DSM-IV BN or EDNOS (\<2 episodes per week; or purging only), 13--20 years old   BMI \< 10th percentile, substance dependence, severe mental illness             13 weeks\                                             Abstinence from binge eating, vomiting, EATATE, EDE         ORFI, health costs                                                 CBTgsh \> FT on abstinence of binge eating at 6 months CBTgsh = FT on abstinence of binge eating at 12 months, purging at 6, 12 months         CBTgsh = FT
                                                                                                                                                                                                                                                                                         Outpatient -- Family Therapy (FT)-- CBTgsh                                                                                                                                                                                                                                                                                          

  **Psychopharmacological + Psychosocial Interventions**                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

  Mitchell et al.[@b71-sart-6-2012-033]                    91 (100)           Community and outpatient clinic            DSM-III-R BN (≥3 episodes/week) \>18 years old, \>85% IBW                       Serious medical condition, adverse reaction to fluoxetine                       16 weeks\                                             Frequency of binge, vomit episodes, EDQ, EDI                HRSD, CGI, PGI                                                     FLX \> PL on vomiting SH + FLX, SH +PL \> FLX, PL on vomiting                                                                                  FLX \> PL on CGI, PGI
                                                                                                                                                                                                                                                                                         Outpatient -- FLX 60 mg-- PL-- SH +FLX-- SH +PL                                                                                                                                                                                                                                                                                     

  Walsh et al.[@b72-sart-6-2012-033]                       91 (100)           Community                                  DSM-IV BNp (≥1 episode/week), 18--60 years old, BMI \> 17.5                     Pregnancy, serious medical or psychiatric illness, concurrent tx                16 weeks\                                             Frequency of binge, vomit episodes, EDE                     BDI, SCL-53,                                                       FLX \> PL On frequency of binge, vomit episodes, EDE dietary restraint CBTgsh = FLX                                                            FLX \> PL CBTgsh = FLX
                                                                                                                                                                                                                                                                                         Outpatient -- FLX-- PL-- FLX + CBTgsh-- PL + CBTgsh                                                                                                                                                                                                                                                                                 
  -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

**Note:** Greater than symbol (\>) refers to significantly better outcome.

**Abbreviations:** AN, Anorexia Nervosa; BDI, Beck Depression Inventory; BED, Binge Eating Disorder; BMI, Body Mass Index; BN, Bulimia Nervosa; BT, Behavior Therapy; CBT, Cognitive Behavioral Therapy; CGI, Clinical Global Impression; CTRL, Control group; DBT, Dialectical Behavior Therapy; EDI, Eating Disorders Inventory; EDE, Eating Disorders Examination; EES, Emotional Eating Scale; FLX, Fluoxetine; FLV, Fluvoxamine; FT, Family-Based Therapy; g, Group Therapy; gsh, Guided Self Help; HDI, Healthy Diet Intervention; HRSD, Hamilton Rating Scale for Depression; IIP, Inventory of Interpersonal Problems; IMP, Imipramine; IPT, Interpersonal Psychotherapy; K-SADS, Kiddie Schedule of Affective Disorders; NMRS, Negative Mood Regulation Scale; ORFI, Oxford Risk Factor Inventory; NST, Nonspecific Supportive Therapy; PANAS, Positive and Negative Affectivity Scale; PL, Placebo; PGI, Patient Global Improvement; RSES, Rosenberg Self Esteem Scale; SAS, Weissman Social Adjustment Scale; SCL-90, Symptom Checklist; SER, Sertraline; SH, Self Help; SIB, Sibutramine; SM, Self-Monitoring; SPT, Supportive Psychotherapy; TFEQ, Three Factor Eating Questionnaire; TOP, Topiramate; VAS, Visual Analog Scale; WL, Wait List Control; YCB-EDS, Yale Cornell Brown Eating Disorder Scale.

###### 

Interventions for Binge Eating Disorder.

  -----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
  **Author**                                               **N (% female)**   **Recruitment source**                             **Diagnostic/inclusion criteria**                                  **Exclusion criteria**                                                           **Tx conditions (duration and setting)**                                                **Primary outcome assessed**                                               **Secondary outcome assessed**              **Primary results**                                                                                                   **Secondary results**
  -------------------------------------------------------- ------------------ -------------------------------------------------- ------------------------------------------------------------------ -------------------------------------------------------------------------------- --------------------------------------------------------------------------------------- -------------------------------------------------------------------------- ------------------------------------------- --------------------------------------------------------------------------------------------------------------------- -----------------------------------------------------
  **Psychopharmacological Interventions**                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 

  Antidepressants                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         

  *Fluoxetine*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            

  Arnold et al.[@b76-sart-6-2012-033]                      60 (93)            Community advertisement                            DSM-IV BED (≥3 episodes/week), 18--60 years old, \>85% IBW         Pregnancy, AN, relevant and severe medical or psychiatric condition, recent tx   6 weeks\                                                                                Weekly binge frequency, % reduction in binge frequency                     Weight, BMI, CGI, HRSD                      FLX \> PL\                                                                                                            FLX \> PL\
                                                                                                                                                                                                                                                                                     Outpatient\                                                                                                                                                                                                    On weekly binge frequency                                                                                             On BMI, weight, CGI
                                                                                                                                                                                                                                                                                     20--80 mg -- FLX-- PL                                                                                                                                                                                                                                                                                                                

  *Fluvoxamine*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           

  Pearlstein et al.[@b79-sart-6-2012-033]                  20 (85)            Community advertisement/referral                   DSM-IV BED                                                         Concurrent tx                                                                    12 weeks\                                                                               Binge eating frequency, EDE                                                Weight, HRSD, CGI, SCL-90, BDI              FLV = PL                                                                                                              FLV = PL
                                                                                                                                                                                                                                                                                     Outpatient\                                                                                                                                                                                                                                                                                                                          
                                                                                                                                                                                                                                                                                     Up to 150 mg -- FLV-- PL                                                                                                                                                                                                                                                                                                             

  *Citalopram*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            

  McElroy et al.[@b78-sart-6-2012-033]                     38 (95)            Community advertisement                            DSM-IV BED (≥3 episodes/week), 18--60 years old, \>85% IBW         Pregnancy, AN, relevant and severe medical or psychiatric condition, recent tx   6 weeks\                                                                                Frequency of binge days and episodes, YBOC-BE                              BMI, weight, CGI, HRSD                      CIT\> PL                                                                                                              CIT\> PL\
                                                                                                                                                                                                                                                                                     Outpatient\                                                                                                                                                                                                                                                                                                                          On weight, CGI
                                                                                                                                                                                                                                                                                     20--60 mg -- CIT-- PL                                                                                                                                                                                                                                                                                                                

  *Sertraline*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            

  McElroy et al.[@b77-sart-6-2012-033]                     34 (94)            Outpatients                                        DSM-IV BED (≥3 episodes/week), 18--60 years old, \>85% IBW         Current AN, psychosis, mania, severe suicidality, concurrent tx                  6 weeks\                                                                                \% decrease in binge frequency                                             CGI, BMI, HRSD                              SER \> PL                                                                                                             SER \> PL\
                                                                                                                                                                                                                                                                                     Outpatient\                                                                                                                                                                                                                                                                                                                          On CGI, BMI
                                                                                                                                                                                                                                                                                     50--200 mg (mean: 187 mg) -- SER-- PL                                                                                                                                                                                                                                                                                                

  Other                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   

  *Topiramate*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            

  McElroy et al.[@b80-sart-6-2012-033]                     61 (--)            Community advertisement                            DSM-IV-TR BED (≥3 episodes/week), 18--60 years old, BMI \> 30      Substance use disorder, severe psychiatric, medical condition, concurrent tx     14 week\                                                                                Binge episodes and days in last week                                       CGI, YBOCS, HRSD, BMI, weight, % body fat   TOP\> PL                                                                                                              TOP \> PL On BMI, weight CGI, YBOCS
                                                                                                                                                                                                                                                                                     Outpatient\                                                                                                                                                                                                                                                                                                                          
                                                                                                                                                                                                                                                                                     25--600 mg -- TOP-- PL                                                                                                                                                                                                                                                                                                               

  McElroy et al.[@b81-sart-6-2012-033]                     394 (86)           Outpatients from private and university settings   DSM-IV BED (≥3 episodes/week), 18--65 years old, 30 \< BMI \< 50   Significant medical condition, psychosis, depression, concurrent tx              16 weeks\                                                                               Binge eating days and episodes per week, YBOCS-BE, TFEQ                    BMI, CGI, BIS-11, SDS, HRSD, MADRS          TOP\> PL                                                                                                              TOP\> PL\
                                                                                                                                                                                                                                                                                     Outpatient\                                                                                                                                                                                                                                                                                                                          On BMI, CGI, BIS-11, SDS
                                                                                                                                                                                                                                                                                     Up to 400 mg -- TOP-- PL                                                                                                                                                                                                                                                                                                             

  *Sibutramine*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           

  Appolinario et al.[@b82-sart-6-2012-033]                 60 (88)            Community advertisement                            DSM-IV BED, 18--60 years old, BMI 30--45                           Pregnancy, BN, serious medical or psychiatric condition, concurrent tx           12 weeks\                                                                               Frequency of binge days in past week, body esteem scale                    BDI, weight                                 SIB \> PL\                                                                                                            SIB \> PL
                                                                                                                                                                                                                                                                                     Outpatient\                                                                                                                                                                                                    On frequency of binge days                                                                                            
                                                                                                                                                                                                                                                                                     15 mg -- SIB-- PL                                                                                                                                                                                                                                                                                                                    

  Milano et al.[@b83-sart-6-2012-033]                      20 (100)           Outpatient                                         DSM-IV BED, 24--36 years old                                                                                                                        12 weeks\                                                                               Frequency of binge days, body esteem scale                                 Weight                                      SIB \> PL                                                                                                             SIB \> PL
                                                                                                                                                                                                                                                                                     Outpatient\                                                                                                                                                                                                                                                                                                                          
                                                                                                                                                                                                                                                                                     10 mg/kg/day -- SIB-- PL                                                                                                                                                                                                                                                                                                             

  Wilfley et al.[@b84-sart-6-2012-033]                     304 (90)           Community outpatient advertisement                 DSM-IV BED, 18--65 years old, BMI \< 45                            Serious medial or psychiatric condition, concurrent tx, AN,                      24 weeks\                                                                               Frequency of binge episodes and days per week, TFEQ                        Weight, BMI, global improvement, IWOQL      SIB \> PL                                                                                                             SIB \> PL\
                                                                                                                                                                                                                                                                                     Outpatient\                                                                                                                                                                                                                                                                                                                          On weight, BMI, global improvement
                                                                                                                                                                                                                                                                                     15 mg -- SIB-- PL                                                                                                                                                                                                                                                                                                                    

  **Psychosocial Interventions**                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          

  *Cognitive Behavioral Therapy*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          

  Wilfley et al.[@b89-sart-6-2012-033]                     162 (83)           Community advertisement                            DSM-IV BED, 18--65 years old, BMI 27--48                           Pregnancy, concurrent tx, severe psychiatric conditions                          20 sessions\                                                                            Recovery, EDE, Binge eating days/episodes                                                                              gCBT = gIPT\                                                                                                          
                                                                                                                                                                                                                                                                                     Outpatient -- gCBT-- gIPT\                                                                                                                                                                                     Follow-up: gCBT = gIPT                                                                                                
                                                                                                                                                                                                                                                                                     1 year follow-up                                                                                                                                                                                                                                                                                                                     

  Hilbert and Tuschen-Caffier [@b96-sart-6-2012-033]       28 (100)           Community advertisement                            DSM-IV-TR BED (≥1 episode/week)                                    Concurrent tx, suicidality, psychosis, substance dependence, pregnancy           19 sessions -- CBT body exposure (CBT-E)-- CBT cognitive restructuring (CBT-C)          EDE weight and shape concern, BSQ, EDE restraint, eating concerns          BDI                                         CBT-E = CBT-C                                                                                                         CBT-E = CBT-C

  Grilo and Masheb[@b88-sart-6-2012-033]                   90 (79)            Community advertisement                            DSM-IV BED, 18--60 years old, BMI \> 27                            Concurrent tx, serious medical or psychiatric conditions, pregnancy              12 weeks\                                                                               Remission over the past month, EDE-Q, TFEQ, frequency of binge eating      BDI, RSES, BMI                              CBTgsh \> BWLgsh, CTRL on remission\                                                                                  CBTgsh = BWLgsh
                                                                                                                                                                                                                                                                                     Outpatient -- CBTgsh-- BWLgsh-- Self-monitoring (CTRL)                                                                                                                                                         CBTgsh \> BWLgsh on frequency of binge eating, hunger BWLgsh \>\                                                      
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    CBTgsh on increasing restraint                                                                                        

  Wilson et al.[@b90-sart-6-2012-033]                      208 (85)           Community advertisement and clinic referrals       DSM-IV BED, \>18 years old, BMI 27--45                             Concurrent tx, serious medical or psychiatric conditions, pregnancy              24 weeks -- IPT-- BWL-- CBTgsh-- 1 and 2 year follow-up                                 Binge eating days per month, weight, EDE                                   BDI, RSES, SAS,                             BWL \> IPT, CBTgsh on reducing BMI, body weight BWL \> CBTgsh on dietary restraint On bingeing:\                      IPT = BWL = CBTgsh
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1-year follow-up:\                                                                                                    
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    BWL = IPT = CBTgsh 2-year follow-up:\                                                                                 
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    IPT, CBTgsh \> BWL                                                                                                    

  Grilo et al.[@b91-sart-6-2012-033]                       125 (67)           Community advertisement                            DSM-IV BED, 18--65 years old, BMI 30--55                           Concurrent tx, serious medical or psychiatric conditions                         16 sessions\                                                                            Abstinence from binge eating, EDE                                          BDI, BMI                                    BWL= CBT +BWL = CBT on binging At follow-up: CBT\> BWL on binge eating                                                BWL, CBT + BWL \> CBT on BMI
                                                                                                                                                                                                                                                                                     Outpatient -- CBT-- BWL-- CBT +BWL (32 sessions for combined)-- 6, 12 month follow-up                                                                                                                                                                                                                                                

  *Dialectical Behavior Therapy*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          

  Telch et al.[@b92-sart-6-2012-033]                       44 (100)           Community advertisement                            DSM-IV BED, 18--65 years old                                       Concurrent tx, suicidality, psychosis, substance abuse, pregnancy                20 weeks\                                                                               Binge days and episodes, EDE, BES, EES                                     Weight, BDI, PANAS, NMRS, RSES              DBT\> WL\                                                                                                             DBT = WL
                                                                                                                                                                                                                                                                                     Outpatient -- DBT-- WL                                                                                                                                                                                         On binge days and episodes, on emotional eating in response to anger                                                  

  *Weight Loss Treatment*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 

  Grilo and Masheb[@b88-sart-6-2012-033]                   90 (79)            Community advertisement                            DSM-IV BED, 18--60 years old, BMI \> 27                            Concurrent tx, serious medical or psychiatric conditions, pregnancy              12 weeks\                                                                               Remission over the past month, EDE-Q, TFEQ, frequency of binge eating      BDI, RSES, BMI                              CBTgsh \> BWLgsh, CTRL on remission\                                                                                  CBTgsh = BWLgsh
                                                                                                                                                                                                                                                                                     Outpatient -- CBTgsh-- BWLgsh-- Self-monitoring (CTRL)                                                                                                                                                         CBTgsh \> BWLgsh on frequency of binge eating, hunger\                                                                
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    BWLgsh \> CBTgsh on increasing restraint                                                                              

  Wilson et al.[@b90-sart-6-2012-033]                      208 (85)           Community advertisement and clinic referrals       DSM-IV BED, \>18 years old, BMI 27--45                             Concurrent tx, serious medical or psychiatric conditions, pregnancy              24 weeks -- IPT-- BWL-- CBTgsh-- 1 and 2 year follow-up                                 Binge eating days per month, weight                                        BDI, RSES, SAS                              BWL \> IPT, CBTgsh on reducing BMI, body weight 1 year follow-up:\                                                    BWL \> CBTgsh on increasing dietary restraint
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    BWL = IPT = CBTgsh on binge eating 2-year follow-up:\                                                                 
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    IPT, CBTgsh \> BWL on binge eating                                                                                    

  *Interpersonal Psychotherapy*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           

  Wilfley et al.[@b89-sart-6-2012-033]                     162 (83)           Community advertisement                            DSM-IV BED, 18--65 years old, BMI 27--48                           Pregnancy, concurrent tx, severe psychiatric conditions                          20 sessions\                                                                            Recovery, EDE, binge eating days, episodes                                                                             gCBT = gIPT\                                                                                                          
                                                                                                                                                                                                                                                                                     Outpatient -- gCBT-- gIPT 1 year follow-up                                                                                                                                                                     Follow-up: gCBT = gIPT                                                                                                

  Wilson et al.[@b90-sart-6-2012-033]                      208 (85)           Community advertisement and clinic referrals       DSM-IV BED, \>18 years old, BMI 27--45                             Concurrent tx, serious medical or psychiatric conditions, pregnancy              24 weeks -- IPT-- BWL-- CBTgsh-- 1 and 2 year follow-up                                 Binge eating days per month, weight, EDE                                   BDI, RSES, SAS                              BWL \> IPT, CBTgsh on reducing BMI, body weight\                                                                      IPT = BWL = CBTgsh
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    BWL \> CBTgsh on dietary restraint On bingeing: 1-year follow-up:\                                                    
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    BWL = IPT = CBTgsh 2-year follow-up:\                                                                                 
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    IPT, CBTgsh \> BWL                                                                                                    

  **Psychopharmacological + Psychosocial Interventions**                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  

  Grilo et al.[@b95-sart-6-2012-033]                       50 (88)            Community, outpatient                              DSM-IV BED, 35--60 years old, BMI \> 30                            Concurrent tx, severe medical or psychiatric condition, pregnancy                12 weeks, outpatient -- CBTgsh + PL-- CBTgsh + orlistat (860 mg)                        Remission, binge episodes per month, EDE                                   BDI, RSES, weight loss, weight loss \>5%    CBTgsh + ORL \> CBTgsh + PL on remission                                                                              CBTgsh + ORL \> CBTgsh + PL on weight loss

  Grilo et al.[@b93-sart-6-2012-033]                       108 (78)           Community outpatient                               DSM-IV BED, 18--60 years old, 100%--200% IBW                       Concurrent tx, severe medical or psychiatric condition, pregnancy                16 weeks\                                                                               Remission (abstinence from binge eating in last month), EDE-Q, TFEQ, BSQ   BDI, BMI                                    CBT + FLX, CBT + PL \>\                                                                                               FLX = PL CBT + FLX = CBT +PL CBT + PL\> FLX on BDI\
                                                                                                                                                                                                                                                                                     Outpatient\                                                                                                                                                                                                    FLX, PL CBT +PL \>\                                                                                                   CBT + FLX \> FLX on BDI
                                                                                                                                                                                                                                                                                     60 mg -- CBT +FLX-- CBT +PL-- FLX-- PL                                                                                                                                                                         FLX on binge episodes, EDE-Q, cognitive restraint, BSQ CBT +FLX \> FLX binge episodes, EDE-Q, hunger, disinhibition   
  -----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

**Note:** Greater than symbol (\>) refers to significantly better outcome.

**Abbreviations:** AN, Anorexia Nervosa; BDI, Beck Depression Inventory; BED, Binge Eating Disorder; BES, Binge Eating Scale; BIS-11, Barrett Impulsivity Scale; BMI, Body Mass Index; BN, Bulimia Nervosa; BSQ, Body Shape Questionnaire; BT, Behavior Therapy; BWL, Behavioral Weight Loss; CBT, Cognitive Behavioral Therapy; CBTsh, Cognitive Behavioral Therapy self-help; CGI, Clinical Global Impression; CIT, Citalopram; CT, Cognitive Therapy; CTRL, Control group; DBT, Dialectical Behavior Therapy; DES, Desipramine; ED, Eating Disorder; EDE, Eating Disorders Examination; EDE-Q, Eating Disorders Examination Questionnaire; EES, Emotional Eating Scale; FLX, Fluoxetine; FLV, Fluvoxamine; FCI, Food Craving Index; g, Group Therapy; gsh, Guided Self Help; HRSD, Hamilton Rating Scale for Depression; IBW, Ideal Body Weight; IIP, Inventory of Interpersonal Problems; IWOQL, Impact of Weight on Quality of Life-Lite; IPT, Interpersonal Psychotherapy; MADRS, Montgomery Asberg Depression Rating Scale; NMRS, Negative Mood Regulation Scale; ORL, Orlistat; PANAS, Positive and Negative Affectivity Scale; PL, Placebo; RSES, Rosenberg Self Esteem Scale; SAS, Weissman Social Adjustment Scale; SCL-90, Symptom Checklist; SER, Sertraline; SFT, Separated Family Therapy; SDS, Sheehan Disability Scale; SH, Self Help; SIB, Sibutramine; TFEQ, Three Factor Eating Questionnaire; TOP, Topiramate; WL, Wait List Control; YBOCS-BE, Yale-Brown Obsessive Compulsive Scale-Binge Eating.

###### 

Emerging Directions in Treatment.

  -----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
  **Treatment**                                                 **Authors/PI**                                                                       **Sample (N/anticipated N)**   **Study design**       **Tx conditions**
  ------------------------------------------------------------- ------------------------------------------------------------------------------------ ------------------------------ ---------------------- --------------------------------------------------------------------------------------------------------
  **Anorexia Nervosa**                                                                                                                                                                                     

  Olanzapine                                                    Kaplan, Marcus, Attia, and Guarda[@b97-sart-6-2012-033]                              Adults (160)                   RCT                    16 weeks\
                                                                                                                                                                                                           Olanzapine vs. PL

  Testosterone                                                  Klibanski[@b133-sart-6-2012-033]                                                     Adults (90)                    RCT                    24 weeks\
                                                                                                                                                                                                           Transdermal testosterone vs. PL

  Uniting Couples in the treatment of anorexia nervosa (UCAN)   Bulik et al[@b100-sart-6-2012-033],[@b102-sart-6-2012-033],[@b103-sart-6-2012-033]   Adults (32)                    RCT                    UCAN + CBT vs.Unstructured supportive therapy + CBT

  Cognitive remediation therapy (CRT)                           Lock et al[@b104-sart-6-2012-033]                                                    Adults (46)                    RCT                    6 months\
                                                                                                                                                                                                           CBT vs. CBT + CRT

  Emotional acceptance behavior therapy (EABT)                  Wildes and Marcus[@b107-sart-6-2012-033]                                             Adults (5)                     Case series            24 weeks\
                                                                                                                                                                                                           EABT

  Exposure and response prevention (AN-EXRP)                    Steinglass[@b105-sart-6-2012-033]                                                    Adults (9)                     Open series            12 sessions over 4 weeks AN-EXRP

  Internet-based relapse prevention                             Fichter et al[@b108-sart-6-2012-033]                                                 Adults (258)                   RCT                    9 months\
                                                                                                                                                                                                           Internet-based relapse prevention vs. TAU

  Loughborough eating disorder activity therapy (LEAP)          Touyz et al[@b109-sart-6-2012-033]                                                   Adults (19)                    Open trial             8 sessions\
                                                                                                                                                                                                           LEAP

  LEAP                                                          Hay[@b110-sart-6-2012-033]                                                           Adults (200)                   RCT                    Outpatient\
                                                                                                                                                                                                           8 sessions LEAP + 6--8 months CBT vs. 8--10 months CBT

  Family therapy                                                Eisler[@b112-sart-6-2012-033]                                                        Adolescents (400)              RCT                    12 months\
                                                                                                                                                                                                           Inpatient treatment vs. outpatient family therapy vs. multi-day family treatment

  Family therapy                                                Gowers[@b111-sart-6-2012-033]                                                        Adolescents (167)              RCT                    6 months\
                                                                                                                                                                                                           Specialized outpatient family treatment vs. general outpatient treatment (TAU) vs. inpatient treatment

  **Bulimia Nervosa**                                                                                                                                                                                      

  Internet-based CBT                                            Sanchez--Ortiz et al[@b117-sart-6-2012-033]                                          Adults (76)                    RCT                    12 weeks\
                                                                                                                                                                                                           Internet CBT vs. WL

  Internet-based CBT                                            Bulik[@b134-sart-6-2012-033]                                                         Adults (180)                   RCT                    20 weeks\
                                                                                                                                                                                                           Internet CBT vs. face-to-face CBT

  Telemedicine CBT                                              Mitchell et al[@b116-sart-6-2012-033]                                                Adults (128)                   RCT                    20 sessions\
                                                                                                                                                                                                           Telemedicine CBT vs. face-to-face CBT

  Text messaging                                                Shapiro et al[@b118-sart-6-2012-033]                                                 Adults (31)                    Non-randomized pilot   12 weeks\
                                                                                                                                                                                                           CBT + text message self-monitoring

  Integrative cognitive affective therapy (ICAT)                Wonderlich et al[@b119-sart-6-2012-033]                                              Adults (21)                    Non-randomized pilot   16 weeks\
                                                                                                                                                                                                           ICAT

  CBT-Enhanced (CBT-E)                                          Fairburn et al[@b120-sart-6-2012-033]                                                Adults (154)                   RCT                    20 weeks\
                                                                                                                                                                                                           CBT vs. CBT-E vs. WL

  Stepped-care approach                                         Mitchell et al[@b121-sart-6-2012-033]                                                Adults (293)                   RCT                    20 sessions\
                                                                                                                                                                                                           Stepped-Care vs. CBT + FLX

  **Binge Eating Disorder**                                                                                                                                                                                

  Buproprion                                                    White[@b123-sart-6-2012-033]                                                         Adults (68)                    RCT                    8 weeks\
                                                                                                                                                                                                           Buproprion vs. PL

  Pramipexole                                                   Steffen[@b124-sart-6-2012-033]                                                       Adults (8)                     Open label trial       Pramipexole

  Armodafinil                                                   McElroy[@b125-sart-6-2012-033]                                                       Adults (60)                    RCT                    Armodafinil vs. PL

  Acamprosate                                                   McElroy et al[@b129-sart-6-2012-033]                                                 Adults (40)                    RCT                    Acamprosate vs. PL

  Dialectical behavior therapy                                  Chen et al[@b126-sart-6-2012-033]                                                    Adults (5)                     RCT                    24 weeks\
                                                                                                                                                                                                           DBT vs. WL

  Dialectical behavior therapy                                  Chen[@b135-sart-6-2012-033]                                                          Adults (100)                   RCT                    DBT vs. CBT vs. guided self help

  Integrative response therapy (IRT)                            Robinson[@b136-sart-6-2012-033]                                                      Adults (100)                   RCT                    10 sessions\
                                                                                                                                                                                                           Group IRT vs. group CBT guided self-help

  Bariatric surgery                                             Wadden et al[@b127-sart-6-2012-033]                                                  Adults (85)                    Non-randomized         Bariatric surgery vs. BWL

  Stepped-care approach                                         Grilo[@b130-sart-6-2012-033]                                                         Adults (175)                   RCT                    Stepped-Care vs. BWL
  -----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

**Abbreviations:** BWL, Behavioral Weight Loss; CBT, Cognitive Behavioral Therapy; FLX, Fluoxetine; PL, Placebo; RCT, Randomized Controlled Trial; TAU, Treatment as Usual; WL, Waitlist Control.
