Scott Crow

End Binge Eating Disorder

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Case study

I'm a 45-year-old woman who presented for treatment of BED at a multi-disciplinary eating disorder treatment program. I began engaging in episodes of binge eating in the seventh grade. About three times a week I eat a large amount of food with loss of control, usually in secret. I don't have a history of purging, except for brief experimentation when I started college. I have begun psychotherapy sessions and have been working with a dietician about two months prior to this latest medication evaluation. I feel my "relationship with food" has improved substantially, and the amount of time I spend thinking about eating, weight, and shape-related issues has diminished somewhat. The frequency of eating binges has gone from four or five times a week down to three a week, but I believe this has plateaued.

I have had "lifelong depression", which my therapist says sounds like recurring episodes of major depression, about nine bouts in total, each lasting six months to a year. I've no history of substance use disorder except for a drinking pattern suggestive of alcohol abuse in college. I've had occasional panic attacks and some diffuse anxiety, primarily focused on eating-related issues. My therapist says I've no OCD, no PTSD, and no social phobia.

I'm interested in considering medication to try to get my binge eating under better control, and I want to lose at least 50lbs (my current height is 5'5" and my current weight is 212lbs for a BMI of 35.3). My therapist and dietician are somewhat hesitant about desire for weight loss; the internist feels that I should consider trying to lose weight, but suggests a weight loss goal of between 15 and 20lbs.

Miss A

Introduction

Medications provide one potential treatment approach for BED. As with other eating disorders, medications play a less prominent role than psychotherapy and/

or changes in nutritional patterns. However, there are specific situations in which medications may be particularly useful. Certainly, the other approaches do not work optimally for every person with binge eating disorder (this may be particularly true when weight change is the desired outcome). Effective pharmacologic treatments are available essentially anywhere, in contrast to specialized psycho-therapies. Also, medicines may be useful in treating comorbid conditions such as depression or anxiety disorders.

For all these reasons, medication treatment represents a viable approach to BED. This chapter reviews the rationale for and potential goals of medication treatment for BED. The existing literature regarding controlled trials of medications for BED will be discussed, and its strengths and limitations reviewed. Finally, summary recommendations will be made.

Rationale for and goals of medication treatment for BED

Several clinical situations may prompt consideration of medication treatment for BED. First, while response rates to psychotherapy and dietary interventions for binge eating reduction and abstinence are impressive, a significant number of patients do not improve fully in terms of binge eating when receiving those other treatments. This may prompt consideration of medication treatment to address binge eating symptoms, or perhaps associated eating disorder cognitions. In addition, psychotherapy for BED typically is associated with degrees of weight loss which fall far short of even minimally desired amounts of weight loss for individuals receiving treatment. As the following review will show, currently available medications that have been studied for BED vary widely in terms of their impact of weight, but some do appear to be associated with significant amounts of weight loss in short term treatment. Therefore, certain medication choices may be useful when weight loss is desired. Third, as discussed elsewhere in this volume, BED is strongly associated with forms of psychopathology; medications may be quite useful in treating these other forms of psychopa-thology. often, it's possible to identify medication options which would have the potential to improve multiple types of psychopathology encountered in the same person. Last, while a number of effective psychotherapy approaches and nutritional approaches to binge eating disorder have been identified (as discussed elsewhere in this volume), they typically require significant amounts of training and experience to execute properly and, as such, these treatments are typically most readily found in specialized eating disorder centers. While many such centers now exist, it seems likely that most people in most countries do not have practical access to such treatments, simply for geographical reasons. The situation is potentially far better for medications. In other areas (bulimia nervosa, for example) there is evidence that pharmacologic treatments are not always used optimally (for example, see Crow et al. 1999). However, while they often may not be employed optimally, they are available to be used in an optimal fashion at essentially any pharmacy; therefore, pharmacologic treatments are much more widely available. Furthermore, it would likely be easier to train a non-specialist practitioner to provide adequate pharmacotherapy (for example, adequate doses of SSRI's) than it would be to train a non-specialist practitioner to effectively employ a manual-based psychotherapy.

There are several potential goals for medication treatment. A first goal, assessed in nearly all controlled trials conducted so far, is the cessation of binge eating. Much emphasis in this area has been placed on abstinence from binge eating (just as in bulimia nervosa) relating to a concern that persisting binge eating (even at low rates) at the end of treatment may be associated with a high rate of relapse. Most trials also report information on the percentage decrease in binge eating. Both are potentially useful pieces of information, as it is not formally known whether patients receiving treatment value full abstinence from binge eating substantially more highly than marked decreases in the rate of binge eating. A second potential goal of treatment is the reduction in eating disorder cognitions related to BED, though this overall has received less attention in pharmaco-therapy trials to date. Third, another critical potential outcome variable is change in weight. Given that weight loss might carry significant medical benefit for many obese individuals with binge eating disorder, most trials conducted in this area have reported data on weight loss. Clinically, this is a particularly salient outcome since it appears that many, perhaps most people seeking treatment for binge eating disorder, would categorize weight loss as being of equal or more importance to them as cessation of binge eating. A final goal of medication treatment, as referenced above, could be the treatment of comorbid psychopathology (particularly mood and anxiety disorders).

Review of controlled treatment trials for binge eating disorder

Initial medication development in this area followed along the lines of that conducted in bulimia nervosa. As such, the work focused initially on antidepres-sants but in more recent years, medications with the potential to impact food intact directly have also been examined. These studies will be reviewed here in brief and are summarized in Table 12.1.

SSRI trials

Multiple SSRIs have been studied, and these represent the largest number of trials in BED at this point. Marcus and colleagues conducted the initial trial of fluoxetine (1990). Twenty-two people participated in this year-long trial, in which improvements in binge eating were seen, but abstinence rates were not reported. Weight loss was significantly greater in the active drug than the placebo-treated group. Three subsequent trials have also examined fluoxetine (Arnold et al. 2002; Devlin et al. 2004; Grilo, Masheb and Wilson 2005). The Arnold et al. study examined medication treatment alone in 60 participants over 6 weeks of treatment and both binge-eating abstinence and weight change favored the active drug. Both the Grilo and Devlin studies combined pharmacotherapy treatment with cognitive behavioral treatment and each lasted somewhat longer (16 and 20 weeks, respectively), but neither found significant benefit for fluoxetine.

A second SSRI receiving attention is fluvoxamine with a 9-week study in 85 subjects finding greater efficacy for active drug in binge abstinence and weight loss (Hudson et al. 1998) but a substantially smaller (20 subject) study finding no difference between active drug and placebo (Pearlstein et al. 2003). Smaller studies have been conducted using citalopram (McElroy et al. 2003) and escitalopram (Guerdjikova et al. 2008). In each of these trials, abstinence rates were substantially higher with active drug than placebo and weight loss results modestly favored active drug. Finally, one study has examined sertraline (McElroy et al. 2000); in this small study, binge eating outcomes favored active drug and weight loss was greater with active drug than placebo.

In summary, many of these trials have found some advantage for active drug over placebo in terms of cessation of binge eating, but weight loss results have been for the most part quite modest.

Other antidepressants

An early study of desipramine was conducted by Agras and colleagues (1994). The design was an additive one, wherein participants were randomized to receive or not receive desipramine; all received CBT. Notably, the treament was not placebo-controlled, but binge eating and weight loss outcomes were more favorable in those receiving desipramine.

Other agents one study has examined atomoxetine for BED (McElroy, Guerdjikova et al. 2007). This 10-week study included 40 people and abstinence rates were substantially higher with active drug compared with placebo, with modest weight losses in the active drug group and no weight change with placebo.

Agents selected for weight loss properties

A number of studies have employed agents selected at least in part for their tendency to cause weight loss and/or diminish appetite. In this group, however, some of the studied agents also have other putative mechanisms including direct impact on binge eating (topiramate) or indirect impact to diminish binge eating by virtue of adverse consequences of binge eating while on the active agent (orlistat). Notably, two of the agents in this group have been withdrawn from the market for safety reasons (sibutramine and d-fentluramine). The currently available agents and withdrawn agents will be reviewed separately.

Agents currently available

One medication that has received substantial attention is the anticonvulsant topiramate, selected in large part for its tendency to diminish appetite and weight (first noted in studies of people with seizure disorders). A total of three studies have been conducted (Claudino et al. 2007; McElroy et al. 2003; McElroy, Hudson et al. 2007), and long-term outcome is available from one of these studies (McElroy et al. 2006). In each of these studies, substantially greater rates of abstinence from binge eating behavior were observed with active drug than placebo, and weight loss also favored active drug. Moreover, in the long-term extension and follow-up study reported by McElroy et al. (2006) it appeared that a substantial amount of the benefit was preserved and moreover that subjects who crossed over to placebo experienced some improvement.

Two studies have examined orlistat (Golay et al. 2005; Grilo, Masheb, and Salant 2005). In each of these studies greater weight loss and greater binge eating abstinence was seen with active drug.

Agents withdrawn from the market

Stunkard and colleagues (1996) described the results of a study of d-fenfluramine for the treatment of BED. Notably, although benefits were observed with regard to binge eating, no statistically or clinically significant difference in weight change was seen between active drug and placebo (albeit in a relatively brief, eight-week study). More recently, several studies examined sibutramine, a noradrenergic and serotonergic reuptake inhibitor subsequently withdrawn from the market because of concerns about impact on blood pressure. In these studies, higher rates of abstinence from binge eating were seen with active drug than placebo, and weight loss results also favored active drug (Appolinario et al. 2003; Milano et al. 2005; Wifley et al. 2008).

Limitations of the existing literature

As the above section details, there is ample knowledge about pharmacologic treatments for BED. However, the existing literature is marked by several very significant limitations. These limitations do not invalidate the existing literature but they do tend to limit somewhat how well it can inform current practice.

First, placebo rate response rates are high, perhaps higher than that seen in some other areas of psychopharmacology research. This sometimes has been used to argue for diminished importance for BED, yet examination of the outcome of placebo responders suggests that most people with BED who have placebo response revert to symptomatic status relatively promptly (Jacobs-Pilipski et al. 2007). Such a high placebo response rate might be better viewed not as an indictment of BED as a diagnostic construct but rather as a significant

Table 12.1 Controlled Pharmacotherapy Trials for BED

Author

Year

n

Drug

Duration (Weeks) Drug

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