Binge Eating Disorder: The Search for Better Treatments

Although currently consigned to the “eating disorders not otherwise specified” diagnostic category, binge eating disorder may well achieve canonical status as a fully independent eating disorder in DSM-V. Based on the DSM-IV-TR research criteria set, epidemiological studies have shown binge eating disorder to be the most common of the eating disorders, with lifetime prevalence estimates in the community of 3.5% among women and 2.0% among men (1). Obesity, seen in approximately 65% of patients with binge eating disorder (2), increases progressively over time with continued binge eating. Patients with binge eating disorder suffer higher rates of comorbid psychiatric diagnoses, particularly major depression, as well as generalized anxiety disorder, panic attacks, and alcoholism or other substance abuse disorders (2, 3). Eating binges are initiated by numerous factors, including dietary restraint, hunger, and negative mood states.

Given the significant psychological and physical impairments associated with binge eating disorder, the search for effective treatments has been ongoing and has produced some modest advances. Careful systematic reviews suggest that the strength of evidence of published studies of medication and psychotherapeutic-based interventions can only be rated as “moderate” because of frequent methodological shortcomings, such as the relatively short length of most studies, high dropout and placebo-response rates in medication trials, and lack of long-term follow-up. Consequently, only tentative conclusions are possible (4). Short-term placebo-controlled trials have suggested that several selective serotonin reuptake inhibitors (SSRIs) and some other agents lead to reductions in eating and psychiatric symptoms. Cognitive behavior therapy (CBT) may effectively reduce binge days and episodes and improve the psychological features of binge eating disorder, such as measures of restraint, hunger, and disinhibition surrounding eating. However, CBT alone has not resulted in decreased weight. In most treatments specifically designed to treat eating binges per se, weight loss has been poor. Therefore, interventions using agents such as sibutramine and topiramate, which may affect both binge eating disorder and weight, are of particular interest. The study by Wilfley et al. [“Efficacy of Sibutramine for the Treatment of Binge Eating Disorder: A Randomized Multicenter Placebo-Controlled Double-Blind Study.” Am J Psychiatry 2008; 165:5–58] should be evaluated within these contexts.

Sibutramine, a serotonin-norepinephrine reuptake inhibitor (SNRI), has been approved by the Food and Drug Administration for the long-term treatment of obesity. In clinical trials of up to 18 months, when combined with carefully monitored dietary control programs, sibutramine has resulted in weight loss of up to 10% of initial body weight, a clinically significant feature, with weight loss nadirs usually seen at approximately 6 months (5, 6). When the medication is discontinued, weight is regained, not unlike other agents effective in promoting weight loss (7). In contrast to other SNRIs, sibutramine has not been shown to be particularly effective for the treatment of depression. Similar to other SNRIs, treatment may result in usually mild blood pressure elevations in some patients, and other adverse effects may occur, particularly headache, constipation, dizziness, and dry mouth. Since some questions pertaining to adverse effects remain, ongoing monitoring has been recommended to determine the long-term safety and efficacy of the drug (8). Regarding real-world impact, a community-based study conducted in British Columbia reported that 1-year persistence rates among patients who refilled their sibutramine prescriptions were <10%, and 2-year persistence rates were 2%, which is much lower than reported in clinical trials (9).

Based on previous short-term studies that have shown sibutramine to be safe and effective for the treatment of binge eating disorder, Wilfley and a group of distinguished eating disorder researchers not employed by the sponsor, Abbott Laboratories, worked together with sponsor-supported investigators to develop a multisite study to examine sibutramine's effect on binge eating disorder and weight in a large population. The study has many strengths, including a sufficiently large sample size to achieve necessary power to adequately test the hypotheses and a randomized double-blind controlled design. The practical difficulties investigators encounter in conducting such studies are evident. First, of 543 participants initially enrolled in the placebo lead-in, 147 were placebo responders and 92 discontinued for other reasons, resulting in 304 patients who could be randomly assigned to a treatment condition. Of these, 50 in the sibutramine group (approximately one-third) and 65 in the placebo group did not complete all 24 weeks of treatment. That is, only 189 of 543 patients who were initially enrolled stayed the course. Furthermore, in efforts to focus on binge eating disorder alone and reduce study complications, the investigators recruited patients with few psychiatric or medical comorbidities. Accordingly, the researchers' list of exclusion criteria for patients attempting to enroll in the study was extensive and included hypertension and many other medical conditions, other psychiatric conditions currently being treated with medications or psychotherapy, current major depression or other significant psychiatric disorders, and other features. In my own experience and in the experiences of several colleagues with whom I've consulted, the patients who ultimately entered into this study were much healthier than the patients with binge eating disorder we ordinarily encounter in our clinical practices.

That said, the results of this study clearly show that binge eating disorder patients receiving 15 mg/day of sibutramine lost significantly more weight (mean=4.3 kg) during the study's 24 weeks compared with subjects receiving placebo (mean=0.8 kg), which is consistent with other studies of sibutramine in obese patients. With respect to the effects on binge frequency, although a statistically significant difference occurred between medication and placebo, the effect size was “moderate,” with those in the sibutramine group reporting an average of 2.7 fewer eating binges per week relative to 2.0 fewer eating binges per week in the placebo group. Abstinence from binge eating was achieved by 58.7% of those receiving sibutramine versus 42.8% of those receiving placebo. The medications and the assessments ended at 24 weeks, and, as the authors point out, additional investigations will be needed to determine the subsequent effect of continuing (or discontinuing) sibutramine from that point forward.

The study raises several interesting questions. For example, given that patients who were randomly assigned to sibutramine versus placebo reported average reductions of 2.7 versus 2.0 binges per week, is it possible that in addition to any specific effects sibutramine may have had on binge eating that sibutramine also induced “active placebo” effects? That is, patients receiving medications that cause physiological effects of any kind (such as dry mouth) are even more likely to have placebo responses than those receiving inert placebos. If so, might this factor have even further enhanced the placebo effect to even further reduce binge eating episodes in those receiving sibutramine? Moreover, since several medications that reduce binge eating also promote weight loss (e.g., topiramate and zonisamide, in addition to sibutramine), is it possible that weight loss per se may contribute to reducing binge eating in some binge eating disorder patients? The literature is unclear on this point.

Even in the absence of obesity, patients suffering from binge eating disorder seek and merit treatment because they experience significant distress over their loss of control with respect to eating binges and because they experience significant distress, including feeling disgust, guilt, or depression, after overeating. In addition, as previously mentioned, associated psychiatric and medical comorbidities often add to their plight. With respect to clinical guidance, the current literature suggests that for binge eating disorder per se, CBT is the most widely studied treatment, and strong evidence supports its efficacy for behavioral and psychological symptoms. Interpersonal therapy and dialectical behavior therapy have also been shown to have utility. With respect to medications, antidepressants, particularly SSRIs dosed at the high end of the recommended range, have been associated with at least short-term reductions in binge eating but usually without substantial weight loss (10).

Among patients with binge eating disorder for whom obesity is the major additional consideration, the study conducted by Wilfley et al. supports the potential value of sibutramine, at least in the short run. However, it may not be the best choice when other psychiatric comorbidities are also prominent. For obese binge eating disorder patients, some evidence also exists for the short-term efficacy of topiramate and zonisamide, but adverse effects, including cognitive impairment and paresthesias, are concerns with these agents. Some severely obese patients with binge eating disorder choose bariatric surgery, but the effect of this intervention on binge eating disorder per se has been highly variable; patients with binge eating disorder have less successful surgical outcomes, and surgery has not been shown to “cure”the psychological features of binge eating (11).

For those who opt for sibutramine treatment, Wilfley et al. raise concerns about the potential adverse effect on blood pressure in some patients and suggest that practitioners might want to prescribe sibutramine in doses of 10 mg/day rather than the 15 mg/day used in their study (and in most other studies). However, many clinicians would probably treat patients with the 15-mg/day dose used in this and other studies that show effectiveness, but they would probably carefully monitor blood pressures and modify treatment accordingly.

In summary, even for binge eating disorder patients for whom weight loss is highly desirable in order to reduce medical risks, with respect to the role of sibutramine over the long run, the juries are still out.