Pharmacological Treatment of Bulimia Nervosa

There was an unusually low dropout rate among the 60 participants, possibly because the study enrolled only patients with moderate BN, or because the dose was increased slowly and remained relatively low (25 to 250 mg/d).²⁹ Despite the report that there were few intolerable adverse effects in these small studies, adverse reactions to topiramate are common in clinical psychiatric practice, which tends to limit its use.

Ondansetron
Another novel agent proposed for treatment of BN is the antiemetic ondansetron, a selective 5-HT3 antagonist approved for the prevention of nausea and vomiting in cancer patients undergoing chemotherapy or radiation treatment. It targets serotonin release from enterochromaffin cells in the gut that may cause the symptoms by stimulating afferent branches of the vagus nerve and thereby initiating the vomiting reflex. One group of investigators has postulated that an escalating cycle of bingeing and purging behaviors in chronic BN results at least in part from a desensitization in the threshold for activation of vagal afferent fibers, with dysregulation of satiety mechanisms.³⁰ The results of a randomized, double-blind trial of 25 patients with severe, chronic BN showed that ondansetron was more effective than placebo in reducing binge eating and purging by vomiting during a 4-week period.³¹ Past criticisms of potential ondansetron use have included expense and short half-life. While the drug is now available as a generic, the problem of multiple daily dosing still remains. If an extended-release version of ondansetron becomes available, larger and longer studies that include an assessment of the impact on psychological features of BN could be of interest.

Other medications
A few other medications have been studied in a limited number of small trials. Endogenous opioids are believed to be involved in the regulation of food intake, and the opioid antagonist naltrexone attracted attention in the late 1980s after it was observed to decrease appetite in some patients recently detoxified from opioid dependence. Unfortunately, when subsequently tested in patients with BN, the standard naltrexone doses used in addiction were found ineffective. There appeared to be some efficacy in open-label studies at 200 to 300 mg/d, but because this dosage is high enough to raise concerns of liver toxicity, naltrexone is not recommended.^32-35

Lithium carbonate was no more effective than placebo for symptoms of BN in one controlled trial. Mean plasma concentrations at the low end of the usual therapeutic range may have affected outcome³⁶; nonetheless, lithium use entails a potential toxicity risk for patients who continue purging. Carbamazepine did not prove beneficial in an early controlled trial with 6 patients.³⁷

A future direction of research may involve the atypical antipsychotics, which have not been formally studied for use in BN. Interest in this medication class stems from preliminary data that show efficacy in some patients with anorexia nervosa, as well as reports of efficacy when used as an augmenting agent in depression and anxiety disorders.^38-43

At the University of California San Diego Center for Eating Disorders Treatment and Research, we occasionally use low-dose atypical antipsychotics to augment antidepressants in some of our patients who have more chronic and severe BN and whose disorder has proved refractory to the established treatments (typically, these patients also have not achieved remission of comorbid depression or anxiety on various antidepressants). These patients often are also of relatively low weight and display the rigid, restrictive thought processes more typical of patients with anorexia nervosa.

While case reports and small open trials of anorexia nervosa, mostly with inpatients, have focused on olanzepine, quetiapine, and risperidone, in consideration that the weight gain sometimes attributed to these medications may benefit emaciated patients, we have found use of these particular medications in our BN outpatients to be problematic. Even in cases where patients accept the need to attain a higher target weight, fear of uncontrollable weight gain prevents most patients from agreeing to a medication trial, and those who do rarely remain adherent. In addition, some investigators have expressed concern that these medications, especially olanzapine, might exacerbate binge eating symptoms in patients with eating disorders.⁴⁴