Two Drugs Tested for BED, AN, and Low-Weight BN

Promising results for challenging patients

Two studies recently evaluated two drugs, sodium oxybate for treating binge eating disorder (BED), and aripiprazole for treating anorexia nervosa (AN) or low-weight bulimia nervosa (BN).

Despite growing awareness of the seriousness of BED, there is currently no pharmacological treatment for it that is approved by the FDA. Several selective serotonin reuptake inhibitors (SSRIs) can reduce binge eating but not all patients respond; these agents are also ineffective for the obesity associated with BED. Adverse effects have limited the use of antiepileptic such as topiramate and zonisamide and the selective serotonin-norepinephrine reuptake inhibitor sibutramine, which is no longer marketed.

Susan L. McElroy, MD, and colleagues at the University of Cincinnati College of Medicine and Harvard Medical School conducted an open-label, prospective 16-week flexible dose study of sodium oxybate for treatment of BED (Int J Eat Disord 2011; 44:262). Gamma-hydroxybutyrate (GHB) is both a drug of abuse (illicit GHB) and a drug marketed for treatment of narcolepsy (sodium oxybate, or Xyrem™); recently it is also being studied as a treatment for fibromyalgia. The drug has been of interest because of the findings of weight loss in patients treated with it for narcolepsy, and the fact that GHB has been effective in suppressing cravings for alcohol and reducing alcohol consumption. Some early evidence suggests that BED and substance use disorders may be related (In J Eat Disord 2007; 40:687).

Twelve individuals were enrolled in the open-label, 22-week prospective, flexible-dose, single-center study (5 others were not enrolled because they were at risk of sleep apnea). During treatment, participants met with clinicians weekly for the first 6 weeks and then every 2 weeks for the remaining 10 weeks. Since GHB is very dose-sensitive, and individual responses vary, participants were instructed to take 4.5 g of sodium oxybate at night, divided into 2 doses of 2.25 g, for the first 2 weeks; the dosage was then increased by 1.5 g per night, as tolerated, to a maximum dosage of 9 g per night.

Good results, but a high dropout rate

Ten of the 12 participants had a significant reduction in the frequency of binge-eating episodes and binge days, as well as reduction of weight, body mass index (BMI, kg/m²), severity of illness, obsessive-compulsive features of binge-eating symptoms, eating pathology, and food cravings. Nine participants had remission of binge eating, and 5 lost at least 5% of their baseline weight; all 5 also had remission of binge eating. Five of the 12 original participants dropped out of the study due to lack of effectiveness, adverse effects (FDA guidelines), and dosing inconvenience. The most common side effects were sleepiness, difficulty falling asleep or staying asleep, vivid dreams, anxiety, nausea, edema, flu-like symptoms, and frequent urination. No serious adverse events were reported.

A second study highlights an atypical antipsychotic

Atypical antipsychotic agents have shown some efficacy for treating patients with AN (see also Questions and Answers in this issue). For example, a controlled trial of olanzapine among 34 day hospital patients with AN increased the rate of weight gain and reduced obsessionality (Am J Psychiatry 2008; 39:941); however, weight gain, a side effect of olanzapine, may have been one reason for the high rate of treatment refusal in that study.

A team of researchers at University of California, San Diego, treated 8 patients with aripiprazole for periods of 4 months to more than 3 years. Mary Ellen Trunko, MD, reported that 5 patients had AN and 3 had BN (Int J Eat Disord 2011; 44:269). The patients’ BMIs ranged from 14 kg/m² to 26 kg/m²

After beginning aripiprazole, all patients experienced reduced distress around eating, and fewer obsessional thoughts about food, weight, and body image. They also reported significant lessening of eating-disordered behaviors and gradual weight restoration (when appropriate). Levels of depression, generalized anxiety, and cognitive flexibility improved as well.

The authors feel that the positive results in this small study group support the need to perform controlled trials of aripiprazole in patients with AN and BN.