Memantin Shows Early Promise for Binge Eating Disorder

Binge eating disorder (BED) affects approximately 2.8% of the general population, making it more common than anorexia nervosa or bulimia nervosa. In addition, BED has substantial comorbidity with other psychiatric disorders and is strongly linked to severe obesity.

Currently there are no FDA-approved pharmacologic treatments for BED. While some drugs have helped reduce the number of binge episodes and reduced body weight, including several serotonin reuptake inhibitors (SSRIs) such as fluvoxamine and citalopram, and the antiepileptic agents topiramate and zonisamide. However, side effects such as increased blood pressure and cognitive dysfunction have limited use of all of these agents.

Memantine is a noncompetitive n-methyl D asparatate (NMDA) receptor antagonist that is currently used to treat Alzheimer’s disease. Like other NMDA receptor antagonists, it acts upon the hypothalamus to regulate appetite. A small open-label trial of memantine in persons with BED and obesity showed that memantine was effective in reducing binge-eating episodes and subjects also lost weight during the study (Econ Hum Biol. 2005; 3:329). This led Brian P. Brennan, MD and colleagues at McLean Hospital, Belmont, MA and Harvard Medical School, Boston, to design another trial. This time the researchers would study the effects of memantine in persons with BED.

The small study offers hope for reducing binge-eating episodes

A 12-week, open-label, single-center, flexible-dose study evaluated a group of 13 women and 3 men with DSM-IV criteria for BED (Int J Eat Disord. 2008; 41:520). To be eligible, participants had to have had 3 or more binge eating episodes per week for the 2 weeks prior to screening. All patients underwent physical examination and were given diet cards on which they recorded the number of binge eating episodes each day, the time spent binge eating, foods eaten during the binges, and the number of memantine tablets taken.

Memantine was dispensed in 5- or 10-mg tablets at an initial dosage of 5 mg per day for 7 days; after this, the dosage was increased by 5 mg each 7 days, as tolerated, to a maximum dose of 20 mg/day. Those who completed the initial 12 weeks of the study were eligible to continue on to a 12-week open-label phase; those who were not eligible to go on were tapered off the study medication over 7 days. The primary outcome measure was the number of binge days per week during treatment.

“Binge days” were defined as days where one or more binge episodes occurred and a binge was defined as eating an amount of food larger than most people would eat and feeling a loss of control over eating. All participants also filled out several questionnaires that measured restrictive eating, inhibition, hunger, and obsessive-compulsiveness.

Marked reduction in binge eating

At the end of the 12 weeks, the authors reported that the subjects had marked and statistically significant reductions in the frequency of binge-eating episodes, binge-eating days, and obsessive-compulsive features of binge eating and severity of illness. The binge eating episodes lessened steadily throughout the 12 weeks. There was little evidence that memantine affected body weight or body mass index among those with BED. The drug was relatively well tolerated. Nine subjects completed the 12-week study and 7 withdrew prematurely: 1 for an adverse event, 1 for lack of efficacy, and the rest for non-clinical reasons.

Theories about how the drug works

It is still unknown how memantine acts to reduce binge eating. One possibility is that the drug recalibrates appetite regulation by ‘reducing NMDA-receptor-mediated excitotoxicity in the brain’s arcuate nucleus,’ according to the authors. Since subjects had a significant decrease in the obsessive-compulsive features of binge eating, it is also possible that memantine reduces both the obsession to binge and the compulsive act of purging by reducing glutamatergic neurotoxicity in the caudate nucleus and anterior cingulate.

According to the authors, the next step will be a larger placebo-controlled study to see if the results from this small investigation can be replicated.