Drugs for Bulimia
The word comes from the Greek “boulimia,” for bous (ox) plus limos (hunger). Bulimia is ox hunger, which could mean something like “hungry as a horse.” In practice, it means “to gorge.” It is also known as bulimia nervosa, or binge-purge syndrome. Bulimia is a disorder marked by the consumption of large amounts of food over a short period of time, followed by “compensatory behavior,” usually in the form of vomiting, to rectify this loss of control. It is often grouped with anorexia, and while the two conditions share many symptoms –abnormal food consumption patterns, body image distortion, anxiety — none is stranger than the ailment clinicians have dubbed “body dysmorphic disorder” or BDD. People with this disorder feel deeply unattractive because of a perceived flaw in skin, hair, or facial features — minor flaws at best, or defects which demonstrably are not there — and cannot be reasoned out of this core belief. What they see in the mirror is simply different from what others objectively see about them.
There are also significant differences between the two eating disorders. Recent brain imaging work has shown that bulimia and anorexia show different activity in the frontal, cingulate and parietal cortical regions. Other studies have shown that bulimics exhibit low endogenous levels of serotonin at 5-HT receptor and transporter sites.
Bulimics show more activity than non-bulimics or other binge eaters in the nucleus accumbens—a prime site of action for addictive drugs — when they are shown tasty food, such as cakes. Moreover, for many bulimics there is a definite “high,” which comes with the purging, and which has no analogue in anorexia. Bulimia’s impact on the brain’s reward center also seems to be quite direct, judging by the high relapse rates of bulimics.
All of this suggests that bulimics are overly sensitive to certain kinds of food, in the same way that drug addicts are hypersensitive to the reward aspect of certain kinds of drugs. The fact that bulimics (and alcoholics, and heroin addicts) have a tendency to binge on high carbohydrate foods rich in tryptophan, serotonin’s precursor chemical, is well documented. Richard Wurtman and coworkers at MIT identified a subset of bulimics who binge severely on carbohydrate foods. These bulimics tended to be mildly obese, severely depressed, and came from families with a strong history of alcohol abuse. Other researchers have reported that a significant number of bulimics are themselves abusers of alcohol and other drugs.
The first major breakthrough in the treatment of bulimia came with the era of SSRI antidepressant medications. The initial motivation was a perceived link between bulimia and depression, which commonly exist as co-morbid disorders. Serotonin was clearly involved in some way in the mechanisms of active bulimia. In 1997, Prozac became the first drug ever licensed by the FDA for the treatment of bulimia nervosa. The drug’s formal approval was based on clinical studies showing median reductions in binging of as much as 67 per cent for Prozac, compared with 33 per cent for placebo. Vomiting was reduced by 56 per cent, compared to 5 per cent for female placebo users. (About 10 per cent of diagnosed bulimics are males.) While cure is too strong a word, the benefits were quite dramatic in some cases.
What about the roughly 50% of bulimics who do not respond to serotonin-boosting medications? Recent research covered by the science blog Neurotopia points the finger at a long nerve running through the cranium. The tenth cranial nerve, better known as the vagus nerve, branches through the neck, thorax and abdomen, and is involved in breathing, tasting, swallowing, and digestion. Most of the signal traffic carried by the vagus nerve is one way: from the body to the brain. Suspicion fell on the vagus nerve because of its direct involvement with one of bulimia’s most salient traits — the inability to feel normal levels of fullness, or satiety.
Bulimics must eat more at a sitting than non-bulimics in order to feel satisfied. There is evidence of vagus nerve involvement in meal satiation, portion size, and, notably, control of vomiting. Researchers have suggested that bulimics have a relatively insensitive vagus nerve, made even less sensitive by the debilitating cycle of overeating and vomiting. Hence, bulimia patients need greater vagus nerve stimulation in order to stop eating. Interestingly, studies have also shown that people suffering from bulimia have high pain thresholds, compared to non-bulimics.
This dysregulation of the vagus nerve responds to the drug ondansetron, according to recent research published in Physiology & Behavior by Patricia L. Faris and colleagues. The antiemetic effects of ondansetron, which reduce vagus nerve activity by acting on the 5-HT3 serotonin receptor, seem to decrease vomiting while increasing the number of normal meals eaten.
Finally, a third path toward treatment has been sparked by research on opioid receptors. Decreased endogenous opioid activity may also underpin bulimia. A small 2005 study by Johns Hopkins University School of Medicine analyzed the results of brain MRIs on eight bulimic women and eight controls. Bulimics showed decreased opioid receptor binding in the insula, another area of the brain implicated in MRI studies of addiction. The insula has been called the brain’s “gustatory cortex,” and it may be that the repeating cycle of binge and purge activates the opioid system. Opioid receptors are involved in the processing of the reward value of food. This suggests that a drug like naltrexone, which blocks opiate receptors, might also have a role to play in the treatment of bulimia.
Bencherif B, Guarda AS, Colantuoni C, Ravert HT, Dannals RF, & Frost JJ (2005). Regional mu-opioid receptor binding in insular cortex is decreased in bulimia nervosa and correlates inversely with fasting behavior. Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 46 (8), 1349-51 PMID: 16085593
FARIS, P., HOFBAUER, R., DAUGHTERS, R., VANDENLANGENBERG, E., IVERSEN, L., GOODALE, R., MAXWELL, R., ECKERT, E., & HARTMAN, B. (2008). De-stabilization of the positive vago-vagal reflex in bulimia nervosa Physiology & Behavior, 94 (1), 136-153 DOI: 10.1016/j.physbeh.2007.11.036
KAYE, W., FRANK, G., BAILER, U., HENRY, S., MELTZER, C., PRICE, J., MATHIS, C., & WAGNER, A. (2005). Serotonin alterations in anorexia and bulimia nervosa: New insights from imaging studies Physiology & Behavior, 85 (1), 73-81 DOI: 10.1016/j.physbeh.2005.04.013
Schienle, A., Schäfer, A., Hermann, A., & Vaitl, D. (2009). Binge-Eating Disorder: Reward Sensitivity and Brain Activation to Images of Food Biological Psychiatry, 65 (8), 654-661 DOI: 10.1016/j.biopsych.2008.09.028