Why Are There No Approved Drugs for Anorexia?

Drug testing is difficult when the end goal is a patient’s biggest fear.

Posted May 14, 2019

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Source: ivan_kislitsin/Shutterstock

By Tara Santora

Anorexia nervosa is the deadliest eating disorder, killing about 10 percent of patients. Many survivors never recover, even after decades. Yet there are no drugs approved to treat this dangerous illness.

Some medications have shown promise, but they have not conclusively demonstrated that they aid in recovery, according to a 2017 review article in the journal Expert Review of Clinical Pharmacology. As a result, the standard treatment remains psychotherapy. However, only about 30 percent of anorexia patients recover after nine years, and just 60 percent after 22 years, so treatments have a long way to go.

“Psychological treatment is really insufficient,” says Hubertus Himmerich, who studies eating disorders at King’s College London and is the lead author of the review. “I hope that drug discovery will take place someday, because we have so many patients with anorexia nervosa who aren't able to lead the lives they want to lead.”

Several studies have shown that three promising medications—olanzapine, aripiprazole, and dronabinol—may help anorexia patients gain weight. Yet none of these drugs, which are sold under the trade names Zyprexa, Abilify, and Marinol, respectively, have been approved by the U.S. Food and Drug Administration to treat anorexia. Nonetheless, some psychiatrists prescribe these drugs as so-called “off-label” treatments, which the FDA permits under most circumstances.

The FDA has moved slowly to evaluate potential drug treatments for anorexia in part because the nature of the illness makes it difficult to test them, experts say. If you run a clinical trial for an anorexia drug, the chief measure of success is weight gain, says Himmerich. But a major symptom of anorexia is the fear of gaining weight, making it difficult to recruit patients for a trial.  

“Patients often refuse to take part in the study,” Himmerich explains. “They are afraid of the main treatment goal.”

Of the patients who do sign up for a trial, it’s not unusual for 25 percent to stop taking the drug and drop out of the study. The small number of anorexia patients willing to take the medication makes it difficult for researchers to conclude whether the drugs are effective, according to a 2016 review by Italian psychiatrists.

Olanzapine is the most promising and well-researched drug for anorexia treatment, according to Himmerich. Sold under the trade name Zyprexa, the antipsychotic is approved by the FDA to treat bipolar disorder, schizophrenia, and severe depression. Olanzapine increases appetite, which, in theory, leads patients to put on much-needed pounds. The drug led to more weight gain than a placebo in at least five clinical trials. However, at least three other studies contradict those findings.

“The issue with anorexia is that patients are hungry all the time anyway,” says Vivian Kafantaris of the Feinstein Institute for Medical Research in New York. She is the principal investigator of a study in which olanzapine failed to increase weight more than a placebo in anorexia patients. “Even if the olanzapine increased that feeling of hunger, patients were very good at not giving into that feeling.”

Aripiprazole is another antipsychotic approved by the FDA for many of the same psychiatric conditions as olanzapine (but again, not for anorexia). However, aripiprazole, sold under the trade name Abilify, works differently than olanzapine. Instead of increasing appetite, aripiprazole may reduce patients’ distress about eating, case studies suggest.

“It may help patients with their thoughts of being too big or too fat,” Himmerich says. For anorexic patients, he adds, “anxieties, depressed moods, and disturbances of body image may be even more important than the body mass index.” After all, one out of five deaths of anorexia patients is due to suicide.

Aripiprazole has not yet been studied in a clinical trial for anorexia. But a chart review showed that 22 adolescent patients who took aripiprazole gained more weight on average than 84 patients who didn’t take the drug.

“So far it has been quite successful, with the caveat that this is anecdotal,” says Guido Frank, who teaches psychiatry at the University of Colorado and is the lead author of the chart review.

The third promising drug is dronabinol (trade name Marinol), a synthetic form of THC, the key ingredient of marijuana. Dronabinol increases appetite, similar to olanzapine, and is approved to treat weight loss in people with HIV/AIDS. In a 2013 trial of 25 patients, anorexia patients who took dronabinol gained significantly more weight than those who took a placebo. But in a 2017 pilot study, nine women with anorexia did not experience a significant change in BMI after taking the drug for four weeks, though they did report improvements in measures such as depression and care for their bodies.

While olanzapine, aripiprazole, and dronabinol are promising, they won’t be standard treatment for anorexia anytime soon. It will take at least 10 years for any of these medications to be approved for anorexia treatment, Himmerich says, and no companies are undertaking the testing process. Drug treatments probably won’t be widely used for anorexia for at least a decade, he says, concluding “this is a really, really sad situation.”

Tara Santora is an Editorial Intern at Psychology Today.