Successful treatment of anorexia nervosa remains a significant challenge, as there is no medically approved drug specifically designed for the disorder.
Current medical regimens include the use of off-label medications (medications that are normally used for other psychiatric conditions). These medications have rarely been tested for their effectiveness in animal models.
In a new study, University of Chicago researchers used low doses of a commonly used atypical antipsychotic drug for a mouse model of anorexia nervosa. They discovered an improved survival rate suggesting the medication may offers promise for the relatively common disorder.
In the experiment, mice treated with small doses of the drug olanzapine (brand name Zyprexa) were more likely to maintain their weight when given an exercise wheel and restricted food access, conditions that produce activity-based anorexia (ABA) in animals. The antidepressant fluoxetine (Prozac), commonly prescribed off-label for anorexic patients, did not improve survival in the experiment.
“We found over and over again that olanzapine was effective in harsher conditions, less harsh conditions, adolescents, adults — it consistently worked,” said the paper’s first author, doctoral student Stephanie Klenotich.
The study, published in Neuropsychopharmacology, was the product of a rare collaboration between laboratory scientists and clinicians seeking new treatment options for anorexia nervosa.
As many as one percent of American women will suffer from anorexia nervosa during their lifetime, but only one-third of those people will receive treatment.
Patients with anorexia are often prescribed off-label use of drugs designed for other psychiatric conditions, but few studies have tested the drugs’ effectiveness in animal models.
“Anorexia nervosa is the most deadly psychiatric disorder, and yet no approved pharmacological treatments exist,” said senior author Stephanie Dulawa, Ph.D. “One wonders why there isn’t more basic science work being done to better understand the mechanisms and to identify novel pharmacological treatments.”
Experts say the solution is more difficult than expected. One challenge is finding a medication that patients with anorexia nervosa will agree to take regularly, said co-author Daniel Le Grange, Ph.D. Drugs that directly cause weight gain or carry strong sedative side effects are often rejected by patients.
“Patients are almost uniformly very skeptical and very reluctant to take any medication that could lower their resolve to refrain from eating,” Le Grange said. “There are long-standing resistances, and I think researchers and clinicians have been very reluctant to embark on that course, since it’s just littered with obstacles.”
Both fluoxetine and olanzapine have been tried clinically to supplement interventions such as family-based treatment and cognitive-behavioral therapy. But their direct effect on anorexia nervosa behavior — in humans or animals — has not been detected.
Given the success of the study, researchers hope to investigate the effect of olanzapine on a more detailed basis hoping to discover the mechanisms of action, and targeted receptor systems.
Klenotich said, “Hopefully, we can develop a newer drug that we can aim towards the eating disorders clinic as an anorexic-specific drug that might be a little more acceptable to patients.”
The study offers support for the clinical use of olanzapine, for which clinical trials are already under way to test in patients.
Le Grange said the development of a pharmacological variant that more selectively treats anorexia nervosa could be a helpful way to avoid the “stigma” of taking an antipsychotic while giving clinicians an additional tool for helping patients.
“I think the clinical field is certainly very ready for something that is going to make a difference,” Le Grange said.
“I’m not saying there’s a ‘magic pill’ for anorexia nervosa, but we have been lacking any pharmacological agent that clearly contributes to the recovery of our patients. Many parents and many clinicians are looking for that, because it would make our job so much easier if there was something that could turn symptoms around and speed up recovery.”