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July 17, 2008 — Preliminary results from a randomized, double-blind, placebo-controlled trial suggest olanzapine (Zyprexa, Eli Lilly), an atypical antipsychotic used to treat schizophrenia and bipolar disorder, may be a safe, effective therapy for women with severe anorexia nervosa.

Led by Hany Bissada, MD, investigators at the Ottawa Health Hospital, in Ontario, found that compared with placebo, olanzapine resulted in a greater rate of increase in weight, earlier achievement of target body-mass index, and a greater rate of decrease in obsessive symptoms, with no difference in adverse effects between the 2 study groups.

“We need to do a much larger study, but nevertheless, based on these results, we can confidently say there is a reason to believe olanzapine may be useful in the initial treatment for anorexia nervosa, where to date, we’ve had no consistently successful drugs,” Dr. Bissada told Medscape Psychiatry & Mental Health.

The study is published online July 16 in the American Journal of Psychiatry.

Highest Mortality Rate

Notoriously difficult to treat, anorexia nervosa has the highest mortality rate of all psychiatric disorders, affecting 0.5% of women aged 15 to 24 years, said Dr. Bissada.

Treatment consists of extended hospital stays to stabilize weight, as well as psychological counseling. Drug therapy with selective serotonin reuptake inhibitors (SSRIs) and standard neuroleptics have not been effective in increasing the rate of weight gain or reducing the psychological symptoms, including depression, anxiety, distorted body image, and obsessions that perpetuate resistance to weight gain.

One of the major reasons for looking at olanzapine in anorexia, said Dr. Bissada, was its observed long-term adverse effect of weight gain in patients with schizophrenia. Further, the drug produces a mood-modulating effect observed in bipolar patients and has also been used as adjunctive therapy to antidepressant treatment in patients with obsessive disorders.

“This was an interesting and attractive medication for many reasons, so we decided to conduct this randomized controlled trial,” he said.

No Difference in Adverse Effects

For the study, the investigators recruited 34 female patients with confirmed anorexia nervosa who had been referred to a hospital-based daytime eating-disorders program at a single center.

Patients were randomly assigned to olanzapine or placebo, plus day hospital treatment, for a 10-week period. The drug was prescribed according to a flexible-dose regimen, starting at a minimum dose of 2.5 mg and titrated slowly by increments of 2.5 mg/week to a maximum dose of 10 mg/day.

The study’s primary end point was the effect of the drug on weight gain. A secondary end point was to look at its impact on other psychological symptoms, including anxiety, depression, and obsessive/compulsiv e behavior.

After 10 weeks, patients in the active-treatment group gained more weight, at a faster rate, than those on placebo, a finding that was statistically significant, said Dr. Bissada. In addition, patients’ obsession about weight gain was also significantly reduced.

While there was a trend toward antianxiety and antidepressant effects, this did not reach statistical significance. However, said Dr. Bissada, this may have been due to the small number of study subjects. In addition, the researchers found no difference in adverse effects between the 2 study groups.

Potentially serious adverse effects associated with olanzapine, including excessive weight gain, hyperglycemia, and diabetes, are linked to high-dose, long-term therapy and do not apply to short-term treatment with a smaller dose.

“In anorexia, we use olanzapine temporarily to get patients to a level where they can tolerate eating and accept the idea of weight gain,” he said.

Panic Often First Reaction

One of the major challenges in treating this disease with olanzapine, said Dr. Bissada, is getting patients to agree to the therapy. “Anorexia nervosa patients are so afraid of weight gain that, when you offer them a medication that induces weight gain, their first reaction is panic.

“You have to be patient and explain and reassure these patients that this drug will not make them overweight or obese overnight and underscore the fact that the doses prescribed for anorexia are much, much smaller than doses prescribed for schizophrenia, ” he said.

Dr. Bissada hopes to conduct a similar, but much larger, multicenter trial and is currently looking for collaborators. In the meantime, he said, olanzapine may be worth a try in refractory anorexic patients.

“Clinicians treating patients with severe anorexia nervosa, who adamantly refuse to eat, may want to consider offering such patients a trial of this drug at a small dose (2.5 to 5 mg/day), with the understanding that the patient can stop it at any time,” he said.

The study was supported by a grant from Eli Lilly. The authors report no competing interests.

Am J Psychiatry. Published online June 16, 2008. Abstract

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