Does Olanzapine Affect the Rate of Weight Gain Among Inpatients with Eating Disorders?

The atypical antipsychotic agent olanzapine (Zyprexa®) is associated with significant weight gain in treated patients with psychotic disorders (J Clin Psychiatry 1999; 60 Suppl 20:21). On average, patients receiving olanzapine gain more than 2 kg/month (Drug Safety 2001; 24:59).

Since weight gain is a critical target in the treatment of anorexia nervosa, eating disorders researchers have been very interested in the potential use of olanzapine to treat low-weight patients. La Via and colleagues reported that use of olanzapine led to weight gain and reduction of symptoms of anxiety in two patients with treatment-refractory anorexia nervosa (Int J Eat Disord 2000; 7:363).

A Larger Study

We designed a study to examine the effect of olanzapine on weight gain in a larger case series of patients with anorexia nervosa. The participants were consecutively admitted patients with anorexia nervosa who were treated in our inpatient unit for at least 14 days. We compared the outcome of 23 patients who were treated with olanzapine with 23 patients who did not receive olanzapine treatment, in an open, non-randomized trial.

The typical dosage range for the use of olanzapine in the treatment of psychotic disorders is 15 to 20 mg/day. For patients with anorexia nervosa, we started at doses of 1.25 mg unless the individual was taking a higher dose of olanzapine on admission. The dosage was then increased by 1.25 mg every 2 to 4 days, as tolerated, to a target dosage of 5 mg/day. The mean dosage was 5.5 mg, with a range of between 1.25 to 15 mg/day at discharge.

Some Subtle Differences Emerged

There were no differences in weight gain between patients who were and were not treated with olanzapine. The average weight gain for olanzapine-treated patients was 1.24 kg/week versus 1.18 kg/week for patients who did not receive olanzapine. Moreover, the rate of regain was not related to the dosage of olanzapine or diagnostic subtype (purging versus restricting anorexia nervosa). However, in this uncontrolled study, there were systematic differences between patients who received olanzapine and those who did not.

Patients treated with olanzapine had more previous hospitalizations for treatment of eating disorders, longer lengths of stay for the current hospitalization, and higher scores on the Eating Disorders Examination Questionnaire. This suggested that the individuals selected for olanzapine treatment were more distressed and more likely to have chronic disease. Controlling for these group differences in statistical analyses did not change the results.

Thus, in contrast to previous case reports, olanzapine treatment was not associated with an increased weight gain in this inpatient setting. It may be that the effects of the drug were not seen in this controlled setting because we maximize and monitor calorie intake. Thus, additional randomized, controlled research is needed to determine if the use of olanzapine promotes weight gain in an outpatient setting where the ability of anorexia nervosa patients to comply with a nutrition plan varies considerably among patients.