A Pilot Study of Olanzapine in Teens with Restrictive AN

Patients with restricting-type anorexia nervosa (AN-R) have intense fears of becoming overweight and distorted perceptions of their bodies, and as a result severely limit their caloric intake. This leads to serious nutritional deficiencies, electrolyte and acid-base imbalance, dehydration, cardiac irregularities, and a hypometabolic state due to malnutrition. Among adolescents, this can lead to reductions in peak bone mass, delayed puberty, and significant growth retardation. Most importantly, the mortality rate for patients with AN-R has been reported as between 6% and 18%.

Olanzapine, a second-generation antipsychotic agent developed for the treatment of schizophrenia, acts on the 5-HT neuronal system, which regulates appetite, motor activity, and mood, and has effects on obsessions and impulsive behavior as well. Thus, it seemed like a natural agent to try among patients with AN-R. Dr. Vivian Kafantaris and colleagues designed a double-blind, placebo-controlled pilot study of olanzapine and enrolled 20 underweight females diagnosed with AN-R (J Child Adolesc Psychopharmacol 2011; 21: 207).

All females between 12 and 21 years who were receiving treatment for AN over a 4-year period were screened for eligibility for the study. This included inpatients, those attending day hospital treatment, and outpatients. Recruitment was challenging, for of the 94 women eligible for the study, 74 (79%) chose not to participate. The most common reasons given for declining the study were fear of gaining weight or wanting to gain weight without the need for medication.

The primary measure of efficacy was percentage of mean body weight (%MBW), which was measured at baseline and at weeks 5 and 10. Secondary measures were physician-rated and reported measures of psychological functioning, measured at 2-week intervals, and eating disorder symptoms recorded at baseline and then at weeks 5 and 10. Laboratory assessments, including indirect calorimetry, were also part of the study. The patients received a daily dose of 2.5 mg olanzapine, or placebo, in a single oral dose in the evening or at bedtime for one week. The daily dosage was then increased by 2.5 mg each week to a target dose of 10 mg per day by week 4. The research psychiatrists evaluated tolerability of medication weekly by physical examination, including blood pressure and pulse.

Week 10: No weight gain, and increased serum glucose and insulin levels

Mean %MBW improved in both treatment arms, and at the 10-week point, this differed significantly from baseline. Contrary to the researchers’ hypothesis, adding olanzapine to a comprehensive eating disorder treatment program did not improve %MBW at any time point during the study. However, by week 10 the researchers did record significant increases in serum insulin and fasting glucose levels in the group receiving olanzapine. According to the authors, these increases suggest a direct metabolic effect of olanzapine and the need for closely monitoring patients during long-term use.

Three women in the olanzapine group withdrew before week 5, citing dissatisfaction with the medication, whereas the two non-completers from the placebo arm were removed by investigators because of worsening symptoms. The mean dose achieved at week 10 was 8.5 mg. Both treatment groups remained at low body weights at the end of the study, and did not have improved attitudes or behaviors. In other words, they remained at high risk.

On the clinician-administered scale of functional abilities, the Toronto Extremity Salvage score, or TESS, there were no significant group-by-time interactions for any of the categories, including increased appetite, drowsiness, increased motor activity, rigidity, tremors, dystonia, akathisia or dyskinesia.

On the basis of their results, the authors do not feel there is a role for olanzapine in the treatment of underweight teens with AN-R receiving standard care in an eating disorders treatment center.