Effectiveness of Olanzapine Versus Placebo in Treating Outpatients With Anorexia Nervosa

Anorexia nervosa (AN) is a disease of disordered eating and is characterized by
self-starvation, extreme weight loss, and difficulty maintaining a normal weight. Symptoms
and behaviors of AN may include distorted body image, obsessive exercise, lack of
menstruation among women, binge and purge eating behaviors, and intense fear of weight gain.
Furthermore, people with AN are at a high risk of other mental disorders, such as depression
and anxiety, and medical complications, such as organ damage, heart failure, and
osteoporosis. Current treatments for AN include nutrition counseling, psychotherapy, and
medication. Although weight restoration is a treatment priority, no particular therapeutic
approach for patients with AN has clear empirical support. Previous studies have suggested
that certain medications usually used to treat schizophrenia, also known as atypical
antipsychotic drugs, may be helpful in increasing appetite and reducing anxiety related to
weight gain and eating in people with AN. Specifically, the atypical antipsychotic medication
olanzapine may be effective in improving overall symptoms of AN and in restoring weight to
normal levels. This study will compare the effectiveness of the antipsychotic medication
olanzapine versus placebo in treating outpatients with AN.

Participation in this study will last 8 weeks. All participants will first undergo baseline
assessments that will include questionnaires and interviews about AN symptoms, a physical
exam, vital sign measurements, an electrocardiograph (EKG), and a blood draw. Participants
will then be assigned randomly to 8 weeks of daily treatment with olanzapine or placebo.
Participants will meet with a study doctor weekly over the 8 weeks of treatment. During these
visits, the study doctor will monitor participants' progress, medication dosage, vital signs,
and side effects. Participants will also fill out weekly questionnaires about the status of
their condition and monthly repeat baseline questionnaires. In addition, participants will
undergo blood draws every 2 weeks for the first month of the study and every 4 weeks for the
remainder of the study. Upon completing the 8 weeks of treatment, participants will repeat
the baseline assessments. During the next 5 years, participants may be contacted to complete
a follow-up interview.

Inclusion Criteria:

- Meets DSM-IV criteria (not including amenorrhea) for AN

- Body mass index (BMI) less than 19 kg/m2 and greater than 14 kg/m2

- Patient (or family if the patient is a minor) refuses hospitalization

- Free of psychotropic medication (4 weeks medication free for fluoxetine and
antipsychotic medication; 2 weeks medication free for all others) OR on a stable dose
of an SSRI or SNRI (venlafaxine) for 4 weeks before study entry

- Prior treatment of AN

Exclusion Criteria:

- Any medical or psychiatric problem requiring urgent attention and/or any significant
comorbid illness not likely to benefit from proposed treatments

- Allergy to olanzapine

- Significant orthostatic high blood pressure

- Recent commencement of psychotherapy in the community

- Diabetes mellitus, with a fasting serum glucose greater than 120 mg/dL or nonfasting
serum glucose greater than 140 mg/dL

- Known history of current or past jaundice

- Known history of narrow angle glaucoma

- Active substance abuse or dependence

- Schizophrenia, schizophreniform disorder, or bipolar illness

- Movement disorder or presence of tics

- History of tardive dyskinesia

- History of seizures

- Pregnant