Olanzapine Versus Placebo for Outpatients With Anorexia Nervosa

This study is a 16-week randomized, double-blind, placebo-controlled trial of olanzapine in
adult outpatients with AN. 160 individuals with AN, ages > 18, will be randomly assigned to
receive olanzapine or placebo for 16 weeks together with a medication management treatment.
Primary outcomes will include weight gain as well as psychological symptoms known to be
associated with AN, including obsessionality, mood, and anxiety.

This project is based on evidence from a recently completed 8-week pilot study comparing the
efficacy of olanzapine to placebo in outpatients with AN (PI: Evelyn Attia, MD), as well as a
recently published 12-week trial of olanzapine vs placebo (Bissada et al, Am J Psychiatry,
2007) in which outpatient treatment with olanzapine was associated with weight improvement,
improved psychological status, and no untoward metabolic effects among low-weight patients.

The investigators hypothesize that among underweight adult outpatients with AN receiving
olanzapine vs. placebo, together with medication management treatment: 1)patients with AN
receiving olanzapine will gain weight at a faster rate than those receiving placebo; and 2)
patients with AN receiving olanzapine will demonstrate greater reduction in psychological
symptoms, including obsessionality, mood, anxiety and eating disorder symptoms, than those
receiving placebo.

Inclusion Criteria:

- Diagnosis of Anorexia Nervosa

- Body Mass Index (BMI) between 14.0 and 18.5 kg/m2

- Between 18-75 years old

- Patient not pursuing intensive treatment (inpatient or day treatment) for weight
restoration if BMI less than 18 kg/m2

- serum potassium > 2.5 mEq/L

Exclusion Criteria:

- Any medical or psychiatric problem requiring medical or psychiatric attention,
significant metabolic disturbance upon psychiatrist presentation, and/or significant
co-morbid illnesses that are not likely to benefit from proposed treatments or that
need specialized treatments for non-eating disorder symptoms.

- Diabetes mellitus

- QTc > 480 msec at baseline or increase in QTc of > 35 msec since baseline ECG

- Significant hyperlipidemia (cholesterol, triglycerides > 1.5 x upper limit of normal)

- Current diagnosis of substance abuse or dependence

- Diagnosis of schizophrenia, schizophreniform disorder, bipolar illness (type I)

- Presence of movement disorder, tardive dyskinesia

- History of seizure disorder

- Dementia (subjects over age 55 will be assessed by an MMSE administered by a
psychiatrist; those who receive an MMSE score >25 will be excluded)

- Allergy to olanzapine

- Documented treatment with 10 mg/day olanzapine x 8 weeks or known inability to
tolerate olanzapine 10 mg/day

- Taking psychotropic (antidepressant, antianxiety, mood stabilizer, antipsychotic)
medication within the 4 weeks prior to randomization, other than stable dose of
Selective Serotonin Reuptake Inhibitor (SSRI) or Serotonin/Norepinephrine Reuptake
Inhibitor (SNRI), or use of benzodiazepine or non-benzodiazepine sleep agents. These
permissible medications may be continued during the trial if they have been in use by
the patient for a period of > 4 weeks at an unchanged dose without any evidence of
consistent weight gain (i.e., > 3 lbs/months)

- Taking other medication within the last four weeks prior to randomization, known to
affect weight (e.g., steroids)

- Participation in a psychotherapeutic intervention associated with consistent weight
gain (i.e. > 3 lbs/month). (Subjects may participate in the study if they are
receiving stable outpatient psychotherapy for the 4 weeks prior to randomization as
long as there have been no changes in therapy intensity and the psychotherapy has not
been associated with weight gain > 3 lbs over the previous 4 weeks. Subjects may also
participate if they recently received partial weight restoration treatment in an
intensive inpatient or day program as long as they can document that they have not
consistently gained weight in their current treatment setting for the 4 weeks prior to
baseline screening.)