This study will compare the effectiveness of two atypical antipsychotic medications, olanzapine and aripiprazole, in treating people with anorexia nervosa.

Anorexia nervosa (AN) is a disease of disordered eating that is characterized by self-starvation, often leading to 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. Previous studies have suggested that certain medications usually used to treat schizophrenia, also known as atypical antipsychotic drugs, may be helpful in treating people with AN. Specifically, the atypical antipsychotic medications olanzapine and aripiprazole may be effective in improving overall symptoms of AN and in restoring weight to normal levels. This study will compare the effectiveness of olanzapine and aripiprazole in treating people with AN.

Participation in this study will last 12 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 12 weeks of treatment with daily olanzapine or aripiprazole. Participants will meet with a study doctor weekly over the 12 weeks of treatment. During these visits, the study doctor will monitor participants' progress, medication dosage, vital signs, and side effects. In addition, participants will undergo repeat blood draws every 4 weeks and repeat questionnaires every month of the treatment period. Upon completing the 12 weeks of treatment, participants will repeat most baseline assessments.

Inclusion Criteria:

• Meets DSM-IV criteria for AN (DSM-IV criteria for amenorrhea will not be strictly applied, as these patients have been shown to be clinically indistinguishable from those with full criteria AN)
• Body mass index (BMI) less than 19 kg/m2 and greater than 14 kg/m2 (BMI of 19 is equivalent to approximately 85% of ideal body weight [IBW] according to Metropolitan Life standards, and BMI of 14 is equivalent to approximately 65% IBW)
• Unwilling to pursue inpatient treatment if BMI is less than 18 kg/m2
• Free of psychotropic (e.g., antidepressant, antianxiety, mood stabilizer, antipsychotic) medication for 2 weeks before study entry (free for 4 weeks before study entry if taking fluoxetine or antipsychotic medications)
• Prior treatment of AN

Exclusion Criteria:

• Any medical or psychiatric problem requiring urgent clinical attention (e.g., metabolic disturbance, acute suicidality) and/or significant comorbid illnesses that are not likely to benefit from proposed treatments
• Significant orthostatic high blood pressure (systolic change greater than 30 mmHg upon changing from supine to standing position)
• Allergy to olanzapine or aripiprazole
• Commencing psychotherapy in the community within 3 months of study entry
• Diabetes mellitus, with fasting serum glucose greater than 120 mg/dL or nonfasting serum glucose less 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