In a medically stabilized patient with anorexia nervosa who is engaged in structured nutritional rehabilitation, what is the recommended pharmacologic regimen, including first‑line atypical antipsychotic (olanzapine) dosing and titration, monitoring requirements, and second‑line medication options?

Pharmacological Management for Anorexia Nervosa

Primary Recommendation

No medications are approved for anorexia nervosa, and current evidence does not support routine pharmacologic treatment for weight restoration. 1 Eating disorder-focused psychotherapy combined with nutritional rehabilitation and weight restoration is the cornerstone of anorexia nervosa treatment. 1

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Mandatory Pre-Treatment Safety Assessment

Before considering any pharmacologic intervention, the following assessments are required:

• Electrocardiogram (ECG) must be obtained because QTc prolongation is common in restrictive anorexia nervosa, and both the disorder and certain psychiatric medications can further prolong the QTc interval. 1
• Comprehensive metabolic panel including electrolytes is required prior to medication initiation. 1
• Vital signs including orthostatic blood pressure measurement must be recorded. 1
• Complete blood count should be obtained before any pharmacologic intervention. 1

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Olanzapine as First-Line Adjunctive Pharmacotherapy

When pharmacologic intervention is considered as an adjunct to psychotherapy and nutritional rehabilitation:

Dosing and Titration

• Start olanzapine at 5 mg daily as the initial dose. 2
• The dose may be increased to 10 mg daily based on clinical response and tolerability. 3, 4
• Treatment duration should be at least 10 weeks to assess efficacy. 3, 4

Evidence Supporting Olanzapine

• Olanzapine resulted in greater rate of weight gain and earlier achievement of target BMI compared to placebo in a randomized controlled trial. 3
• Olanzapine significantly reduced obsessive symptoms related to eating disorder pathology. 3
• Multiple open-label trials demonstrated clinically significant weight gain (mean 8.75 lb over 10 weeks) with reduction in anxiety, depression, and core eating disorder symptoms. 5, 6, 4

Monitoring Requirements During Olanzapine Treatment

• Repeat ECG monitoring is advised when prescribing olanzapine due to its QT-prolonging potential. 1
• Weekly weight monitoring to track progress toward target weight goals. 1
• Regular vital sign assessment including orthostatic measurements. 1
• Periodic metabolic panel to monitor electrolytes, especially during refeeding. 1

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Second-Line Medication Options

For Comorbid Psychiatric Symptoms

• Selective serotonin reuptake inhibitors (SSRIs) may be beneficial for treating comorbid anxiety, depression, and obsessive-compulsive behaviors. 7
• Mirtazapine 7.5–30 mg at bedtime can be considered if depression is prominent, as it also has appetite-stimulating properties. 2

Alternative Appetite Stimulants (Limited Evidence in AN)

While the following are mentioned in palliative care guidelines for cancer-related anorexia, their use in anorexia nervosa is not evidence-based:

• Megestrol acetate 400–800 mg/day 2
• Dexamethasone 2–8 mg/day 2

Important caveat: These agents are NOT recommended for primary anorexia nervosa treatment, as they do not address the underlying eating disorder pathology and may create false reassurance without promoting true recovery. 1

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Critical Pitfalls to Avoid

• Do not initiate psychotropic medication without prior cardiac evaluation, as both anorexia nervosa and certain psychiatric drugs can prolong the QTc interval. 1
• Do not use oral contraceptives to "treat" amenorrhea in anorexia nervosa, as they create false reassurance with withdrawal bleeding but do not restore spontaneous menses and may compromise bone health. 1
• Do not rely on medication alone without concurrent eating disorder-focused psychotherapy and nutritional rehabilitation. 1
• Monitor for refeeding syndrome during nutritional rehabilitation, characterized by fluid and electrolyte disturbances, cardiac complications, and potentially sudden death in severely malnourished patients. 8

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Treatment Intensity Considerations

• Outpatient treatment is appropriate for most medically stable patients. 7
• Inpatient care is necessary when BMI <16 kg/m², severe orthostatic hypotension, rapid weight loss, severe electrolyte abnormalities, or QTc prolongation on ECG are present. 7, 9

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Multidisciplinary Coordination

All eating disorder treatment requires coordination among medical, psychiatric, psychological, and nutritional expertise. 1 For adolescents and young adults with a caregiver present, family-based treatment is the recommended approach. 1, 7