A 19-year-old female presents with a 2-year history of severe dietary restriction. She weighs 38 kg at height 162 cm (BMI 14.5 kg/m²). She reports intense fear of weight gain, distorted body image (perceives herself as overweight despite being underweight), and amenorrhoea for 18 months. She denies binge eating or purging. Physical examination reveals lanugo on the trunk, bradycardia (HR 48/min), and hypotension (BP 88/56 mmHg). Laboratory findings: Hb 10.2 g/dL, albumin 2.8 g/dL, TSH 8.5 mIU/L (low T3 syndrome). What is the most appropriate first-line pharmacological intervention?

Explanation

## Management of Anorexia Nervosa: Role of Pharmacotherapy ### Diagnosis Confirmation **Key Point:** This patient meets DSM-5 criteria for anorexia nervosa, restrictive type: - Severe dietary restriction → BMI 14.5 (significantly low) - Intense fear of weight gain - Distorted body image - Amenorrhoea (indicator of physiological impact) - No binge-eating or purging ### Why Pharmacotherapy Is NOT First-Line **High-Yield:** In anorexia nervosa, **nutritional rehabilitation and psychotherapy are the cornerstones of treatment**. Pharmacotherapy has limited efficacy in weight restoration and is NOT recommended as monotherapy. | Intervention | Evidence Base | Role in AN | |--------------|---------------|----------| | Nutritional rehabilitation | Strong | **First-line** — restores weight, reverses metabolic complications | | Psychotherapy (CBT, family-based) | Strong | **First-line** — addresses cognitions, behaviours, family dynamics | | SSRIs (fluoxetine, sertraline) | Weak–moderate | Adjunctive only; minimal benefit for weight restoration | | Antipsychotics (olanzapine) | Moderate | May reduce anxiety/obsessions; not first-line | **Clinical Pearl:** SSRIs are often ineffective in underweight patients because malnutrition impairs serotonergic neurotransmission. Weight restoration must precede or accompany SSRI use. ### Why Each Drug Option Is Suboptimal 1. **Fluoxetine** — While some evidence supports fluoxetine for relapse prevention *after* weight restoration, it is NOT first-line for acute anorexia nervosa. Monotherapy with fluoxetine without nutritional support is ineffective. 2. **Olanzapine** — May reduce anxiety and obsessive thoughts about food/weight, but does not directly address malnutrition or restore weight. Used adjunctively, not as first-line. 3. **Sertraline** — Similar to fluoxetine; limited efficacy in underweight patients without concurrent nutritional rehabilitation. ### Acute Medical Priorities This patient has severe physiological complications requiring urgent intervention: - **Bradycardia (HR 48)** — risk of arrhythmia - **Hypotension (88/56)** — cardiovascular instability - **Anaemia (Hb 10.2)** — malnutrition-induced - **Hypoalbuminaemia (2.8)** — protein malnutrition - **Low T3 syndrome** — metabolic adaptation to starvation **Warning:** These complications require inpatient medical stabilization with cardiac monitoring, electrolyte correction, and supervised nutritional rehabilitation — NOT pharmacotherapy alone. ### Recommended Approach ```mermaid flowchart TD A[Anorexia Nervosa Diagnosis]:::outcome --> B{Medically Stable?}:::decision B -->|No| C[Inpatient Medical Stabilization]:::action C --> D[Cardiac monitoring, electrolyte correction]:::action D --> E[Nutritional Rehabilitation]:::action E --> F[Psychotherapy: CBT or Family-Based]:::action B -->|Yes| F F --> G{Weight Restored?}:::decision G -->|Yes| H[Consider SSRI for Relapse Prevention]:::action G -->|No| E ``` **Mnemonic:** **NARP** — **N**utrition, **A**ssessment (medical), **R**ehabilitation, **P**sychotherapy (first-line in AN; pharmacotherapy is adjunctive). [cite:Harrison 21e Ch 385; DSM-5 Feeding and Eating Disorders]