Key Facts

Anorexia nervosa is a severe eating disorder with the highest mortality of any psychiatric condition. Early intervention significantly improves outcomes.

Epidemiology

Prevalence approximately 0.3-0.5%; F:M ~10:1. Peak onset 14-18 years. Incidence increasing. Highest mortality of any psychiatric disorder (SMR 5-6×).

Aetiology

• Genetic: Heritability ~50-80% (highest of eating disorders); genome-wide studies implicate metabolic and psychiatric loci
• Personality: Perfectionism, harm avoidance, obsessionality, low self-esteem
• Neurobiological: Altered serotonergic function, reward pathway dysfunction, set-point theory
• Environmental: Diet culture, social media, bullying, athletic/dance careers

Pathophysiology

Starvation syndrome (Keys Minnesota Experiment):

• Metabolic adaptation: Reduced BMR, hypothermia, bradycardia
• Hormonal: Low leptin, low T3, high cortisol, suppressed HPG axis
• Cardiac: Myocardial atrophy, QTc prolongation, pericardial effusion
• Haematological: Pancytopenia (gelatinous bone marrow transformation)
• Skeletal: Osteoporosis (oestrogen deficiency + hypercortisolaemia + poor nutrition)
• Cerebral: Grey matter loss (partially reversible with weight restoration)

Physical Signs

• Emaciation, cachexia, muscle wasting
• Lanugo hair, dry skin, hair loss, orange discolouration of palms (hypercarotenaemia)
• Hypothermia, bradycardia (<40 bpm), hypotension, postural drop
• Peripheral oedema, parotid swelling (binge-purge subtype)
• Russell's sign (calluses on knuckles from self-induced vomiting)
• Amenorrhoea

Psychological Features

• Body image distortion — overestimation of body size
• Intense fear of weight gain despite being underweight
• Denial of severity, poor insight (egosyntonic)
• Food-related rituals, calorie counting, body checking
• Social withdrawal, mood disturbance, irritability

Red Flags — MARSIPAN Criteria for Medical Emergency

• BMI <13 or rapid weight loss >1kg/week
• HR <40 bpm, QTc >450ms
• K⁺ <2.5, Na⁺ <130, glucose <3.0
• Temperature <35°C
• Unable to stand from squatting (SUSS test score 0)
• Syncope, seizures, cardiac failure

Bedside

• BMI: Height and weight — calculate and plot trend
• Vital signs: HR, BP (lying/standing), temperature
• ECG: Bradycardia, QTc prolongation, ST changes
• SUSS test: Sit up, squat, stand — assess proximal myopathy

Bloods

• U&Es: K⁺, Na⁺, urea, creatinine — electrolyte disturbance
• FBC: Pancytopenia (bone marrow suppression)
• LFTs: Raised transaminases (starvation hepatitis or refeeding)
• Phosphate, Mg²⁺: Refeeding risk; phosphate <0.5 = critical
• Glucose: Hypoglycaemia
• TFTs: Low T3 (sick euthyroid)
• Bone profile, vitamin D: Osteoporosis risk
• LH, FSH, oestradiol: Suppressed (functional hypothalamic amenorrhoea)
• Cortisol: Elevated (HPA axis activation)

Imaging

• DEXA scan: If amenorrhoea >12 months or BMI <15 for >1 year
• Echocardiogram: If cardiac symptoms or BMI <14

Special Tests

• EDE-Q: Eating disorder severity measure
• CIA (Clinical Impairment Assessment): Functional impact

Non-pharmacological (NICE NG69)

Children and adolescents:

• FBT (Family-based treatment): First-line; 3 phases over 12 months: Phase 1 (parents take control of eating), Phase 2 (gradual return of control to adolescent), Phase 3 (establishing healthy independence)
• Adolescent-focused therapy as alternative

Adults:

• CBT-ED: Individual CBT adapted for eating disorders (40 sessions)
• MANTRA: Maudsley Model of AN Treatment for Adults — addresses maintaining factors
• SSCM: Specialist Supportive Clinical Management — nutritional counselling + supportive therapy

Medical stabilisation:

• Refeeding protocol: Start 10 kcal/kg/day (5 if critical); increase by 200-300 kcal every 2-3 days
• Supplement: Pabrinex IV (B vitamins), phosphate (Phosphate-Sandoz 2 tablets TDS), K⁺, Mg²⁺
• Cardiac monitoring: Continuous if HR <40 or QTc >450ms
• Target weight gain: 0.5-1kg/week (inpatient), 0.5kg/week (outpatient)

Pharmacological

• No medication has robust evidence for weight gain in AN
• Olanzapine 2.5-5mg: Small studies suggest modest weight gain; may reduce rumination (off-label)
• SSRIs: For comorbid depression/anxiety AFTER weight restoration (ineffective at low weight)
• Calcium + vitamin D: Bone protection
• Not recommended: Appetite stimulants, zinc, multi-vitamins (beyond standard supplementation)

Referral Criteria

• Suspected AN — specialist eating disorder service
• BMI <15 or medically unstable — urgent medical assessment
• Under 18 — CAMHS eating disorder service
• Refusing treatment with life-threatening illness — consider MHA (rare, case-by-case)

• Recovery: ~50% fully recover; ~30% partial recovery; ~20% chronic course
• Mortality: ~5-20% lifetime; ~5-6× expected (SMR); leading causes: cardiac arrest, suicide
• Suicide: Second leading cause of death in AN; lifetime rate ~5-7%
• Duration of illness before treatment is the strongest prognostic factor
• Good prognostic factors: Younger onset, shorter duration, restricting subtype, good premorbid functioning
• Poor prognostic factors: Late onset, binge-purge subtype, lower BMI at presentation, comorbid depression/OCD, longer duration
• Osteoporosis: May not fully reverse even with weight restoration

MARSIPAN Risk Assessment Framework

Weight Restoration Goals