Anorexia nervosa

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Anorexia nervosa (AN) is a complex eating disorder with a high mortality rate. It is characterized by deliberate restriction of energy intake, resulting in significantly low body weight. Causes are multifactorial and include genetic factors, psychiatric disorders, and psychosocial factors (e.g., trauma). Typical features include body image disturbance and fear of weight gain. There are two subtypes of AN: restrictive (weight loss is achieved by reducing intake and increasing calorie expenditure, e.g., with excessive exercise) and binge eating/purging (if those behaviors are present). Individuals without low body weight but who otherwise meet the diagnostic criteria for AN are diagnosed with atypical AN. It is important to assess for malnutrition severity in affected individuals, regardless of body weight or body mass index (BMI). Diagnostic workup should include evaluation for associated complications (e.g., electrolyte abnormalities) and, in some cases, any underlying conditions that may affect weight or cause a change in eating behaviors (e.g., thyroid disorder). Management should be provided in an outpatient setting if possible, but the presence of red flags in eating disorders may indicate the need for hospitalization for acute stabilization. All patients should be referred for psychotherapy and nutritional management for weight restoration in AN. Pharmacotherapy may be used as adjunctive therapy to help manage comorbid psychiatric conditions (e.g., depression) or promote weight gain in selected patients. AN has the highest mortality rate of all psychiatric disorders because of the high incidence of serious medical complications.

• Prevalence ^[2][3][4]
  • ♀: 0.9–1.4%
  • ♂: 0.1–0.3%
• Age: Onset usually occurs between ∼ 12 and 25 years of age. ^[2][5]
• Sex: ♀ > ♂ (3–12:1) ^[2][3][4]

AN is likely underdiagnosed in boys and men, as the condition is more commonly associated with girls and women. ^[6]

Epidemiological data refers to the US, unless otherwise specified.

The etiology of AN is multifactorial and not entirely understood. Several factors are thought to contribute to the development of the disorder:

• Genetic factors: There is a higher concordance of AN in identical twins than in fraternal twins. ^[7]
• Neurobiological factors: e.g., abnormal reward processing ^[8]
• Psychiatric factors: associated with obsessive-compulsive disorder, anxiety disorders, mood disorders, and personality disorders ^[7][9]
• Psychosocial factors
  • Traumatization ^[10]
  • Caregiver with disordered eating ^[11]
  • Careers or sports that prioritize leanness and/or target weights (e.g., modeling, ballet, gymnastics, wrestling) ^[12]
  • Societal idealization of thinness ^[13]
  • Food insecurity ^[10]

• Most patients present with a low BMI. ^[14]
• Associated features of severe malnutrition may be present.

Patients with AN who engage in purging behavior may also exhibit clinical features of bulimia nervosa such as dental damage, sialadenosis, and Russell sign. ^[10]

General principles

• See “Screening for eating disorders” for indications and screening modalities.
• Obtain height and weight measurements to calculate BMI and malnutrition severity.
• Determine if individuals fulfill the DSM-5 diagnostic criteria for AN to confirm the diagnosis.
• Evaluate for complications and comorbidities, and rule out possible organic etiologies; see “Initial evaluation for a suspected eating disorder.”

DSM-5 diagnostic criteria ^[5][7][20]

Patients who have a normal or elevated BMI but meet all other criteria for AN are diagnosed with atypical AN, which is in the DSM-5 category of Other Specified Feeding and Eating Disorders. ^[5][9]

Subtypes ^[5][7][20]

• Anorexia nervosa, restricting type (ANR)
  • Weight loss is achieved by any of the following:
    • Excessive dieting
    • Exercise
    • Fasting
  • No recurrent binge eating or purging over a 3-month period
• Anorexia nervosa, binge eating/purging type (ANBP):
  • Patients have restricted energy intake
  • AND there has been recurrent binge eating and/or purging (i.e., vomiting or misuse of laxatives, diuretics, and/or enemas) in the last 3 months

Severity ^[6][7]

• For adults, BMI is used to assess severity.
• For adolescents and children, severity is calculated using:
  • BMI percentiles for sex and age according to the CDC growth charts
  • Malnutrition severity for eating disorders

Approach ^[9][10][14]

• Determine if the patient has red flags in eating disorders that require inpatient management (see “Disposition for eating disorders”).
• Co-manage weight restoration for AN with a dietitian.
  • Provide nutritional rehabilitation, including nutritional education and the promotion of healthy eating habits.
  • Promote and monitor weight gain.
• Refer all patients for psychotherapy, e.g.:
  • Family-based therapy for adolescents and young adults
  • Cognitive behavioral therapy (CBT) or psychodynamic psychotherapy for adults
• Manage any medical complications of eating disorders.
• Screen for and treat comorbid psychiatric conditions, e.g., SSRIs for depression.
• A specialist may consider olanzapine for weight gain in selected patients.
• Encourage physical activity for a healthy lifestyle rather than for weight control.
  • For underweight patients:
    • Supervise patients during physical activity and limit exercise to <1.5 hours/week.
    • Exercise should be stopped if there is no weight gain.
  • Once normal weight has been restored: Encourage team sports and weight training for bone health.

Weight gain may initially worsen the patient's mood and disordered behaviors, though this should improve over time. Counsel patients to anticipate this and monitor them appropriately. ^[10]

Weight restoration for AN ^[10][19][23]

Goal weight range ^[6][10]

• Individualize the goal for each patient, considering: ^[10]
  • Weight at which reproductive function is restored (for postmenarchal patients)
  • Growth and pubertal development trajectories in adolescents and young adults
  • Possible initial goal: BMI > 20 kg/m² for adults
• During growth periods in children: Reassess goal weight every 3–6 months.
• Carefully consider if the goal weight should be shared with the patient.

Weigh patients after voiding, with their shoes removed. ^[10]

Nutritional rehabilitation

• An individualized diet plan should be created in collaboration with a registered dietitian nutritionist. ^[10]
• Patients should be carefully monitored to prevent refeeding syndrome.
• Weekly weight goals are recommended in addition to a final target weight.
• Promote healthy eating habits, including:
  • Eating regular meals and snacks
  • Expanding food variety
  • Focusing on food with a high energy density
• Enteral and parenteral nutrition are avoided, if possible.
  • Enteral nutrition: may be used short-term for selected patients ^[10][23]
  • Parenteral nutrition: should only be considered if all other methods have been exhausted
  • Involuntary feeding may be considered by specialists for patients with impaired decision-making capacity and a high risk of morbidity and mortality.
  • For more information, see “Specialized nutrition support.”

Early and rapid weight gain are associated with a better prognosis. ^[10][23]

Psychotherapy ^[7][9][10]

• Psychotherapy is often needed for ≥ 1 year. ^[10]
• Type of therapy depends on the age of the patient, availability, and patient preference. ^[10]

Therapy for caregivers (e.g., Experienced Carers Helping Others) improves outcomes for patients with AN. ^[10]

Pharmacotherapy ^[7][9][10]

• Although frequently prescribed, there is limited evidence to support the use of pharmacotherapy in AN. ^[9]
• SSRIs have a limited role.
  • Not effective if prescribed solely for the management of AN
  • Can help manage comorbid psychiatric conditions ^[10]
• Olanzapine may be considered in selected patients to assist with weight gain. ^[24]

The antidepressant bupropion lowers the seizure threshold and is contraindicated in individuals with a history of eating disorders because these individuals have an increased risk of dehydration and electrolyte imbalances, which can also cause seizures. ^[10]

Management of common complications

• Vitamin deficiencies: Treat with supplements (e.g., multivitamins, zinc, calcium, vitamin D3).
• Amenorrhea or menstrual abnormalities ^[18]
  • Hormonal contraception should not be used to restore menstrual cycles or improve bone mineral density.
  • The use of hormonal contraception may mask the spontaneous return of menses.
  • In patients requiring contraception, a copper coil may be preferred, as it does not interfere with the menstrual cycle.
• See also “Complications of eating disorders”.

Sexually active patients with amenorrhea or irregular menses can still become pregnant; counsel patients appropriately on contraception. ^[18]

• Bulimia nervosa: Consider for patients with ANBP subtype.
• Avoidant restrictive food intake disorder
• Body dysmorphic disorder

The differential diagnoses listed here are not exhaustive.

• Outcomes in AN vary from chronic, relapsing course to a gradual but complete recovery. ^[7][10]
  • Factors associated with a poorer prognosis
    • Onset before 15 years of age
    • Psychiatric comorbidities
  • Factors associated with a better prognosis
    • ANR subtype
    • Early and rapid weight gain
• Malnutrition can cause long-term physical complications, e.g., stunted growth, secondary osteoporosis (see “Clinical features of AN”).
• Psychiatric comorbidities are common, e.g.: ^[10][25]
  • Obsessive-compulsive disorder
  • Personality disorders
  • Anxiety disorders (e.g., generalized anxiety disorder, social anxiety disorder)
  • Mood disorders (e.g., depression, bipolar disorder)
• AN has the highest mortality rate among all psychiatric disorders. ^[15]
  • Mortality rate: 5.1 deaths per 1000 person-years ^[26]
  • Most commonly due to sudden cardiac death, suicide, and organ dysfunction resulting from severe cachexia/starvation (e.g., liver failure) ^[15][25]

Individuals with AN may switch from one subtype to another or develop a different eating disorder, such as bulimia nervosa. ^[7][13]

The high mortality rate in AN is due to associated medical complications (e.g., arrhythmia, bradycardia) and the high suicide rate in affected individuals. ^[15][25]

Anorexia nervosa in pregnant patients ^[27]

• Patients with AN may experience worsening of symptoms or relapse during pregnancy and the postpartum period. ^[28]
• Screen patients for a history of eating disorders at the initial OBGYN visit, and, if present, refer to psychiatry. ^[27]
• Refer affected individuals to a dietitian to ensure the increased energy requirements and micronutrient needs of pregnancy are met. ^[29]
• Monitor for common complications during pregnancy, e.g.: ^[27]
  • Maternal complications
    • Hyperemesis gravidarum
    • Anemia
    • Acute liver failure
    • Miscarriage or premature birth
    • Need for cesarean delivery
  • Fetal complications
    • Intrauterine growth restriction
    • Low birth weight
    • Fetal distress

Pregnant patients with AN require multidisciplinary care involving their primary care doctor, obstetrician, psychiatrist, and dietitian. ^[29]