Eating Disorders: Anorexia Nervosa, Bulimia Nervosa, and Binge-Eating Disorder

1. Introduction

Eating disorders represent a group of severe psychiatric conditions characterized by persistent disturbances in eating behaviors and associated distressing thoughts and emotions. These disorders are associated with significant morbidity and mortality, impacting physical health, psychological well-being, and overall quality of life. The core diagnostic categories include anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED). Their complex etiology involves a multifactorial interplay of genetic, neurobiological, psychological, and sociocultural factors. The management of these conditions necessitates an integrated, multidisciplinary approach, wherein pharmacotherapy often plays a crucial adjunctive role alongside nutritional rehabilitation and psychotherapy.

1.1. Historical Context

The conceptualization of eating disorders has evolved considerably. Historical descriptions of self-starvation, such as those in medieval religious contexts, differ markedly from modern medical understandings. Anorexia nervosa was first formally described in the medical literature in the late 19th century. Bulimia nervosa gained recognition as a distinct syndrome in the 1970s, while binge-eating disorder was formally codified as a diagnosis much later, in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). This evolution reflects a growing understanding of the distinct psychopathological mechanisms underlying these conditions.

1.2. Importance in Pharmacology and Medicine

From a pharmacological and medical perspective, eating disorders present unique challenges. They are associated with profound medical complications across all organ systems due to malnutrition, purging behaviors, and weight fluctuations. Pharmacotherapy is rarely a standalone treatment but is integral for managing comorbid psychiatric conditions, addressing specific behavioral symptoms, and facilitating engagement in broader therapeutic programs. Understanding the pharmacokinetic and pharmacodynamic alterations caused by the physiological sequelae of these disorders is essential for safe and effective prescribing.

1.3. Learning Objectives

• Define the diagnostic criteria, epidemiology, and core psychopathology of anorexia nervosa, bulimia nervosa, and binge-eating disorder.
• Explain the proposed neurobiological and psychological models underlying the development and maintenance of eating disorders.
• Analyze the medical complications associated with each disorder and their implications for overall patient assessment and management.
• Evaluate the evidence base for pharmacological interventions, including drug classes, mechanisms of action, and their role within a multidisciplinary treatment framework.
• Apply knowledge of eating disorders to clinical case scenarios, considering integrated treatment planning and monitoring parameters.

2. Fundamental Principles

The fundamental principles of eating disorders are rooted in their classification, core psychopathology, and epidemiological patterns. A clear understanding of these foundations is prerequisite to exploring their complex management.

2.1. Core Concepts and Definitions

The diagnostic criteria are centered on specific behavioral and cognitive patterns. Anorexia nervosa is characterized by energy intake restriction leading to significantly low body weight, an intense fear of gaining weight or becoming fat, and a disturbance in the way one’s body weight or shape is experienced. Two subtypes are recognized: restricting type and binge-eating/purging type. Bulimia nervosa involves recurrent episodes of binge eating, which are defined by consuming an objectively large amount of food in a discrete period while experiencing a sense of loss of control. These episodes are followed by recurrent inappropriate compensatory behaviors to prevent weight gain, such as self-induced vomiting, misuse of laxatives or diuretics, fasting, or excessive exercise. Binge-eating disorder is defined by recurrent binge-eating episodes without the regular use of inappropriate compensatory behaviors, marked by distress regarding the binge eating.

2.2. Theoretical Foundations

Several theoretical models attempt to explain the etiology and maintenance of eating disorders. The biopsychosocial model is predominant, positing that genetic vulnerability interacts with psychological traits (e.g., perfectionism, negative affect) and sociocultural pressures (e.g., thin-ideal internalization) to precipitate disorder. Cognitive-behavioral models, particularly for BN and BED, emphasize the role of overvaluation of weight and shape in self-evaluation, dietary restraint, and the use of binge eating as a maladaptive coping mechanism for negative mood states. Neurobiological models focus on dysregulation within brain circuits governing reward, appetite, and cognitive control, often implicating neurotransmitters such as serotonin, dopamine, and norepinephrine.

2.3. Key Terminology

• Binge Eating: Consumption of an amount of food that is definitively larger than what most individuals would eat in a similar period under similar circumstances, accompanied by a feeling of loss of control.
• Compensatory Behaviors: Actions intended to prevent weight gain following food intake, including purging (vomiting, laxative/diuretic abuse), non-purging (excessive exercise, fasting), and misuse of medications (e.g., insulin, thyroid hormone).
• Body Image Disturbance: A distorted perception of one’s body size or shape, and/or an excessive influence of body weight or shape on self-evaluation.
• Refeeding Syndrome: A potentially fatal shift in fluids and electrolytes that may occur in malnourished patients receiving nutritional rehabilitation, characterized by hypophosphatemia, hypokalemia, hypomagnesemia, and fluid-balance abnormalities.
• Set Point Theory: A biological theory suggesting body weight is regulated around a genetically predetermined range, which may be altered by chronic dieting and eating disorder behaviors.

3. Detailed Explanation

This section provides an in-depth examination of the epidemiology, pathophysiology, and medical complications of each primary eating disorder.

3.1. Anorexia Nervosa (AN)

Anorexia nervosa has the highest mortality rate of any psychiatric disorder, with standardized mortality ratios estimated to be over five times higher than the general population. Mortality arises from medical complications of starvation and high rates of suicide.

3.1.1. Epidemiology and Risk Factors

The lifetime prevalence of AN is approximately 0.5-1% among females, with a female-to-male ratio of about 10:1. Onset typically occurs during adolescence. Identified risk factors include female sex, genetic heritability (estimated at 50-60%), certain personality traits (e.g., obsessive-compulsive, perfectionistic), and involvement in activities that emphasize leanness (e.g., ballet, long-distance running).

3.1.2. Pathophysiology and Neurobiology

The pathophysiology of AN is complex and involves both state-related consequences of starvation and potential trait-related vulnerabilities. Starvation induces a hypometabolic state, reducing resting energy expenditure and altering endocrine function. Key neurobiological findings may include:

• Serotonergic Dysfunction: Altered serotonin activity is implicated in anxiety, obsessionality, and appetite regulation. Post-illness, increased serotonin turnover may contribute to persistent dysphoria.
• Dopaminergic Alterations: Disturbances in dopamine-mediated reward processing may contribute to anhedonia and the ability to persist with restrictive eating despite negative consequences.
• Neuroendocrine Changes: Amenorrhea results from suppression of the hypothalamic-pituitary-gonadal axis. Elevated cortisol levels and reduced triiodothyronine (T3) are common adaptations to starvation.
• Structural Brain Changes: Starvation can lead to reductions in gray and white matter volume, which may be partially reversible with weight restoration.

3.1.3. Medical Complications

The medical sequelae of AN are systemic. A summary of key complications is presented in the table below.

3.2. Bulimia Nervosa (BN)

Bulimia nervosa is characterized by a cycle of dietary restriction, binge eating, and purging. It is more prevalent than AN, with a lifetime prevalence of 1-2% in women.

3.2.1. Epidemiology and Clinical Course

Onset is typically in late adolescence or early adulthood. The disorder often follows a chronic, fluctuating course. Comorbid conditions, particularly mood, anxiety, and substance use disorders, are highly prevalent. Impulsivity is a common associated feature.

3.2.2. Pathophysiology and Maintenance Cycles

The cognitive-behavioral model is central to understanding BN. The cycle often begins with rigid dietary rules and weight/shape overvaluation. Dietary restraint leads to physiological and psychological deprivation, increasing vulnerability to binge eating triggered by negative affect or dietary lapses. The binge episode temporarily alleviates distress but is followed by intense guilt and fear of weight gain, prompting purging. Purging reinforces the cycle by reducing anxiety about weight gain and disrupting normal satiety cues, while also perpetuating the belief that dietary control is possible.

3.2.3. Medical Complications of Purging Behaviors

Complications are primarily related to the methods of purging.

• Self-Induced Vomiting: Can cause dental erosion (perimolysis), parotid gland enlargement, esophageal tears (Mallory-Weiss syndrome), electrolyte disturbances (hypokalemic, hypochloremic metabolic alkalosis), and aspiration pneumonia.
• Laxative Abuse: Leads to dehydration, electrolyte imbalances (hypokalemia), metabolic acidosis, cathartic colon (loss of normal colonic motility), and dependence.
• Diuretic Abuse: Results in dehydration, hypokalemia, and potential renal impairment.

3.3. Binge-Eating Disorder (BED)

BED is the most common eating disorder among adults, with a lifetime prevalence of approximately 2-3% and a more equal gender distribution than AN or BN.

3.3.3. Epidemiology and Comorbidity

BED is frequently associated with obesity, though it can occur at any weight. High rates of comorbid psychiatric disorders, particularly mood and anxiety disorders, are observed. Onset can occur across the lifespan, including in middle age.

3.4.2. Pathophysiology and Psychological Models

Similar to BN, dietary restraint and negative affect are key triggers for binge episodes in BED. However, the absence of regular compensatory behaviors differentiates its maintenance. Neurobiological research suggests alterations in reward sensitivity and impulse control circuits. There may be heightened responsivity of the dopaminergic reward system to palatable food cues coupled with reduced prefrontal cortical inhibition. Emotional dysregulation is a core feature, with binge eating serving as a maladaptive coping strategy for negative emotions.

3.4.3. Health Consequences

The primary health risks are those associated with obesity and the psychological distress of the disorder itself. These include increased risk for type 2 diabetes mellitus, hypertension, dyslipidemia, cardiovascular disease, and impaired quality of life. The distress and shame associated with binge eating often perpetuate social isolation and delay seeking help.

4. Clinical Significance

The clinical significance of eating disorders extends beyond psychiatry into all areas of medicine and has profound implications for pharmacotherapy, necessitating a careful, informed approach to drug selection and monitoring.

4.1. Relevance to Drug Therapy: General Principles

Pharmacotherapy in eating disorders is complicated by several factors. Altered body composition and organ function affect pharmacokinetics. For instance, in AN, reduced lean body mass and fat stores, decreased cardiac output, and altered hepatic metabolism can change drug distribution, metabolism, and elimination. Patients may be highly sensitive to medication side effects, particularly those affecting weight, gastrointestinal function, or cardiac conduction. A strong therapeutic alliance is critical, as ambivalence about treatment and medication non-adherence are common.

4.2. Pharmacological Interventions by Disorder

The evidence base for pharmacotherapy varies significantly across disorders.

4.2.1. Anorexia Nervosa

No medication is approved for the treatment of AN, and pharmacotherapy has a limited primary role in weight restoration. The mainstay of treatment is structured nutritional rehabilitation and psychotherapy. Medications are used primarily to address comorbid conditions or specific symptoms.

• Antidepressants (SSRIs): Selective serotonin reuptake inhibitors are not effective for promoting weight gain in underweight patients with AN. Their utility may increase after partial weight restoration for treating comorbid depression, anxiety, or obsessive-compulsive symptoms. Initiation at very low doses is advised due to increased sensitivity.
• Atypical Antipsychotics: Drugs such as olanzapine and quetiapine are sometimes used off-label. Proposed mechanisms include reduction of severe anxiety and obsessive thoughts about food and weight, and mild appetite stimulation via histamine H1 and serotonin 5-HT2C receptor antagonism. Careful monitoring for metabolic side effects (weight gain, dyslipidemia, glucose dysregulation) and QTc prolongation is mandatory, with the former being a potential therapeutic effect in this context.
• Hormonal Therapies: While estrogen replacement does not effectively reverse bone loss in AN, transdermal estrogen may be considered in persistent cases. The primary treatment for osteoporosis remains weight restoration and nutritional supplementation.

4.2.2. Bulimia Nervosa

Pharmacotherapy has a more established role as an adjunct to psychotherapy, particularly cognitive-behavioral therapy (CBT).

• Antidepressants (SSRIs): Fluoxetine at a dose of 60 mg daily is FDA-approved for the treatment of BN. SSRIs reduce the frequency of binge-eating and purging behaviors, independent of the presence of depression. The mechanism is thought to involve modulation of serotonergic pathways involved in impulse control and satiety. Other SSRIs (e.g., sertraline, citalopram) are also used.
• Other Antidepressants: Tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) have demonstrated efficacy but are rarely used first-line due to their side effect profiles and toxicity in overdose.
• Topiramate: This anticonvulsant has shown efficacy in reducing binge/purge frequency, possibly through modulation of glutamate and GABA, appetite suppression, and cognitive effects. Side effects such as cognitive slowing, paresthesia, and risk of metabolic acidosis necessitate cautious use.

4.2.3. Binge-Eating Disorder

Several medications have demonstrated efficacy in reducing binge-eating frequency.

• Lisdexamfetamine: This prodrug stimulant is FDA-approved for the treatment of moderate-to-severe BED in adults. Its mechanism involves increasing synaptic dopamine and norepinephrine, which may enhance cognitive control over binge-eating impulses. It is contraindicated in patients with cardiovascular disease, and its abuse potential requires careful patient selection and monitoring.
• Antidepressants (SSRIs/SNRIs): SSRIs (e.g., fluoxetine, sertraline) and the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine have shown efficacy in reducing binge days. Effects on weight are variable.
• Anticonvulsants: Topiramate is associated with reductions in binge eating and often with weight loss, which can be a desirable outcome for patients with co-occurring obesity. Zonisamide has shown similar effects in some studies.

4.3. Management of Medical Complications

Pharmacological management of complications is a critical aspect of care.

• Refeeding Syndrome: Prophylaxis and treatment involve cautious, gradual nutritional advancement with close electrolyte monitoring. Oral or intravenous phosphate, potassium, and magnesium supplementation are often required. Thiamine must be administered prior to and during refeeding.
• Electrolyte Imbalances: Correction of hypokalemia, hypomagnesemia, and metabolic alkalosis in purging disorders is essential to prevent cardiac arrhythmias. Oral supplementation is preferred; intravenous correction may be necessary in severe cases.
• Osteoporosis: Beyond weight restoration, calcium and vitamin D supplementation are standard. The use of bisphosphonates in young patients with AN is controversial due to teratogenic potential and long half-life.

5. Clinical Applications and Examples

The following case scenarios illustrate the application of knowledge regarding eating disorders in clinical decision-making and integrated treatment planning.

5.1. Case Scenario 1: Anorexia Nervosa, Restricting Type

Presentation: A 17-year-old female is brought by her parents due to significant weight loss over 8 months. She is 165 cm tall and weighs 42 kg (BMI 15.4). She exercises for two hours daily, restricts her diet to vegetables and low-fat yogurt, and expresses intense fear of becoming “fat.” Physical exam reveals bradycardia (48 bpm), hypotension (90/60 mmHg), lanugo hair, and cool extremities. Labs show leukopenia, mild transaminitis, and a normal potassium level.

Pharmacotherapeutic Considerations: The immediate priority is medical stabilization and nutritional rehabilitation, not initiating psychotropic medication. If, after several weeks of structured refeeding and weight gain to a BMI of approximately 17.5, she exhibits severe, persistent obsessive anxiety about food and weight that impedes further progress, a low dose of an atypical antipsychotic such as olanzapine (2.5 mg daily) could be considered. The rationale would be to reduce anxiety and rigidity. A baseline ECG to assess QTc interval and ongoing monitoring of weight, lipids, and glucose would be required. An SSRI for comorbid anxiety would be deferred until further weight restoration due to limited efficacy and potential side effect sensitivity in the underweight state.

5.2. Case Scenario 2: Bulimia Nervosa with Comorbid Depression

Presentation: A 22-year-old female presents with a 4-year history of binge eating and self-induced vomiting occurring 3-4 times per week. She reports low mood, anhedonia, and guilt about her behaviors. Her weight is stable at a BMI of 21.5. Dental exam reveals enamel erosion. Serum electrolytes reveal hypokalemia (3.1 mmol/L) and metabolic alkalosis.

Pharmacotherapeutic Approach: First-line treatment would involve referral for cognitive-behavioral therapy for eating disorders (CBT-E). Concurrently, pharmacotherapy with an SSRI is indicated. Fluoxetine at 60 mg daily would be an evidence-based choice to target both the bulimic symptoms and depressive symptoms. Oral potassium chloride supplementation is required to correct the hypokalemia. The patient should be educated that the medication is an adjunct to therapy and informed about potential side effects (e.g., nausea, sexual dysfunction). Regular monitoring of electrolytes, mood, and binge/purge frequency is necessary.

5.3. Case Scenario 3: Binge-Eating Disorder and Obesity

Presentation: A 45-year-old male with a BMI of 38 presents with a 10-year history of consuming large amounts of food in secret several times per week, experiencing loss of control and subsequent shame. He has failed multiple commercial diets. He has hypertension managed with lisinopril and impaired fasting glucose.

Pharmacotherapeutic and Integrated Management: Treatment options should be discussed in the context of his metabolic comorbidities. Lisdexamfetamine (starting at 30 mg daily, titrating to 50-70 mg) is an FDA-approved option that may reduce binge days and could have a modest effect on weight. A thorough cardiovascular assessment is mandatory prior to initiation. Alternatively, topiramate (titrated slowly to 100-200 mg daily) could be considered, offering benefits for binge reduction and weight loss, but with a need to monitor for cognitive side effects and metabolic acidosis. A GLP-1 receptor agonist (e.g., semaglutide), while not approved for BED, may be considered for weight management and could potentially impact binge-eating behavior through enhanced satiety. All pharmacologic approaches should be combined with structured behavioral therapy for BED and nutritional counseling.

6. Summary and Key Points

Eating disorders are severe, multifactorial conditions with significant medical and psychiatric morbidity. Their management requires a sophisticated understanding of both psychopathology and physiology.

6.1. Summary of Main Concepts

• Anorexia nervosa, bulimia nervosa, and binge-eating disorder are defined by distinct behavioral and cognitive patterns, with AN carrying the highest mortality risk.
• The etiology is best understood through a biopsychosocial model, integrating genetic vulnerability, neurobiological dysregulation, psychological traits, and sociocultural influences.
• Medical complications are extensive and potentially life-threatening, affecting cardiovascular, gastrointestinal, endocrine, and skeletal systems, necessitating thorough physical assessment.
• Treatment is multidisciplinary, combining nutritional, psychological, and pharmacological interventions. The role of pharmacotherapy varies by diagnosis.
• Pharmacokinetic and pharmacodynamic considerations are crucial due to the physiological alterations caused by these disorders, often necessitating cautious dosing and vigilant monitoring.

6.2. Clinical Pearls

• In anorexia nervosa, weight restoration is the primary biological treatment; SSRIs are generally ineffective for core symptoms in the underweight state.
• Fluoxetine (60 mg/day) is the only FDA-approved medication for bulimia nervosa and is effective independent of comorbid depression.
• Lisdexamfetamine is FDA-approved for binge-eating disorder, but its stimulant properties require careful cardiovascular screening.
• Refeeding syndrome is a medical emergency; nutritional rehabilitation must be initiated cautiously with electrolyte repletion, especially phosphate and thiamine.
• All prescribing in this population requires monitoring for cardiac effects (particularly QTc prolongation), electrolyte disturbances, and sensitivity to side effects that may impact adherence (e.g., weight gain, GI upset).

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