Is it safe to re-initiate bupropion in a patient with a history of anorexia nervosa and previous adverse reaction to Wellbutrin (bupropion) who is currently stable?

Re-initiating Bupropion in a Patient with History of Anorexia Nervosa

Do not re-initiate bupropion in this patient—anorexia nervosa is an absolute contraindication to bupropion use due to significantly elevated seizure risk, regardless of current stability or previous trial.

Absolute Contraindication

• The FDA drug label explicitly contraindicates bupropion in patients with a current or prior diagnosis of anorexia nervosa or bulimia nervosa due to a higher incidence of seizures observed in such patients 1
• This contraindication applies even if the eating disorder is currently in remission or the patient is considered "stable" 1
• The American Academy of Nutrition and Dietetics recommends that patients with bulimia or anorexia nervosa should not be treated with bupropion due to increased seizure risk 2

Seizure Risk in Eating Disorders

• Patients with eating disorders have inherently lower seizure thresholds due to electrolyte abnormalities, malnutrition, and metabolic disturbances that may persist even after apparent clinical stability 3
• The baseline seizure risk with bupropion at standard doses (300 mg/day) is approximately 0.1% (1 in 1,000) in the general population, but this risk is substantially elevated in patients with eating disorder history 2
• Case reports document severe adverse outcomes including grand mal seizures in patients with bulimia nervosa taking bupropion, even at therapeutic doses 4
• One case series documented a patient with bulimia nervosa who experienced seizures and ultimately abused bupropion XR to dangerous levels (3,000-4,500 mg/day), highlighting both seizure risk and potential for misuse in this population 4

Clinical Reasoning for This Contraindication

• The history of anorexia nervosa creates a permanent elevated risk profile that does not resolve with clinical stability 1
• Even patients without active eating disorder symptoms retain metabolic vulnerabilities and potential for relapse that increase seizure susceptibility 3
• The FDA contraindication is based on observed higher seizure incidence in clinical trials and post-marketing surveillance, not theoretical risk 1

Alternative Treatment Options

• For depression in patients with eating disorder history, consider SSRIs (particularly fluoxetine, which is FDA-approved for bulimia nervosa), mirtazapine, or other antidepressants without seizure risk 3
• Fluoxetine is specifically approved for bulimia nervosa and can address both mood symptoms and eating disorder pathology 3
• For comorbid depression and eating disorders, olanzapine shows promise in anorexia nervosa, though primarily for weight restoration rather than mood 3

Critical Safety Consideration

• The fact that the patient "previously tried Wellbutrin" suggests either: (1) it was prescribed before the eating disorder diagnosis was known, (2) it was prescribed inappropriately, or (3) the patient experienced an adverse reaction that led to discontinuation 1
• Regardless of the reason for previous discontinuation, the eating disorder history makes re-initiation contraindicated 1
• No dose adjustment, monitoring protocol, or clinical stability can override this absolute contraindication 1