What if a patient with a history of anorexia nervosa and a previous adverse reaction to bupropion (Wellbutrin) still wants to try it for depression?

Bupropion Should Not Be Prescribed for This Patient

Given the absolute contraindication of bupropion in patients with a history of anorexia nervosa, this medication should not be prescribed regardless of patient preference. 1, 2 The seizure risk is unacceptably elevated due to the synergistic effect between bupropion's inherent seizure threshold-lowering properties and the metabolic/electrolyte disturbances characteristic of eating disorders. 2

Why This Is an Absolute Contraindication

Mechanism of Increased Seizure Risk

• Electrolyte disturbances from purging behaviors lower the seizure threshold, and bupropion further reduces this threshold, creating a dangerous synergistic effect. 2
• Malnutrition and metabolic abnormalities common in eating disorders independently increase seizure susceptibility, which is then compounded by bupropion's inherent seizure-lowering properties. 2
• The 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 higher in patients with eating disorders. 3, 1

Evidence of Real-World Harm

• A case report documented severe bupropion XR abuse in a patient with bulimia nervosa who escalated to 3,000-4,500 mg/day and ultimately suffered grand mal seizures. 4
• The American Gastroenterological Association explicitly recommends that patients with bulimia or anorexia nervosa should not be treated with bupropion due to increased seizure risk. 1, 2
• This contraindication appears in FDA labeling and all major clinical guidelines. 5

Alternative Treatment Options

First-Line Antidepressants for This Population

• SSRIs, particularly fluoxetine 60 mg daily, are recommended for bulimia nervosa and are safe in patients with eating disorder history. 2
• SSRIs do not carry the seizure risk associated with bupropion and have demonstrated efficacy for both depression and eating disorder symptoms. 2

If Patient Had Previous Adverse Reaction to Other Antidepressants

• Consider other SSRIs (sertraline, escitalopram, paroxetine) or SNRIs (venlafaxine, duloxetine) as alternatives. 3
• Mirtazapine may be considered, particularly if weight gain is not a concern. 3
• Augmentation strategies with psychotherapy should be emphasized. 3

Critical Counseling Points

What to Tell the Patient

• Explain that this is not a matter of clinical judgment or risk-benefit analysis—bupropion is contraindicated because the seizure risk is unacceptably high in patients with eating disorder history. 1, 2
• Emphasize that even if the patient is currently weight-restored and not actively engaging in eating disorder behaviors, the history alone constitutes a contraindication. 2
• Discuss that a previous adverse reaction to bupropion further supports avoiding this medication. 5

Addressing Patient Concerns About Alternative Medications

• If the patient is concerned about sexual dysfunction or weight gain with SSRIs (common reasons patients request bupropion), acknowledge these concerns but explain that safety must take priority. 3
• Discuss strategies to mitigate SSRI side effects, such as dose adjustments, timing of administration, or adding medications to address specific side effects. 3
• Consider referral to psychiatry if the patient remains resistant to alternative treatments. 3

Documentation Recommendations

• Document the patient's history of anorexia nervosa and previous adverse reaction to bupropion clearly in the medical record. 2
• Document that the patient requested bupropion despite contraindication and that you explained the rationale for not prescribing it. 2
• Document the alternative treatment plan offered and the patient's response. 2

Common Pitfall to Avoid

• Do not prescribe bupropion even if the patient reports being "recovered" from their eating disorder for years. 2 The contraindication is based on history, not current status, because the metabolic and neurological vulnerabilities may persist even after behavioral recovery. 2