Why Bupropion (Wellbutrin) is Contraindicated in Eating Disorders
Bupropion is absolutely contraindicated in patients with current or prior anorexia nervosa or bulimia nervosa because these patients have a significantly higher incidence of seizures when treated with this medication. 1
The Seizure Risk Mechanism
The FDA drug label explicitly states this as an absolute contraindication, not merely a precaution. 1 The mechanism relates to several factors:
Electrolyte disturbances from purging behaviors (vomiting, laxative abuse) lower the seizure threshold, and bupropion further reduces this threshold, creating a dangerous synergistic effect. 2, 3
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 contraindication applies to both current AND prior diagnosis of bulimia or anorexia nervosa, meaning even patients in remission should not receive bupropion. 1
Clinical Evidence Supporting the Contraindication
Historical clinical trial data demonstrated a higher incidence of seizures in eating disorder patients treated with bupropion, which led to the FDA contraindication. 1 This finding has been reinforced by case reports, including a documented case of a 22-year-old woman with bulimia nervosa who abused bupropion XR and subsequently experienced grand mal seizures. 4
Additional Concerns Beyond Seizures
Abuse potential is a significant secondary concern in this population:
Patients with eating disorders may abuse bupropion for its appetite-suppressing and stimulant-like effects, as documented in case reports where patients took doses as high as 3,000-4,500 mg/day (10-15 times the therapeutic dose). 4
The medication's anorexic effects can reinforce disordered eating behaviors and weight control obsessions. 4
Binge-Eating Disorder: A Critical Exception
Binge-eating disorder (BED) is NOT included in this contraindication. This is a crucial distinction:
The FDA contraindication specifically names only anorexia nervosa and bulimia nervosa. 1
Naltrexone-bupropion combination therapy has been studied and shown efficacy for BED, with a 57.1% remission rate when combined with behavioral weight loss therapy. 5
However, bupropion monotherapy showed no benefit for binge eating in BED patients, though it did produce modest weight loss (1.8% vs 0.6% BMI loss compared to placebo). 6
The key difference is that BED patients typically do not engage in purging behaviors that cause the electrolyte disturbances seen in bulimia nervosa. 5
Practical Clinical Implications
Screening is mandatory before prescribing bupropion:
Always obtain a detailed eating disorder history, including past diagnoses, even if the patient is currently asymptomatic. 2, 7
Ask specifically about purging behaviors (self-induced vomiting, laxative abuse), dietary restriction patterns, and compensatory exercise. 8
Document weight control behaviors and any history of significant weight fluctuations. 8
If seizures occur in a patient on bupropion:
Consider occult eating disorder behaviors, particularly in young women, as eating disorders may be concealed from clinicians. 4
The American Gastroenterological Association and other guideline societies specifically recommend that patients with bulimia or anorexia nervosa should not be treated with bupropion due to increased seizure risk. 2
Alternative Antidepressant Options
For patients with eating disorders who need antidepressant treatment:
SSRIs (particularly fluoxetine 60 mg daily) are recommended for bulimia nervosa and are safe in this population. 8, 7
Mirtazapine can be considered for comorbid depression, though weight gain is a potential concern. 7
Other SSRIs like citalopram, sertraline, duloxetine, and venlafaxine are appropriate for anxiety and depression in eating disorder patients. 9