What alternative to bupropion (Wellbutrin) can be used for a 59-year-old patient with depression, anxiety, history of smoking cessation, and an eating disorder, currently taking fluoxetine?

Alternative Antidepressant for Patient with Eating Disorder

Avoid bupropion entirely in patients with eating disorders (anorexia nervosa or bulimia nervosa) due to significantly increased seizure risk, and instead continue optimizing the current fluoxetine regimen or consider adding/switching to sertraline, venlafaxine, or mirtazapine. 1

Why Bupropion is Contraindicated

• Anorexia nervosa and bulimia nervosa are absolute contraindications for bupropion due to substantially elevated seizure risk in these populations 1, 2
• The baseline seizure risk with bupropion is approximately 1 in 1,000 (0.1%), but this increases dramatically in patients with eating disorders 3, 2
• This contraindication applies to all formulations and doses of bupropion, including its use for depression, smoking cessation, or weight management 1

Recommended Alternatives

First-Line Options (Already on Fluoxetine)

Optimize current fluoxetine therapy first:

• The patient is already taking fluoxetine, which is the only FDA-approved medication for bulimia nervosa and is weight-neutral to weight-loss promoting with short-term use 4, 1
• Fluoxetine demonstrates similar efficacy to other second-generation antidepressants for depression with accompanying anxiety symptoms 4
• Consider increasing the fluoxetine dose if not already at therapeutic levels before switching agents 4

Alternative Monotherapy Options

Sertraline:

• Shows similar antidepressive efficacy to fluoxetine for patients with depression and anxiety symptoms 4
• Weight-neutral with long-term use, making it appropriate for patients with eating disorder history 4
• May have superior efficacy for psychomotor agitation if present 4

Venlafaxine (extended-release):

• May be superior to fluoxetine for treating comorbid anxiety, showing statistically significantly better response and remission rates in one trial 4
• Considered weight-neutral 4
• Effective alternative when initial SSRI therapy fails, with no significant difference compared to switching to other agents 4

Mirtazapine:

• Has significantly faster onset of action than fluoxetine (within 1-2 weeks versus 4 weeks) 4
• Shows no difference in efficacy compared to other second-generation antidepressants after 4 weeks 4
• Important caveat: Associated with weight gain and increased appetite, which may be problematic in eating disorder patients depending on their specific presentation 2, 5
• May be beneficial if the patient has significant insomnia or needs rapid symptom improvement 4

Augmentation Strategy (If Fluoxetine Partially Effective)

Continue fluoxetine and add an alternative agent:

• If fluoxetine has provided partial benefit after 6-8 weeks, augmentation may be preferable to switching to avoid discontinuation symptoms 4
• Cannot use bupropion for augmentation due to eating disorder contraindication 1
• Consider augmenting with mirtazapine if insomnia is prominent, though monitor for weight changes 4

Addressing Smoking Cessation History

Since the patient has a history of smoking cessation needs:

• Nicotine replacement therapy (NRT) alone is the safest option for smoking cessation in patients with eating disorders, as bupropion cannot be used 3
• Varenicline could be considered as an alternative smoking cessation aid (not contraindicated in eating disorders) 6
• The combination of an SSRI (fluoxetine or sertraline) with NRT addresses both depression and smoking cessation without the seizure risk of bupropion 3

Critical Monitoring Parameters

Before initiating or changing therapy:

• Confirm the specific type and current status of the eating disorder (active versus history) 1
• Screen for suicidal ideation, particularly given age 59 and multiple psychiatric comorbidities 3
• Assess current weight, nutritional status, and electrolyte balance 1

Ongoing monitoring:

• Reassess response after 6-8 weeks at therapeutic doses before considering further medication changes 4, 3
• Monitor for worsening eating disorder symptoms, as some antidepressants may affect appetite and weight 4, 1
• Watch for neuropsychiatric adverse effects including increased anxiety or agitation 3

Treatment Algorithm

1. Optimize current fluoxetine to maximum therapeutic dose if not already achieved 4
2. If inadequate response after 6-8 weeks: Switch to sertraline or venlafaxine XR based on symptom profile (sertraline for agitation, venlafaxine for prominent anxiety) 4
3. If partial response: Consider augmentation with mirtazapine if rapid improvement or sleep benefits needed, while monitoring weight 4, 2
4. For smoking cessation needs: Use NRT or varenicline, never bupropion 3, 6

Common Pitfall to Avoid

Never prescribe bupropion in any form (Wellbutrin, Zyban, Contrave) to patients with current or past eating disorders, regardless of how well-controlled the eating disorder appears or how beneficial bupropion might seem for other indications like smoking cessation or avoiding sexual side effects 1, 2. The seizure risk is unacceptably elevated and this is an absolute contraindication 3, 1.