What is the best course of action for a patient experiencing severe anxiety after taking Wellbutrin (bupropion) for low motivation, who is also taking Prozac (fluoxetine)?

Management of Anxiety Induced by Bupropion in a Patient on Fluoxetine

Discontinue bupropion and consider switching to an alternative medication with a more favorable anxiety profile such as mirtazapine or trazodone. 1

Assessment of Current Situation

The patient is experiencing severe anxiety after starting Wellbutrin (bupropion), while also taking Prozac (fluoxetine). This reaction is concerning because:

• The patient originally had low anxiety levels (2/21) with primary complaints of low motivation and inability to get out of bed
• Bupropion is known to cause anxiety as a common side effect 2, 3
• The combination of bupropion and fluoxetine (Prozac) increases the risk of serotonin syndrome 4

Immediate Management

1. Discontinue bupropion immediately

   • Anxiety is a documented adverse effect of bupropion 2, 3
   • Continuing the medication may worsen anxiety symptoms

2. Monitor for serotonin syndrome

   • Watch for symptoms including confusion, agitation, tremors, hyperreflexia, hypertension, tachycardia, diaphoresis 2
   • The combination of bupropion and SSRIs like fluoxetine can trigger serotonin syndrome 4

Alternative Medication Options

First-line alternatives:

1. Mirtazapine

   • Starting dose: 7.5mg at bedtime, maximum 30mg at bedtime 1
   • Benefits: Promotes sleep, appetite, and weight gain while treating depression
   • Less likely to cause anxiety compared to bupropion 1

2. Trazodone

   • Starting dose: 25-50mg at bedtime, therapeutic dose 50-100mg 1
   • Benefits: Sedative properties can help with sleep while addressing depression
   • Less activating than bupropion, reducing anxiety risk 1

Second-line alternatives:

1. Switch to a different SSRI

   • Consider sertraline or citalopram if fluoxetine is not adequately addressing depression
   • Moderate-quality evidence shows no difference in response when switching from one SGA to another 2

2. Duloxetine (SNRI)

   • Starting dose: 30mg daily, increasing to 60mg after 1 week 1
   • Provides both serotonergic and noradrenergic effects
   • May help with motivation while causing less anxiety than bupropion 1

Important Considerations

• Bupropion's anxiety effect is controversial: Recent research suggests that when properly matched for other variables, bupropion may not increase anxiety more than SSRIs over a 12-week period 5. However, individual responses vary significantly.

• Dose-related effects: If motivation remains a significant concern and bupropion is reconsidered later, use lower doses as adverse effects may be dose-related 6

• Risk of serotonin syndrome: The combination of bupropion and fluoxetine increases risk of serotonin syndrome, particularly at higher doses 4

• Discontinuation approach: Taper bupropion gradually if it has been used for more than a few days to minimize withdrawal effects 1

Follow-up Plan

• Schedule follow-up within 1-2 weeks to assess response to medication changes
• Evaluate both anxiety symptoms and original complaints of low motivation
• Allow 4-6 weeks at therapeutic doses to evaluate efficacy of any new medication 1
• Consider psychotherapy (CBT) as an adjunct to medication management, as evidence shows it can be as effective as medication for some patients 2

Pitfalls to Avoid

• Misinterpreting worsening anxiety as depression: Early manifestations of medication adverse effects can be misinterpreted as worsening of the underlying condition 4
• Combining multiple serotonergic medications: Adding more serotonergic agents can increase risk of serotonin syndrome 2
• Inadequate trial duration: Allow sufficient time (8-12 weeks) at therapeutic doses before concluding a medication is ineffective 1
• Abrupt discontinuation: Gradually taper medications to minimize withdrawal effects 1