In a 54-year-old man with hyperlipidemia who is taking bupropion 150 mg daily and fluoxetine 60 mg daily and now has anxiety, should I taper the bupropion or can I stop it abruptly and start aripiprazole (Abilify) 2 mg?

Taper Bupropion Gradually Before Stopping—Do Not Discontinue Abruptly

You should taper the bupropion gradually over 1-2 weeks before discontinuing it, rather than stopping it abruptly. While bupropion does not have the same severe withdrawal risks as benzodiazepines or SSRIs, abrupt discontinuation can still cause rebound anxiety, irritability, and mood destabilization 1. The FDA label for bupropion emphasizes monitoring for "anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness" when discontinuing antidepressants 1.

Why Tapering Matters

Although bupropion withdrawal is generally less severe than SSRI discontinuation syndrome, stopping it suddenly in a patient already experiencing anxiety could worsen their symptoms. The general principle from antidepressant management is that gradual tapering minimizes withdrawal symptoms and allows you to distinguish true relapse from discontinuation effects 2.

A practical taper schedule: Reduce the dose by 25-50% every 1-2 weeks. For your patient on 150 mg daily, this could mean:

• Week 1-2: 75 mg daily (or 150 mg every other day)
• Week 3: Discontinue

This approach is consistent with standard tapering practices, though bupropion typically requires less aggressive tapering than SSRIs 2.

Addressing the Anxiety

The key question is whether bupropion is causing the anxiety or whether the patient has developed anxiety despite treatment. Recent evidence suggests bupropion can have mixed effects on anxiety:

• Bupropion may actually improve anxiety in patients with depression and comorbid anxiety symptoms, showing comparable efficacy to SSRIs in mild-to-moderate anxiety 3, 4
• However, its stimulating properties (norepinephrine and dopamine reuptake inhibition) can provoke or worsen anxiety, particularly at higher doses or in susceptible individuals 4

Before discontinuing bupropion entirely, consider:

1. Is the anxiety new or worsening since starting bupropion? If so, it may be medication-induced
2. Is the patient's depression adequately treated? Undertreated depression commonly presents with anxiety
3. The patient is already on fluoxetine 60 mg—a high dose that should provide anxiolytic effects. The combination of fluoxetine + bupropion is actually evidence-based for treatment-resistant depression

Regarding Aripiprazole (Abilify)

Adding aripiprazole 2 mg is a reasonable option, but should be considered as augmentation rather than replacement. The evidence supports this approach:

• Aripiprazole has demonstrated efficacy as adjunctive treatment for major depressive disorder when added to antidepressants 5, 6
• In one case series, low-dose aripiprazole (2.5-10 mg) produced rapid improvement when added to bupropion in treatment-resistant depression 5
• Aripiprazole may have anxiolytic properties through its 5-HT1A partial agonism and 5-HT2A antagonism 6

However, the FDA label warns that aripiprazole can cause akathisia, restlessness, and anxiety as side effects 7. Starting at 2 mg is appropriately conservative, but monitor closely for these symptoms.

Recommended Approach

Step 1: Optimize the current regimen first

• The fluoxetine 60 mg + bupropion 150 mg combination is evidence-based for depression
• Before discontinuing bupropion, ensure adequate trial duration (6-8 weeks at current doses)
• Consider whether anxiety is a withdrawal effect from recent dose changes

Step 2: If bupropion discontinuation is necessary

• Taper over 1-2 weeks as outlined above
• Monitor closely for worsening depression or anxiety during taper
• The fluoxetine will provide some protection against mood destabilization

Step 3: Consider aripiprazole augmentation

• Can be started during the bupropion taper or after discontinuation
• Begin at 2 mg daily and titrate based on response
• Monitor for akathisia, restlessness, and metabolic effects
• Assess response after 1-2 weeks; most patients in case reports showed rapid improvement 5

Critical Caveats

• Do not abruptly stop bupropion while simultaneously starting aripiprazole—this creates two medication changes at once and makes it impossible to determine which is causing any new symptoms
• The anxiety may worsen temporarily during bupropion taper due to withdrawal effects, even with gradual reduction
• Aripiprazole carries metabolic risks (weight gain, glucose dysregulation) that require monitoring, particularly relevant given the patient's hyperlipidemia 7
• Consider whether the anxiety warrants specific treatment beyond medication adjustment—cognitive behavioral therapy has strong evidence for anxiety disorders 8

If anxiety is severe and impairing function, you could start aripiprazole 2 mg while maintaining the current regimen, then taper bupropion once anxiety is stabilized. This sequential approach provides better symptom control and clearer attribution of effects.