What are the next steps for a 55-year-old male with depression on 300mg of bupropion (Wellbutrin) who did not tolerate an increase to 450mg?

Augmentation Strategies for Depression in a 55-Year-Old Male on Bupropion 300mg

For a 55-year-old male with depression who did not tolerate an increase from 300mg to 450mg of bupropion, the most effective next step is to augment the current 300mg bupropion dose with an SSRI or other complementary antidepressant rather than attempting further dose increases.

Assessment of Current Treatment

Bupropion is a norepinephrine and dopamine reuptake inhibitor that has several advantages in depression treatment:

• Maximum recommended dose is 300mg daily for extended-release formulations 1
• Attempting to exceed 450mg daily significantly increases seizure risk 1
• Has activating properties that can increase energy levels 2
• Associated with lower rates of sexual dysfunction compared to SSRIs 2
• May cause mild weight loss rather than weight gain 2

Augmentation Strategy Algorithm

Step 1: Evaluate Adequacy of Current Treatment

• Determine if patient has been on 300mg for at least 6-8 weeks
• Assess for partial response vs. non-response
• If partial response, augmentation is preferred over switching

Step 2: Select Appropriate Augmentation Based on Symptom Profile

First-Line Options:

1. SSRI Augmentation (e.g., sertraline, escitalopram)

   • Provides complementary neurotransmitter effects
   • Evidence shows no difference in response or remission rates between switching to another antidepressant versus augmentation 3
   • Particularly useful if residual symptoms include anxiety or obsessive features

2. Buspirone Augmentation

   • Low-quality evidence showed no difference in response or remission for augmentation of antidepressant treatment with bupropion compared with augmentation with buspirone 3
   • May be preferred if anxiety is a prominent feature

Second-Line Options:

1. Cognitive Behavioral Therapy (CBT)

   • Low-quality evidence showed no difference in response, remission, or depression severity for augmentation with another antidepressant versus augmentation with cognitive therapy 3
   • Non-pharmacological option if patient prefers to avoid additional medications

2. Aripiprazole or Other Atypical Antipsychotic

   • Consider for more treatment-resistant cases
   • Low-quality evidence reported higher remission rates for augmentation with aripiprazole than bupropion (55.4% vs. 34.0%) 3

Step 3: Monitor for Response and Side Effects

• Evaluate response after 4-6 weeks of augmentation therapy
• Monitor for potential drug interactions, particularly with SSRIs that inhibit CYP2D6 1
• Watch for emergence of serotonin syndrome if combining with serotonergic agents

Special Considerations

Cautions with Bupropion

• Contraindicated in patients with seizure disorders, eating disorders, or abrupt discontinuation of alcohol or sedatives 1
• Can increase blood pressure; monitor regularly 1
• Risk of neuropsychiatric adverse events including agitation, anxiety, and mania 1
• Maximum dose should not exceed 300mg daily in extended-release formulation 1

Potential Pitfalls to Avoid

1. Exceeding maximum recommended dose

   • Doses >450mg/day significantly increase seizure risk 1, 4
   • Doses >450mg/day may also increase risk of manic switch in patients with bipolar disorder 4

2. Ignoring partial response

   • Open-label studies show that 54% of patients with inadequate response to SSRIs benefited from bupropion augmentation 5
   • Augmentation may be more effective than switching for partial responders

3. Overlooking medical comorbidities

   • Greater medical burden predicts slower recovery with augmentation strategies 6
   • Consider medical conditions that may contraindicate certain augmentation strategies

Conclusion for This Patient

For this 55-year-old male who did not tolerate an increase to 450mg of bupropion:

1. Maintain the 300mg daily dose of bupropion
2. Add an SSRI (such as escitalopram 10mg daily) as first-line augmentation
3. If anxiety is prominent, consider buspirone augmentation instead
4. If the patient prefers non-pharmacological approaches, add cognitive behavioral therapy
5. Monitor closely for side effects and reassess in 4-6 weeks

This approach maximizes the benefits of the well-tolerated 300mg bupropion dose while adding complementary mechanisms to address remaining depressive symptoms.