What can be added to bupropion (Wellbutrin SR) 150MG twice daily (bid) and aspirin 81mg for treatment of Major Depressive Disorder (MDD)?

Augmentation Strategy for Bupropion SR in Major Depressive Disorder

If bupropion SR 150mg BID is not achieving adequate response for MDD, add an SSRI (such as citalopram, sertraline, or escitalopram) or switch to cognitive behavioral therapy (CBT), as these strategies show equivalent efficacy with moderate-quality evidence. 1

Evidence-Based Augmentation Options

First-Line Augmentation: Add an SSRI

• Adding an SSRI to bupropion is supported by moderate-quality evidence from the STAR*D trial, which demonstrated similar efficacy when augmenting citalopram with bupropion compared to augmenting with buspirone or cognitive therapy 1

• Bupropion augmentation had significantly fewer discontinuations due to adverse events (12.5%) compared to buspirone augmentation (20.6%; P < 0.001), making it a better-tolerated option 1

• The combination leverages bupropion's dopamine-norepinephrine reuptake inhibition with SSRI's serotonergic effects, providing complementary mechanisms of action 2, 3

Alternative: Switch to Cognitive Behavioral Therapy

• Low-quality evidence from STAR*D showed no difference in response or remission when switching from bupropion to cognitive therapy versus switching to another antidepressant (sertraline or venlafaxine) 1

• CBT had numerically lower discontinuation rates due to adverse events (9.2%) compared to medication augmentation (18.8%), though this difference was not statistically significant (P = 0.086) 1

Other Switching Strategies

• Moderate-quality evidence shows no difference in efficacy when switching from bupropion to other second-generation antidepressants including sertraline, venlafaxine, escitalopram, or duloxetine 1

• Switching strategies are equivalent to augmentation strategies in terms of efficacy and safety based on trials comparing these approaches 1

Clinical Decision Algorithm

Step 1: Assess Current Response

• If partial response after adequate trial (typically 8-12 weeks at therapeutic dose): Consider augmentation
• If no response or intolerable side effects: Consider switching

Step 2: Choose Augmentation Strategy

• Preferred: Add SSRI (citalopram 20-40mg daily, sertraline 50-200mg daily, or escitalopram 10-20mg daily) 1
• Alternative: Add CBT if patient prefers non-pharmacologic approach or has concerns about polypharmacy 1

Step 3: Monitor for Adverse Events

• Bupropion combined with SSRIs is generally well-tolerated with lower rates of sexual dysfunction compared to SSRI monotherapy 4, 5
• Monitor for serotonin syndrome when combining antidepressants, though risk is low with this combination

Important Caveats

Aspirin 81mg Consideration

• The aspirin 81mg mentioned in your regimen is likely for cardiovascular prophylaxis rather than depression treatment
• There is no evidence in the provided guidelines supporting aspirin as an augmentation strategy for MDD
• Continue aspirin for its indicated cardiovascular purpose, but do not rely on it for antidepressant effects

Dosing Optimization

• Ensure bupropion SR 150mg BID (total 300mg/day) is at adequate dose before augmenting, as this is the standard therapeutic dose 4, 5
• Maximum recommended dose is 400mg/day (200mg BID) if needed, though seizure risk increases above 300mg/day 6

Evidence Limitations

• Most augmentation evidence is of low to moderate quality, with the STAR*D trial providing the strongest data 1
• The absence of statistically significant differences between strategies does not prove equivalence, but rather suggests similar effectiveness in available trials 1