Treatment Approach for GAD and MDD with Buspirone Intolerance
Continue Zoloft 100mg and augment with bupropion rather than attempting buspirone rechallenge, as bupropion demonstrates superior tolerability with lower discontinuation rates due to adverse events (12.5% vs 20.6%, P<0.001) and greater reduction in depression severity compared to buspirone augmentation. 1
Rationale for Bupropion Augmentation
The American College of Physicians guidelines show that when augmenting SSRI therapy (like your patient's sertraline/Zoloft), bupropion produces significantly fewer treatment discontinuations due to adverse events compared to buspirone (12.5% vs 20.6%, P<0.001) 1
Bupropion augmentation decreases depression severity more effectively than buspirone augmentation, though both show similar response and remission rates 1
Since this patient already experienced adverse effects from buspirone, rechallenge carries high risk of recurrent intolerance and treatment failure 1
Dosing Strategy
Start bupropion SR at 150mg once daily in the morning, then increase to 150mg twice daily after one week if tolerated 1
Continue Zoloft 100mg unchanged during augmentation 1
Allow 2-4 weeks to assess full therapeutic response to the combination 2
Critical Safety Monitoring
Monitor for serotonin syndrome risk in the first 24-48 hours after initiating bupropion augmentation, as the FDA label warns that combining sertraline with other serotonergic agents increases this risk 3
Serotonin syndrome symptoms include mental status changes (agitation, confusion), autonomic instability (tachycardia, labile blood pressure, hyperthermia), neuromuscular symptoms (tremor, rigidity, hyperreflexia), and GI symptoms 3
Screen for seizure history or risk factors, as bupropion carries a 0.1% seizure risk 4
Alternative Considerations if Augmentation Fails
Switching from sertraline to another SSRI (escitalopram) or SNRI (venlafaxine, duloxetine) shows equivalent efficacy to augmentation strategies 1
Adding cognitive behavioral therapy to ongoing sertraline shows similar efficacy to medication augmentation strategies 1
For GAD specifically, SSRIs like sertraline remain first-line treatment per consensus guidelines 5, 6, 7
Common Pitfalls to Avoid
Do not rechallenge with buspirone given prior intolerance—the moderate-quality evidence shows significantly higher discontinuation rates with buspirone 1
Do not discontinue sertraline prematurely, as switching strategies show no superiority over augmentation approaches 1
Do not combine with MAOIs, linezolid, or intravenous methylene blue due to absolute contraindication for serotonin syndrome 3