What are good options for augmenting Lexapro (escitalopram) in patients with inadequate response?

Effective Options for Lexapro (Escitalopram) Augmentation

Bupropion (Wellbutrin SR) is the preferred augmentation strategy for patients with inadequate response to escitalopram due to its superior efficacy in reducing depression severity and lower discontinuation rates due to adverse events. 1

First-Line Augmentation Options

Bupropion Augmentation

• Most evidence-supported option with demonstrated efficacy in clinical trials

• Dosing recommendations:

  • Start at 150 mg daily
  • Increase by 100 mg every 5-7 days as tolerated
  • Target dose: 300-400 mg daily 1
  • Mean effective dose in clinical trials: 327-329 mg/day 2

• Benefits:

  • Greater reduction in depressive symptoms compared to buspirone (25.3% vs 17.1%) 3
  • Lower discontinuation rates due to side effects (12.5% vs 20.6% with buspirone) 3
  • Response rates of 54% when added to SSRIs 4
  • Particularly helpful for patients with fatigue, low energy, or SSRI-induced sexual dysfunction 5

Second-Line Augmentation Options

Buspirone

• Can be effective but with some limitations compared to bupropion:
  • Similar remission rates to bupropion (30.1% vs 29.7%) 3
  • Higher discontinuation rates due to side effects (20.6%) 3
  • Dosing: Typically 15-60 mg/day in divided doses

Cognitive Therapy Augmentation

• Non-pharmacological alternative with similar efficacy to medication augmentation
• Low-quality evidence showed no difference in response or remission compared to medication augmentation 5
• Particularly beneficial for patients concerned about additional medication side effects 1

Monitoring and Follow-up

1. Begin monitoring 1-2 weeks after initiating augmentation therapy 5

2. Assess for:

   • Treatment response (reduction in depressive symptoms)
   • Adverse effects (headache, insomnia, agitation with bupropion)
   • Vital signs (particularly blood pressure with bupropion)
   • Suicidal thoughts (especially in first 1-2 months) 5

3. If inadequate response after 6-8 weeks of optimized augmentation, consider:

   • Switching to a different augmentation strategy
   • Switching antidepressant class entirely 5

Clinical Considerations and Caveats

• Bupropion has a lower risk of sexual dysfunction compared to other antidepressants 5

• Avoid bupropion in patients with seizure disorders, eating disorders, or recent head trauma

• Common pitfalls in augmentation therapy:

  • Inadequate dosing of the augmenting agent
  • Premature discontinuation before adequate trial period (minimum 6-8 weeks)
  • Failure to monitor for drug interactions 1

• Escitalopram has a favorable pharmacokinetic profile with low drug interaction potential 6, making it generally safe to combine with bupropion

• Combination of escitalopram (mean dose 18 mg/day) and bupropion-SR (mean dose 327 mg/day) has shown 50% remission rates in open-label studies 2

The American College of Physicians strongly recommends modifying treatment if patients do not have adequate response to initial therapy within 6-8 weeks 5, and bupropion augmentation represents an evidence-based approach with favorable efficacy and tolerability profiles compared to alternatives.