What alternative treatment options are available for a patient with significant anxiety who had no relief from Lexapro (escitalopram) and was inappropriately switched to Wellbutrin (bupropion)?

Alternative Treatment for Anxiety After Lexapro Failure

Switch immediately to another SSRI (sertraline 25-50 mg daily or paroxetine 10 mg daily) or an SNRI (venlafaxine XR 75 mg daily), as bupropion lacks efficacy for anxiety and may worsen symptoms. 1, 2

Why Wellbutrin Was Wrong

• Bupropion is contraindicated for anxiety disorders because it is activating and can exacerbate anxiety symptoms, agitation, and nervousness 1, 3
• Bupropion should specifically be avoided in agitated patients and is only appropriate when treating depression with prominent apathy or low energy 1
• The evidence-based first-line treatments for anxiety are SSRIs and SNRIs, not norepinephrine-dopamine reuptake inhibitors like bupropion 1, 2

Recommended Next Steps

First-Line Medication Options

Switch to a different SSRI:

• Sertraline: Start 25-50 mg daily, titrate by 25-50 mg every 1-2 weeks, target 100-200 mg/day 3, 2
• Paroxetine: Start 10 mg daily, titrate to 40 mg/day (though higher discontinuation symptoms than sertraline) 1
• Fluvoxamine: Start 50 mg twice daily, titrate to 150 mg twice daily 1

Alternative: Switch to an SNRI:

• Venlafaxine XR: Start 75 mg daily, titrate to 75-225 mg/day; requires blood pressure monitoring 1, 2
• Duloxetine: Start 30 mg daily for one week, then 60-120 mg/day; beneficial if comorbid pain 2

Critical Treatment Principles

Timeline expectations:

• Statistically significant improvement may begin by week 2 3, 2
• Clinically significant improvement expected by week 6 3, 2
• Maximal therapeutic benefit requires 12+ weeks at therapeutic dose 3, 2
• Do not declare treatment failure before completing a full 12-week trial at adequate dosing 3

Common pitfalls to avoid:

• Escalating doses too quickly—allow 1-2 weeks between increases to assess tolerability 2
• Abandoning treatment prematurely before week 12 3, 2
• Using benzodiazepines for chronic treatment (reserve only for short-term use due to dependence risk) 3, 2, 4

Combination with Psychotherapy

Cognitive Behavioral Therapy (CBT) should be added or initiated:

• Combining medication with CBT provides superior outcomes compared to either treatment alone 3, 2, 4
• Individual CBT is prioritized over group therapy for cost-effectiveness and clinical outcomes 2
• CBT should include 12-20 structured sessions with cognitive restructuring, relaxation techniques, and exposure when appropriate 2

Monitoring and Side Effects

Expected side effects in first few weeks (typically resolve with continued treatment):

• Nausea, headache, insomnia or somnolence, dizziness, sexual dysfunction, dry mouth, diarrhea 3, 2
• Start with lower doses to minimize initial anxiety/agitation that can occur with SSRIs 3, 2

Critical monitoring:

• Monitor closely for suicidal thinking and behavior, especially in first months and after dose adjustments (pooled risk 1% vs 0.2% placebo) 3, 2
• For venlafaxine: monitor blood pressure due to risk of sustained hypertension 2

If Second SSRI/SNRI Also Fails

After 8-12 weeks at therapeutic doses with inadequate response:

• Switch to a different class (if tried SSRI, switch to SNRI or vice versa) 3, 2
• Consider pregabalin or gabapentin as second-line options, particularly if comorbid pain 2
• Ensure CBT has been adequately implemented 3, 2

Adjunctive Non-Pharmacological Strategies

• Regular cardiovascular exercise provides moderate to large reduction in anxiety symptoms 2
• Breathing techniques, progressive muscle relaxation, grounding strategies, mindfulness 2
• Psychoeducation for family members about anxiety symptoms and treatment 2