For a patient with Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD) on escitalopram (Lexapro) 20mg, is ordering bupropion (Wellbutrin) 75mg with instructions to take half a tablet a suitable starting dose?

Bupropion 75mg with Half-Tablet Dosing: Not Recommended

No, ordering bupropion 75mg with instructions to take half a tablet (37.5mg) is not an appropriate starting dose for augmenting escitalopram in a patient with MDD and GAD. While 37.5mg is used as a starting dose in specific populations (elderly patients), the standard approach for augmentation therapy requires higher initial dosing to achieve therapeutic effect 1.

Why This Dosing Strategy Is Problematic

Standard Augmentation Dosing

• The recommended starting dose for bupropion SR when augmenting an SSRI is 150mg once daily for 3 days, then increasing to 150mg twice daily (300mg total daily dose) 1.
• The FDA-approved dosing for MDD established efficacy at 300-450mg daily, with 78% of patients in clinical trials treated with doses of 300-450mg per day 2.
• Bupropion demonstrates efficacy primarily at therapeutic doses of 300mg/day or higher 1.

The 37.5mg Dose Is Reserved for Special Populations

• The 37.5mg starting dose (which would require splitting a 75mg tablet) is specifically recommended only for older adults to minimize adverse reactions, with gradual titration by 37.5mg every 3 days 1.
• This conservative approach is not standard for general adult populations with MDD 1.

Correct Prescribing Approach for This Patient

Initial Prescription

• Order bupropion SR 150mg tablets, with instructions to take one tablet once daily in the morning for 3 days 1.
• After 3 days, increase to 150mg twice daily (one tablet in the morning, one tablet before 3 PM) 1.
• The target therapeutic dose is 300mg daily (150mg twice daily) 1.

Critical Timing Considerations

• The second dose must be administered before 3 PM to minimize insomnia risk, as bupropion has activating properties 1.
• Morning dosing leverages bupropion's activating effects, which may benefit patients with low energy or apathy 1.

Evidence Supporting Augmentation Strategy

Efficacy Data

• The STAR*D trial demonstrated that augmenting citalopram (an SSRI similar to escitalopram) with bupropion SR achieved similar efficacy to buspirone augmentation, but with significantly lower discontinuation rates due to adverse events (12.5% vs 20.6%, P < 0.001) 3.
• Augmenting SSRIs with bupropion decreases depression severity more effectively than buspirone augmentation 1.
• The combination of escitalopram and bupropion-SR achieved 62% response rates and 50% remission rates in an open-label study, significantly higher than typical SSRI monotherapy 4.

Comorbid Anxiety Considerations

• The presence of comorbid GAD does not significantly affect the comparative efficacy of bupropion based on STAR*D trial analyses 1.
• A pilot controlled trial demonstrated that bupropion XL (150-300mg/day) showed comparable anxiolytic efficacy to escitalopram in patients with GAD 5.
• This suggests bupropion augmentation is appropriate even with comorbid anxiety 5.

Pre-Treatment Safety Screening Required

Absolute Contraindications to Verify

• Seizure history or any condition predisposing to seizures (bupropion lowers seizure threshold) 1.
• Current or recent MAOI use (within 14 days) 1.
• Eating disorders (bulimia or anorexia nervosa) due to increased seizure risk 1.
• Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs 1.
• Uncontrolled hypertension 1.

Baseline Monitoring Parameters

• Blood pressure and heart rate (bupropion can elevate both) 1.
• Mental status examination focusing on suicidal ideation, particularly critical in patients under 24 years old 1.

Monitoring Timeline

Early Phase (Weeks 1-2)

• Monitor for neuropsychiatric adverse effects including agitation, restlessness, and behavioral changes 1.
• Assess for worsening depression or suicidal ideation (highest risk in first 1-2 months) 1.
• Monitor blood pressure and heart rate 1.

Efficacy Assessment (Weeks 6-8)

• Assess for adequate response at 6-8 weeks before considering treatment modification 1.
• If no adequate response occurs by 6-8 weeks at therapeutic doses, modify the treatment approach 1.

Maximum Dosing Limits

• The maximum dose for bupropion SR is 400mg per day (200mg twice daily) 1.
• Do not exceed 450mg/day total to maintain seizure risk at 0.1% 1.

Common Pitfalls to Avoid

• Do not prescribe sub-therapeutic doses (like 37.5mg) for general adult populations, as this delays achieving therapeutic effect and may lead to premature treatment discontinuation due to perceived inefficacy 1.
• Do not administer the second dose after 3 PM, as this significantly increases insomnia risk 1.
• Do not discontinue treatment prematurely before 6-8 weeks unless significant adverse effects occur 1.