What adjustments should be made to the patient's current medication regimen to optimize treatment for mood and anxiety?

Medication Optimization for Mood and Anxiety

The current regimen requires increasing the bupropion dose to the therapeutic target of 450 mg daily (combining the existing 150 mg and 300 mg tablets), as the patient is currently underdosed for major depressive disorder, and this should be prioritized over adjusting other medications since depression treatment takes precedence when both mood and anxiety symptoms coexist. 1

Primary Recommendation: Optimize Antidepressant Dosing

Increase bupropion XL to 450 mg daily by continuing both the 150 mg and 300 mg tablets together each morning. 2, 3, 4 The current total dose of 450 mg daily is already being taken but needs clarification—if the patient is alternating or only taking one tablet, both should be taken together. The maximum FDA-approved dose for bupropion XL is 450 mg daily, and doses of 300-600 mg/day have demonstrated efficacy in clinical trials. 2, 5, 6

• Bupropion has proven efficacy for major depressive disorder with the advantage of less somnolence and sexual dysfunction compared to SSRIs. 3, 4
• The dose should be increased gradually to minimize seizure risk, which is dose-related. 2
• Monitor for 4-8 weeks after dose optimization before making further adjustments, as antidepressant effects take 2-4 weeks to manifest. 1

Address Anxiety Management Hierarchy

When depression and anxiety coexist, treat depression first, as recommended by multiple guidelines. 1 The current regimen includes:

• Buspirone 10 mg TID PRN: This should be changed to scheduled dosing (not PRN) for generalized anxiety, as buspirone requires consistent dosing to achieve therapeutic effect. 1
• Clonidine 0.1 mg BID: Appropriate for anxiety and autonomic hyperarousal, particularly in the context of opioid use disorder (patient is on Brixadi). 1
• Prazosin 2 mg QHS: Appropriate for nightmares/PTSD symptoms if present. 1

Medication Interactions and Safety Concerns

Critical safety consideration: The combination of bupropion with gabapentin requires monitoring, as gabapentin lowers seizure threshold and bupropion carries dose-dependent seizure risk. 2 However, gabapentin 600 mg TID (1800 mg daily) is reasonable for neuropathic pain or anxiety if clinically indicated. 1

• Avoid adding SSRIs to this regimen without careful consideration, as the patient is already on bupropion. While combination therapy can be effective, higher doses of SSRIs or bupropion are indicated only with significant psychiatric comorbidity. 1
• Monitor blood pressure regularly, as bupropion, clonidine (paradoxically during initiation), and atomoxetine can all affect blood pressure. 2

Specific Adjustments to Consider

Buspirone optimization: Change from "PRN" to scheduled 10 mg TID (30 mg daily). 1 Buspirone is not effective as PRN medication and requires consistent dosing for 2-4 weeks to achieve anxiolytic effects.

Gabapentin consideration: The current dose of 1800 mg daily is appropriate for chronic pain or anxiety. 1 However, if being used primarily for anxiety in the context of adequate depression treatment, consider whether this is still necessary after optimizing bupropion, as neuromodulators like gabapentin should be reserved for patients with significant anxiety/depression or intractable symptoms. 1

Monitoring Plan

Assess treatment response at 4 and 8 weeks using standardized instruments (PHQ-9 for depression, GAD-7 for anxiety). 1

• If symptoms are stable or worsening after 8 weeks despite good adherence, adjust the regimen by adding an SSRI (sertraline preferred for safety profile) or switching strategies. 1
• Monitor for suicidal ideation, particularly in the first weeks after dose changes, as bupropion carries a black box warning for increased suicidal thinking. 2
• Watch for seizure risk factors: avoid alcohol, ensure adequate sleep, and monitor for electrolyte abnormalities. 2

Common Pitfalls to Avoid

• Do not use buspirone PRN—it requires scheduled dosing for efficacy. 1
• Do not exceed bupropion 450 mg daily—seizure risk increases significantly above this dose. 2
• Do not abruptly discontinue clonidine—taper if discontinuation is needed to avoid rebound hypertension. 1
• Avoid combining multiple serotonergic agents without careful monitoring for serotonin syndrome, though bupropion has minimal serotonergic activity. 1, 2