Is it safe to restart Wellbutrin (bupropion) in an elderly patient with a history of embolic stroke, Non-ST-Elevation Myocardial Infarction (NSTEMI), stage 3 kidney disease (Impaired renal function), osteopenia, and previous colon resection, who is currently recovering and taking mirtazapine and hydroxyzine, and has previously responded well to Wellbutrin?

Restarting Low-Dose Wellbutrin in This Elderly Patient

Yes, it is reasonable to restart low-dose Wellbutrin (bupropion) in this elderly patient, with careful dose adjustment for stage 3 kidney disease and close monitoring for drug interactions with mirtazapine, given the patient's prior positive response and current clinical stability following recovery from embolic stroke and NSTEMI.

Key Considerations for Safe Restart

Renal Dose Adjustment is Mandatory

• Bupropion and its metabolites are cleared renally and accumulate in patients with impaired renal function (GFR <90 mL/min) 1
• For stage 3 CKD, consider a reduced dose and/or reduced dosing frequency 1
• Start with 150 mg once daily (rather than standard dosing) and monitor closely for adverse reactions that could indicate high bupropion or metabolite exposures 1
• The risk of adverse reactions is greater in patients with impaired renal function, and elderly patients are more likely to have decreased renal function 1

Timing After Cardiovascular Events

• The patient is currently recovering from embolic stroke and NSTEMI, which requires careful consideration 2
• For post-stroke patients, management decisions should be patient-centered, considering comorbidities, functional status, and life expectancy 2
• Pharmacotherapy in older patients with NSTE-ACS should be individualized and dose-adjusted by weight and/or creatinine clearance 2
• Since the patient is neurologically stable and in recovery phase (not acute phase), restarting antidepressant therapy is appropriate 2

Drug Interaction Concerns with Current Medications

Mirtazapine Combination:

• Both bupropion and mirtazapine are antidepressants with complementary mechanisms 3, 4
• Mirtazapine has excellent safety and tolerability, including in patients with cardiovascular and kidney disease 4
• This combination is sometimes used clinically, but requires monitoring for serotonin syndrome risk and additive CNS effects
• The combination may actually be beneficial as mirtazapine's sedating effects can counterbalance bupropion's activating properties

Hydroxyzine Combination:

• Monitor for QTc prolongation risk, as multiple medications can have additive effects on cardiac conduction 5
• In elderly CKD patients, 29.5% are at risk of QTc-interval prolongation from medication combinations 5
• Obtain baseline and follow-up ECGs given the patient's history of NSTEMI and embolic stroke

Cardiovascular Safety Profile

• Bupropion causes fewer cardiac conductive side effects than tricyclic antidepressants 6
• It has minimal orthostatic effects compared to other antidepressants, which is advantageous in elderly patients with cardiovascular disease 6
• The patient's normal blood pressure is favorable for bupropion use 6

Osteopenia Considerations

• Bupropion does not have known direct adverse effects on bone density
• The osteopenia itself is not a contraindication to bupropion use 7
• Continue appropriate management of osteopenia separately

Post-Colon Resection Status

• No specific contraindications related to prior colon resection
• Bupropion is extensively metabolized in the liver, not significantly affected by GI anatomy changes 1

Practical Dosing Algorithm

Starting Dose:

• Begin with bupropion XL 150 mg once daily in the morning 1
• Do NOT use standard dosing (300-450 mg/day) due to stage 3 CKD 1

Monitoring Schedule:

• Week 1-2: Monitor for adverse reactions including agitation, insomnia, tremor, or seizure risk 1
• Week 2-4: Assess renal function (creatinine, GFR) to detect any accumulation 1
• Week 4: Obtain ECG to assess QTc interval given polypharmacy 5
• Ongoing: Monitor blood pressure, mood response, and side effects

Dose Titration:

• If well-tolerated after 4 weeks and therapeutic response is inadequate, may cautiously increase to 150 mg twice daily (maximum 300 mg/day total) 1
• In stage 3 CKD, avoid doses above 300 mg/day total 1
• Monitor closely for signs of drug accumulation with any dose increase

Critical Safety Warnings

Seizure Risk:

• Bupropion lowers seizure threshold, particularly at higher doses 1
• The patient's history of embolic stroke may increase baseline seizure risk
• Keep total daily dose ≤300 mg in this patient 1
• Avoid if patient develops new seizures

Avoid These Pitfalls:

• Do NOT use standard adult dosing without renal adjustment 1
• Do NOT combine with other medications that lower seizure threshold
• Do NOT abruptly discontinue if side effects occur; taper gradually
• Do NOT ignore new cardiac symptoms given NSTEMI history 2

Signs Requiring Immediate Discontinuation:

• New seizure activity 1
• Severe hypertension (though patient has normal BP baseline) 1
• Cardiac arrhythmias or chest pain 2
• Acute worsening of renal function 1
• Signs of serotonin syndrome (with mirtazapine combination)

Rationale for Proceeding

The patient's prior positive response to Wellbutrin is a strong predictor of future response 6. Bupropion has been shown to be as effective as tricyclic antidepressants with a superior side-effect profile, particularly regarding anticholinergic, orthostatic, and cardiac conductive effects 6. In elderly patients, full adult doses have been safely used historically, though renal adjustment is now recognized as essential 1, 6. The patient's current clinical stability, normal blood pressure, and recovery status make this an appropriate time to restart, provided proper dose adjustment and monitoring are implemented 2.