How to manage hypertension in a patient taking Wellbutrin (bupropion)?

Management of Hypertension in Patients Taking Wellbutrin (Bupropion)

When a patient develops hypertension on Wellbutrin, initiate standard antihypertensive therapy with an ACE inhibitor or ARB at low dose, titrate to full dose as needed, and target blood pressure <130/80 mmHg while continuing the bupropion if it remains clinically necessary. 1

Understanding Bupropion's Hypertensive Effects

Bupropion can cause elevated blood pressure and hypertension through its effects on dopaminergic and noradrenergic activity. 2 The FDA label specifically warns that treatment with bupropion can result in elevated blood pressure, requiring assessment before initiating treatment and periodic monitoring during therapy. 2 In clinical trials of bupropion extended-release for seasonal affective disorder, 2% of patients developed hypertension (compared to 0% on placebo), with mean systolic blood pressure increases of 1.3 mmHg. 2

The risk of hypertension increases substantially when bupropion is combined with MAOIs or other drugs that increase dopaminergic or noradrenergic activity. 2 Additionally, when combined with nicotine replacement therapy, the incidence of treatment-emergent hypertension rises to 6.1% compared to 2.5% with bupropion alone. 2

Initial Pharmacological Management

First-Line Therapy

Start with an ACE inhibitor or ARB at low dose, then titrate to full dose if needed. 1 This recommendation comes from the American Heart Association and aligns with standard hypertension management guidelines. 3, 4

For non-Black patients, the stepwise approach is:

• Step 1: Low-dose ACE inhibitor or ARB 3
• Step 2: Increase to full dose 3
• Step 3: Add a thiazide or thiazide-like diuretic 3

For Black patients, the preferred initial approach is:

• Step 1: Low-dose ARB combined with either a dihydropyridine calcium channel blocker or thiazide/thiazide-like diuretic 3, 1

Combination Therapy for Uncontrolled Blood Pressure

If blood pressure remains uncontrolled on dual therapy, add a calcium channel blocker to create triple therapy (RAS blocker + CCB + thiazide/thiazide-like diuretic), preferably as a single-pill combination. 3, 1 The European Society of Cardiology strongly recommends combination therapy for most patients with confirmed hypertension (BP ≥140/90 mmHg) as initial therapy, with exceptions for patients aged ≥85 years, those with symptomatic orthostatic hypotension, or moderate-to-severe frailty. 3

Managing Resistant Hypertension

If blood pressure remains uncontrolled on triple therapy, add low-dose spironolactone (25 mg daily) as the preferred fourth agent. 4, 1 This is the first-choice medication for resistant hypertension according to the European Society of Cardiology. 1 Monitor serum potassium and renal function within 1-2 weeks of initiation, particularly in patients with reduced kidney function. 4

Alternative fourth-line agents if spironolactone is not tolerated or contraindicated include:

• Eplerenone (alternative mineralocorticoid receptor antagonist) 4
• Beta-blockers such as bisoprolol 4
• Alpha-blockers such as doxazosin 3
• Amiloride, clonidine, or eplerenone 3

Note the critical caveat: While clonidine is listed as an option for resistant hypertension, it should be used cautiously as another drug in the same class (moxonidine) was associated with increased mortality in heart failure patients. 3

Blood Pressure Targets

Target blood pressure should be <130/80 mmHg for most patients, with an optimal range of 120-129/70-79 mmHg if well tolerated. 3, 4, 1 The European Society of Cardiology recommends achieving this target within 3 months, aiming for at least a 20/10 mmHg reduction. 3, 1

In cases where treatment is poorly tolerated and achieving 120-129 mmHg is not possible, target a systolic BP level that is "as low as reasonably achievable" (ALARA principle). 3

Lifestyle Modifications

Reinforce the following lifestyle measures, which are particularly important in bupropion-induced hypertension:

• Sodium restriction: Limit intake to <2.3g sodium per day (approximately 100 mEq/24-hour) 4, 1
• Exercise: At least 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity aerobic exercise weekly, with resistance training 2-3 times/week 4
• Diet: Follow a DASH-style diet rich in whole grains, fruits, vegetables, polyunsaturated fats, and dairy products 4
• Alcohol limitation: <14 units/week for men, <8 units/week for women, preferably avoiding alcohol completely 4
• Tobacco cessation: Stop all tobacco use 4
• Weight management: Aim for healthy BMI and waist circumference 4

Monitoring Strategy

Check blood pressure within 4 weeks of any medication adjustment. 4 Consider home blood pressure monitoring with a target of <135/85 mmHg. 4 Use validated automated upper arm cuff devices with appropriate cuff size. 3

Monitor serum potassium and renal function after adding spironolactone, particularly in patients with reduced kidney function. 4

When to Consider Discontinuing Bupropion

The FDA label notes that bupropion treatment was discontinued in 14% of cardiac patients due to adverse effects, including exacerbation of baseline hypertension in two patients. 5 If hypertension becomes severe or difficult to control despite appropriate antihypertensive therapy, consider whether the benefits of continuing bupropion outweigh the cardiovascular risks. 2

In the clinical trial data, two patients discontinued bupropion specifically due to hypertension. 2 However, bupropion has a relatively favorable cardiovascular profile compared to tricyclic antidepressants, with no significant conduction complications, no exacerbation of ventricular arrhythmias, and low rates of orthostatic hypotension. 5

Special Considerations

Avoid combining bupropion with MAOIs or other drugs that increase dopaminergic or noradrenergic activity, as this substantially increases hypertension risk. 2

If the patient is also using nicotine replacement therapy, monitor blood pressure more closely as the combination increases treatment-emergent hypertension risk to 6.1% compared to 2.5% with bupropion alone. 2

Maintain antihypertensive therapy lifelong, even beyond age 85 years, if well tolerated. 3 Simplify regimens with once-daily dosing and single-pill combinations to improve adherence. 3

Common Pitfalls

Nonadherence affects 10-80% of hypertensive patients 4, so simplify regimens when possible and take medications at the most convenient time of day to establish habitual patterns. 3, 4

Do not combine two RAS blockers (ACE inhibitor and ARB together) as this is not recommended. 3

Avoid nondihydropyridine calcium channel blockers (diltiazem, verapamil) in patients with heart failure due to negative inotropic effects. 3

Screen for secondary hypertension in young patients and those with resistant hypertension. 4