What is the best course of action for a patient with persistent hypertension on amlodipine (calcium channel blocker) and losartan (angiotensin II receptor antagonist) 50 mg, who is also taking Wellbutrin (bupropion)?

Management of Persistent Hypertension on Amlodipine and Losartan 50mg with Concurrent Wellbutrin Use

Add a thiazide-like diuretic (chlorthalidone 12.5-25mg daily or hydrochlorothiazide 25mg daily) as your third agent to achieve guideline-recommended triple therapy, while being aware that Wellbutrin does not significantly interfere with blood pressure control. 1

Immediate Action: Add a Diuretic

The patient has uncontrolled hypertension despite dual therapy with amlodipine and losartan 50mg. Before proceeding, you must:

• Verify medication adherence first, as non-adherence is the most common cause of apparent treatment resistance 1
• Confirm true hypertension with home blood pressure monitoring (≥135/85 mmHg) or 24-hour ambulatory monitoring (≥130/80 mmHg) to rule out white-coat hypertension 1
• Review for interfering substances: NSAIDs, decongestants, oral contraceptives, systemic corticosteroids, and herbal supplements can all elevate blood pressure 1

Optimizing Current Regimen Before Adding Third Agent

First, uptitrate losartan from 50mg to 100mg daily, as the patient is on a submaximal dose of the ARB component. 1 This represents standard dose optimization within the current two-drug regimen before adding a third agent. 1

If blood pressure remains uncontrolled after optimizing to losartan 100mg plus amlodipine (assuming amlodipine is at 5-10mg daily), then proceed to add the diuretic. 1

Third Agent Selection: Thiazide Diuretic

The guideline-recommended sequence for triple therapy is: ARB + calcium channel blocker + thiazide diuretic. 1 This combination targets three complementary mechanisms:

• Volume reduction (thiazide diuretic)
• Vasodilation (calcium channel blocker)
• Renin-angiotensin system blockade (ARB) 1

Chlorthalidone is preferred over hydrochlorothiazide due to its longer half-life (24-72 hours vs 6-12 hours) and superior cardiovascular outcomes data from the ALLHAT trial. 1 Start chlorthalidone 12.5-25mg once daily in the morning, or hydrochlorothiazide 25mg once daily if chlorthalidone is unavailable. 1

Wellbutrin (Bupropion) Considerations

Wellbutrin does not appear in major hypertension guidelines as a significant interfering medication for blood pressure control. Unlike NSAIDs, decongestants, or systemic corticosteroids, bupropion is not listed among substances that commonly elevate blood pressure or interfere with antihypertensive efficacy. 1 Therefore, continue Wellbutrin without modification while intensifying antihypertensive therapy.

Monitoring After Adding Diuretic

• Check serum potassium and creatinine 2-4 weeks after initiating diuretic therapy to detect hypokalemia or changes in renal function 1
• Monitor for hyperkalemia risk given the combination of losartan (which raises potassium) and a thiazide diuretic, though thiazides typically lower potassium 2
• Reassess blood pressure within 2-4 weeks, with the goal of achieving target BP within 3 months of treatment modification 1

Blood Pressure Targets

• Primary target: <130/80 mmHg for most patients 1, 3
• Minimum acceptable: <140/90 mmHg 1, 3
• Optimal target: 120-129 mmHg systolic if well tolerated 1

If Blood Pressure Remains Uncontrolled on Triple Therapy

If BP remains ≥140/90 mmHg despite optimized triple therapy (losartan 100mg + amlodipine 10mg + chlorthalidone 25mg), add spironolactone 25-50mg daily as the preferred fourth-line agent for resistant hypertension. 1 Spironolactone provides additional BP reductions of 20-25/10-12 mmHg when added to triple therapy. 1

Monitor potassium closely when adding spironolactone to losartan, as hyperkalemia risk is significant with dual agents affecting the renin-angiotensin-aldosterone system. 1, 2 Check serum potassium within 2-4 weeks after initiating spironolactone. 1

Critical Pitfalls to Avoid

• Do NOT add a beta-blocker as the third agent unless there are compelling indications (angina, post-MI, heart failure with reduced ejection fraction, or heart rate control needed), as beta-blockers are less effective than diuretics for stroke prevention and cardiovascular events 1, 3
• Do NOT combine losartan with an ACE inhibitor (dual RAS blockade), as this increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit 1, 2
• Do NOT use non-dihydropyridine calcium channel blockers (diltiazem or verapamil) if the patient has left ventricular dysfunction or heart failure 4
• Do NOT delay treatment intensification for stage 2 hypertension (≥160/100 mmHg), as prompt action is required to reduce cardiovascular risk 1

Essential Lifestyle Modifications

Reinforce these interventions, which provide additive BP reductions of 10-20 mmHg: 1

• Sodium restriction to <2g/day (provides 5-10 mmHg systolic reduction) 1, 3
• Weight loss if overweight (10 kg loss associated with 6.0/4.6 mmHg reduction) 1, 3
• Regular aerobic exercise (minimum 30 minutes most days, produces 4/3 mmHg reduction) 1, 3
• Alcohol limitation to ≤2 drinks/day for men or ≤1 drink/day for women 1, 3

When to Refer to Hypertension Specialist

Consider referral if: 1

• BP remains ≥160/100 mmHg despite four-drug therapy at optimal doses
• Multiple drug intolerances occur
• Concerning features suggest secondary hypertension (primary aldosteronism, renal artery stenosis, obstructive sleep apnea, pheochromocytoma)