What to do if a patient's blood pressure is severely elevated after starting Wellbutrin (bupropion)?

Immediate Discontinuation of Wellbutrin and Blood Pressure Management

Discontinue bupropion (Wellbutrin) immediately if a patient develops severely elevated blood pressure, as the FDA label explicitly warns that bupropion can cause hypertension that may be severe, and treatment should be stopped in cases of significant blood pressure elevation. 1

Immediate Actions Required

Discontinue the Offending Agent

• Stop bupropion immediately—the FDA label states that "treatment with bupropion hydrochloride extended-release tablets (XL) can result in elevated blood pressure and hypertension" and this is a recognized adverse effect requiring medication cessation 1
• Do not restart bupropion if severe hypertension developed, as the risk of recurrence is high 1

Assess Severity and Need for Acute Management

• Determine if this represents a hypertensive emergency (severely elevated BP with acute end-organ damage to cardiovascular, cerebrovascular, or renal systems) versus hypertensive urgency (severely elevated BP without end-organ damage) 2
• If hypertensive emergency is present, initiate immediate parenteral antihypertensive therapy to prevent permanent organ damage 2
• If hypertensive urgency without end-organ damage, blood pressure can be controlled with oral medications over 24-48 hours 2

Blood Pressure Monitoring Protocol

Initial Assessment

• Measure blood pressure using proper technique with a validated device and appropriate cuff size 3
• Confirm elevated readings are not due to measurement error or white-coat effect 3
• Assess for signs of end-organ damage (chest pain, dyspnea, neurological symptoms, visual changes, acute kidney injury) 2

Ongoing Monitoring After Discontinuation

• Monitor blood pressure closely for 1-2 weeks after stopping bupropion, as the hypertensive effect should resolve once the drug is eliminated 1, 4
• The rise in blood pressure seen with bupropion is typically reversible upon discontinuation 4

Antihypertensive Treatment if Needed

If Blood Pressure Remains Elevated After Bupropion Discontinuation

• Initiate standard antihypertensive therapy following guideline-recommended algorithms 5
• For most patients, start with either an ACE inhibitor/ARB or a calcium channel blocker as first-line therapy 6
• Target blood pressure <140/90 mmHg minimum, ideally <130/80 mmHg for higher-risk patients 5, 6

Stepwise Approach if Single Agent Insufficient

• Add a second agent from a complementary class (if started on ACE inhibitor/ARB, add calcium channel blocker; if started on calcium channel blocker, add ACE inhibitor/ARB) 6
• If blood pressure remains uncontrolled on two agents, add a thiazide or thiazide-like diuretic as the third agent 6
• This creates the evidence-based triple therapy combination recommended by guidelines 5, 6

Alternative Antidepressant Selection

Safer Options for Patients with Hypertension

• Selective serotonin reuptake inhibitors (SSRIs) are the safest class with limited effects on blood pressure and represent the preferred choice for patients with cardiovascular disease or hypertension 7
• Mirtazapine has minimal effects on blood pressure but may rarely cause orthostatic hypotension 7
• Avoid serotonin-norepinephrine reuptake inhibitors (SNRIs), particularly venlafaxine, which carry greater risk of hypertension 7

Medications to Avoid

• Do not use other dopamine-norepinephrine reuptake inhibitors, as bupropion's mechanism of increasing noradrenergic activity is what causes the blood pressure elevation 7
• Tricyclic antidepressants have also been associated with blood pressure increases and should be avoided in this context 7

Critical Clinical Context from Evidence

Bupropion's Hypertensive Risk Profile

• In clinical trials of bupropion for seasonal affective disorder, 2% developed hypertension requiring discontinuation, with mean systolic blood pressure increases of 1.3 mmHg 1
• The risk is higher when bupropion is combined with nicotine replacement therapy (6.1% incidence of treatment-emergent hypertension with combination therapy) 1
• In patients with pre-existing cardiovascular disease, bupropion caused exacerbation of baseline hypertension in approximately 14% of cases, leading to treatment discontinuation 4

Mechanism of Blood Pressure Effect

• Bupropion increases dopaminergic and noradrenergic activity, which can elevate blood pressure through sympathetic nervous system activation 1, 7
• This effect is dose-related and more pronounced at higher doses 1

Common Pitfalls to Avoid

• Do not continue bupropion while attempting to control blood pressure with antihypertensive medications—the offending agent must be stopped 1
• Do not assume the blood pressure elevation will spontaneously resolve without discontinuing bupropion 1, 4
• Do not restart bupropion after severe hypertension has occurred, even if blood pressure normalizes, as recurrence risk is high 1
• Do not delay switching to an alternative antidepressant, as untreated depression also carries cardiovascular risks 7