What are the recommendations for stimulant use in patients with hypertension?

Stimulant Use in Hypertension

Stimulants should generally be discontinued or dose-reduced in patients with hypertension, and they must be avoided entirely in those with severe or uncontrolled hypertension. 1

Primary Recommendation

The 2017 ACC/AHA Hypertension Guidelines explicitly list amphetamines (including methylphenidate, dexmethylphenidate, and dextroamphetamine) as medications that cause elevated blood pressure and recommend discontinuation or dose reduction as the primary management strategy. 1 When stimulants cannot be discontinued, behavioral therapies for ADHD should be considered as alternatives. 1

Cardiovascular Risk Profile

Absolute Contraindications

The FDA labels for both amphetamine and methylphenidate state that stimulants should not be used in patients with: 2, 3

• Known structural cardiac abnormalities or cardiomyopathy 2, 3
• Serious heart rhythm abnormalities 2, 3
• Coronary artery disease 2, 3
• Recent myocardial infarction 2, 3
• Severe or uncontrolled hypertension 2, 3

Sudden death, stroke, and myocardial infarction have been reported in adults taking stimulants at usual ADHD doses, making pre-existing cardiovascular disease a critical consideration. 2

Blood Pressure Effects

Stimulant medications cause measurable increases in blood pressure and heart rate: 2, 3

• Mean systolic blood pressure increase: 2-4 mmHg 2, 3
• Mean diastolic blood pressure increase: 2-4 mmHg 2, 3
• Mean heart rate increase: 3-6 bpm 2, 3
• Individual patients may experience substantially larger increases 2, 3

Research data demonstrate that specific stimulants produce the following changes from baseline: 4

• Amphetamine: +5.4 mmHg systolic (p<0.05) 4
• Bupropion: +5.9 mmHg systolic and +6.9 bpm heart rate (p<0.05) 4
• Desipramine: +7.1 mmHg diastolic (p<0.05) 4
• Methylphenidate: +4.5 bpm heart rate (p<0.05) 4

New-onset hypertension (BP ≥140/90) occurred in 10% of patients receiving active ADHD medication versus 8% receiving placebo. 4

Clinical Management Algorithm

Step 1: Pre-Treatment Cardiovascular Assessment

Before initiating stimulants in any patient, obtain: 2, 3

• Detailed cardiovascular history including family history of sudden death or ventricular arrhythmia 2, 3
• Assessment for pre-existing hypertension, heart failure, or recent MI 2, 3
• Physical examination to assess for cardiac disease 2, 3
• Further cardiac evaluation (ECG, echocardiogram) if findings suggest cardiac disease 2, 3

Step 2: Blood Pressure Monitoring Protocol

All patients on stimulants require systematic blood pressure monitoring: 2, 3

• Baseline blood pressure measurement before starting therapy 2, 3, 4
• Periodic monitoring throughout treatment for hypertension and tachycardia 2, 3
• More frequent monitoring during dose adjustments 5

A novel protocol using 36-hour ambulatory blood pressure monitoring can compare BP on days without versus with stimulant medication, allowing personalized treatment decisions. 5

Step 3: Management of Hypertension in Stimulant Users

If hypertension develops or worsens on stimulants: 1

1. First-line: Discontinue or decrease stimulant dose 1
2. Second-line: Consider behavioral therapies for ADHD as alternatives 1
3. If stimulants must be continued: Initiate or intensify antihypertensive therapy while continuing close BP monitoring 1

Step 4: Long-Term Considerations

Over 10 years of follow-up in children, stimulant treatment did not increase risk for prehypertension or hypertension, though stimulants maintained a persistent adrenergic effect on heart rate during active treatment. 6 However, this pediatric data cannot be extrapolated to adults who have higher baseline cardiovascular risk. 2

Critical Caveats

Drug Interactions

Stimulants are contraindicated with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation due to risk of hypertensive crisis. 3

Dose-Response Relationship

Higher stimulant doses correlate with greater blood pressure increases. Positive correlations (p<0.05) exist between stimulant dose (mg/kg) and percent change in systolic BP (r=0.56), diastolic BP (r=0.61), and heart rate (r=0.58). 7

Ambulatory Monitoring Findings

24-hour ambulatory monitoring reveals that diastolic blood pressure load increases significantly on stimulant therapy (9.0% on vs 4.8% off therapy, p<0.05), with more pronounced nocturnal dipping during treatment periods. 7 Approximately 12% of children met criteria for hypertension based on ambulatory monitoring while on stimulant therapy. 7

Screening for Secondary Causes

The International Society of Hypertension recommends screening all patients with hypertension for medications that may increase blood pressure, including sympathomimetics like stimulants. 1, 8 This is particularly important in resistant hypertension, where substance-induced increases must be excluded before diagnosing true resistant hypertension. 1

Alternative Considerations

When stimulants cannot be used due to hypertension, non-stimulant ADHD medications may be considered, though these also carry cardiovascular effects. Atomoxetine (Strattera), a selective norepinephrine reuptake inhibitor, similarly increases blood pressure and should be avoided in uncontrolled hypertension or severe cardiovascular disease. 8