What Attention Deficit Hyperactivity Disorder (ADHD) medications are not associated with an increase in Blood Pressure (BP) in patients with pre-existing Hypertension (HTN) or Cardiovascular Disease (CVD)?

ADHD Medications Without Blood Pressure Elevation

Alpha-2 adrenergic agonists (guanfacine and clonidine) are the only ADHD medications that actually lower blood pressure rather than raise it, making them uniquely suitable for patients with hypertension or cardiovascular disease. 1

First-Line Non-Stimulant Options for Patients with Hypertension

Alpha-2 Adrenergic Agonists (Preferred)

Extended-release guanfacine and clonidine are particularly beneficial for hypertensive patients because they produce hypotensive effects, potentially helping to lower blood pressure rather than raising it. 1

• These medications cause modest decreases in both blood pressure (1-4 mmHg) and heart rate (1-2 bpm), which is the opposite effect of stimulants. 1, 2
• Guanfacine has higher specificity for alpha-2A receptors compared to clonidine, resulting in less sedation while maintaining therapeutic efficacy. 2
• Effect sizes for ADHD symptoms are approximately 0.7 compared to placebo, which is lower than stimulants (1.0) but clinically meaningful. 1, 2
• Evening administration is generally preferable to minimize daytime somnolence while providing around-the-clock symptom control. 1, 2

Critical Safety Warning: Never abruptly discontinue alpha-2 agonists—they must be tapered by 1 mg every 3-7 days to avoid rebound hypertension. 1, 2

Atomoxetine (Alternative Non-Stimulant)

The American Heart Association recommends atomoxetine as a first-choice non-stimulant option for patients with controlled hypertension, due to its minimal impact on blood pressure compared to stimulants. 1

• Atomoxetine is a selective norepinephrine reuptake inhibitor providing 24-hour symptom control with once-daily dosing. 1, 3
• While atomoxetine has noradrenergic activity, increases in pulse and blood pressure are small and of little clinical significance. 4
• Cardiovascular effects are statistically significant but not clinically significant in most patients, with minimal increases in heart rate and blood pressure. 3, 4
• Effect sizes are medium-range (approximately 0.7) compared to stimulants, and full therapeutic effect requires 6-12 weeks. 1, 3
• Pre-existing cardiovascular conditions do not reduce the likelihood of atomoxetine initiation, unlike stimulants. 5

Stimulants: Use with Extreme Caution

The American College of Cardiology recommends that stimulants (methylphenidate or amphetamine derivatives) be used with caution in hypertensive patients, due to the potential to worsen blood pressure control. 1

• All stimulants increase blood pressure and heart rate, with average increases of 1-4 mmHg for systolic and diastolic blood pressure, and 1-2 beats per minute for heart rate. 1, 6
• The American College of Cardiology/American Heart Association explicitly recommends discontinuing or decreasing the dose of amphetamines when blood pressure becomes elevated. 1
• If stimulants must be used, long-acting formulations provide smoother cardiovascular effects with more stable blood pressure and heart rate profiles throughout the day, avoiding the peaks and troughs that can exacerbate hypertension. 1
• More frequent blood pressure and pulse monitoring is necessary when using stimulants in hypertensive patients. 1

Clinical Management Algorithm

Prerequisites Before Starting Any ADHD Medication

• Confirm blood pressure is well-controlled (target <130/80 mmHg) before initiating ADHD treatment. 1
• Establish baseline cardiovascular parameters including blood pressure, heart rate, and personal/family cardiac history. 1, 6
• Screen for sudden death in family members, cardiovascular symptoms, Wolff-Parkinson-White syndrome, hypertrophic cardiomyopathy, and long QT syndrome. 1

Treatment Selection for Hypertensive Patients

1. First-line: Extended-release guanfacine (1 mg nightly, titrate by 1 mg weekly to target 0.05-0.12 mg/kg/day or maximum 7 mg/day) 1, 2

   • Provides blood pressure-lowering effects while treating ADHD
   • Requires 2-4 weeks for therapeutic effects to emerge 2

2. Alternative first-line: Atomoxetine (start 0.5 mg/kg/day, target 1.2 mg/kg/day or 60-100 mg daily) 1, 3

   • Minimal cardiovascular impact
   • Requires 6-12 weeks for full therapeutic effect 1, 3

3. If non-stimulants fail: Long-acting stimulant formulations with careful monitoring 1

   • Implement more frequent blood pressure monitoring (at each dose adjustment)
   • Consider dose reduction if blood pressure rises above target
   • Adjust antihypertensive therapy if necessary 1

Monitoring During Treatment

• Check blood pressure and pulse at each dose adjustment of any ADHD medication. 1
• If blood pressure increases above target on ADHD medication, consider: 1
  • Dose reduction of ADHD medication
  • Switching to alternative ADHD medication (preferably alpha-2 agonist)
  • Intensifying antihypertensive therapy with addition of calcium channel blocker or thiazide diuretic

Important Precautions

• Avoid combining two RAS blockers (e.g., ACE inhibitor plus ARB) when managing hypertension in ADHD patients. 1
• The risk for serious cardiovascular adverse events with ADHD medications is extremely low, and benefits of treating ADHD outweigh risks after adequate assessment. 6
• However, great caution is advised when considering any ADHD medication for patients with personal or family history of cardiovascular disease. 6
• Pre-existing cardiovascular conditions reduce the likelihood of stimulant therapy initiation but not atomoxetine treatment in adult ADHD patients. 5