How do amphetamines affect blood pressure in patients, particularly those with pre-existing hypertension or at risk for cardiovascular disease?

Amphetamines and Blood Pressure

Direct Answer

Amphetamines consistently elevate both systolic and diastolic blood pressure by approximately 2 mmHg and increase heart rate by 3-4 beats per minute, effects that persist with chronic use and pose cardiovascular risks particularly in patients with pre-existing hypertension or cardiovascular disease. 1

Mechanism and Magnitude of Blood Pressure Effects

Amphetamines are non-catecholamine sympathomimetic amines that produce peripheral actions including elevations of both systolic and diastolic blood pressures through sympathetic nervous system activation 2. The most robust evidence comes from a 2025 Cochrane systematic review of 56 randomized controlled trials involving 10,583 participants, which demonstrated:

• Systolic blood pressure increases by 1.93 mmHg (95% CI 1.54 to 2.31) 1
• Diastolic blood pressure increases by 1.84 mmHg (95% CI 1.51 to 2.16) 1
• Heart rate increases by 3.71 beats per minute (95% CI 3.27 to 4.14) 1

These effects are sustained over time—subgroup analysis limited to studies with at least 8 weeks of amphetamine use showed similar magnitudes, indicating these are not merely transient effects 1.

Clinical Recognition and Screening

Multiple hypertension guidelines identify amphetamines as blood pressure-raising substances that require systematic screening 3. The ACC/AHA guidelines recommend suspecting drug-induced hypertension in several clinical scenarios:

• Loss of previously well-controlled hypertension 3
• Abrupt onset of hypertension, particularly in patients <30 years of age 3
• Atypical hypertension patterns (severe but transient hypertension in young patients) 3
• Resistant hypertension (uncontrolled on ≥3 drugs including a diuretic) 3

The International Society of Hypertension specifically recommends screening all patients with hypertension or at risk for hypertension for sympathomimetic medications 4, 5.

Risk Stratification by Patient Population

Patients with Pre-existing Hypertension

The deleterious effects of amphetamines are more pronounced in patients with pre-existing hypertension 6. In adults with ADHD treated with amphetamines, new-onset hypertension (BP ≥140/90) occurred in 10% of actively treated patients compared to 8% on placebo 7. Amphetamines should be avoided entirely in patients with uncontrolled hypertension or severe cardiovascular disease 4.

Patients with Cardiovascular Disease

The sustained blood pressure and heart rate increases suggest that people taking daily oral amphetamines are at increased risk of adverse cardiovascular events 1. A small subgroup of patients, especially those with pre-existing cardiovascular diseases, may experience clinically relevant cardiovascular effects despite small average increases at the population level 3.

Elderly and Renal Failure Patients

Drug-induced blood pressure increases are more pronounced in the elderly and in those with renal failure 6.

Acute vs. Chronic Effects

While behavioral stimulant doses of amphetamine exert only transient effects on blood pressure in intact animals due to central nervous system dampening mechanisms 8, human data clearly demonstrate sustained effects with chronic use 1. The Cochrane review found consistent blood pressure elevations across all time points, including:

• Short duration (≤4 weeks) 1
• Medium duration (>4 weeks to <8 weeks) 1
• Long duration (≥8 weeks) 1

Overdose and Severe Hypertension

In overdose situations, amphetamines can cause severe hypertension as part of a constellation of cardiovascular effects including arrhythmias and potential circulatory collapse 2. Manifestations include restlessness, tremor, hyperreflexia, and cardiovascular instability 2. If acute severe hypertension complicates amphetamine overdosage, intravenous phentolamine has been suggested, though gradual blood pressure reduction typically occurs with adequate sedation 2.

Clinical Management Algorithm

For Patients Requiring Amphetamines

1. Baseline assessment: Measure blood pressure and heart rate before initiating therapy 3, 7

2. Ongoing monitoring: Clinical guidelines recommend monitoring pulse and blood pressure when prescribing psychostimulant medication 3. Check blood pressure and heart rate periodically during treatment 7

3. If hypertension develops: Blood pressure should be treated to target regardless if amphetamine therapy must continue 4. However, avoid amphetamines entirely in uncontrolled hypertension or severe cardiovascular disease 4

For Patients with Existing Hypertension

When evaluating loss of blood pressure control or resistant hypertension, take a careful medication history including prescription medications, over-the-counter substances, and illicit drugs 5. When feasible, reduce or discontinue drugs associated with increased blood pressure and use alternative agents 5.

Adverse Effect Profile

Participants taking amphetamines were significantly more likely to withdraw from studies due to adverse effects compared to placebo (risk ratio 2.69,95% CI 2.13 to 3.40), representing an absolute risk increase of 4.3% over an average duration of 1 month 1. Common adverse effects beyond cardiovascular changes include decreased appetite, sleep disturbances, headaches, irritability, and stomach pain 3.

Critical Pitfalls to Avoid

• Do not use β-blockers alone for amphetamine-induced hypertension, as this may cause paradoxical rise in blood pressure due to unopposed α-adrenergic stimulation 9
• Do not assume blood pressure effects are transient—the Cochrane review demonstrates sustained effects with chronic use 1
• Do not overlook amphetamines when evaluating secondary causes of hypertension, particularly in younger patients with new-onset or resistant hypertension 3