Can modafinil (provigil) increase blood pressure in patients, particularly those with pre-existing hypertension, depression, or anxiety?

Does Modafinil Increase Blood Pressure?

Yes, modafinil can increase blood pressure, though the effect is generally modest in most patients, with clinically significant increases occurring in fewer than 1% of patients. However, increased monitoring is essential in patients with pre-existing hypertension or cardiovascular disease, as a greater proportion of modafinil-treated patients require new or increased antihypertensive medications compared to placebo. 1

Cardiovascular Effects and Monitoring Requirements

Baseline and ongoing blood pressure monitoring is recommended before initiating modafinil and when adjusting doses, specifically assessing for hypertension, palpitations, or arrhythmias. 2 The FDA label emphasizes that while short-term controlled trials (≤3 months) showed no clinically significant changes in mean systolic and diastolic blood pressure compared to placebo, retrospective analysis revealed important differences in antihypertensive medication requirements. 1

Key Blood Pressure Data:

• Clinically significant increases in diastolic blood pressure occurred in fewer than 1% of patients in pooled analysis of 1,529 patients 3
• Only 1 patient had a clinically significant increase in heart rate in these studies 3
• 2.4% of modafinil patients required new or increased antihypertensive medications versus 0.7% on placebo 1
• In obstructive sleep apnea patients specifically, 3.4% required antihypertensive medication adjustments versus 1.1% on placebo 1

Contraindications and High-Risk Populations

Modafinil is contraindicated in patients with moderate to severe hypertension. 4 The FDA label specifically states that modafinil is not recommended in patients with:

• History of left ventricular hypertrophy 1
• Mitral valve prolapse who have experienced mitral valve prolapse syndrome when previously receiving CNS stimulants 1
• Recent myocardial infarction or unstable angina (requires increased monitoring) 1

Cardiovascular Events Reported:

In clinical studies, cardiovascular adverse reactions including chest pain, palpitations, dyspnea, and transient ischemic T-wave changes on ECG occurred in three subjects with mitral valve prolapse or left ventricular hypertrophy. 1 One case involved a 35-year-old obese narcoleptic male who experienced a 9-second episode of asystole after 27 days of treatment. 1

Special Considerations for Patients with Depression and Anxiety

Caution should be exercised when prescribing modafinil to patients with a history of psychosis, depression, or mania. 1 While modafinil has shown preliminary evidence of benefit in treatment-resistant depression (mean dose 184.3 mg/day), with significant improvements on multiple depression rating scales at 2 weeks and 3 months 5, psychiatric adverse reactions can occur.

• Psychiatric symptoms leading to discontinuation occurred more frequently with modafinil than placebo: anxiety (1%), nervousness (1%), insomnia (<1%), confusion (<1%), agitation (<1%), and depression (<1%) 1
• Postmarketing reports include mania, delusions, hallucinations, and suicidal ideation 1

Common Adverse Effects

The most common adverse effects include:

• Headache (34% vs 23% placebo) 3
• Nausea (11% vs 3% placebo) 3
• Nervousness and hypertension 6
• Insomnia and anxiety 7

Clinical Monitoring Algorithm

For patients initiating modafinil:

1. Measure baseline blood pressure and heart rate before starting treatment 2
2. Screen for cardiovascular contraindications (left ventricular hypertrophy, mitral valve prolapse syndrome, recent MI, unstable angina) 1
3. Assess psychiatric history (psychosis, depression, mania) 1
4. Monitor blood pressure and heart rate more frequently when starting or adjusting doses 2, 1
5. Question patients about excessive stimulatory effects at each visit 2
6. Consider cardiac evaluation if new onset chest pain, arrhythmia, or ischemic ECG changes occur 1

For patients with pre-existing hypertension: Increased monitoring is appropriate, as these patients are more likely to require antihypertensive medication adjustments. 1 The blood pressure effects, while modest on average, can be clinically significant in vulnerable populations and warrant careful surveillance throughout treatment.