Can Trazodone (triazolopyridine antidepressant) cause headaches and increase blood pressure, particularly in patients with pre-existing hypertension or those at risk for cardiovascular disease?

Trazodone and Headaches/Blood Pressure

Trazodone commonly causes headaches but does not increase blood pressure; in fact, it tends to lower blood pressure through orthostatic hypotension, which is a significant cardiovascular risk, particularly in patients with pre-existing heart disease. 1

Headache as an Adverse Effect

• Headache is one of the most commonly reported adverse effects of trazodone, appearing consistently across clinical trials and FDA labeling alongside somnolence, dizziness, and dry mouth 1, 2, 3
• The incidence of headache with trazodone is comparable to other second-generation antidepressants, where headache ranks among the most frequent side effects reported in efficacy studies 4
• Headaches may also occur as part of discontinuation syndrome if trazodone is stopped abruptly, along with other symptoms like dizziness, confusion, and sensory disturbances 1

Blood Pressure Effects: Hypotension, Not Hypertension

Trazodone does not increase blood pressure—it causes the opposite problem: orthostatic hypotension and syncope. 1

Cardiovascular Risks

• The FDA label explicitly warns that hypotension, including orthostatic hypotension and syncope, has been reported in patients receiving trazodone 1
• Trazodone tends to lower heart rate rather than increase it, distinguishing it from some other antidepressants 5
• Concomitant use with antihypertensive medications may require dose reduction of the antihypertensive drug due to additive hypotensive effects 1
• Orthostatic hypotension is particularly problematic in elderly patients and those with pre-existing cardiovascular disease 2, 6, 3

Cardiac Arrhythmia Concerns

• Trazodone may be arrhythmogenic in patients with preexisting cardiac disease, with identified arrhythmias including isolated PVCs, ventricular couplets, tachycardia with syncope, and torsade de pointes 1
• Trazodone prolongs the QT/QTc interval and should be avoided in patients with known QT prolongation or when combined with CYP3A4 inhibitors or other QT-prolonging drugs 1
• Post-marketing events, including torsade de pointes, have been reported at doses as low as 100 mg or less 1
• Trazodone should be avoided during the initial recovery phase of myocardial infarction and used with caution in patients with cardiac disease, who require close monitoring 1

Clinical Context for Cardiovascular Patients

The American Heart Association recommends sedating antidepressants like trazodone or mirtazapine for insomnia in cardiovascular patients only after cognitive behavioral therapy for insomnia has failed, due to cardiovascular risks 4

• Trazodone is associated with significant risks including priapism, orthostatic hypotension, and cardiac arrhythmias when used off-label as a hypnotic in older adults 4
• Sertraline is the preferred SSRI in cardiovascular disease patients due to minimal cardiovascular toxicity and lower QTc prolongation risk compared to other agents 7, 8
• Mirtazapine is considered a safer alternative to trazodone for cardiovascular patients, with demonstrated cardiovascular safety and additional benefits like appetite stimulation 4, 7

Critical Pitfalls to Avoid

• Do not combine trazodone with antihypertensives or diuretics without careful monitoring, as this increases fall risk and hypotension severity 7
• Monitor for cardiac arrhythmias in any patient with pre-existing cardiac disease, as trazodone has little effect on cardiac conduction but can worsen ventricular irritability in susceptible patients 5
• Lower doses (100-300 mg) are better tolerated in patients with significant cardiovascular disease compared to higher therapeutic doses 5
• Avoid trazodone in patients with known QT prolongation, recent MI, or those taking other QT-prolonging medications 1

Practical Dosing Considerations

• Maximum tolerated doses in elderly patients are 300-400 mg/day, though younger patients may tolerate up to 600 mg/day 6
• The usual adult daily dose is 150-400 mg given in two divided doses 9
• A gradual reduction in dosage rather than abrupt cessation is recommended to avoid discontinuation syndrome symptoms including headache 1