From the Research
Trazodone typically causes orthostatic hypotension at doses of 50 mg or higher, with the risk increasing significantly at doses above 100 mg, as reported in the most recent study 1. The effect is most pronounced when initiating therapy or increasing dosage, particularly in elderly patients or those with cardiovascular conditions. To minimize this risk, start with a low dose of 25-50 mg at bedtime and gradually increase by 25-50 mg every 3-7 days as needed and tolerated. Divided dosing may help if higher daily amounts are required. Orthostatic hypotension occurs because trazodone blocks alpha-1 adrenergic receptors, causing vasodilation and reduced peripheral vascular resistance. This effect is typically most severe within 1-3 hours after dosing. Patients should be advised to rise slowly from sitting or lying positions, stay well-hydrated, and report symptoms like dizziness, lightheadedness, or fainting. The orthostatic effect often diminishes with continued use as tolerance develops, but dose-dependent risk remains, especially at therapeutic antidepressant doses (150-400 mg daily) 2, 1. Key considerations for minimizing risk include:
- Starting with a low dose and gradually increasing as needed and tolerated
- Using divided dosing for higher daily amounts
- Advising patients on how to manage orthostatic hypotension symptoms
- Monitoring for increased risk in elderly patients or those with cardiovascular conditions. The most recent and highest quality study 1 provides the strongest evidence for the dose-dependent risk of orthostatic hypotension with trazodone, guiding the recommendation for cautious dosing and monitoring.