Is hypotension a significant side effect of trazodone?

Orthostatic Hypotension is a Significant Side Effect of Trazodone

Yes, orthostatic hypotension is a significant side effect of trazodone that can impact morbidity, mortality, and quality of life, particularly in elderly and hypertensive patients. The FDA drug label explicitly identifies orthostatic hypotension as a notable adverse effect that requires monitoring and potential dose adjustment of antihypertensive medications when used concomitantly 1.

Evidence for Trazodone-Induced Hypotension

Mechanism

Trazodone antagonizes alpha-1 adrenergic receptors (Ki = 153 nM), which directly contributes to its hypotensive effects 1. This pharmacological property explains why trazodone can cause significant blood pressure drops, particularly when changing positions.

Clinical Significance

• The American Academy of Sleep Medicine specifically mentions trazodone's association with orthostatic hypotension as a significant risk, alongside cardiac arrhythmias 2.
• In a study of veterans prescribed trazodone, orthostatic hypotension was among the top five reported side effects, with 60% of patients experiencing adverse effects 2.
• A recent 2025 study of hypertensive geriatric patients found that trazodone users showed:
  • Lower office diastolic BP (71.8 vs 80.1 mmHg)
  • Greater systolic BP reduction immediately after standing (23.8 vs 14.3 mmHg)
  • Higher incidence of syncope and falls (58.3% vs 21.2%) 3

Risk Factors for Trazodone-Induced Hypotension

The risk of orthostatic hypotension with trazodone is particularly concerning in:

1. Elderly patients - More susceptible to BP fluctuations and have reduced compensatory mechanisms 3, 4
2. Patients with hypertension - May experience additive hypotensive effects, especially when combined with antihypertensive medications 1
3. Patients taking other medications with hypotensive effects - Combination with phenothiazines has been documented to cause additive hypotensive effects 5
4. Patients with cardiac conditions - Trazodone should be used with caution in patients with cardiac disease 1

Clinical Implications and Management

Monitoring

• Regular blood pressure measurements in both supine and standing positions are necessary when initiating trazodone 6
• Particular vigilance is needed in elderly patients, where the risk of falls is significantly increased 3

Dose Considerations

• Start with lower doses in elderly patients and those with cardiovascular conditions 4
• The FDA label notes that concomitant use with antihypertensive medications may require reduction in the dose of the antihypertensive drug 1

Precautions

• Avoid rapid position changes, particularly in the morning
• Consider the timing of trazodone administration to minimize orthostatic effects
• Be aware that trazodone overdose can manifest as severe hypotension and QT prolongation 7

Comparative Risk

When considering trazodone's hypotensive effects in context:

• It has fewer anticholinergic side effects than tricyclic antidepressants 8
• However, its cardiovascular effects (including orthostatic hypotension) are significant enough to warrant caution
• The 2019 VA/DoD clinical practice guidelines advised against using trazodone for chronic insomnia disorder, noting that its adverse effect profile (including orthostatic hypotension) outweighed its limited efficacy 2

Conclusion

Orthostatic hypotension is indeed a significant side effect of trazodone that warrants careful consideration, especially in vulnerable populations such as the elderly and those with cardiovascular conditions. The most recent evidence from 2025 confirms that trazodone is associated with greater orthostatic blood pressure drops and increased risk of syncope and falls in older hypertensive patients 3.