Can trazodone be taken with or without food, and should elderly patients prone to orthostatic hypotension take it with food?

Trazodone Administration with Food

Trazodone should be taken shortly after a meal or light snack, and this is particularly important for elderly patients prone to orthostatic hypotension. 1

FDA-Approved Administration Guidelines

The FDA label explicitly states that trazodone hydrochloride tablets should be taken shortly after a meal or light snack. 1 This recommendation is based on the drug's pharmacokinetic profile and safety considerations.

Pharmacokinetic Rationale

Taking trazodone with food significantly improves its tolerability by reducing peak plasma concentrations while maintaining therapeutic efficacy:

• Food decreases maximum serum concentration (Cmax) from 1.88 to 1.47 micrograms/ml, a reduction that helps minimize side effects. 2
• Time to peak concentration (Tmax) increases from approximately 1 hour on an empty stomach to 2 hours with food. 1, 2
• Critically, total drug absorption (area under the curve) remains unchanged whether taken with or without food, meaning therapeutic efficacy is preserved. 1, 2
• Food improves the irregularity of absorption seen in fasting subjects, providing more predictable drug levels. 2

Special Considerations for Elderly Patients and Orthostatic Hypotension

For elderly patients prone to orthostatic hypotension, taking trazodone with food is especially important because:

• Trazodone antagonizes alpha-1 adrenergic receptors, a property directly associated with postural hypotension. 1
• Orthostatic hypotension is one of the notable adverse effects that requires close monitoring, particularly in elderly patients. 3
• The lower peak concentrations achieved when taken with food reduce the risk of acute hypotensive episodes. 2
• Elderly patients typically require lower maximum doses (300-400 mg/day versus 600 mg/day in younger patients), making dose-related side effects more manageable. 3

Clinical Management Algorithm

For all patients initiating trazodone:

1. Instruct to take shortly after a meal or light snack. 1
2. Avoid administration on an empty stomach due to irregular absorption and higher peak levels. 2

For elderly patients or those with cardiovascular risk factors:

1. Measure orthostatic vital signs at baseline (blood pressure after 5 minutes sitting/lying, then at 1 and 3 minutes after standing). 4
2. Emphasize food administration to minimize orthostatic hypotension risk. 1, 2
3. Implement non-pharmacological measures for orthostatic hypotension: gradual positional changes, adequate hydration (2-3 liters daily if not contraindicated), increased salt intake (6-9 grams daily if not contraindicated), and compression garments. 5
4. Monitor for somnolence, dizziness, and orthostatic symptoms at follow-up visits. 6

Common Pitfalls to Avoid

• Do not allow patients to take trazodone on an empty stomach, as this leads to irregular absorption and higher peak concentrations that increase side effect risk. 2
• Do not assume that taking with food reduces efficacy—bioavailability remains at 63-65% regardless of food intake. 2
• Do not overlook orthostatic vital sign monitoring in elderly patients, as trazodone's alpha-1 antagonism directly causes postural hypotension. 1, 3
• Do not combine with other medications that worsen orthostatic hypotension (alpha-blockers, diuretics, vasodilators) without careful monitoring and consideration of alternatives. 4