What are the side effects of trazodone?

Side Effects of Trazodone

Trazodone's most common side effects are somnolence (drowsiness), dizziness, headache, and dry mouth, while serious but rare adverse effects include orthostatic hypotension, cardiac arrhythmias with QT prolongation, priapism, and increased bleeding risk. 1

Common Adverse Effects

The FDA-approved labeling identifies the following frequently occurring side effects 1:

• Somnolence/sedation - Most common, occurring in a significant proportion of patients
• Dizziness - Often related to blood pressure changes
• Headache
• Dry mouth (xerostomia)
• Nausea and vomiting (10-13% incidence)
• Blurred vision
• Constipation
• Fatigue/tiredness

Comparative guideline data shows trazodone has a higher incidence of somnolence than bupropion, fluoxetine, mirtazapine, paroxetine, or venlafaxine 2. Recent meta-analysis confirms somnolence occurs 7.34 times more frequently with trazodone compared to other antidepressants (OR = 7.34,95% CI: 2.91-18.50) 3.

Serious Adverse Effects Requiring Immediate Attention

Cardiovascular Effects

• Orthostatic hypotension and syncope - Particularly dangerous in elderly patients (≥75 years) or those with pre-existing cardiovascular disease 1, 4
• Cardiac arrhythmias including ventricular tachycardia, atrial fibrillation, and cardiac arrest 1
• QT prolongation and torsade de pointes - Can occur even at doses ≤100 mg/day 1
• Recent 2025 data shows trazodone users have significantly greater systolic BP drops immediately after standing (23.8 vs 14.3 mmHg, p=0.037) and 58.3% experienced syncope/falls versus 21.2% in non-users 4

Priapism

• Prolonged erection lasting >6 hours requires emergency intervention 1
• Rare but serious complication that can result in permanent erectile dysfunction if not treated promptly

Bleeding Risk

• Increased risk of gastrointestinal and other bleeding, especially when combined with NSAIDs, aspirin, or anticoagulants 5, 1

Neurological Effects

• Serotonin syndrome when combined with other serotonergic drugs - presents with agitation, hallucinations, coordination problems, fast heartbeat, muscle rigidity, fever, nausea, vomiting, and diarrhea 1
• Seizures - reported in post-marketing surveillance 1
• Extrapyramidal symptoms and parkinsonism - rare but documented, including tremors, cogwheel rigidity, and shuffling gait that resolves upon discontinuation 6

Psychiatric Effects

• Suicidal thoughts and behavior - FDA black box warning for patients <25 years old 1
• Activation of mania/hypomania in bipolar patients 1

Metabolic/Hematologic

• Hyponatremia (low sodium) - 0.5-12% incidence in older adults, typically within first month 5, 1
• Hemolytic anemia and leukocytosis (post-marketing) 1

Hepatotoxicity

• Liver enzyme elevations, cholestasis, jaundice - 0.5-3% may have asymptomatic transaminase elevation, typically within 6 months 5, 1

Ocular Effects

• Angle-closure glaucoma - eye pain, vision changes, swelling or redness in/around eye 1
• Blurred vision occurs more frequently (OR = 17.50,95% CI: 2.28-134.02) 3

Dose-Dependent Considerations

Low doses (25-100 mg) primarily used for insomnia cause predominantly sedation through H1-receptor blockade 7. Higher doses (150-300 mg) for depression produce broader side effect profiles including more cardiovascular and anticholinergic effects 8, 9.

Critical Drug Interactions Amplifying Side Effects

Trazodone metabolism can be impaired by CYP3A4 inhibitors (like amiodarone), leading to higher blood levels and increased adverse effects 6. Combining with other CNS depressants (alcohol, benzodiazepines) significantly increases sedation and respiratory depression risk 1.

Withdrawal Symptoms

Do not abruptly discontinue - withdrawal can cause anxiety, agitation, and sleep disturbances 1. Taper gradually under medical supervision.

Special Population Warnings

Elderly patients face substantially higher risks of orthostatic hypotension, falls, fractures, and cognitive impairment 1, 9, 4. The 2025 study demonstrates trazodone independently predicts syncope and falls in geriatric hypertensive patients 4.

Overdose can cause priapism, respiratory arrest, seizures, ECG changes including QT prolongation, and death (especially when combined with other CNS depressants) 1.