Trazodone Side Effects
Trazodone commonly causes daytime sedation, dizziness, headache, and dry mouth, with rare but serious risks including priapism, orthostatic hypotension, cardiac arrhythmias with QT prolongation, and serotonin syndrome. 1
Most Common Side Effects
The FDA-approved labeling and clinical studies identify the following frequent adverse effects:
- Sedation/drowsiness is the most common side effect, occurring in a substantial proportion of patients 1, 2
- Dizziness is frequently reported, particularly when changing positions due to orthostatic effects 1
- Headache affects approximately 30% of patients in clinical trials 3
- Dry mouth occurs commonly, though less severe than with tricyclic antidepressants 1, 2
- Nausea and vomiting affect 10-13% of patients 1
- Blurred vision is reported in post-marketing surveillance 1
In a veteran population study using trazodone for nightmares (mean dose 212 mg), 60% of patients experienced side effects in decreasing order of frequency: daytime sedation, dizziness, headache, priapism, and orthostatic hypotension. Notably, 19% discontinued the drug due to intolerable side effects. 3
Serious and Rare Side Effects
Cardiovascular Effects
- Orthostatic hypotension and syncope can occur, particularly in elderly patients or those with pre-existing heart disease 1, 2
- QT prolongation with risk of torsade de pointes and ventricular tachycardia has been reported even at doses ≤100 mg/day 1
- Cardiac arrhythmias including ventricular ectopic activity, atrial fibrillation, and rare cases of cardiac arrest 1
- Use caution in patients with premature ventricular contractions 4
Priapism
- Priapism (erection lasting >6 hours) is a rare but serious adverse effect requiring immediate medical attention 1
- This occurred in the veteran study population and led to discontinuation in some cases 3
Neuropsychiatric Effects
- Serotonin syndrome can occur, especially when combined with other serotonergic agents, presenting with agitation, hallucinations, coordination problems, fast heartbeat, muscle rigidity, fever, nausea, vomiting, and diarrhea 1
- Activation of mania or hypomania may occur in susceptible patients 1
- Suicidal thoughts and behavior particularly in children, adolescents, and young adults 1
- Parkinsonism has been reported in case studies, with symptoms including tremors, cogwheel rigidity, and shuffling gait that resolved upon discontinuation 5
- Cognitive and motor impairment affecting driving ability and coordination 1
Hematologic and Metabolic
- Hyponatremia presenting with headache, weakness, confusion, trouble concentrating, memory problems, and unsteadiness 1
- Increased bleeding risk, particularly when combined with NSAIDs, aspirin, or warfarin 1
- Hemolytic anemia reported in post-marketing surveillance 1
Other Serious Effects
- Angle-closure glaucoma with eye pain, vision changes, and eye swelling or redness 1
- Hepatotoxicity including cholestasis, jaundice, and liver enzyme elevations 1
- Withdrawal symptoms including anxiety, agitation, and sleep problems upon abrupt discontinuation 1
Dose-Related Considerations
Higher doses (100 mg vs 25 mg) are associated with increased incidence of adverse effects, particularly daytime sedation and dizziness. 6 The mean effective dose of 212 mg for PTSD-related nightmares was associated with a 60% side effect rate. 3
Comparative Safety Profile
Trazodone demonstrates minimal anticholinergic activity compared to tricyclic antidepressants, making it better tolerated in elderly patients. 4, 2, 7 It is relatively safe in overdose with no deaths reported when taken alone, unlike tricyclic antidepressants. 7, 8
Clinical Pitfalls
- Drug interactions can amplify side effects; for example, amiodarone may inhibit trazodone metabolism, leading to higher blood levels and increased risk of adverse effects like parkinsonism 5
- Timing of administration matters: taking trazodone after meals or at bedtime can minimize daytime sedation 1, 9
- Patients should avoid alcohol and other CNS depressants, which potentiate sedation and dizziness 1