What are the side effects of trazodone (antidepressant)?

Trazodone Side Effects

Trazodone's most prominent side effect is somnolence (sedation), occurring at higher rates than bupropion, fluoxetine, mirtazapine, paroxetine, or venlafaxine, making it particularly useful for depression with insomnia but problematic for daytime functioning. 1, 2

Common Side Effects

The most frequently reported adverse effects include:

• Somnolence/sedation - the predominant side effect, occurring more commonly than with other second-generation antidepressants 1, 2, 3
• Dizziness and orthostatic hypotension - particularly problematic in elderly patients or those with heart disease 4, 3
• Headache - commonly reported across clinical trials 1, 4, 3
• Dry mouth - though less anticholinergic activity than tricyclic antidepressants 3, 5
• Nausea and vomiting - gastrointestinal effects mirror serotonergic activity 1, 4, 6
• Diarrhea - reported in controlled trials 4
• Blurred vision and visual disturbances - may require ophthalmologic evaluation 4

Serious Adverse Effects Requiring Immediate Attention

Cardiovascular Effects

• QT prolongation and torsade de pointes - can occur even at doses ≤100 mg/day, though relatively rare 2, 4, 3
• Cardiac arrhythmias including ventricular tachycardia, atrial fibrillation, and conduction blocks 4
• Orthostatic hypotension and syncope - use caution in patients with premature ventricular contractions 2, 7, 4
• Bradycardia - occasional sinus bradycardia in long-term studies 4

Priapism

• Prolonged erection >6 hours - rare but serious, requiring emergency intervention 1, 4, 3

Psychiatric Effects

• Serotonin syndrome - when combined with other serotonergic agents, presenting with agitation, hallucinations, coordination problems, fast heartbeat, muscle rigidity, fever, nausea, vomiting, and diarrhea 4
• Activation of mania/hypomania - feeling high, irritable, excessive energy, pressured speech, decreased need for sleep 4
• Suicidal ideation - particularly in children, adolescents, and young adults 4, 3

Hematologic Effects

• Increased bleeding risk - especially when combined with NSAIDs, aspirin, or warfarin 8, 4
• Hemolytic anemia - reported in post-marketing surveillance 4

Neurologic Effects

• Extrapyramidal symptoms and parkinsonism - rare but documented, including tremors, cogwheel rigidity, shuffling gait 9
• Seizures - grand mal seizures reported 4

Metabolic Effects

• Hyponatremia - presenting with headache, weakness, confusion, trouble concentrating, memory problems, and unsteady gait 4

Dose-Dependent Side Effect Profile

In a study of 60 veterans prescribed trazodone for nightmares (mean dose 212 mg, range 25-600 mg):

• 60% experienced side effects in decreasing frequency: daytime sedation, dizziness, headache, priapism, orthostatic hypotension 1
• 19% discontinued due to intolerable side effects including priapism, daytime sedation, more vivid nightmares, severe dry mouth 1

Withdrawal Symptoms

• Discontinuation syndrome can occur with abrupt cessation, including anxiety, agitation, and sleep problems 4
• Gradual tapering is essential rather than abrupt discontinuation 4

Important Clinical Caveats

• Minimal anticholinergic activity compared to tricyclic antidepressants, making it better tolerated in elderly patients 2, 7, 3
• Drug interactions must be carefully monitored, particularly with other serotonergic medications, CYP3A4 inhibitors (like amiodarone), and anticoagulants 4, 9
• Take with food to reduce peak plasma concentrations and improve tolerability 4, 5
• Avoid alcohol and CNS depressants as trazodone potentiates sedation and impairs motor coordination 4