Trazodone Side Effects
Trazodone's most prominent side effect is somnolence (daytime sedation), occurring at significantly higher rates than bupropion, fluoxetine, mirtazapine, paroxetine, or venlafaxine, making it particularly problematic for daytime functioning. 1
Common Side Effects
The most frequently reported adverse effects include:
- Somnolence/sedation - The hallmark side effect, occurring more commonly than with other second-generation antidepressants 1
- Dizziness - Commonly reported across clinical trials 1
- Headache - Frequent complaint among patients 1, 2
- Dry mouth - Though less severe than tricyclic antidepressants 2
- Nausea/vomiting - Common gastrointestinal complaint 1, 3
- Constipation and diarrhea - Both reported with similar frequency 1
- Blurred vision - Listed among common adverse effects 3
- Swelling (edema) - Reported in post-marketing surveillance 3
Serious and Potentially Life-Threatening Side Effects
Cardiovascular Effects
- Orthostatic hypotension - Particularly dangerous in elderly patients or those with pre-existing heart disease 1, 3, 2, 4
- QT prolongation and torsade de pointes - Can occur even at doses of 100 mg/day or less 5, 3, 2
- Cardiac arrhythmias - Including ventricular tachycardia, atrial fibrillation, bradycardia, and cardiac arrest 3, 2
- Syncope - Related to blood pressure changes 3
Clinical Pitfall: Always monitor blood pressure when initiating trazodone, especially in elderly patients. Consider baseline ECG in patients with cardiac risk factors. 3
Priapism
- Prolonged erection lasting more than 6 hours - Rare but requires immediate medical attention 3, 2, 4
- Can occur at any dose and may require surgical intervention if not promptly treated 3
Serotonin Syndrome
Symptoms include: 3
- Agitation and hallucinations
- Problems with coordination
- Fast heartbeat
- Tight muscles and trouble walking
- Sweating and fever
- Nausea, vomiting, and diarrhea
This is particularly concerning when trazodone is combined with other serotonergic agents. 3
Bleeding Risk
- Increased risk of unusual bruising or bleeding - Especially when combined with NSAIDs, aspirin, or warfarin 3
Psychiatric Effects
- Activation of mania/hypomania - Patients may feel excessively energetic, irritable, or have decreased need for sleep 3
- Suicidal ideation - Particularly in children, adolescents, and young adults 3, 2
Neurological Effects
- Withdrawal symptoms - Including anxiety, agitation, and sleep problems when discontinued abruptly 3
- Cognitive and motor impairment - Can affect driving and operating machinery 3
- Parkinsonism - Rare but documented, including tremors, rigidity, and shuffling gait 6
- Seizures - Reported in post-marketing surveillance 3
Metabolic and Hematologic Effects
- Hyponatremia (low sodium) - Symptoms include headache, weakness, confusion, trouble concentrating, memory problems, and unsteady gait 3
- Hemolytic anemia - Rare post-marketing report 3
Ophthalmologic Effects
- Angle-closure glaucoma - Eye pain, vision changes, swelling or redness in or around the eye 3
Specific Context: PTSD-Associated Nightmares
When used for PTSD nightmares at a mean dose of 212 mg/day (range 25-600 mg): 1
60% of patients experienced side effects in decreasing order of frequency: 1
- Daytime sedation
- Dizziness
- Headache
- Priapism
- Orthostatic hypotension
19% discontinued the drug due to intolerable side effects including priapism, daytime sedation, more vivid nightmares, and severe dry mouth. 1
Comparative Tolerability Profile
Trazodone has minimal anticholinergic activity compared to tricyclic antidepressants, making it potentially better tolerated in elderly patients. 5, 7, 8, 4 However, the high incidence of somnolence and orthostatic hypotension remains problematic, particularly in this population. 1
Weight gain is less common with trazodone than with mirtazapine or paroxetine. 1