Side Effects of Trazodone
Trazodone causes significant side effects that frequently lead to discontinuation, with the most common being daytime sedation, dizziness, headache, and orthostatic hypotension, while rare but serious effects include priapism, cardiac arrhythmias, and QT prolongation. 1, 2
Most Common Side Effects
The side effect profile of trazodone is dominated by:
- Daytime sedation/somnolence - This is the most prominent side effect and occurs at higher rates than other second-generation antidepressants like bupropion, fluoxetine, mirtazapine, paroxetine, or venlafaxine 3, 4
- Dizziness - Frequently reported, particularly with position changes due to orthostatic hypotension 1, 3, 2
- Headache - A common complaint among users 1, 3, 4
- Dry mouth - Regularly reported, though trazodone has minimal anticholinergic activity compared to tricyclic antidepressants 3, 4
- Nausea and vomiting - Gastrointestinal effects occur frequently 3, 2, 5
Discontinuation Rates and Serious Side Effects
In clinical studies, 19% of patients (14/74) discontinued trazodone due to intolerable side effects, and 60% of those who continued therapy experienced at least one side effect 1. The reasons for discontinuation included:
Cardiovascular Effects
- Orthostatic hypotension - Can cause dizziness or fainting when changing positions, particularly problematic in elderly patients or those with heart disease 1, 2, 4
- QT prolongation and cardiac arrhythmias - Including torsade de pointes and ventricular tachycardia, reported even at doses of 100 mg per day or less 2, 4, 5
- Bradycardia and atrial fibrillation - Occasional sinus bradycardia has occurred in long-term studies 2
Serious Urogenital Effects
- Priapism - Erections lasting more than 6 hours; occurred in approximately 7% of patients who discontinued therapy in one study 1, 2, 6
Neuropsychiatric Effects
- More vivid nightmares - Paradoxically reported as a reason for discontinuation 1
- Severe agitation - Can occur in some patients 1
- Parkinsonism - Rare but documented, including tremors, cogwheel rigidity, and shuffling gait 6
- Activation of mania or hypomania - Risk of mood switching 2
- Suicidal ideation - Particularly in children, adolescents, and young adults 2, 4
Other Serious Effects
- Serotonin syndrome - Symptoms include agitation, hallucinations, coordination problems, fast heartbeat, tight muscles, sweating, fever, nausea, vomiting, and diarrhea 2
- Hyponatremia - Low sodium levels causing headache, weakness, confusion, trouble concentrating, memory problems, and unsteadiness 2
- Increased bleeding risk - Particularly when combined with NSAIDs, aspirin, or warfarin 2
- Angle-closure glaucoma - Eye pain, vision changes, swelling or redness in or around the eye 2
Additional Side Effects from FDA Labeling
The FDA label lists additional adverse reactions including 2:
- Hematologic: Hemolytic anemia, leukocytosis
- Hepatic: Cholestasis, jaundice, hyperbilirubinemia, liver enzyme alterations
- Dermatologic: Alopecia, hirsutism, pruritus, rash, urticaria
- Musculoskeletal: Aches and pains 2
- Weight changes: Both weight gain and weight loss reported 3, 2
- Blurred vision 2
- Nasal/sinus congestion 2
Withdrawal Symptoms
Discontinuation syndrome can occur with abrupt cessation, including anxiety, agitation, and sleep problems 2. Trazodone should not be stopped without consulting a healthcare provider 2.
Clinical Context
The 2019 VA/DoD guidelines specifically advise against using trazodone for chronic insomnia disorder because the low-quality evidence supporting its efficacy is outweighed by its adverse effect profile 1. Despite this, trazodone remains widely prescribed off-label for insomnia at lower doses (25-100 mg) 3, 7, 5.
Important Drug Interactions
Trazodone's side effects can be amplified by drug interactions, particularly with medications that inhibit its metabolism (such as amiodarone) or increase serotonergic activity 6. The sedative effects are worsened by alcohol and other CNS depressants 2.