Trazodone Overdose: Lethal Dose and Clinical Management
Direct Answer to Lethal Dose Question
There is no established lethal dose of trazodone, and death from trazodone overdose alone is extremely rare—fatalities have occurred only when trazodone was combined with other CNS depressants such as alcohol, benzodiazepines, or barbiturates. 1
Key Safety Profile
Trazodone is relatively safe in overdose compared to tricyclic antidepressants, with no deaths reported from trazodone alone in overdose cases 2
The FDA label explicitly states that deaths from trazodone overdose have occurred only when ingested concurrently with other CNS depressants including alcohol, chloral hydrate, diazepam, amobarbital, chlordiazepoxide, or meprobamate 1
Therapeutic doses in elderly patients range from 300-400 mg/day, while younger patients tolerate up to 600 mg/day 3
Most Severe Overdose Reactions
The most serious reactions reported with trazodone overdose alone include 1:
- Priapism (most characteristic severe reaction)
- Respiratory arrest
- Seizures
- ECG changes, including QT prolongation
The most frequently reported reactions are drowsiness and vomiting 1
Critical Management Principles
Immediate Supportive Care
There is no specific antidote for trazodone overdose—management is entirely supportive 1
Establish and maintain airway patency, provide bag-mask ventilation for respiratory depression, followed by endotracheal intubation when appropriate 4
Contact a regional poison center (1-800-222-1222 or www.poison.org) for expert guidance 1
Essential Monitoring
Cardiac monitoring is mandatory to detect QT prolongation and arrhythmias 1
Monitor for respiratory depression, as this is the primary cause of tissue injury and death in CNS depressant overdose 4
Assess for hypoxemia and hypercarbia continuously 4
Multiple Drug Involvement
Always consider the possibility of multiple drug ingestion, as this is common in overdose scenarios and dramatically increases mortality risk 1, 4
If combined opioid and trazodone poisoning is suspected, administer naloxone first before considering other interventions for respiratory depression 4
Avoid flumazenil if benzodiazepine co-ingestion is suspected along with trazodone, as flumazenil is contraindicated with co-ingestion of drugs that lower seizure threshold 4
Common Clinical Pitfalls
Underestimating polypharmacy risk: The vast majority of trazodone-related deaths involve co-ingestion with alcohol or benzodiazepines 1, 2
Inadequate respiratory support: Focusing on pharmacological interventions while neglecting basic airway management and ventilatory support can result in poor outcomes 4
Missing cardiac complications: QT prolongation can occur and requires continuous ECG monitoring 1
Overlooking priapism: This is a characteristic severe reaction to trazodone that requires urgent urological intervention 1