- USE: Trazodone is an atypical tetracyclic antidepressant that possesses antidepressant, anxiolytic and hypnotic properties. It is used for the treatment of depression and is particularly beneficial to older patients because it causes sedation without anticholinergic effects. PHARMACOLOGY: It is an antagonist of the 5-hydroxytryptamine-2A (5HT2A) receptor as well as a selective inhibitor of reuptake of serotonin. The metabolite, m-chlorophenyl piperazine (m-CPP) is a potent postsynaptic serotonin agonist. It is also an antagonist at the alpha 1 adrenergic receptor. EPIDEMIOLOGY: Trazodone exposures are common. Inadvertent exposures rarely produce significant toxicity. Overdoses generally produce no more than moderate symptoms. Deaths from single agent ingestion of trazodone are extremely rare. OVERDOSE: MILD TO MODERATE TOXICITY: Drowsiness, ataxia, nausea, vomiting, tinnitus, myoclonus and peripheral edema can occur. SEVERE TOXICITY: Lethargy, seizures, coma, bradycardia, hypotension and priapism can develop. There are sporadic reports of nonspecific ST-T wave changes, QT prolongation, ventricular premature depolarization, right bundle-branch block, T-wave inversion, first-degree atrioventricular block and torsade de pointes; though in some cases ingestants or underlying cardiac disease may have played a role. Serotonin syndrome has been reported in conjunction with other serotonergic drugs. ADVERSE EFFECTS: Drowsiness, nausea, vomiting, myoclonus, tinnitus, peripheral edema and priapism have developed. Toxic hepatitis has been reported with therapeutic use. A trazodone withdrawal syndrome has been reported following the gradual discontinuation of therapeutic doses of trazodone. Withdrawal signs/symptoms have consisted of insomnia, vivid dreams, nausea, diarrhea, abdominal pain, anxiety and palpitations.
Range of Toxicity:
- TOXIC DOSE: PEDIATRIC: Experience is limited, but ingestions of up to 500 mg have been well tolerated by toddlers. ADULT: The range of toxicity is variable as ingestions of 2 to 3 g have produced respiratory arrest and 4 to 5 g have resulted in moderate drowsiness and ataxia. Overdoses of 2 to 4 g have recovered with supportive care. Deaths have been described following ingestions of 400 to 3650 mg in combination with other drugs. THERAPEUTIC DOSE: ADULT: DEPRESSION: Initial dose: 150 mg/day in divided dose. May increase dose in increments of 50 mg/day every 3 to 4 days. The maximum dose is 400 mg/day for outpatients and 600 mg/day for inpatients. EXTENDED RELEASE: 150 mg once a day. May be increased in increments of 75 mg/day every 3 days; maximum dose is 375 mg/day. PEDIATRIC: Trazodone is not indicated for use in adolescents or children.
- Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Treatment is symptomatic and supportive. MANAGEMENT OF SEVERE TOXICITY: Treat hypotension with intravenous fluids, add vasopressors, if hypotension persists. Treat bradycardia associated with hypotension with atropine. Treat seizures with benzodiazepines initially.
- Decontamination: PREHOSPITAL: Consider activated charcoal in patients with a recent potentially toxic ingestion who are awake and able to protect their airway. HOSPITAL: Consider activated charcoal in patients with a recent potentially toxic ingestion who are awake and able to protect their airway. Most effective when administered within one hour of ingestion. Gastric lavage is not warranted because a trazodone ingestion is not life-threatening.
- Airway management: Endotracheal intubation should be performed in patients with excessive drowsiness and the inability to protect their own airway.
- Hypotensive episode: Administer isotonic fluid for hypotension, add vasopressors if hypotension persists.
- Bradycardia: Treat hemodynamically significant bradycardia with atropine.
- Torsades de pointes: Hemodynamically unstable patients require electrical cardioversion. Treat stable patients with magnesium and/or atrial overdrive pacing. Correct electrolyte abnormalities (ie, hypomagnesemia, hypokalemia, hypocalcemia) and hypoxia.
- Seizure: Benzodiazepines for initial control; consider propofol or phenobarbital, if seizures not controlled with benzodiazepines.
- Priapism: An immediate urological consult is necessary. Clinical history should include the use of other agents (ie, antihypertensives, antidepressants, illegal agents) that may also be contributing to priapism. In a patient with ischemic priapism the corpora cavernosa are often completely rigid and the patient complains of pain, while nonischemic priapism the corpora are typically tumescent, but not completely rigid and pain is not typical. Aspirate blood from the corpus cavernosum with a fine needle. Blood gas testing of the aspirated blood may be used to distinguish ischemic (typically PO2 less than 30 mmHg, PCO2 greater than 60 mmHg, and pH less than 7.25) and nonischemic priapism. Color duplex ultrasonography may also be useful. If priapism persists after aspiration, inject a sympathomimetic. PHENYLEPHRINE: Dose: Adult: For intracavernous injection, dilute phenylephrine with normal saline for a concentration of 100 to 500 mcg/mL and give 1 mL injections every 3 to 5 minutes for approximately 1 hour (before deciding that treatment is not successful). For children and patients with cardiovascular disease: Use lower concentrations in smaller volumes. NOTE: Treatment is less likely to be effective if done more than 48 hours after the development of priapism. Distal shunting (NOT a first-line therapy) should only be considered after a trial of intracavernous injection of sympathomimetics.
- Monitoring of patient: Monitor vital signs and mental status. Institute continuous cardiac monitoring and obtain an ECG in symptomatic patients or after significant overdose. Monitor fluid and electrolyte balance in symptomatic patients. Serum trazodone concentrations are NOT rapidly available or clinically useful in guiding patient management.
- Enhanced elimination procedure: Hemodialysis is not likely to be useful because of the high degree of protein binding.
- Patient disposition: HOME CRITERIA: An asymptomatic adult with an inadvertent ingestion of an extra dose can be managed at home. Asymptomatic children with inadvertent ingestions of up to 200 mg can be managed at home. OBSERVATION CRITERIA: Symptomatic patients, those with deliberate ingestions, and children ingesting more than 200 mg should be referred to a healthcare facility. IMMEDIATE RELEASE: Patients ingesting an immediate release product should be observed for approximately 4 to 6 hours (peak plasma levels occur about 1 hour after dosing when taken on an empty stomach or 2 hours after dosing when taken with food). EXTENDED RELEASE: Patients ingesting an extended-release preparation should be observed for 12 to 16 hours (Tmax is 9 hours at a therapeutic dose of extended release trazodone (300 mg)). ADMISSION CRITERIA: Patients with cardiac toxicity, persistent hypotension, seizures, or with CNS depression that persists after 12 hours of observation should be admitted. CONSULT CRITERIA: Consult a medical toxicologist for assistance with medical management if the patient develops more than moderate symptoms or if the symptoms are not consistent with a trazodone exposure.