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Tricyclic Antidepressant Overdose
- Tricyclic antidepressants (TCAs) are secondary or tertiary amines that have variable abilities to inhibit reuptake of neurotransmitters (norepinephrine, dopamine, and serotonin) and to be anticholinergic, antihistaminic, and sedating.
- These properties are important to consider when prescribing these agents and when managing an intentional or accidental overdose.
Synonyms
- TCA OD
- Tricyclic antidepressant intoxication or poisoning
Epidemiology & Demographics
How common is this condition?
- Pharmacokinetic interactions of TCAs are often clinically important. The below table summarizes selected drug interactions with TCAs.
- Commonly used TCAs include amitriptyline, imipramine, desipramine, nortriptyline, doxepin, amoxapine, clomipramine, and protriptyline.
Selected Drug Interactions With Tricyclic Antidepressants
From Stern TA et al: Massachusetts General Hospital handbook of general hospital psychiatry, ed 7, Philadelphia, 2018, Elsevier.
| Drug | Potential Interaction |
|---|---|
| Carbamazepine | Decreased TCA plasma levels |
| Phenobarbital | |
| Rifampin | |
| Isoniazid | |
| Antipsychotics | Increased TCA plasma levels |
| Methylphenidate | |
| SSRIs | |
| Quinidine | |
| Propafenone | |
| Antifungals | |
| Macrolide antibiotics | |
| Verapamil | |
| Diltiazem | |
| Cimetidine | |
| Class I antiarrhythmics | Depression of cardiac conduction; ventricular arrhythmias |
| Guanethidine | Interference with antihypertensive effect |
| Clonidine | |
| Sympathomimetic amines (e.g., epinephrine) | Arrhythmias, hypertension (e.g., isoproterenol, epinephrine) |
| Antihypertensives | Hypotension |
| Vasodilator drugs | |
| Low-potency antipsychotics | |
| Anticholinergic drugs | Additive anticholinergic toxicity |
| MAOIs | Delirium, fever, convulsions |
| Sulfonylurea hypoglycemics | Hypoglycemia |
MAOI, Monoamine oxidase inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant.
Physical Findings & Clinical Presentation
Cardiovascular:
- Intraventricular conduction delay (QRS prolongation)
- Sinus tachycardia
- Atrioventricular block
- Prolongation of the QT interval
- Ventricular tachycardia
- Wide complex tachycardia without P waves
- Refractory hypotension (the most common cause of death from TCA overdose)
- Late arrhythmias or sudden death (in addition to the arrhythmias, which occur during the first 24 to 48 h; late problems can occur up to 5 days after the overdose)
Central nervous system:
- Coma
- Delirium
- Myoclonus
- Seizures
Other:
- Hyperthermia
- Ileus
- Urinary retention
- Rhabdomyolysis
- Kidney failure
- Pulmonary complications (e.g., aspiration pneumonitis)
- Life-threatening overdose exists with the ingestion of >1 g of a TCA. Among patients who reach a hospital, most deaths occur within the first 24 h; lack of initial symptoms can be deceptive
Etiology & pathogenesis
- Mechanisms of TCA cardiovascular toxicity.
- Central nervous system toxicity:
- 1.Cholinergic blockade is believed to cause hyperthermia, ileus, urinary retention, pupillary dilation, delirium, and coma.
- 2.The mechanism of myoclonus and seizures is not fully understood.
Mechanism of Tricyclic Antidepressant Cardiovascular Toxicity
| Toxic Effect | Mechanism |
|---|---|
| Conduction delays, arrhythmias | |
| QRS prolongation atrioventricular block | Cardiac sodium channel → slowed depolarization in atrioventricular node, His-Purkinje fibers, and ventricular myocardium |
| Sinus tachycardia | Cholinergic blockade, inhibition of norepinephrine reuptake |
| Ventricular tachycardia | |
| Monomorphic | Cardiac sodium channel inhibition → reentry |
| Torsades de pointes | Cardiac potassium channel inhibition → prolonged repolarization |
| Ventricular bradycardia | Impaired cardiac automaticity |
| Hypotension | |
| Vasodilation | Vascular alpha-adrenergic receptor blockade |
| Decreased cardiac contractility | Cardiac sodium channel inhibition → impaired excitation-contraction coupling |
Differntial Diagnosis
- Cardiotoxicity from TCA can be confused with intoxication by drugs that cause QRS prolongation. These include class Ia antiarrhythmic agents (disopyramide, procainamide, quinidine), class Ic antiarrhythmic agents (encainide, flecainide, propafenone), cocaine, propranolol, quinine, chloroquine, neuroleptics, propoxyphene, and digoxin.
- Other causes of QRS prolongation include hyperkalemia, ischemic heart disease, cardiomyopathy, and cardiac conduction system dysfunction.
Workup
- Clinical presentation
- Knowledge of the overdose
- Although serum drug levels do not correlate well with toxicity, TCA concentration >1 mcg/ml can be life threatening; TCA concentration >3 mcg/ml is often fatal
- Baseline CBC, prothrombin time, blood urea nitrogen, creatinine, and electrolytes
How is this condition treated?
Acute General Treatment
- Initial measures:
- 1.Hospitalization with cardiac monitoring as well as monitoring of vital signs and temperature.
- 2.Initiate intravenous access.
- 3.Administer activated charcoal with sorbitol.
- 4.Large-bore tube gastric lavage is of unproven benefit.
- 5.Ipecac is contraindicated.
- 6.12-lead ECG.
- 7.If no evidence of cardiotoxicity has been noted during the first 6 h of observation, further monitoring is not necessary; if there is evidence of cardiotoxicity, monitoring should continue for 24 h after all signs of toxicity have resolved.
- Hemodialysis is not effective.
- When the patient is medically stable, psychiatric evaluation should be obtained.
Treatment of Complications of Tricyclic Antidepressant Toxicity
| Toxic Effect | Treatment |
|---|---|
| Cardiovascular | |
| QRS prolongation | Hypertonic NaHCO 3 if QRS prolongation is marked or progressing; not clear if treatment is needed in the absence of hypotension or arrhythmias |
| Hypotension | Intravascular volume expansion, NaHCO 3 vasopressors (norepinephrine) or inotropic agents (dopamine). Correct hyperthermia, acidosis, seizures. Consider mechanical support |
| Ventricular tachycardia | NaHCO 3 , lidocaine, overdrive pacing. Correct hypotension, hypothermia, acidosis, seizures |
| Torsade des pointes | Overdrive pacing |
| Ventricular bradycardia | Chronotropic agent (epinephrine), pacemaker |
| Sinus tachycardia | Treatment rarely needed |
| Atrioventricular block type II second or third degree | Pacemaker |
| Hypertension | Rapidly titratable antihypertensive agent (nitroprusside) |
| Central Nervous System | |
| Delirium | Restraints, benzodiazepine. Neuromuscular blockade for hyperthermia, acidosis |
| Seizures | Benzodiazepine. Neuromuscular blockade for hyperthermia, acidosis |
| Coma | Intubation, ventilation if needed |
| Other | |
| Hyperthermia | Control seizures, agitation. Cooling measures |
| Acidosis | NaHCO 3 . Correct hypotension, hypoventilation |
