Tricyclic antidepressant (TCA) overdose represents a serious medical emergency due to its narrow therapeutic index and significant cardiotoxic and neurotoxic effects. Prompt recognition and evidence-based intervention are vital to improve survival and reduce complications. TCAs, commonly prescribed for depression, neuropathic pain, and insomnia, include drugs such as amitriptyline, nortriptyline, imipramine, and doxepin.
Pathophysiology of Tricyclic Antidepressant Toxicity
TCAs exert their toxic effects through multiple mechanisms:
- Sodium Channel Blockade: Leads to QRS prolongation and arrhythmias.
- Inhibition of Norepinephrine Reuptake: Results in sympathetic overstimulation.
- Anticholinergic Effects: Causes delirium, tachycardia, urinary retention, and hyperthermia.
- GABA Antagonism: Contributes to seizures.
Common TCAs Implicated in Overdose
| Drug | Therapeutic Range (mg/day) | Toxic Dose (mg) |
|---|---|---|
| Amitriptyline | 75–150 | >10 mg/kg |
| Nortriptyline | 75–100 | >10 mg/kg |
| Imipramine | 75–150 | >10 mg/kg |
| Doxepin | 75–300 | >10 mg/kg |
Clinical Presentation of TCA Overdose
Anticholinergic Symptoms
- Dilated pupils
- Dry mucous membranes
- Urinary retention
- Decreased bowel sounds
Cardiovascular Manifestations
- Sinus tachycardia (early finding)
- QRS widening >100 ms (predictor of seizures)
- Ventricular arrhythmias
- Hypotension due to myocardial depression and vasodilation
Central Nervous System Symptoms
- Confusion
- Agitation
- Seizures
- Coma
Diagnostic Approach to TCA Overdose
Initial Assessment
- Airway, Breathing, Circulation (ABCs) must be stabilized immediately.
Electrocardiogram (ECG)
ECG changes are critical for risk stratification:
Laboratory Investigations
- Serum electrolytes
- Arterial blood gas (ABG) analysis
- Serum drug levels (not routinely helpful in acute management)
- Renal and hepatic function tests
Management of Tricyclic Antidepressant Overdose
Immediate Interventions
- Airway Protection
- Early intubation in patients with altered consciousness or seizures.
- Gastrointestinal Decontamination
- Activated charcoal (50g) if within 1–2 hours of ingestion and airway protected.
Antidote: Sodium Bicarbonate
- Indication: QRS >100 ms, hypotension, ventricular arrhythmias.
- Mechanism: Alkalinizes serum (target pH 7.45–7.55) and counters sodium channel blockade.
- Dose: 1–2 mEq/kg IV bolus, repeated every 3–5 minutes as needed.
Seizure Control
- First-line agent: Benzodiazepines (e.g., lorazepam, diazepam).
- Avoid: Phenytoin (ineffective in TCA-induced seizures due to sodium channel effects).
Hypotension Management
- Initial fluid resuscitation with isotonic saline.
- If unresponsive, norepinephrine is preferred over dopamine due to better alpha-agonist activity.
Intralipid Therapy
- Consider in refractory hypotension or cardiac arrest unresponsive to standard measures.
- Acts as a “lipid sink” for lipophilic TCAs.
Monitoring and Disposition
- Admission to ICU for all symptomatic patients or QRS widening >100 ms.
- Continuous cardiac monitoring for at least 24 hours.
- Mental health evaluation post-recovery for intentional ingestions.
Complications of TCA Overdose
- Cardiac arrest
- Prolonged coma
- Aspiration pneumonia
- Rhabdomyolysis
- Renal failure secondary to myoglobinuria
Prognostic Indicators
| Predictor | Significance |
|---|---|
| QRS >160 ms | High risk of seizures/arrhythmias |
| Hypotension unresponsive to fluids | Poor outcome indicator |
| Refractory seizures | Associated with higher mortality |
Preventive Strategies
- Prescribe TCAs in limited quantities for patients at risk of overdose.
- Educate patients and families about toxicity risks.
- Consider alternative agents (SSRIs, SNRIs) with better safety profiles.
Tricyclic antidepressant overdose is a rapidly progressive, life-threatening condition requiring early recognition, ECG-based risk stratification, and aggressive targeted therapy. Sodium bicarbonate remains the cornerstone of treatment for cardiovascular toxicity, while benzodiazepines are essential for seizure control. Adherence to structured protocols significantly improves patient outcomes in TCA toxicity scenarios.
Frequently Asked Questions:
Q1. What is the most dangerous complication of TCA overdose?
Life-threatening arrhythmias due to sodium channel blockade are the most critical complication.
Q2. How quickly do symptoms of TCA overdose appear?
Symptoms often begin within 1–2 hours of ingestion, peaking around 6–8 hours.
Q3. Can TCA overdose be fatal?
Yes. Severe cardiac toxicity and refractory seizures can lead to death without prompt intervention.
Q4. What is the role of sodium bicarbonate in TCA toxicity?
It narrows the QRS complex and corrects acidosis, reducing the risk of arrhythmias.
Q5. Are TCAs safe in overdose compared to other antidepressants?
No. TCAs have a narrow therapeutic index and are more dangerous than SSRIs in overdose.
