Antidepressant toxicity is a common reason for emergency admissions, particularly in cases of intentional self-harm. Antidepressants include various drug classes such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), and atypical agents. Each class has distinct toxic manifestations, with TCAs being associated with the highest morbidity and mortality. Recognizing toxic features and initiating timely management are essential to prevent serious complications.
1. Tricyclic Antidepressants (TCA) Poisoning
TCAs such as amitriptyline, imipramine, and nortriptyline are highly lipophilic and rapidly absorbed, causing early and severe toxicity.
Mechanism of Toxicity
- Inhibition of norepinephrine and serotonin reuptake
- Blockade of sodium channels causing cardiotoxicity
- Anticholinergic effects due to muscarinic receptor blockade
- GABA antagonism contributing to seizures
Clinical Features
Central Nervous System
- Agitation and confusion
- Seizures
- Coma in severe cases
Cardiovascular System
- Sinus tachycardia
- Prolonged QRS and QT intervals
- Hypotension
- Life-threatening arrhythmias
Anticholinergic Effects
- Dry mouth
- Mydriasis
- Urinary retention
- Flushed skin and hyperthermia
Management
- Immediate ECG monitoring
- Sodium bicarbonate for QRS widening and arrhythmias
- Benzodiazepines for seizures
- IV fluids and vasopressors for hypotension
- Avoid antiarrhythmics like class IA agents
2. Selective Serotonin Reuptake Inhibitors (SSRIs)
SSRIs such as fluoxetine, sertraline, escitalopram, and paroxetine are safer in overdose compared to TCAs. However, complications such as serotonin syndrome may occur.
Mechanism of Toxicity
SSRIs increase synaptic serotonin levels by inhibiting serotonin reuptake. Excessive serotonergic activity can lead to nervous system hyperstimulation.
Clinical Features
- Nausea, vomiting, and dizziness
- Tremors and agitation
- Mild tachycardia
- Seizures (rare, but possible)
Serotonin Syndrome
A life-threatening condition caused by excessive serotonin activity, often due to drug interactions.
Symptoms Include:
- Hyperreflexia and clonus
- Agitation and confusion
- Hypertension and tachycardia
- Hyperthermia
Management of SSRI Toxicity
- Supportive care and monitoring
- Benzodiazepines for agitation
- Cyproheptadine for serotonin syndrome
- Cooling measures for hyperthermia
3. Serotonin–Norepinephrine Reuptake Inhibitors (SNRIs)
SNRIs such as venlafaxine and duloxetine can cause more serious toxicity compared to SSRIs, especially at high doses.
Mechanism
- Inhibition of serotonin and norepinephrine reuptake
- Risk of seizures due to CNS stimulation
- Cardiac toxicity at very high doses
Clinical Features
- Tachycardia and hypertension
- Tremors and diaphoresis
- Seizures
- Serotonin syndrome (in severe cases)
Management
- Airway and breathing support
- Benzodiazepines for seizures
- Activated charcoal if early ingestion
- Monitor for cardiac conduction abnormalities
4. Atypical Antidepressants
Atypical agents such as bupropion, mirtazapine, and trazodone have unique toxicity profiles.
Bupropion
- High risk of seizures
- Cardiotoxicity in massive overdose
Trazodone
- Hypotension
- Serotonin syndrome when combined with other serotonergic drugs
Mirtazapine
- Relatively safe in overdose
- Mild CNS depression
General Principles of Management
- Stabilization of airway, breathing, and circulation
- Decontamination with activated charcoal for recent ingestion
- Continuous ECG and vital sign monitoring
- Correct metabolic acidosis
- Manage seizures promptly with benzodiazepines
- Avoid flumazenil in mixed overdose
When to Admit Patients
- Altered mental status
- Cardiotoxicity (QRS widening or arrhythmias)
- Seizures
- Serotonin syndrome features
- Suspected large intentional overdose
Detailed Notes:
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PATH: PHARMD/ PHARMD NOTES/ PHARMD FOURTH YEAR NOTES/ CLINICAL TOXICOLOGY/ ANTIDEPRESSANTS.