Pharmacology, Toxicology and Addiction MedicineTier 1Disease (DEADMAN)

Poisoning from - antidepressants

Description

Risk profile differs sharply by class
- TCAs - the dangerous ones: cardiotoxic, proconvulsant, anticholinergic
- SSRIs/SNRIs - generally safe in overdose alone; risk is serotonin syndrome, esp. with co-ingestants or MAOI interaction
- Venlafaxine - the "SNRI exception" - seizures and cardiotoxicity (QRS/QT) at high doses, more like a TCA in overdose
- MAOIs - delayed, severe hypertensive crisis or serotonin syndrome; rare now

Epidemiology

Antidepressants are among the commonest agents in deliberate self-poisoning (reflecting prescribing prevalence in patients with mental illness)
TCA overdose deaths have fallen as SSRIs replaced TCAs as first-line therapy

Aetiopathogenesis

TCA:
- Cardiac fast Na-channel blockade -> wide QRS, ventricular arrhythmia
- K-channel blockade -> QT prolongation
- Antimuscarinic + alpha-1 blockade -> anticholinergic toxidrome + hypotension
- GABA-A antagonism -> seizures
Serotonin syndrome (any serotonergic overdose/combination): excess synaptic 5-HT -> triad of neuromuscular excitation (clonus, hyperreflexia - lower limb > upper), autonomic instability, altered mental state

Diagnosis

TCA

ECG is the key investigation: QRS >100 ms predicts seizures; QRS >160 ms predicts ventricular arrhythmia; terminal R wave in aVR >3mm is a sensitive early marker
TCA level not clinically useful acutely - treat the ECG, not the level

Serotonin syndrome

Clinical triad: clonus (esp. inducible/spontaneous), agitation/confusion, autonomic instability (fever, tachycardia, diaphoresis, diarrhoea)
Distinguish from NMS: faster onset (hours not days), clonus/hyperreflexia (vs NMS lead-pipe rigidity/hyporeflexia), history of serotonergic drug

Management

TCA

Sodium bicarbonate - first-line for QRS widening or arrhythmia/hypotension - narrows QRS by overcoming Na-channel blockade + serum alkalinisation
Avoid Class Ia/Ic antiarrhythmics (flecainide, quinidine) - worsen Na-channel blockade
Benzodiazepines for seizures
Activated charcoal if early and airway protected
IV lipid emulsion / hyperinsulinaemia-euglycaemia for refractory cardiotoxicity

Serotonin syndrome

Stop the causative agent(s)
Benzodiazepines for agitation/muscle activity
Cyproheptadine - 5-HT2A antagonist, for moderate-severe cases
Active cooling, aggressive management of hyperthermia (paralysis + intubation if severe - NOT antipyretics, hyperthermia here is from muscle activity not hypothalamic set-point)

Associations

TCA + anticholinergic co-ingestion compounds cardiotoxicity
Serotonin syndrome risk inc with MAOI + SSRI combination (avoid; requires washout period between switching)
SSRIs alone in overdose - usually benign, main risks are seizure (esp. bupropion, venlafaxine) and QT prolongation (citalopram)

Natural history & complications

TCA toxicity - death from refractory arrhythmia/seizure if untreated; deterioration can be rapid
Serotonin syndrome - usually resolves within 24h of stopping the causative drug(s) with supportive care; severe cases can be life-threatening (hyperthermia, DIC, rhabdomyolysis)

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