Makindo Medical Notes

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Selective Serotonin Reuptake Inhibitors (SSRIs) are widely prescribed antidepressants. They are safer than tricyclic antidepressants (TCAs) in overdose, but can still cause significant toxicity. The most feared complication is serotonin syndrome, a potentially fatal state of neuromuscular hyperactivity and autonomic instability. ⚠️

About

• SSRIs (e.g. fluoxetine, sertraline, citalopram, escitalopram, paroxetine) act by blocking presynaptic reuptake of serotonin (5-HT), enhancing serotonergic signalling. 🌐
• Generally considered safer than TCAs: less cardiotoxic, fewer fatal arrhythmias, but overdose can still be dangerous, especially with citalopram/escitalopram (QTc prolongation). ❤️
• Venlafaxine, though technically an SNRI, is often grouped here; its toxicity is more severe, with seizures and cardiotoxicity more likely. ⚡

Clinical Presentation 🩺

• Central Nervous System: Agitation, tremor, drowsiness; seizures more common with venlafaxine.
• GI: Nausea, vomiting, diarrhoea (due to serotonin’s effect on enteric nervous system).
• Cardiovascular: Tachycardia, hypertension; high-dose citalopram/escitalopram → QT prolongation, torsades de pointes. 📉
• Key complication: Serotonin syndrome — confusion, agitation, diaphoresis, hyperreflexia, clonus, hyperthermia, autonomic instability. 🚨

Serotonin Syndrome 🔥

• Caused by excess serotonin, usually from SSRI overdose or combination with other serotonergic drugs (e.g. MAOIs, tramadol, linezolid, MDMA).
• Hunter Criteria (high yield for exams): Serotonin syndrome diagnosed if patient on serotonergic agent has:
  • Spontaneous clonus
  • Inducible or ocular clonus + agitation/diaphoresis
  • Tremor + hyperreflexia
  • Hypertonia + temperature >38°C + clonus
• Distinguish from Neuroleptic Malignant Syndrome (NMS): NMS has "lead-pipe" rigidity, slower onset, normal reflexes. SS has clonus + hyperreflexia + rapid onset. 🧠

Investigations 🔬

• Vitals: Monitor HR, BP, temperature, O₂ sats.
• ECG: Check for QT prolongation, arrhythmias (especially with citalopram/escitalopram). 📈
• Bloods:
  • U&E for electrolyte derangement
  • Glucose (exclude hypoglycaemia as a cause of altered mental status)
  • LFTs (SSRIs metabolised hepatically)
  • CK (rhabdomyolysis risk in severe serotonin syndrome)
• Neurological exam: Look for hyperreflexia, clonus (ankle clonus is highly suggestive).

Management 💊

• Initial measures:
  • Activated charcoal if >10 tablets ingested and within 1h of ingestion, airway protected.
  • Supportive care is mainstay — most patients recover within 12–24h.
• For serotonin syndrome:
  • Benzodiazepines (diazepam/lorazepam) for agitation and seizures. 😴
  • Cyproheptadine (5-HT antagonist) in severe cases — given orally/nasogastrically. Rare but exam-worthy. 🌿
  • Cooling, IV fluids, sedation for hyperthermia & autonomic instability.
  • Severe cases → ICU, possible paralysis and intubation to control hyperthermia. ❄️
• Cardiac monitoring: Continuous ECG if large overdose, esp. citalopram/escitalopram.
• Seizure management: Benzodiazepines preferred; avoid phenytoin (ineffective, pro-arrhythmic).
• Psychiatric assessment: All deliberate overdoses → assess suicide risk and arrange follow-up. 🧑‍⚕️

Prognosis 📉

• Most SSRI overdoses are mild; serious toxicity is rare compared with TCAs.
• Complications: Severe serotonin syndrome, status epilepticus, torsades, or multiorgan failure (rare).
• With prompt recognition and supportive care, mortality is very low. ✅

Prevention 🛡️

• Careful prescribing: avoid combining SSRIs with MAOIs, tramadol, triptans, or linezolid. ⚠️
• Patient education: warn about serotonin syndrome signs (sweating, tremor, confusion, fever, jerks).
• Medication reconciliation: check for multiple serotonergic drugs prescribed by different clinicians.
• Safe storage and regular psychiatric follow-up to reduce risk of overdose. 🔑

Conclusion 🧾

SSRI toxicity is usually less dramatic than TCA overdose but can still be dangerous. Serotonin syndrome is the key life-threatening complication and must be recognised quickly. Supportive care, benzodiazepines, and cyproheptadine (if severe) are the cornerstones of management. Prevention and patient education remain vital. 🌟

References 📚

• Hunter JD. The Hunter Serotonin Toxicity Criteria. QJM. 2003.
• UpToDate. Selective Serotonin Reuptake Inhibitor (SSRI) Overdose. Available at: https://www.uptodate.com
• National Poisons Information Service (TOXBASE UK).
• American Association of Poison Control Centers (AAPCC). SSRI Overdose. https://www.aapcc.org