GPAtlas🧭 When to suspect
Serotonin syndrome (serotonin toxicity) is a potentially life-threatening, drug-induced reaction caused by excess serotonergic activity in the central nervous system.
• It is defined by a clinical triad of altered mental state, autonomic hyperactivity and neuromuscular excitation.
• It spans a dose-related spectrum from mild, self-limiting effects through to fatal toxicity.
• It can follow a single drug at a therapeutic dose, but most cases arise from a combination of serotonergic drugs, a recent dose increase, or an overdose.
Onset is characteristically rapid:
• Features usually appear within 24 hours, and about 60% within 6 hours, of starting, increasing or combining a serotonergic drug.
• Severe, life-threatening toxicity (rigidity and hyperthermia) almost always requires two or more serotonergic agents, one of which is often a monoamine oxidase inhibitor (MAOI).
Think of it in any patient on a serotonergic drug with new neuromuscular signs, examine for clonus, and diagnose using the Hunter Serotonin Toxicity Criteria rather than waiting for the full triad.
| Severity | Typical features | Action |
|---|---|---|
| Mild | • Tachycardia, shivering, diaphoresis, mydriasis, tremor, mild hyperreflexia • Afebrile and haemodynamically stable |
Often manageable in the community: stop the agent, supportive care, review – with a low threshold to refer |
| Moderate | Above plus inducible/ocular clonus, agitation, marked hyperreflexia, temperature up to ~40°C, hypertension | Emergency hospital assessment |
| Severe | Spontaneous/sustained clonus, truncal rigidity, hyperthermia > 41°C, autonomic instability, delirium or reduced consciousness | • 999 – life-threatening • Requires intensive care |
| Drug group | Common UK examples (brands) |
|---|---|
| SSRIs/SNRIs | • Sertraline (Lustral), fluoxetine (Prozac), citalopram, escitalopram, paroxetine (Seroxat) • Venlafaxine (Efexor), duloxetine (Cymbalta) |
| MAOIs (incl. "hidden") | • Phenelzine (Nardil), tranylcypromine, isocarboxazid, moclobemide (Manerix) • The antibiotic linezolid (Zyvox) and methylene blue |
| Opioids | • Tramadol (Zydol), pethidine, fentanyl, methadone • Dextromethorphan |
| Other prescribed | • Triptans e.g. sumatriptan (Imigran) • Lithium • Tricyclics e.g. clomipramine (Anafranil) • Mirtazapine • Ondansetron/metoclopramide (weak) |
| OTC/recreational | • St John's wort • MDMA ("ecstasy"), amphetamines, cocaine |
Source: Hunter Criteria · BMJ (Isbister, 2014)
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