Serotonin Syndrome Pathogenesis and Clinical Findings

Serotonin Syndrome: Pathogenesis and Clinical Findings
Serotonergic Agents SSR1s, SNRIs, MOAIs, TCAs, atypical antidepressants, antibiotics, mood stabilizers (valporate, lithium), opioids, antiemetic agents, triptans, weight loss agents, drugs of abuse (e.g. cocaine, amphetamines)
Therapeutic drug use
• Drug interactions (esp. combo of serotonergic agents) Serotonin Syndrome Variable combination of mental status changes, autonomic instability, and neuromuscular hyperactivity ranging from mild to life-threatening with an abrupt onset (within minutes to hours) after medication ingestion and most cases resolving within 24 hours of cessation of offending medication
Intentional self-poisoning
Excessive serotonergic activity at 5-HT receptors centrally (brainstem) and peripherally
serotonin synthesis and release
serotonin reuptake and metabolism
IN receptor agonism and sensitivity
Drug-induced changes in the relative ratio of non-serotonergic neurotransmitters (e.g. increase in noradrenaline)
Altered Mental Status
Anxiety, confusion, agitation, hypervigilance, pressured speech, delirium, coma
Autonomic Instability
Shivering, diaphoresis, fever, diarrhea, tachycardia, mydriasis, hypertension
Authors: Preeti Kar Reviewers: Erika Russell Usama Malik Aaron Mackie* * MD at time of publication
Notes: The Hunter Serotonin Toxicity Criteria is used to make a clinical diagnosis • History of serotonergic agent taken within past 5 weeks + any of the following clinical features: • Spontaneous clonus • Inducible clonus and either agitation or diaphoresis • Ocular clonus and either agitation or diaphoresis • Tremor and hyperreflexia • Hypertonia, temperature > 38 °C, and either ocular clonus or inducible clonus
Neuromuscular Hyperactivity
Hyperreflexia, muscle rigidity (esp. lower extremities), myoclonus, tremor, incoordination, trismus*, opisthotonus*, ocular clonus*, seizures
*Notes: • Trismus or lockjaw, is the reduced opening of the jaw • Opisthotonus is an abnormal body position where the person is usually rigid and arches their back, with their head thrown backwards • Ocular Clonus is rhythmic or equal movements of both eyes; should be distinguished from nystagmus which has a fast and slow component
Legend: Pathophysiology Mechanism
Sign/Symptom/Lab Finding
Abbreviations: • 5-HT = serotonin • SSRI = selective serotonin reuptake inhibitors • SNRI = selective noradrenaline reuptake inhibitors • MOAI = monoamine oxidase inhibitors • TCA = tricyclic antidepressants