K2iv: Serotonin Syndrome

  • Serotonin = monoamine neurotransmitter
  • SS = potentially life threatening condition associated with ↑serotonergic activity within CNS

Synthesis & Metabolism

  • From precursor L-tryptophan
  • 2 sites of synthesis:
    1. ENTEROCHROMAFFIN cells of gut mucosa
    2. Serotonergic neurons of CNS
  • Stored in 3 sites:
    1. Serotonergic neurons of CNS & myenteric plexus
    2. Enterochromaffin cells of gut mucosa
    3. Platelets (rely on uptake)

Role of Serotonin

  • CNS →attention, behaviour, thermoregulation
  • PNS →GI motility, VC, uterine contraction, bronchoconstriction
  • Platelets →platelet aggregation

Serotonin Syndrome

A triad of neuro-excitatory features

  • NM hyperactivity: tremor, clonus, myoclonus, hyperreflexia, pyramidal rigidity
  • Autonomic hyperactivity: diaphoresis, fever, tachycardia, tachypnoea
  • Altered mental status: agitation, excitement, confusion

→Features to distinguish it in a DDx are myoclonus, clonus & hyperreflexia & acute onset over 24hrs

Drugs Implicated

  • SS occurs when there is a combination of drug ingestion which affects serotonergic transmission
  • Stimulation of 5HTIA & 5HT2A receptors have been implicated, but no single receptor is solely responsible

1) ↑ Serotonin Synthesis

  • L-tryptophan

2) ↑ Serotonin Release

  • NMDA (ecstasy)

3) Inhibit Serotonin Reuptake

  • SSRIs (fluoxetine)
  • Phenylpinedine opioids →weak serotonin reuptake Is (pethidine, fentanyl, methadone, tramadol)
  • TCAs (amitriptyline) →inhibits MAO uptake mechanisms

4) Inhibit Serotonin Metabolism

  • Fever & rev MAO inhibitors (phenelzine)

5) Directly Stimulate Serotonin Receptors

  • Lithium

NB: Pethidine + phenelzine →Libby Zion Law


  • Admit to ICU early
  • Discontinue serotonergic agents
  • Supportive care
  • Sedation with benzos
  • Serotonin antagonists
    • Chlorpromazine (5HT1 & 5HT2 antagonist – also antagonist at dopamine receptors, histamine receptors & α12 receptors ∴ advise fluid loading to prevent ↓BP)
    • Cyproheptadine (histamine, 5HT1 & 5HT2 antagonist)