SSRI poisoning

1
SSRI poisoning

• Emma Borthwick
• RVH ICM seminar
• 27th April 2007.

2
SSRI pharmacology

• Serotonin produced from tryptophan in nerve
  terminals
• In CNS, serotonergic neurons found in brainstem
  regulating mood, personality, temperature,
  wakefulness
• 98 of body serotonin found peripherally
  regulate vascular tone, peristalsis and platelet
  activation
• SSRIs inhibit reuptake ? increasing stimulation
  of receptors

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SSRI kinetics

• Rapidly absorbed, reach peak within 6 hr
• High degree of protein binding
• Long elimination half life, with sustained
  biochemical activity due to active metabolites
• Metabolized in liver by cyP450, metabolites
  renally excreted.

4
SSRI toxicity

• Compared with other anti-depressants, rarely
  produce fatality or serious sequelae
• Most fatalities reported with v high doses e.g
  x150 or because of coingestant.
• Unlikely to cause CNS depression or seizures
• Do not have significant cardiotoxicity (except
  citalopram, prolonged QTc)

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SSRI poisoning

• Do not typically cause anti-cholinergic symptoms,
  significant sedation or hypotension
• May cause hyponatraemia (even at theraputic
  doses)
• Serotonin syndrome is rare unless mixed
  serotonergic ingestion or changes made in
  theraputic SSRI dosing

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Serotonin syndrome

• Life-threatening
• Classical triad of mental status changes,
  autonomic instability and increased neuromuscular
  tone
• BUT actually spectrum from benign to lethal
• Increased serotonergic activity in CNS
• Seen with theraputic use, inadvertant
  interactions and intentional self-poisoning

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Drugs that can precipitate serotonin syndrome

• Increases serotonin formation L-tryptophan
• Increases release amphetamines, cocaine
• Impairs reuptake cocaine, ecstasy, SSRIs,
  SNRI,TCA, St Johns Wort
• Inhibits metabolism ie MAOI linezolid
• Direct serotonin agonist triptans, LSD, fentanyl
• Increases sensitivity of receptor lithium

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Diagnostic criteria
9
Differential diagnosis

• Neuroleptic malignant syndrome
• Anticholinergic toxicity
• Malignant hyperthermia
• Sympathetic toxicity
• Meningitis or encephalitis

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Serotonin syndrome and neuroleptic malignant
syndrome distinguishing features
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Differential diagnosis

• Neuroleptic malignant syndrome
• Anticholinergic toxicity
• Malignant hyperthermia
• Sympathetic toxicity
• Meningitis or encephalitis

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Management

• Discontinuation all serotonergic agents
• Supportive care - may need sedatedparalysed
• Sedation with benzodiazepines
• Administration serotonin antagonist
• Cyproheptadine 12mg (PO)2mg every 2 hr until
  clinical response
• ?Olanzapine, chlorpromazine
• Assess need to restart drug.