SSRIs work by inhibiting the reuptake of serotonin in the brain and periphery. They have a rapid absorption, high protein binding, and long elimination half-life due to active metabolites. SSRI overdoses rarely cause death on their own and are unlikely to cause CNS depression, seizures, or significant cardiotoxicity. Serotonin syndrome can occur from mixed ingestion of serotonergic drugs or changes to SSRI dosing, but is typically mild and treated supportively.

1. SSRI poisoning Emma Borthwick RVH ICM seminar 27 th 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

3. 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)

5. 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

6. 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

7. Drugs that can precipitate serotonin syndrome Increases serotonin formation L-tryptophan Increases release amphetamines, cocaine Impairs reuptake cocaine, ecstasy, SSRIs, SNRI,TCA, St John’s Wort Inhibits metabolism ie MAOI linezolid Direct serotonin agonist triptans, LSD, fentanyl Increases sensitivity of receptor lithium

8. Diagnostic criteria

9. Differential diagnosis Neuroleptic malignant syndrome Anticholinergic toxicity Malignant hyperthermia Sympathetic toxicity Meningitis or encephalitis

10. Serotonin syndrome and neuroleptic malignant syndrome: distinguishing features

11. Differential diagnosis Neuroleptic malignant syndrome Anticholinergic toxicity Malignant hyperthermia Sympathetic toxicity Meningitis or encephalitis

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