SSRI poisoning Emma Borthwick RVH ICM seminar 27 th  April 2007.
SSRI pharmacology <ul><li>Serotonin produced from tryptophan in nerve terminals </li></ul><ul><li>In CNS, serotonergic neu...
SSRI kinetics <ul><li>Rapidly absorbed, reach peak within 6 hr </li></ul><ul><li>High degree of protein binding </li></ul>...
SSRI toxicity <ul><li>Compared with other anti-depressants, rarely produce fatality or serious sequelae </li></ul><ul><li>...
SSRI poisoning <ul><li>Do not typically cause anti-cholinergic symptoms, significant sedation or hypotension </li></ul><ul...
Serotonin syndrome <ul><li>Life-threatening </li></ul><ul><li>Classical triad of mental status changes, autonomic instabil...
Drugs that can precipitate serotonin syndrome <ul><li>Increases serotonin formation  L-tryptophan </li></ul><ul><li>Increa...
Diagnostic criteria
Differential diagnosis <ul><li>Neuroleptic malignant syndrome </li></ul><ul><li>Anticholinergic toxicity </li></ul><ul><li...
Serotonin syndrome and neuroleptic malignant syndrome: distinguishing features
Differential diagnosis <ul><li>Neuroleptic malignant syndrome </li></ul><ul><li>Anticholinergic toxicity </li></ul><ul><li...
Management <ul><li>Discontinuation all serotonergic agents </li></ul><ul><li>Supportive care - may need sedated&paralysed ...
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SSRI poisoning

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  • SSRI poisoning

    1. 1. SSRI poisoning Emma Borthwick RVH ICM seminar 27 th April 2007.
    2. 2. SSRI pharmacology <ul><li>Serotonin produced from tryptophan in nerve terminals </li></ul><ul><li>In CNS, serotonergic neurons found in brainstem – regulating mood, personality, temperature, wakefulness </li></ul><ul><li>98% of body serotonin found peripherally – regulate vascular tone, peristalsis and platelet activation </li></ul><ul><li>SSRIs inhibit reuptake -> increasing stimulation of receptors </li></ul>
    3. 3. SSRI kinetics <ul><li>Rapidly absorbed, reach peak within 6 hr </li></ul><ul><li>High degree of protein binding </li></ul><ul><li>Long elimination half life, with sustained biochemical activity due to active metabolites </li></ul><ul><li>Metabolized in liver by cyP450, metabolites renally excreted. </li></ul>
    4. 4. SSRI toxicity <ul><li>Compared with other anti-depressants, rarely produce fatality or serious sequelae </li></ul><ul><li>Most fatalities reported with v high doses e.g x150 or because of coingestant. </li></ul><ul><li>Unlikely to cause CNS depression or seizures </li></ul><ul><li>Do not have significant cardiotoxicity (except citalopram, prolonged QTc) </li></ul>
    5. 5. SSRI poisoning <ul><li>Do not typically cause anti-cholinergic symptoms, significant sedation or hypotension </li></ul><ul><li>May cause hyponatraemia (even at theraputic doses) </li></ul><ul><li>Serotonin syndrome is rare unless mixed serotonergic ingestion or changes made in theraputic SSRI dosing </li></ul>
    6. 6. Serotonin syndrome <ul><li>Life-threatening </li></ul><ul><li>Classical triad of mental status changes, autonomic instability and increased neuromuscular tone </li></ul><ul><li>BUT actually spectrum from benign to lethal </li></ul><ul><li>Increased serotonergic activity in CNS </li></ul><ul><li>Seen with theraputic use, inadvertant interactions and intentional self-poisoning </li></ul>
    7. 7. Drugs that can precipitate serotonin syndrome <ul><li>Increases serotonin formation L-tryptophan </li></ul><ul><li>Increases release amphetamines, cocaine </li></ul><ul><li>Impairs reuptake cocaine, ecstasy, SSRIs, SNRI,TCA, St John’s Wort </li></ul><ul><li>Inhibits metabolism ie MAOI linezolid </li></ul><ul><li>Direct serotonin agonist triptans, LSD, fentanyl </li></ul><ul><li>Increases sensitivity of receptor lithium </li></ul>
    8. 8. Diagnostic criteria
    9. 9. Differential diagnosis <ul><li>Neuroleptic malignant syndrome </li></ul><ul><li>Anticholinergic toxicity </li></ul><ul><li>Malignant hyperthermia </li></ul><ul><li>Sympathetic toxicity </li></ul><ul><li>Meningitis or encephalitis </li></ul>
    10. 10. Serotonin syndrome and neuroleptic malignant syndrome: distinguishing features
    11. 11. Differential diagnosis <ul><li>Neuroleptic malignant syndrome </li></ul><ul><li>Anticholinergic toxicity </li></ul><ul><li>Malignant hyperthermia </li></ul><ul><li>Sympathetic toxicity </li></ul><ul><li>Meningitis or encephalitis </li></ul>
    12. 12. Management <ul><li>Discontinuation all serotonergic agents </li></ul><ul><li>Supportive care - may need sedated&paralysed </li></ul><ul><li>Sedation with benzodiazepines </li></ul><ul><li>Administration serotonin antagonist </li></ul><ul><li>Cyproheptadine – 12mg (PO)+2mg every 2 hr until clinical response </li></ul><ul><li>?Olanzapine, chlorpromazine </li></ul><ul><li>Assess need to restart drug. </li></ul>
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