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Serotonin Syndrome (Toxicity) Sue Henderson

Serotonin Syndrome (Toxicity) Sue Henderson. Definition. Potentially life threatening adverse drug reaction caused by excessive serotonin in CNS (Dvir & Smallwood, 2008). Role of Serotonin. Serotonin neurotransmission. Cause: Serotonin toxicity. Pharmacological agents:

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Serotonin Syndrome (Toxicity) Sue Henderson

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  1. Serotonin Syndrome (Toxicity)Sue Henderson

  2. Definition • Potentially life threatening adverse drug reaction caused by excessive serotonin in CNS (Dvir & Smallwood, 2008).

  3. Role of Serotonin

  4. Serotonin neurotransmission

  5. Cause: Serotonin toxicity Pharmacological agents: • Increase serotonin neurotransmission • Increased serotonin synthesis • Decreased serotonin metabolism • Increased serotonin release • Inhibition of serotonin reuptake • Agonism of serotonin receptors (Dvir & Smallwood, 2008).

  6. Toxicity (combined bath, tap, plug) Increase serotonin neurotransmission Increased serotonin release Increased serotonin synthesis Inhibition of serotonin reuptake Decreased serotonin metabolism Agonism of serotonin receptors

  7. Triad • Neuromuscular hyperactivity • Autonomic hyperactivity • Altered mental status

  8. Clinical Features

  9. Clinical Features (Boyer & Shannon, 2005)

  10. Causes of toxicity All drugs that directly or indirectly increase serotonin due to: • Overdose - 15% (Isbister et al, 2004 cited in Isbister, Buckley & White,2007) • Adverse drug effect • Drug interaction • Possible genetic contribution (enhanced sensitivity)

  11. Drug Groups Associated • Serotonin reuptake inhibitors • MAOI • Serotonin releasing agents • Miscellaneous (Isbister, Buckley & Whyte, 2007)

  12. Serotonin Reuptake Inhibitors • SSRIs: Fluoxetine, fluvoxamine, paroxetine, citalopram, sertraline, escitalopram • Other antidepressants: Venlafaxine, clomipramine, imipramine, • Opioid analgesics: pethidine, tramadol, fentanyl, dextromethorphan • St. John’s Wort (Isbister, Buckley & Whyte, 2007)

  13. Monoamine oxidase inhibitors • Irreversible monoamine oxidase A inhibitors: Phenelzine, tranylcypromine • Reversible monoamine oxidase A inhibitors: Moclobemide • Others: linezolid (Isbister, Buckley & Whyte, 2007)

  14. Serotonin releasing agents • Fenfluramine • Amphetamines • MDMA, ecstasy Miscellaneous • Lithium • Tryptophan (Isbister, Buckley & Whyte, 2007)

  15. Diagnostic Algorithm (Boyer & Shannon, 2005)

  16. Prevention • Avoid serotonergic drugs but if not possible minimize use of serotonergic drugs (Isbister, Buckley & Whyte, 2007) • Avoid MAOI (to prevent severe toxicity) (Isbister, Buckley & Whyte, 2007) but if not possible ensure a 2 week washout between stopping a MAOI and starting an SSRI

  17. Spectrum of toxicity (Boyer & Shannon, 2005)

  18. Treatment Mild • Discontinue all serotonergic agents • Supportive care: Cooling, IV fluids (Hydration, facilitate diuresis) • Benzodiazepines (prevent agitation) Moderate • Above + Serotonin antagonists (blockers) Severe • Above + intubation, paralysis & sedation (Dvir & Smallwood, 2008).

  19. References Boyer, E. W., & Shannon, M. (2005). The serotonin syndrome. New England Journal of Medicine, 352(11), 1112-1120. Dvir, Y., & Smallwood, P. (2008). Serotonin syndrome: A complex but easily avoidable condition. General Hospital Psychiatry, 30, 284-287. Isbister, G. K., Buckley, N. A., & Whyte, I. M. (2007). Serotonin toxicity: A practical approach to diagnosis and treatment. Medical Journal of Australia, 187(6), 361-365.

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