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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:
• Increase serotonin neurotransmission
• Increased serotonin synthesis
• Decreased serotonin metabolism
• Increased serotonin release
• Inhibition of serotonin reuptake
• Agonism of serotonin receptors (Dvir & Smallwood,
2008).
Toxicity (combined bath, tap, plug)Increase serotonin neurotransmissionIncreased serotonin releaseIncreased serotonin synthesisInhibition of serotonin reuptake
Decreased serotonin metabolismAgonism of serotonin receptors
Triad
• Neuromuscular hyperactivity
• Autonomic hyperactivity
• Altered mental status
Clinical Features
Neuromuscular Autonomic Mental State
Hyper-reflexia Hyperthermia: Agitation
Myoclonus Mild 38.5 C Hypomania
Shivering Severe > 38.5 Anxiety
Tremor Tachycardia Confusion
Hypertonia/rigidity
Diaphoresis
Flushing
Mydriasis
Clinical Features
(Boyer & Shannon, 2005)
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)
Drug Groups Associated
• Serotonin reuptake inhibitors
• MAOI
• Serotonin releasing agents
• Miscellaneous (Isbister, Buckley & Whyte, 2007)
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)
Monoamine oxidase inhibitors
• Irreversible monoamine oxidase A inhibitors: Phenelzine, tranylcypromine
• Reversible monoamine oxidase A inhibitors: Moclobemide
• Others: linezolid (Isbister, Buckley & Whyte, 2007)
Serotonin releasing agents
• Fenfluramine
• Amphetamines
• MDMA, ecstasy
Miscellaneous
• Lithium• Tryptophan (Isbister, Buckley & Whyte, 2007)
Diagnostic Algorithm
(Boyer & Shannon, 2005)
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
Spectrum of toxicity
(Boyer & Shannon, 2005)
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).
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.