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Review ArticlePractice

Demystifying serotonin syndrome (or serotonin toxicity)

Ai-Leng Foong, Kelly A. Grindrod, Tejal Patel and Jamie Kellar
Canadian Family Physician October 2018; 64 (10) 720-727;
Ai-Leng Foong
Completed her Doctor of Pharmacy degree at the University of Waterloo School of Pharmacy in Ontario.
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Kelly A. Grindrod
Assistant Professor in the University of Waterloo School of Pharmacy and a clinical pharmacist at the Kitchener Downtown Community Health Centre.
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  • For correspondence: kgrindrod@uwaterloo.ca
Tejal Patel
Assistant Clinical Professor in the University of Waterloo School of Pharmacy, part-time Assistant Clinical Professor in the Michael G. DeGroote School of Medicine at McMaster University, a clinical pharmacist with the Memory Clinic at the Centre for Family Medicine Family Health Team in Kitchener, a research scientist at the Schlegel–University of Waterloo Research Institute for Aging, and an affiliate researcher with the Waterloo Institute for Complexity and Innovation.
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Jamie Kellar
Assistant Professor and Acting Director of the Doctor of Pharmacy program at the Leslie Dan Faculty of Pharmacy at the University of Toronto in Ontario, an advanced practice hospital pharmacist at the Centre for Addiction and Mental Health in Toronto, a doctoral candidate in the School of Health Professions Education at Maastricht University in the Netherlands, and a research fellow at the Wilson Centre in Toronto.
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    Figure 2.

    Serotonin physiology: Serotonin is formed in the presynaptic terminal from tryptophan. Once packaged into vesicles, it is released into the synaptic cleft where it can bind to serotonin receptors on the postsynaptic neuron to exert its action. Serotonin is transported through a transporter to the presynaptic terminal where it is broken down by monoamine oxidase.15 The 3 classes of drugs that increase serotonin in synapses are highlighted in red.

    5HT—5-hydroxytryptamine.

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    Table 1.

    Evidence supporting the key considerations for practice

    CLINICAL CONSIDERATIONSEVIDENCE RATINGREFERENCES
    The best available evidence for the clinical presentation of toxicity is from the Hunter Area Toxicology Service in AustraliaLevel II*1
    Serotonin toxicity most often happens when 2 serotonin-elevating drugs are used together. The use of an MAOI with an SSRI, an SNRI, or another MAOI is the most concerning drug combinationLevel III†1,3
    Some drugs thought to cause serotonin toxicity do not (eg, triptans, ondansetron)Level III†1,4,7–11
    Prevention of serotonin toxicity through good prescribing practices and monitoring is importantLevel III†2,12
    • MAOI—monoamine oxidase inhibitor, SNRI—serotonin-norepinephrine reuptake inhibitor, SSRI—selective serotonin reuptake inhibitor.

    • ↵* Level II: Comparison trials other than randomized controlled trials, systematic reviews, or meta-analyses; non-randomized, cohort, case-control, or epidemiologic studies; and preferably more than 1 study.

    • ↵† Level III: Expert opinion or consensus statements.

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    Table 2.

    Signs and symptoms of serotonin toxicity

    CATEGORYSIGNS AND SYMPTOMS
    Neuromuscular
    • Tremor

    • Hyperreflexia (increased reflexes)*

    • Clonus (rhythmic muscle spasms that can be spontaneous, inducible, or ocular)*

    Autonomic
    • Mydriasis (dilated pupils)

    • Diaphoresis (sweating)

    • Tachycardia (increased heart rate)

    • Tachypnea (increased breathing rate)

    Mental status
    • Agitation

    • Excitement

    • Restlessness

    • Confusion

    • Delirium

    • Data from Dunkley et al,1 Boyer and Shannon,2 Ables and Nagubilli,12 and Isbister et al.13

    • ↵* Hyperreflexia and clonus are often worse in the legs than in the arms.

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Canadian Family Physician: 64 (10)
Canadian Family Physician
Vol. 64, Issue 10
1 Oct 2018
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Demystifying serotonin syndrome (or serotonin toxicity)
Ai-Leng Foong, Kelly A. Grindrod, Tejal Patel, Jamie Kellar
Canadian Family Physician Oct 2018, 64 (10) 720-727;

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Demystifying serotonin syndrome (or serotonin toxicity)
Ai-Leng Foong, Kelly A. Grindrod, Tejal Patel, Jamie Kellar
Canadian Family Physician Oct 2018, 64 (10) 720-727;
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