Serotonin Toxicity: Associated Agents and Clinical Characteristics

Toxicology Investigators Consortium (ToxIC)

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Serotonin toxicity is a common cause of drug-induced altered mental status. However, data on the causes of serotonin toxicity, symptomatology, complications, and rate of antidotal treatment are limited. METHODS: This study evaluated cases of serotonin toxicity in the ToxIC registry, an international database of prospectively collected cases seen by medical toxicologists. Serotonin toxicity was diagnosed by bedside evaluation of medical toxicology specialists and explicit criteria were not used. The database was searched for "serotonin syndrome" between January 1, 2010, and December 31, 2016. RESULTS: There were 1010 cases included. Females made up 608 (60%) cases. Ages are as follows: younger than 2 years (3, 0.3%), 2 to 6 years (8, 0.8%), 7 to 12 years (9, 0.9%), 13 to 18 years (276, 27.3%), 19 to 65 years (675, 67%), older than 66 years (33, 3.4%), unknown (6, 0.6%). Reasons for encounter: intentional (768, 76%), adverse drug event/reaction (127, 12.6%), unintentional (66, 6%), and unknown (55, 5.4%). Signs/symptoms: hyperreflexia/clonus/myoclonus (601, 59.5%), agitation (337, 33.4%), tachycardia (256, 25.3%), rigidity (140, 13.9%), seizures (139, 13.7%), and hyperthermia (29, 2.9%). COMPLICATIONS: rhabdomyolysis (97, 9.7%), dysrhythmias (8, 0.8%), and death (1, 0.1%). TREATMENTS: benzodiazepines 67% (677/1010), cyproheptadine 15.1% (153/1010). There were 192 different xenobiotics reported with 2046 total exposures. Antidepressants were most common (915, 44.7%) with bupropion the most frequent overall (147, 7.2%). Common non-antidepressants were dextromethorphan (95, 6.9%), lamotrigine (64, 3.1%), and tramadol (60, 2.9%). DISCUSSION: Serotonin toxicity most often occurred in adult patients with intentional overdose. Antidepressants were the most common agents of toxicity. Interestingly, bupropion, a norepinephrine/dopamine reuptake inhibitor, was the most frequently mentioned xenobiotic. Though often cited as a potential antidote, only 15% of patients received cyproheptadine. Severe toxicity was rare. A single death was reported.

Original languageEnglish (US)
Pages (from-to)628-633
Number of pages6
JournalJournal of clinical psychopharmacology
Volume39
Issue number6
DOIs
StatePublished - Nov 1 2019

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Serotonin
Cyproheptadine
Bupropion
Xenobiotics
Drug-Related Side Effects and Adverse Reactions
Antidepressive Agents
Dopamine Uptake Inhibitors
Serotonin Syndrome
Databases
Dextromethorphan
Tramadol
Abnormal Reflexes
Antidotes
Myoclonus
Rhabdomyolysis
Benzodiazepines
Tachycardia
Toxicology
Signs and Symptoms
Registries

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Serotonin Toxicity : Associated Agents and Clinical Characteristics. / Toxicology Investigators Consortium (ToxIC).

In: Journal of clinical psychopharmacology, Vol. 39, No. 6, 01.11.2019, p. 628-633.

Research output: Contribution to journalArticle

Toxicology Investigators Consortium (ToxIC). / Serotonin Toxicity : Associated Agents and Clinical Characteristics. In: Journal of clinical psychopharmacology. 2019 ; Vol. 39, No. 6. pp. 628-633.
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abstract = "BACKGROUND: Serotonin toxicity is a common cause of drug-induced altered mental status. However, data on the causes of serotonin toxicity, symptomatology, complications, and rate of antidotal treatment are limited. METHODS: This study evaluated cases of serotonin toxicity in the ToxIC registry, an international database of prospectively collected cases seen by medical toxicologists. Serotonin toxicity was diagnosed by bedside evaluation of medical toxicology specialists and explicit criteria were not used. The database was searched for {"}serotonin syndrome{"} between January 1, 2010, and December 31, 2016. RESULTS: There were 1010 cases included. Females made up 608 (60{\%}) cases. Ages are as follows: younger than 2 years (3, 0.3{\%}), 2 to 6 years (8, 0.8{\%}), 7 to 12 years (9, 0.9{\%}), 13 to 18 years (276, 27.3{\%}), 19 to 65 years (675, 67{\%}), older than 66 years (33, 3.4{\%}), unknown (6, 0.6{\%}). Reasons for encounter: intentional (768, 76{\%}), adverse drug event/reaction (127, 12.6{\%}), unintentional (66, 6{\%}), and unknown (55, 5.4{\%}). Signs/symptoms: hyperreflexia/clonus/myoclonus (601, 59.5{\%}), agitation (337, 33.4{\%}), tachycardia (256, 25.3{\%}), rigidity (140, 13.9{\%}), seizures (139, 13.7{\%}), and hyperthermia (29, 2.9{\%}). COMPLICATIONS: rhabdomyolysis (97, 9.7{\%}), dysrhythmias (8, 0.8{\%}), and death (1, 0.1{\%}). TREATMENTS: benzodiazepines 67{\%} (677/1010), cyproheptadine 15.1{\%} (153/1010). There were 192 different xenobiotics reported with 2046 total exposures. Antidepressants were most common (915, 44.7{\%}) with bupropion the most frequent overall (147, 7.2{\%}). Common non-antidepressants were dextromethorphan (95, 6.9{\%}), lamotrigine (64, 3.1{\%}), and tramadol (60, 2.9{\%}). DISCUSSION: Serotonin toxicity most often occurred in adult patients with intentional overdose. Antidepressants were the most common agents of toxicity. Interestingly, bupropion, a norepinephrine/dopamine reuptake inhibitor, was the most frequently mentioned xenobiotic. Though often cited as a potential antidote, only 15{\%} of patients received cyproheptadine. Severe toxicity was rare. A single death was reported.",
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N2 - BACKGROUND: Serotonin toxicity is a common cause of drug-induced altered mental status. However, data on the causes of serotonin toxicity, symptomatology, complications, and rate of antidotal treatment are limited. METHODS: This study evaluated cases of serotonin toxicity in the ToxIC registry, an international database of prospectively collected cases seen by medical toxicologists. Serotonin toxicity was diagnosed by bedside evaluation of medical toxicology specialists and explicit criteria were not used. The database was searched for "serotonin syndrome" between January 1, 2010, and December 31, 2016. RESULTS: There were 1010 cases included. Females made up 608 (60%) cases. Ages are as follows: younger than 2 years (3, 0.3%), 2 to 6 years (8, 0.8%), 7 to 12 years (9, 0.9%), 13 to 18 years (276, 27.3%), 19 to 65 years (675, 67%), older than 66 years (33, 3.4%), unknown (6, 0.6%). Reasons for encounter: intentional (768, 76%), adverse drug event/reaction (127, 12.6%), unintentional (66, 6%), and unknown (55, 5.4%). Signs/symptoms: hyperreflexia/clonus/myoclonus (601, 59.5%), agitation (337, 33.4%), tachycardia (256, 25.3%), rigidity (140, 13.9%), seizures (139, 13.7%), and hyperthermia (29, 2.9%). COMPLICATIONS: rhabdomyolysis (97, 9.7%), dysrhythmias (8, 0.8%), and death (1, 0.1%). TREATMENTS: benzodiazepines 67% (677/1010), cyproheptadine 15.1% (153/1010). There were 192 different xenobiotics reported with 2046 total exposures. Antidepressants were most common (915, 44.7%) with bupropion the most frequent overall (147, 7.2%). Common non-antidepressants were dextromethorphan (95, 6.9%), lamotrigine (64, 3.1%), and tramadol (60, 2.9%). DISCUSSION: Serotonin toxicity most often occurred in adult patients with intentional overdose. Antidepressants were the most common agents of toxicity. Interestingly, bupropion, a norepinephrine/dopamine reuptake inhibitor, was the most frequently mentioned xenobiotic. Though often cited as a potential antidote, only 15% of patients received cyproheptadine. Severe toxicity was rare. A single death was reported.

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