Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jul 30;12(8):550.
doi: 10.3390/toxics12080550.

Predictors of Serotonin Syndrome in Acute Poisoning with 5-Hydroxytryptamine Modulators

Asmaa F Sharif  1   2 , Mubarak Nasir M Almulhim  3 , Hadi Mohamed A Almosabeh  3 , Mohammed Essam A Alshammasy  3 , Ali Mohammed A Aljeshi  3 , Taher Mohammed A Mufti  3 , Shahd AlNasser  4 , Khalid A Al-Mulhim  5 , Yousef A AlMubarak  5
Affiliations

Predictors of Serotonin Syndrome in Acute Poisoning with 5-Hydroxytryptamine Modulators

Asmaa F Sharif et al. Toxics. .

Abstract

5-Hydroxytryptamine (5-HT) modulators are commonly prescribed medications with potentially life-threatening outcomes, particularly serotonin syndrome (SS). Early prediction of SS is critical not only to avoid lethal drug combinations but also to initiate appropriate treatment. The present work aimed to recognize the significant predictors of SS through a retrospective cross-sectional study that was conducted among patients exposed to an overdose of 5-HT modulators and admitted to a poison control center where 112 patients were enrolled. Of them, 21 patients were diagnosed with SS, and 66.7% of patients with SS were exposed to long-term co-ingestion. There was a noticeable surge in SS between April and May, and 52.4% of patients who suffered from SS were admitted after suicidal exposure (p < 0.05). Patients with SS showed severe presentation indicated by high-grade poison severity scores (PSS) and low Glasgow coma scales (GCS). PSS was a significant predictor of SS with an area under the curve of 0.879. PCO2, pulse, GCS, HCO3, and erythrocytic count were other significant predictors of SS. Combinations of serotonergic agents increase the likelihood of developing SS. Clinicians should be vigilant when prescribing a combination of serotonergic therapy, particularly for patients on illicit sympathomimetic and over-the-counter medications like dextromethorphan.

Keywords: 5-hydroxytryptophan; Hunter Serotonin Toxicity Criteria; selective serotonin re-uptake inhibitors; serotonergic drugs; serotonin syndrome; serotonin toxicity.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Distribution of admitted patients according to the month of admission.
Figure 2
Figure 2
Proportion of admitted patients according to the type of acute drug poisoning.
Figure 3
Figure 3
Proportion of long-term co-ingested agents reported by the studied patients.
Figure 4
Figure 4
Drug combinations among 49 patients diagnosed with acute poisoning with 5-HT modulators. The red boxes represent the drugs consumed acutely, while the blue boxes represent long-term therapies. The number of circles reflects the number of drug combinations encountered. The red circle refers to a drug–drug combination associated with serotonin syndrome, while the green circle refers to a drug–drug combination not associated with serotonin syndrome. Gray cells mean the intersected agent’s combination was not encountered. Black cells refer to inability to assess DDIs as the acutely consumed and long-term agents are the same. For example, two patients exposed to an overdose of dextromethorphan were on SSRIs. One of these patients suffered from SS, while the other patient did not. Also, three patients on anxiolytics were exposed to an overdose of amphetamine. None of them suffered from SS.
Figure 5
Figure 5
Receiver operating characteristic (ROC) curve analysis for the poison severity score as a predictor of serotonin syndrome.
Figure 6
Figure 6
Receiver operating characteristic (ROC) curve analysis for the pulse and red blood cell count as predictors of serotonin syndrome.
Figure 7
Figure 7
Receiver operating characteristic (ROC) curve analysis for the Glasgow coma scale, HCO3, and PCO2 as predictors of serotonin syndrome.
See this image and copyright information in PMC

References

    1. Talton C. Serotonin Syndrome/Serotonin Toxicity. Fed. Pract. 2020;37:452–459. doi: 10.12788/fp.0042. - DOI - PMC - PubMed
    1. Richerson G.B., Buchanan G.F. The Serotonin Axis: Shared Mechanisms in Seizures, Depression, and SUDEP. Epilepsia. 2011;52:28–38. doi: 10.1111/j.1528-1167.2010.02908.x. - DOI - PMC - PubMed
    1. Lanthier C., Dallemagne P., Lecoutey C., Claeysen S., Rochais C. Therapeutic Modulators of the Serotonin 5-HT4 Receptor: A Patent Review (2014-Present) Expert. Opin. Ther. Pat. 2020;30:495–508. doi: 10.1080/13543776.2020.1767587. - DOI - PubMed
    1. Kavanagh J.J., Taylor J.L. Voluntary Activation of Muscle in Humans: Does Serotonergic Neuromodulation Matter? J. Physiol. 2022;600:3657–3670. doi: 10.1113/JP282565. - DOI - PMC - PubMed
    1. Juza R., Vojtechova I., Stefkova-Mazochova K., Dehaen W., Petrasek T., Prchal L., Kobrlova T., Janousek J., Vlcek P., Mezeiova E. Novel D2/5-HT Receptor Modulators Related to Cariprazine with Potential Implication to Schizophrenia Treatment. Eur. J. Med. Chem. 2022;232:114193. doi: 10.1016/j.ejmech.2022.114193. - DOI - PubMed

LinkOut - more resources