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Serotonin syndrome: A pharmacovigilance comparative study of drugs affecting serotonin levels

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Abstract

Background

Serotonin syndrome is a rare and potentially fatal adverse drug reaction caused by serotonergic drugs and is due to an increase in serotonin concentration or activation of the 5-HT receptor in the central nervous system. We analysed adverse events in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) data set to investigate the main drug classes related to reports of serotonin syndrome and the reporting risk in relation to age and sex.

Methods

We analysed data from the FAERS database to evaluate the main drug classes related to reports of the serotonin syndrome, and the reporting risk in relation to age and sex.

Results

We found 8,997 cases of serotonin syndrome; selective serotonin reuptake inhibitors (SSRIs) was the class of drugs with most reports, followed by opioids and other antidepressants. The highest Reporting Odds Ratios (ROR) for drug classes was for monoamine oxidase (MAO) inhibitors (45.99, 95% confidence interval (CI): 41.21–51.33) and SSRIs (32.66, 95% CI: 31.33–34.04), while the ten active substances with the highest ROR were moclobemide, isocarboxazid, oxitriptane, tranylcypromine, melitracen, phenelzine, linezolid, amoxapine, reboxetine and tryptophan; with values of ROR ranging from 44.19 (95% CI: 25.38–76.94) of tryptophan to 388.36 (95% CI: 314.58-479.46) of moclobemide. The ROR for the most commonly involved drugs was higher in the group of older adults (65 > years old), and higher in males.

Conclusion

Prescribers need to be vigilant about drugs that can raise serotonin concentration or influence serotonergic neurotransmission, also when using drugs with less well-known risk for serotonin syndrome, like linezolid and triptans.

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Data availability

The data are openly available in the FDA Adverse Event Reporting System Public Dashboard at https://openvigil.sourceforge.net/.

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Acknowledgements

All authors participated in the development of the manuscript and approved its final version. We are grateful to J.D. Baggott for language editing.

Funding

No funding was received for conducting this study.

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Authors and Affiliations

  1. Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy

    Chiara Elli

  2. Laboratory of Clinical Pharmacology and Appropriateness of Drug Prescription, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, Milano, 20156, Italy

    Chiara Elli, Alessio Novella & Luca Pasina

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  1. Chiara Elli
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  2. Alessio Novella
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Elli, C., Novella, A. & Pasina, L. Serotonin syndrome: A pharmacovigilance comparative study of drugs affecting serotonin levels. Eur J Clin Pharmacol 80, 231–237 (2024). https://doi.org/10.1007/s00228-023-03596-z

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