IMR Press / JIN / Volume 19 / Issue 4 / DOI: 10.31083/j.jin.2020.04.314
Open Access Commentary
Serotonin syndrome: a clinical review of current controversies
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1 Department of Clinical Sciences - Psychiatry, Sunderby Research Unit, Umeå University,90187, Umeå, Sweden
2 Sunderby Hospital, 97180, Luleå, Sweden
3 Department of Public Health and Clinical Medicine - Medicine, Umeå University, 90187, Umeå, Sweden
*Correspondence: (Ursula Werneke)
J. Integr. Neurosci. 2020, 19(4), 719–727;
Submitted: 7 October 2020 | Revised: 16 December 2020 | Accepted: 16 December 2020 | Published: 30 December 2020
Copyright: © 2020 Werneke et al. Published by IMR Press.
This is an open access article under the CC BY 4.0 license (

Serotonin syndrome is a state of increased central and peripheral serotonin (5-hydroxytryptamine) activity. Unless recognized and treated early, serotonin syndrome can lead to seizures, shock and death. Both substances with direct and indirect serotonergic activity can precipitate the syndrome. Serotonin syndrome can occur not only in psychiatric but also in non-psychiatric settings. Yet, clinicians may not be familiar with the condition. We explore some of the current controversies regarding serotonin syndrome. Specifically, we tested the following assumptions: (i) Despite being rare, serotonin syndrome is still clinically relevant; (ii) The Hunter criteria are the gold standard for diagnosing serotonin syndrome; (iii) Hyperthermia is common in cases of serotonin syndrome; (iv) Serotonin syndrome usually develops fast; (v) Severe serotonin syndrome usually or almost exclusively involves monoamine oxidase inhibitors. We found that (i) despite being rare, serotonin syndrome was clinically relevant, (ii) the Hunter criteria could not be regarded as the gold standard for the diagnosis of serotonin syndrome since they missed more cases than the other two diagnostic criteria systems (Sternbach and Radomski criteria), (iii) Serotonin syndrome could occur in the absence of an elevated temperature, (iv) fast onset could not be regarded as a reliable clinical sign of serotonin syndrome, and (v) absence of monoamine oxidase inhibitors treatment did not exclude a diagnosis of serotonin syndrome. Clinicians should bear in mind that in the context of relevant drug history, serotonin syndrome may still be possible in these circumstances.

Serotonin syndrome
antidepressive agents
monoamine oxidase inhibitors
signs and symptoms
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