Reported Cases of Serotonin Syndrome in MDMA Users in FAERS Database

This study (2022) assessed the occurrence of serotonin syndrome (SS) associated with MDMA use and reported it to the FDA Adverse Event Reporting System (FAERS) through MedWatch. In each of the 20 reported cases of SS, people had also taken one or more substances with serotonergic properties in addition to MDMA, including amphetamines, stimulants and opioids. There were no reports of sole MDMA use leading to SS.

Abstract

“3,4-Methylenedioxymethamphetamine (MDMA), is investigated as a treatment for post-traumatic stress disorder and other anxiety-related conditions in multiple placebo-controlled and open-label studies. MDMA-assisted therapy is projected for approval by the United States Food and Drug Administration (FDA) and other regulatory agencies worldwide within the next few years. MDMA is a monoamine releaser and uptake inhibitor affecting serotonin, potentially increasing the risk of serotonin syndrome (SS). No instances of SS have occurred in clinical trials. The relatively small number of patients in controlled trials warranted a survey of FDA Adverse Event Reporting System data for the occurrence of SS in a larger database. We found 20 SS cases in people exposed to MDMA, all of which had also taken one or more substances with serotonergic properties in addition to MDMA, including amphetamines, stimulants, and opioids. There were no cases of SS associated with MDMA where MDMA was the solely reported compound taken.”

Authors: Tigran Makunts, Lisa Jerome, Ruben Abagyan & Alberdina de Boer

Notes

Serotonin syndrome (SS) is the result of serotonergic overactivity at the synapse and is a potentially life-threatening condition. SS is usually associated with serotonergic medications such as SSRIs and MDMA. Symptoms range in severity from physical restlessness (akathisia) and tremors to more severe symptoms including hyperthermia and muscle rigidity. As the therapeutic potential of MDMA is becoming more well-known thanks to rigorous clinical research, it is important that we understand how MDMA relates to SS.

The present paper explores the risk of MDMA induced SS. Given there have been no reported cases of SS in clinical studies with MDMA, the researchers analysed reported cases of SS in the FDA Adverse Event Reporting System (FAERS). FAERS is a database that contains adverse event reports, medication error reports and product quality complaints resulting in adverse events that are submitted to FDA.

The main findings:

  • 20 out of 1,143 adverse events which included MDMA and were reported to FAERS were reports of SS.
  • There were no reports of SS where MDMA was the sole responsible compound.
  • In each of the 20 reported cases of SS, people had taken one or more substances with serotonergic properties alongside MDMA inlcuing amphetamines, stimulants and opioids.

Overall, the present paper confirms the observation in clinical trials that there have been no reported cases of SS when MDMA is the only substance being administered. The authors do acknowledge limitations including that reporting to FAERS is mostly voluntary and therefore the dataset represents a subset of actual cases. Nonetheless, these findings are positive for MDMA-assisted therapies.

Find this paper

Reported Cases of Serotonin Syndrome in MDMA Users in FAERS Database

https://doi.org/10.3389/fpsyt.2021.824288

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Published in
Frontiers in Psychiatry
January 24, 2022
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Study details

Compounds studied
MDMA

Topics studied
Safety

Study characteristics
Meta-Analysis Observational

Institutes

Institutes associated with this publication

MAPS PBC
MAPS Public Benefit Corporation (MAPS PBC) is the 'benefit above profit' corporation that is fully owned by MAPS.

University of California San Diego
The Psychedelics and Health Research Initiative (PHRI) at UC San Diego conducts novel basic and clinical research on the use of psychedelics.