Concomitant medications associated with ischemic, hypertensive, and arrhythmic events in MDMA users in FDA adverse event reporting system
A survey of the FDA Adverse Event Reporting System identified 17 cardiovascular adverse events in people who had used MDMA alongside other substances, and all concomitant medications or illicit drugs (opioids, stimulants, anticholinergics, amphetamines) had prior associations with cardiovascular harm. In none of the reports was MDMA designated as the primary suspect, suggesting concomitant drugs may have driven the events.
Abstract
3,4-Methylenedioxymethamphetamine (MDMA) is currently being investigated as an adjunctive treatment to therapy for posttraumatic stress and other anxiety related disorders in clinical trials. Within the next few years MDMA-assisted therapy is projected for approval by regulatory authorities. MDMA’s primary mechanism of action includes modulation of monoamine signaling by increasing release and inhibiting reuptake of serotonin, norepinephrine, and, to a lesser extent, dopamine. This pharmacology affects sympathomimetic physiology. In controlled trials, special attention has been given to cardiovascular adverse events (AEs), because transient increases in heart rate and blood pressure have been observed during the MDMA-assisted therapy sessions. Finding and quantifying the potential drivers of cardiac AEs in clinical trials is difficult since only a relatively small number of participants have been included in these studies, and a limited set of allowed concomitant drugs has been studied. In this study a more diverse set of reports from the FDA Adverse Event Reporting System was surveyed. We found 17 cases of cardiovascular AEs, in which the individuals had taken one or more substances in addition to MDMA. Interestingly, all of those concomitant medications and illicit substances, including opioids, stimulants, anticholinergics, and amphetamines, had been previously associated with cardiovascular AEs. Furthermore, in none of the reports MDMA was marked as the primary suspect.
Research Summary of 'Concomitant medications associated with ischemic, hypertensive, and arrhythmic events in MDMA users in FDA adverse event reporting system'
Introduction
MDMA (3,4-methylenedioxymethamphetamine; also known as Ecstasy) is under active investigation as an adjunct to psychotherapy, most notably in Phase III trials for PTSD. Its principal pharmacology includes increased release and inhibited reuptake of serotonin, norepinephrine and, to a lesser extent, dopamine, and it also raises oxytocin levels. While these effects may facilitate fear-extinction learning and enhance therapeutic engagement, modulation of monoamine signalling produces sympathomimetic physiological effects that have been associated with transient increases in heart rate and blood pressure and, more rarely, arrhythmic, hypertensive or ischemic adverse events (AEs) in the literature and in clinical trials. Makunts and colleagues set out to examine reports of arrhythmic, ischemic and hypertensive AEs in MDMA users recorded in the FDA Adverse Event Reporting System (FAERS). The study aimed to determine whether MDMA was reported as the primary suspect in such events and to evaluate the contribution of concomitant prescription drugs and illicit substances to these cardiovascular AEs, recognising that many psychiatric populations exhibit polypharmacy that was excluded from controlled trials.
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Makunts, T., Dahill, D., Jerome, L., de Boer, A., & Abagyan, R. (2023). Concomitant medications associated with ischemic, hypertensive, and arrhythmic events in MDMA users in FDA adverse event reporting system. Frontiers in Psychiatry, 14. https://doi.org/10.3389/fpsyt.2023.1149766
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Sarparast, A., Thomas, K., Malcolm, B. et al. · Psychopharmacology (2022)
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