Concomitant drugs associated with increased mortality for MDMA users reported in a drug safety surveillance database

• Published in: Scientific reports Vol. 11; no. 1; pp. 5997 - 9
• Main Authors: Cohen, Isaac V., Makunts, Tigran, Abagyan, Ruben, Thomas, Kelan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.03.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/154/1438; 631/154/433; 631/154/436/108; 631/154/570; 692/308/153; 692/308/174; 692/308/409; 692/699/476; 692/699/476/1830; Adverse Drug Reaction Reporting Systems; Amphetamines; Anesthetics; Antidepressants; Antidepressive Agents - adverse effects; Antidepressive Agents - therapeutic use; Benzodiazepines; Bupropion; Cause of Death; Citalopram; Clinical trials; Databases, Factual; Drug abuse; Drug interaction; Drug interactions; Drug-Related Side Effects and Adverse Reactions - epidemiology; Drug-Related Side Effects and Adverse Reactions - mortality; Ecstasy; Ethanol; Health Care Surveys; Humanities and Social Sciences; Humans; Ingestion; MDMA; Metabolites; Morbidity; Mortality; multidisciplinary; Multivariate Analysis; Muscle relaxants; N-Methyl-3,4-methylenedioxyamphetamine - adverse effects; N-Methyl-3,4-methylenedioxyamphetamine - therapeutic use; Odds Ratio; Olanzapine; Opioids; Pharmacovigilance; Post traumatic stress disorder; Product safety; Public Health Surveillance; Science; Science (multidisciplinary); Serotonin Agents - adverse effects; Serotonin Agents - therapeutic use; Sertraline; Stimulants; Stress Disorders, Post-Traumatic - complications; Stress Disorders, Post-Traumatic - epidemiology; Stress Disorders, Post-Traumatic - mortality; Stress Disorders, Post-Traumatic - therapy; Surveillance; United States - epidemiology; United States Food and Drug Administration; Venlafaxine; United States
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-85389-x

3,4-Methylenedioxymethamphetamine (MDMA) is currently being evaluated by the Food and Drug Administration (FDA) for the treatment of post-traumatic stress disorder (PTSD). If MDMA is FDA-approved it will be important to understand what medications may pose a risk of drug–drug interactions. The goal of this study was to evaluate the risks due to MDMA ingestion alone or in combination with other common medications and drugs of abuse using the FDA drug safety surveillance data. To date, nearly one thousand reports of MDMA use have been reported to the FDA. The majority of these reports include covariates such as co-ingested substances and demographic parameters. Univariate and multivariate logistic regression was employed to uncover the contributing factors to the reported risk of death among MDMA users. Several drug classes (MDMA metabolites or analogs, anesthetics, muscle relaxants, amphetamines and stimulants, benzodiazepines, ethanol, opioids), four antidepressants (bupropion, sertraline, venlafaxine and citalopram) and olanzapine demonstrated increased odds ratios for the reported risk of death. Future drug–drug interaction clinical trials should evaluate if any of the other drug–drug interactions described in our results actually pose a risk of morbidity or mortality in controlled medical settings.