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

Using FDA drug safety surveillance data, nearly one thousand reports of MDMA use were analyzed to evaluate risks of death when MDMA is taken alone or with other medications. Several drug classes—including MDMA metabolites or analogs, anesthetics, muscle relaxants, amphetamines and stimulants, benzodiazepines, ethanol, and opioids—along with the antidepressants bupropion, sertraline, venlafaxine, and citalopram, and the antipsychotic olanzapine, showed increased odds ratios for reported risk of death. The authors call for future clinical trials to assess whether these drug–drug interactions pose actual harm in controlled medical settings.

Study at a glance

Abstract

Abstract 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.