The impact of antidepressant use on MDMA fatalities: A matched case-control study using a post-mortem database

BACKGROUND: 3,4-methylenedioxymethamphetamine (MDMA) is being investigated as a new therapy for post-traumatic stress disorder (PTSD). With antidepressants as the first-line pharmacotherapy for PTSD, it is important to understand any drug-drug interactions between antidepressants and MDMA. This study aimed to investigate the association between antidepressant use and MDMA fatality using a drug-death database. METHODS: A retrospective case-control study was performed using a dataset from the National Programme on Substance Use Mortality. Deaths reported between 1997 and May 2023 were extracted. Cases were defined as deaths with MDMA detected and were age- and sex-matched to controls, defined as deaths with no MDMA detected. Cases were analysed by post-mortem (PM) detection of antidepressants and prescription of antidepressants. Conditional logistic regression was performed, adjusted for confounders (polysubstance use and intentionality of death). RESULTS: A total of 1328 cases and 5312 matched controls for the PM analysis and 840 cases and 3360 matched controls for the prescribed analysis were included. In the PM analysis, after adjusting for potential confounders, antidepressant use was less likely in MDMA fatalities compared to other drug-related deaths (adjusted OR [aOR] 0.595 [95% Confidence interval (CI) 0.491-0.722]). In the prescribed analysis, there was no significant association between the prescription of antidepressants and MDMA fatalities (aOR 0.838 [95% CI 0.688-1.021]). CONCLUSIONS: An inverse association was found between antidepressant use and MDMA fatality in this retrospective case-control study using a drug-death database.