Temporal trend of drug overdose-related deaths and excess deaths during the COVID-19 pandemic: a population-based study in the United States from 2012 to 2022

Background: Drug overdose is an escalating public health crisis in the United States (U.S.). This study evaluated the temporal trend of drug overdose-related deaths in the U.S., with an emphasis on identifying disparities across subpopulations and the contributing drugs. Methods: Using the nationwide death dataset from the National Vital Statistics System (NVSS), we estimated the drug overdose-related age-standardized mortality rate (ASMR) and temporal trends for individuals aged 12 and older from 2012 to 2022. Excess mortality during the Coronavirus disease 2019 (COVID-19) pandemic was evaluated based on the pre-pandemic trends using predictive modeling analysis. Findings: Among 809,967 overdose-related deaths during 2012–2022, ASMR increased by 8.9% [95% confidence interval (CI): 6.0%–11.9%] per year from 2012 to 2019 and increased to 12.9% (95% CI: 2.1%–24.8%) from 2019 to 2022, with the excess ASMR of 16.9% in 2020, increased to 26.4% in 2021 and then decreased to 19.3% in 2022. Significant age, sex, racial/ethnic and geographic disparities were demonstrated, with adolescents (annual percentage change [APC]:21.6%) and males (APC:13.6%) having the most pronounced increase during the pandemic. Ethnic minorities especially the non-Hispanic American Indian/Alaska Native experienced the highest excess ASMR (33.1% in 2020). Illicit fentanyl and synthetics starting with the lowest ASMR in 2012 (1.0 per 100,000), marked the most dramatic increase and became the leading cause of overdose-related death since 2016 (7.5 per 100,000), leading to the highest ASMR by 2022 (27.4 per 100,000). All drug types except heroin experienced varying degrees of excess ASMRs, with prescription opioid pain relievers (23.5%–55.1%), benzodiazepines (27.4%–40.9%) and antidepressants (10.4%–17.8%) exhibiting consistent increases from 2020 to 2022, while the excess ASMRs for illicit fentanyl and synthetics (25.3%–10.0%), psychostimulants (32.8%–14.6%) and methadone (35.0%–33.3%) decreased between 2021 and 2022. Interpretation: Overdose-related mortality is increasing at an alarming rate, and the stark differences point to the need for targeted interventions to reduce the burden of drug overdose deaths. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.