What does ‘polysubstance’ really mean? Comparing drug-involved deaths in CDC records vs. detailed medical examiner data from Los Angeles

31/12/2025

Int J Drug Policy. 2025 Dec 29;148:105129. doi: 10.1016/j.drugpo.2025.105129. Online ahead of print.

ABSTRACT

INTRODUCTION: Complex polysubstance use is increasing in the United States. However, most epidemiological literature relies on traditional data sources, especially CDC WONDER, which is limited to employing two ICD-10 codes concurrently. We leverage complete medical examiner records from Los Angeles County to examine the limitations of CDC WONDER data for detecting polysubstance drug deaths.

METHODS: Drug-involved deaths occurring in Los Angeles County were described using the CDC WONDER system and Los Angeles County Medical Examiner data. Annual single-drug involvement rates were compared between the two data sources. The average number of drugs, and the proportion of polysubstance deaths involving 3 or more substances was summarized by year. UpSet plot visualization was employed for complex set analysis.

RESULTS: Overall concordance in single-substance death counts between CDC WONDER and medical examiner records was high among n = 6 substances assessed. The average number of drugs reported per death had a skewed distribution and increased from 1.72 in 2012 to 2.29 in 2023. The percentage of polysubstance deaths with 3+ drugs increased from 51% in 2012 to 74% in 2023. The number of unique polysubstance combinations with 3+ substances increased from 11 in 2012 to 57 in 2023.

DISCUSSION: Although concordance is high for single-substance involvement rates, CDC WONDER fails to capture the majority of polysubstance deaths adequately, as about three-quarters of these deaths are incompletely described using its 2-drug limit. This limitation has worsened as deaths increasingly involve more drugs on average. We illustrate a huge variety of polysubstance combinations that can be seen in medical examiner deaths. As the overdose crisis grows increasingly polysubstance in nature, improving the epidemiological tracking of deaths involving multiple drugs, and drugs not captured by ICD-10 codes currently, is of paramount importance.

PMID:41468628 | DOI:10.1016/j.drugpo.2025.105129

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