Gabapentin in Mixed Drug Fatalities: Does this Frequent Analyte Deserve More Attention?

Abstract

From 2000 to 2014, drug overdose deaths increased 137% in the United States, and 61% of these deaths included some form of opiate. The vast majority of opiate-related drug fatalities include multiple drugs, although there is scant data quantitatively describing the exact drugs that contribute to deaths due to multiple drugs. In the present study, we sought to quantitatively identify the drugs that occur with opiates in accidental multidrug-related fatalities. We retrospectively explored fatal drug trends in four Michigan counties, with a focus on profiling drugs present concurrently with opiates. Blood and urine toxicology reports for mixed drug fatalities (N=180) were analyzed using frequent item analysis approaches to identify common analyte trends in opiate-related fatalities. Within our cohort, the most prevalent serum analytes included caffeine (n=147), morphine (n=90), alprazolam (n=69), gabapentin (n=46), and tetrahydrocannabinol (n=44). In 100% of cases where gabapentin was present (n=46), an opiate was also present in the serum or urine. The average gabapentin serum concentration was 13.56 μg/mL (SEM =0.33 μg/mL), with a range of 0.5-88.7 μg/mL. Gabapentin was found at very high frequency in accidental mixed drug fatalities. Gabapentin concentrations were generally within the normal therapeutic range (2-20 μg/mL). It is unknown whether a synergistic effect with opioids may contribute to central respiratory depression. Further research is warranted to determine any contributory role of gabapentin in these deaths. Confirmed interactions could have broad implications for future reporting by forensic pathologists as well as prescribing practices by clinicians.

Analytical Considerations When Developing an LC-MS/MS Method for More than 30 Analytes

“…One mass spectrometer instrument manufacturer has an application note for quantitative analysis of 65 drugs and metabolites on a triple quadrupole mass spectrometer, but the limits are truncated as the highest calibrator investigated was 1000 ng/mL (36). This would prove untenable for many of the analytes listed here as their concentrations are typically much higher than 1000 ng/mL on average in patients (14)(15)(16)(17)(18). To our knowledge this is the first publication of a time-efficient and comprehensive quantitative method that describes in depth these considerations when developing and validating the method.…”

“…This assay was designed around these expectations to capture the most commonly requested assays, except for analytes/assays that require relatively low concentration ranges, which were left out because the dynamic range restrictions of LC-MS/MS made their inclusion problematic. This is not to say that LC-MS/MS cannot analyze very low concentrations, rather that the combination of low limits of quantification (LOQ) 2 with very high upper limits of quantification (ULOQ) as required by opiates and opioids (14)(15)(16)(17)(18) requires a large dynamic range, which is often untenable.…”

Gabapentin—Friend or foe?

“…Concomitant use with opioids significantly increases the risk of fatal opioid overdose, especially at high gabapentin doses, likely due to exacerbated respiratory depression 6 . A study of accidental mixed drug fatalities involving opioids found gabapentin to be present in 26% of cases and typically within normal therapeutic dose ranges 22 …”

“… 6 A study of accidental mixed drug fatalities involving opioids found gabapentin to be present in 26% of cases and typically within normal therapeutic dose ranges. 22 …”

Notes from the Field: Trends in Gabapentin Detection and Involvement in Drug Overdose Deaths — 23 States and the District of Columbia, 2019–2020

“…Gabapentin can be used to potentiate illicit opioids; data indicate gabapentin exposures associated with intentional abuse, misuse, or unknown exposures reported to U.S. poison centers increased by 104% from 2013 to 2017 ( 3 ). However, less is known about the drug’s role in fatal overdoses ( 4 ). To assess quarterly trends in gabapentin-involved overdose deaths of unintentional or undetermined intent during 2019 – 2020, CDC analyzed data from the State Unintentional Drug Overdose Reporting System (SUDORS) in 23 states and the District of Columbia.…”