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.

Keywords: Forensic pathology; Gabapentin; Hydrocodone; Mixed-drug fatality; Opioid overdose; Substance abuse.

Figure 1

The most common analytes when considering both blood and urine toxicology of N=180 subjects that occur with a frequency >0.2.

Figure 2

The most common analytes from the urine samples of n=144 subjects for whom urinalysis was available that occur with a frequency >0.2.

Figure 3

The most common analytes from the blood samples of n=178 subjects for whom blood toxicology was available that occur with a frequency >0.2.

Figure 4

Gabapentin concentration in the presence or absence of hydrocodone. The average blood gabapentin concentration in decedents with positive hydrocodone toxicology (n=12) was 11.98 μg/mL ± 2.52. The average blood concentration of gabapentin in decedents with negative hydrocodone toxicology (n=34) was 14.11 μg/mL ± 2.92.

Figure 5

Hydrocodone concentration in the blood versus gabapentin concentration. There appears to be no significant direct or inverse association between concentrations of blood hydrocodone and blood gabapentin (R² = 0.0051).

Figure 6

Hydrocodone concentration in the urine versus gabapentin concentration. There appears to be no significant direct or inverse association between concentrations of urine hydrocodone and blood gabapentin (R² = 0.28118).