Gabapentin in drugged driving investigations.

The increasing use and misuse of gabapentin pose a major risk to public health and traffic safety. Gabapentin has been approved by the Food and Drug Administration (FDA) since 1993 for adjunctive therapy in the treatment of epilepsy and neuralgia but is increasingly being prescribed for numerous off-label uses including insomnia, anxiety, depression, and migraine. Reported side effects include blurred vision, drowsiness, and loss of coordination. Driving behaviors such as exiting the lane of travel and crashes have been reported in connection to drugged driving investigations concerning gabapentin. To further assist with the toxicological interpretation of gabapentin in driving under the influence of drugs (DUID) scenarios, a review of approximately 108,000 gabapentin-positive DUID cases was conducted. Of those, 858 cases met inclusion criteria and underwent additional evaluation. Blood specimens were screened via enzyme-linked immunosorbent assay (ELISA) and confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS) for quantitation of gabapentin. This review found an overall DUID gabapentin positivity of 7.9% between January 2020 and December 2022; 17 states from various geographical regions had at least one positive gabapentin DUID case. Observations in six driving and human performance cases where gabapentin was the only drug reported were consistent with the known adverse effects of the medication. Half of the case histories reviewed involved crashes where the driver was determined to be at fault. Additionally, 94% of the cases in this review involved gabapentin in combination with other drugs. The most prevalent drug combinations were opioids and gabapentin present in 64% of cases.

Distribution of donepezil in postmortem casework.

Donepezil is one of the primary treatments options for patients suffering from Alzheimer's Disease. In a review of more than 2200 postmortem donepezil positive blood specimens, 76% of concentrations were higher than the proposed therapeutic range. Means and medians were similar between central blood specimens and peripheral specimens, indicating minimal postmortem redistribution. Postmortem concentrations may not reflect those circulating antemortem. Mean and median postmortem blood concentrations were approximately 3-fold higher than those in antemortem blood specimens. Additionally, in cases where antemortem blood was available for testing, large increases in donepezil concentrations were reported between antemortem and postmortem specimens without documented administration by medical personnel. Elevated blood donepezil concentrations have been reported in multiple postmortem cases where cause of death was unrelated. The blood concentrations reported in cases where donepezil did not contribute to death overlapped with those in suspected drug overdose cases where other drugs may have been present. In 4 out of 5 suspected donepezil overdose cases, blood concentrations greater than 1000 ng/mL were reported, whereas less than 1% of all postmortem blood samples reviewed achieved these concentrations. Blood concentrations greater than 1000 ng/mL should be considered contributory when a drug overdose is suspected. Postmortem donepezil concentrations should be interpreted with caution in the context of a comprehensive case history.

11-Year Study of Fentanyl in Driving Under the Influence of Drugs Casework†.

Prior to 2017, heroin and other prescription opioids were the most prevalent opioids implicated in driving under the influence of drugs (DUID) investigation cases, and fentanyl was rarely included in the scope of toxicological analysis. Fentanyl has become the most frequently identified opioid in DUID cases, with many suspected heroin cases turning out to be only fentanyl. A review of fentanyl-positive DUID cases at NMS Labs was performed to provide prevalence information, change in concentration, patterns of combined drug use, indicators of impairment and driving behavior in order to assist with the toxicological interpretation of DUID scenarios involving fentanyl. Fentanyl-positive DUID cases received between January 2010 and December 2020 were examined. Blood results were confirmed and quantitated for fentanyl, norfentanyl and acetylfentanyl using a liquid chromatography--tandem mass spectrometry analysis with a limit of quantitation of 0.10, 0.20 and 0.10 ng/mL, respectively. Of 153,234 blood cases examined for DUID over 11 years, fentanyl was confirmed positive in 6,779 (4.4%) cases. However, there were significant changes in positivity over time. Fentanyl percentage positivity increased from 0.60% in 2010 to 12% in 2020. Of 5,976 confirmed fentanyl-positive cases in 2018-2020, blood concentrations >4.0 ng/mL were observed in 44% (2018), 55% (2019) and 59% (2020) of cases. Polypharmacy was common with 87% of blood samples confirmed positive for fentanyl and at least one other compound. Stimulant was the most commonly identified drug class in cases where at least one additional drug class was present. This study illustrates the importance of including fentanyl in a routine blood DUID panel.