This JAMA Pediatrics Patient Page describes naloxone, a medication that reverses opioid poisoning or overdose.
Gabapentin Increasingly Implicated
in Overdose Deaths
Postmortem toxicology tests detected gabapentin in almost 1 in 10 US overdose deaths
between 2019 and 2020.In about half of the
cases, a medical examiner or coroner ruled
the drug was a cause of the death, according to a report from the CDC’s Division of
Overdose Prevention.
The US Food and Drug Administration
(FDA) approved gabapentin for treating seizures and pain associated with shingles. But
growing off-label prescribing of gabapentin for nerve pain and other conditions contributed to its prescription rate doubling
from about 13 to 27 per 1000 insurance beneficiaries between 2009 and 2016. In fact,
by 2019, gabapentin had become the
seventh most prescribed drug in the US.
Gabapentin is sometimes used to amplify the effects of illicit opioids. In late 2019,
the FDA warned that gabapentin might
cause serious breathing difficulties when
usedwith drugs that depress the central nervous system, such as opioids, antianxiety
medications, and antidepressants.
Now, data from the State Unintentional
Drug Overdose Reporting System from 23
states and the District of Columbia suggest
that gabapentin’s role inUS overdose deaths
may be growing.Overall, toxicology tests detected gabapentin in 5687 overdose deaths
between 2019 and 2020—about 10% of all
cases with test results available. Overdose
deaths in which gabapentin was detected
doubled from 449 in the first quarter of 2019
to 959 in the second quarter of 2020.
The proportion of these cases thatmedical examiners ruled were caused by the drug
increased from 50% in early 2019 to 55% by
late 2020. About 90% of these cases also involved opioids, primarily illicitly manufactured fentanyl. About 83% of deaths caused
by gabapentin occurred amongWhite adults
aged 35 to 54 years.
“Personswho use illicit opioidswith gabapentinshouldbeeducatedabouttheincreased
risk for respiratorydepressionanddeath,” the
authors wrote. − Bridget M. Kuehn, MSJ
Background: Benzodiazepine hypnotics and the related nonbenzodiazepine hypnotics (z-drugs) are among the most frequently prescribed medications for older adults. Both can depress respiration, which could have fatal cardiorespiratory effects, particularly among patients with concurrent opioid use. Trazodone, frequently prescribed in low doses for insomnia, has minimal respiratory effects, and, consequently, may be a safer hypnotic for older patients. Thus, for patients beginning treatment with benzodiazepine hypnotics or z-drugs, we compared deaths during periods of current hypnotic use, without or with concurrent opioids, to those for comparable patients receiving trazodone in doses up to 100 mg.
Methods and findings: The retrospective cohort study in the United States included 400,924 Medicare beneficiaries 65 years of age or older without severe illness or evidence of substance use disorder initiating study hypnotic therapy from January 2014 through September 2015. Study endpoints were out-of-hospital (primary) and total mortality. Hazard ratios (HRs) were adjusted for demographic characteristics, psychiatric and neurologic disorders, cardiovascular and renal conditions, respiratory diseases, pain-related diagnoses and medications, measures of frailty, and medical care utilization in a time-dependent propensity score-stratified analysis. Patients without concurrent opioids had 32,388 person-years of current use, 260 (8.0/1,000 person-years) out-of-hospital and 418 (12.9/1,000) total deaths for benzodiazepines; 26,497 person-years,150 (5.7/1,000) out-of-hospital and 227 (8.6/1,000) total deaths for z-drugs; and 16,177 person-years,156 (9.6/1,000) out-of-hospital and 256 (15.8/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (respective HRs: 0.99 [95% confidence interval, 0.81 to 1.22, p = 0.954] and 0.95 [0.82 to 1.14, p = 0.513] and z-drugs (HRs: 0.96 [0.76 to 1.23], p = 0.767 and 0.87 [0.72 to 1.05], p = 0.153) did not differ significantly from that for trazodone. Patients with concurrent opioids had 4,278 person-years of current use, 90 (21.0/1,000) out-of-hospital and 127 (29.7/1,000) total deaths for benzodiazepines; 3,541 person-years, 40 (11.3/1,000) out-of-hospital and 64 (18.1/1,000) total deaths for z-drugs; and 2,347 person-years, 19 (8.1/1,000) out-of-hospital and 36 (15.3/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (HRs: 3.02 [1.83 to 4.97], p < 0.001 and 2.21 [1.52 to 3.20], p < 0.001) and z-drugs (HRs: 1.98 [1.14 to 3.44], p = 0.015 and 1.65 [1.09 to 2.49], p = 0.018) were significantly increased relative to trazodone; findings were similar with exclusion of overdose deaths or restriction to those with cardiovascular causes. Limitations included composition of the study cohort and potential confounding by unmeasured variables.
Conclusions: In US Medicare beneficiaries 65 years of age or older without concurrent opioids who initiated treatment with benzodiazepine hypnotics, z-drugs, or low-dose trazodone, study hypnotics were not associated with mortality. With concurrent opioids, benzodiazepines and z-drugs were associated with increased out-of-hospital and total mortality. These findings indicate that the dangers of benzodiazepine-opioid coadministration go beyond the documented association with overdose death and suggest that in combination with opioids, the z-drugs may be more hazardous than previously thought.
Purpose: Primary care is challenged with safely prescribing opioids for patients with chronic noncancer pain (CNCP), specifically to address risks for overdose, opioid use disorder, and death. We identify sociotechnical challenges, approaches, and recommendations in primary care to effectively track and monitor patients on long-term opioid therapy, a key component for supporting adoption of opioid prescribing guidelines.
Methods: We examined qualitative data (field notes and postintervention interview and focus group transcripts) from 6 rural and rural-serving primary care organizations with 20 clinic locations enrolled in a study evaluating a practice redesign program to improve opioid medication management for CNCP patients. Two independent researchers used content analysis to categorize data into key themes to develop an understanding of sociotechnical factors critical to creating and implementing an approach to tracking and monitoring of patients on long-term opioid therapy in primary care practices.
Results: Four factors were critical to developing a tracking and monitoring system. For each we describe common challenges and approaches used by the clinics to overcome then. The first factor, buy-in and participation, was essential for accomplishing the other 3. The other factors occurred sequentially: 1) cohort identification-finding the right patients, 2) data collection and extraction-tracking the right data, and 3) data use-monitoring patients and adjusting care processes.
Conclusions: We identified common challenges and approaches to tracking and monitoring patients using long-term opioid therapy for CNCP in primary care. Based on these findings we provide recommendations to build capacity for tracking and monitoring for organizations that are engaged in improving safe opioid-prescribing practices for CNCP in primary care.
