Benzodiazepine and Stimulant Prescriptions Before Overdose in Youth.
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ABSTRACT:
SUBMITTER: Bushnell G
PROVIDER: S-EPMC9097826 | biostudies-literature | 2022 Apr
REPOSITORIES: biostudies-literature
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Benzodiazepine and Stimulant Prescriptions Before Overdose in Youth.
Bushnell Greta G Samples Hillary H Gerhard Tobias T Calello Diane P DP Olfson Mark M
Pediatrics 20220401 4
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Project description:ImportanceThe receipt of overlapping opioid and benzodiazepine prescriptions is associated with increased overdose risk. It is unknown whether this increase in risk varies when overlapping prescriptions are written by multiple prescribers vs 1 prescriber.ObjectiveTo evaluate the association between receipt of overlapping opioid and benzodiazepine prescriptions from multiple prescribers and overdose risk.Design, setting, and participantsThis cohort study was conducted using 2017 to 2018 claims from the Optum deidentified Clinformatics Data Mart. Participants were patients with private insurance or Medicare Advantage aged 12 years or older with overlapping opioid and benzodiazepine prescriptions. Data were analyzed from March through November 2020.ExposuresFor each patient, person-days on which opioid and benzodiazepine prescriptions overlapped were identified. The exposure was whether these prescriptions were written by multiple prescribers vs 1 prescriber.Main outcomes and measuresThe outcome was a treated overdose, defined as the occurrence of 1 or more claims containing a diagnosis code for opioid or benzodiazepine poisoning on a person-day of opioid-benzodiazepine overlap. The association between exposure and outcome at the person-day level was estimated using logistic regression, controlling for opioid and benzodiazepine prescribing patterns, demographics, and comorbidities. The average marginal effect (AME) of the exposure, defined as the absolute difference in the probability of a treated overdose if all person-days of overlap involved prescriptions from multiple prescribers vs 1 prescriber, was calculated.ResultsAmong 529 053 patients, the mean (SD) age was 61.2 (15.6) years and 350 857 (66.3%) were female patients. Mean (SD) follow-up was 198.7 (249.8) days. During follow-up, overdose occurred on 1 or more person-days of opioid-benzodiazepine overlap for 2288 patients (0.4%, or 1 in 231 patients). There were 52 989 316 person-days of opioid-benzodiazepine overlap. Among 19 895 457 person-days (37.5%) involving prescriptions from multiple prescribers, there were 1390 overdoses (7.0 per 100 000 person-days), and among 33 093 859 person-days (62.5%) involving prescriptions from 1 prescriber, there were 1302 overdoses (3.9 per 100 000 person-days). Overdose risk was increased 1.8-fold (95% CI, 1.6-1.9) on person-days of overlap involving prescriptions from multiple prescribers vs 1 prescriber. The association between multiple prescribers and increased risk of overdose persisted in adjusted analyses (adjusted odds ratio, 1.20; 95% CI, 1.10-1.31; AME, 0.91 per 100 000 person-days of overlap; 95% CI, 0.46-1.37).Conclusions and relevanceThis study found that among patients already at increased risk of overdose owing to concurrent treatment with opioids and benzodiazepines, overdose risk was increased further when multiple prescribers were responsible for this treatment regimen compared with 1 prescriber. This increased risk was not fully accounted for by differences in prescribing patterns, demographics, or comorbidities. This finding suggests that other factors, such as poor care coordination, may be associated with the increase in risk.
| S-EPMC8356065 | biostudies-literature
Project description:ImportancePrescription opioid misuse is a public health problem that leads to overdose. Although existing interventions focus on limiting prescribing to patients at high risk, individuals may still access prescription opioids dispensed to family members.ObjectiveTo determine whether opioid prescriptions to family members were associated with overdose for individuals who themselves did not have an opioid prescription.Design, setting, and participantsWe conducted a 1:4 matched case-control study using health care utilization data from 2004 through 2015 from a large US commercial insurance company. Eligible individuals were required to have at least 12 months of continuous enrollment and 1 or more family members in the database. Individuals who experienced overdose were identified by their first opioid overdose after the baseline period and matched to control participants by time in the database, calendar time, age, sex, and number of individuals in the family unit. Both groups were restricted to individuals with no prior opioid dispensing of their own. Data analysis was conducted from January 2018 to August 2018.ExposuresAny prior opioid dispensing to a family member, total morphine milligram equivalents dispensed to family members, and the type of opioid product dispensed.Main outcomes and measuresIndividual odds of opioid overdose resulting in an emergency department visit or hospitalization were the primary end point. The primary analysis evaluated the odds of overdose among individuals whose family members had been dispensed an opioid. Sensitivity analyses examined the odds stratified by age and timing relative to the dispensing of opioids to family members.ResultsA total of 2303 individuals who experienced opioid overdose and 9212 matched control individuals were identified. The mean (SD) age was 23.2 (18.1) years; 1158 affected individuals and 4632 control individuals (50.3%) were female. The mean (SD) time in the database before an overdose case was 3.2 (3.3) years. Prior opioid dispensing to family members was associated with individual overdose (odds ratio [OR], 2.89 [95% CI, 2.59-3.23]). There was a significant dose-response association between increasing amounts of opioids dispensed to family members and odds of overdose (>0-<50 morphine milligram equivalents per day: OR, 2.71 [95% CI, 2.42-3.03]; 50-<90 morphine milligram equivalents per day: OR, 7.80 [95% CI, 3.63-16.78]; ≥90 morphine milligram equivalents per day: OR, 15.08 [95% CI, 8.66-26.27]).Conclusions and relevanceIn this analysis, opioid prescriptions to family members were associated with overdose among individuals who do not receive opioid prescriptions. Interventions may focus on expanding access to opioid antagonists, locking prescription opioids in the home, and providing greater patient education to limit fatal overdose among family members.
| S-EPMC6593630 | biostudies-literature
Project description:Guidelines recommend using caution in co-prescribing opioids with benzodiazepines, yet, in practice, the extent of concurrent prescribing is poorly understood. Notably, no population-based studies, to our knowledge, have investigated concurrent prescribing among patients with cancer. We conducted a retrospective cohort study using data from the Surveillance, Epidemiology, and End Results (SEER) database linked with Medicare claims (2012-2016) for women diagnosed with breast cancer. We used modified Poisson regression to examine predictors of any concurrent prescriptions in the year post-diagnosis and Poisson regression to examine predictors of the number of overlapping days. We found that 13.0% of the 19?267 women in our sample had concurrent prescriptions. Women who underwent more extensive treatment and those with previous use of opioids or benzodiazepines were at increased risk for concurrent prescriptions (adjusted risk ratio of previous benzodiazepine use vs no previous use = 15.05, 95% confidence interval = 13.19 to 17.19). Among women with concurrent prescriptions, overlap was most pronounced among low-income, rural, and Hispanic women (adjusted incidence rate ratio of Hispanic vs non-Hispanic white = 1.25, 95% confidence interval = 1.20 to 1.30). Our results highlight opportunities to reduce patients' unnecessary exposure to this combination.
| S-EPMC7357325 | biostudies-literature
Project description:Overdose prescription errors sometimes cause serious life-threatening adverse drug events, while underdose errors lead to diminished therapeutic effects. Therefore, it is important to detect and prevent these errors. In the present study, we used the one-class support vector machine (OCSVM), one of the most common unsupervised machine learning algorithms for anomaly detection, to identify overdose and underdose prescriptions. We extracted prescription data from electronic health records in Kyushu University Hospital between January 1, 2014 and December 31, 2019. We constructed an OCSVM model for each of the 21 candidate drugs using three features: age, weight, and dose. Clinical overdose and underdose prescriptions, which were identified and rectified by pharmacists before administration, were collected. Synthetic overdose and underdose prescriptions were created using the maximum and minimum doses, defined by drug labels or the UpToDate database. We applied these prescription data to the OCSVM model and evaluated its detection performance. We also performed comparative analysis with other unsupervised outlier detection algorithms (local outlier factor, isolation forest, and robust covariance). Twenty-seven out of 31 clinical overdose and underdose prescriptions (87.1%) were detected as abnormal by the model. The constructed OCSVM models showed high performance for detecting synthetic overdose prescriptions (precision 0.986, recall 0.964, and F-measure 0.973) and synthetic underdose prescriptions (precision 0.980, recall 0.794, and F-measure 0.839). In comparative analysis, OCSVM showed the best performance. Our models detected the majority of clinical overdose and underdose prescriptions and demonstrated high performance in synthetic data analysis. OCSVM models, constructed using features such as age, weight, and dose, are useful for detecting overdose and underdose prescriptions.
| S-EPMC8604308 | biostudies-literature
Project description:IntroductionIt is unknown whether dental opioid prescriptions are associated with opioid overdose in patients or their family members, who may have access to patients' opioids.MethodsDuring July-October 2020, the 2011-2018 IBM MarketScan Dental, IBM MarketScan Commercial, and Medicaid Multi-State Databases were analyzed. Two analyses were conducted. In the patient analysis, dental procedures for privately and publicly insured patients aged 13-64 years were identified. The exposure was ≥1 initial prescription (dispensed opioid prescription within 3 days of the procedure). The association between the exposure and ≥1 overdose within 90 days of the procedure was evaluated using logistic regression. In the family analysis, procedures for privately insured patients in family plans were identified. The association between the exposure and ≥1 overdose in a family member within 90 days was evaluated using logistic regression. In both analyses, the average marginal effect of the exposure was calculated, representing the change in the probability of the outcome if all versus if no procedures were associated with ≥1 initial prescription.ResultsThe patient analysis included 8,544,098 procedures. When ≥1 initial prescription did and did not occur, the 90-day risk of overdose was 5.8 versus 2.2 per 10,000 procedures (average marginal effect=1.5, 95% CI=1.2, 1.8). The family analysis included 3,461,469 procedures. When ≥1 initial prescription did and did not occur, the 90-day risk of overdose in a family member was 1.7 versus 1.0 per 10,000 procedures (average marginal effect=0.4, 95% CI=0.1, 0.7).ConclusionsFindings further highlight the importance of avoiding unnecessary dental opioid prescribing.
| S-EPMC8319034 | biostudies-literature
Project description:BackgroundContrary to most European guidelines, benzodiazepine receptor agonists (BZRA) are often used continuously at a low dosage, being the most common form of long-term use. In Belgium, BZRA use is monitored by analyzing self-report data about medication use in the last 24 h. This method provides insufficient insight into the terms of use of these psychoactive drugs.AimTo describe trends in BZRA prescribing in Flanders, Belgium, between 2000 and 2019.Design and settingPopulation-based trend analysis and a case-control study for the year 2019 were done with data from a morbidity registry in general practice.MethodsRepeated cross-sectional and joinpoint regression analyses revealed trends in sex- and age-standardized prescription rates among adult patients (18+).ResultsOverall, BZRA prescriptions increased. The highest overall increase was found among male patients 18-44 years old, with an average annual percentage change of 2.5 (95% CI: 0.9, 4.3). Among 65+ female patients, a decrease was found since 2006, with an annual percentage change of -0.7 (95% CI: -1.3, -0.1). In 2019, 12% of registered patients received minimally one prescription, long-term use was observed in 5%, back pain was the most common morbidity significantly associated with a rise in BZRA prescriptions, and zolpidem was the most prescribed BZRA (22%).ConclusionDespite some statistically significant decreasing trends, an overall increase in BZRA prescriptions was observed throughout the 19-year study period, especially among long-term users of 18-44 years and 65-plus. Zolpidem became the most prescribed BZRA and warrants more attention.
| S-EPMC9546292 | biostudies-literature
Project description:ImportanceAs opioid-related mortality continues to increase, naloxone remains a critical intervention in preventing overdose death. Opportunities to expand access through the health care setting should be optimized.ObjectiveTo determine the characteristics of naloxone prescribing for US patients at high risk of opioid overdose.Design, setting, and participantsThis retrospective cohort study used Truven Health MarketScan data from October 1, 2015, through December 31, 2016, of individuals with International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes related to opioid use, misuse, dependence, and overdose. The cohort included 138 108 commercially insured individuals aged 15 years or older in the United States with claims related to opioid misuse or dependence, opioid-related overdose, or both.ExposuresOutpatient naloxone pharmacy claims.Main outcomes and measuresDemographic characteristics, clinical characteristics, health care service use, and proportion prescribed naloxone were included in multivariable logistic regression analyses to test the association of opioid risk group with naloxone claim.ResultsOf 138 108 high-risk individuals (mean [SD] age, 43.4 [0.4] years; 72 435 [52.4%] men), 2135 (1.5%) were prescribed naloxone. Having prior diagnoses of both opioid misuse or dependence and overdose was associated with a greater likelihood of receiving naloxone (odds ratio [OR], 2.32; 95% CI, 1.98-2.72; P < .001) compared with having a prior diagnosis of opioid misuse or dependence without overdose. Having a prior diagnosis of opioid overdose alone was associated with a decreased likelihood of receiving naloxone (OR, 0.73; 95% CI, 0.57-0.94; P = .01) compared with having a prior diagnosis of opioid misuse or dependence without overdose. Factors associated with lower naloxone prescription included being aged 30 to 44 years (OR, 0.72; 95% CI, 0.62-0.84; P < .001) and being from the Midwest (OR, 0.62; 95% CI, 0.54-0.71; P < .001) or West (OR, 0.85; 95% CI, 0.74-0.98; P = .03). Opioid use disorder treatment, such as use of medication-assisted therapy (OR, 1.68; 95% CI, 1.53-1.86; P < .001), visiting a detoxification facility (OR, 1.51; 95% CI, 1.31-1.76; P < .001), or receiving other substance use disorder treatment (OR, 1.16; 95% CI, 1.04-1.30; P = .01), were associated with increased likelihood of receiving naloxone, as were receiving outpatient care from a pain specialist (OR, 1.57; 95% CI, 1.40-1.76; P < .001), psychologist (OR, 1.49; 95% CI, 1.29-1.70; P < .001), or surgeon (OR, 1.19; 95% CI, 1.08-1.32; P < .001). Overall, 98.5% (n = 135 973) of high-risk patients did not received naloxone, despite many interactions with the health care system, including 88 618 hospitalizations, 229 680 emergency department visits, 298 058 internal medicine visits, and 568 448 family practice visits.Conclusions and relevancePatients at high risk of opioid overdose rarely received prescriptions for naloxone despite numerous interactions with the health care system. Prescribing in emergency, inpatient, and outpatient settings represents an opportunity to improve access.
| S-EPMC6503491 | biostudies-literature
Project description:Study questionAre women who fill a benzodiazepine prescription before conception at increased risk of ectopic pregnancy?Summary answerRisk of ectopic pregnancy is 50% higher among women who fill a benzodiazepine prescription before conception.What is known alreadyBenzodiazepine use in pregnancy increases the risk of miscarriage, adverse birth outcomes and adverse child development outcomes.Study design, size, durationUsing data from US commercial insurance claims, we performed a cohort study of 1 691 366 pregnancies between 1 November 2008 and 30 September 2015.Participants/materials, setting, methodsWe identified ectopic pregnancies using diagnosis and procedure codes and used unadjusted and inverse probability of treatment (IPT)-weighted log-binomial models to calculate relative risks (RR) of ectopic pregnancy for pregnant women who did and did not fill any prescriptions for benzodiazepines in the 90 days before conception. Two sub-groups of women with specific indications for benzodiazepine use were also examined-women who had a least one diagnosis for anxiety disorder and women who had at least one diagnosis of insomnia in the year before conception.Main results and the role of chanceOf the 1 691 366 pregnancies, 1.06% filled at least two benzodiazepine prescriptions totaling at least 10 days supply in the 90 days before conception. Among women with a benzodiazepine prescription, there was an excess of 80 ectopic pregnancies per 10 000 pregnancies, and their IPT-weighted risk of ectopic pregnancies was 1.47 (95% CI 1.32 to 1.63) times greater relative to women without benzodiazepine prescriptions before conception. The IPT-weighted RR between ectopic pregnancy and benzodiazepine use was 1.34 (95% CI 1.18 to 1.53) among women with anxiety disorder diagnoses and 1.28 (95% CI 0.99 to 1.68) among women with an insomnia diagnosis.Limitations, reasons for cautionWe relied on outpatient prescription data to identify benzodiazepine use before conception, which could result in over- or under-estimation of actual benzodiazepine consumption. We relied on medical claim codes to identify pregnancies and conception date, which may result in misclassification of pregnancy outcomes and gestational length.Wider implications of the findingsThis study found that women who have a benzodiazepine prescription before conception are at an increased risk of ectopic pregnancy. This information can help women, and their healthcare providers make more fully informed decisions about benzodiazepine use in their reproductive years.Study funding/competing interest(s)Funding for this project was provided by a Banting Postdoctoral Fellowship and a Stanford Maternal and Child Health Research Institute Postdoctoral Award. Data access for this project was provided by the Stanford Center for Population Health Sciences Data Core. The PHS Data Core is supported by a National Institutes of Health National Center for Advancing Translational Science Clinical and Translational Science Award (UL1 TR001085) and internal Stanford funding. The authors have no competing interest.Trial registration numberN/A.
| S-EPMC7368395 | biostudies-literature
Project description:BackgroundUS rates of overdose deaths involving stimulants (e.g., cocaine or methamphetamine) have increased, but little is known about non-fatal stimulant overdoses, particularly among vulnerable populations. We characterized rates of non-fatal stimulant overdose identified outside of health care settings among women at high risk.MethodsHomeless and unstably housed women in San Francisco, California using stimulants were administered questionnaires on drug use and outcomes (stimulant overdose, health care utilization) monthly for six months. Based on pilot interviews, stimulant overdose during follow-up was defined as acute toxicity from stimulant use ("over-amping") resulting in "feeling sick, really scared, or like one's life may be in danger". Poisson regression estimated unadjusted incidence rate ratio (IRR) comparing participant characteristics.ResultsWe included 160 women (41% Black, 26% White, 15% Latina, median age 54 years) using crack cocaine (81%), methamphetamine (48%), and powdered cocaine (36%). Participants reported 67 non-fatal stimulant overdoses over 685 person-months of observation, a rate of 117.4 per 100 person-years (95% CI 85.8-160.5). Rates were higher among participants who were Latina vs. White (IRR 4.18 [1.60-10.94]), used methamphetamine (IRR 1.80 [0.96-3.38]), or used any stimulant daily/almost daily (IRR 2.63 [1.41-4.91]). Among women reporting stimulant overdose, 4% received emergency and 3% inpatient care for overdose of any drug.ConclusionsWomen in this setting, particularly those who used stimulants frequently or used methamphetamine, experienced high non-fatal stimulant overdose and rarely received health care for these events. Efforts should be made to increase awareness and reduce harms of stimulant toxicity in vulnerable populations.
| S-EPMC8595709 | biostudies-literature
Project description:ImportanceBenzodiazepines are prescribed for the treatment of adolescent sleep disorders; however, benzodiazepine overdoses occur, often in combination with opioids.ObjectiveTo evaluate whether benzodiazepine treatment for sleep disorders, compared with alternative pharmacologic treatments (trazodone, hydroxyzine, zolpidem, zaleplon, and eszopiclone), is associated with increased risk of drug overdose for young people.Design, setting, and participantsThis cohort study included privately insured people 10 to 29 years of age identified from a US commercial claims database (MarketScan), from January 1, 2009, to December 31, 2018. Young people with a sleep disorder diagnosis initiating benzodiazepine (n = 23 084) or comparator pharmacologic treatments (n = 66 706) were included in the study. Statistical analysis was performed from November 1, 2021, to May 16, 2022.ExposuresNew use of benzodiazepine treatment or comparator pharmacologic treatments (defined as ≥1 year without a prescription for benzodiazepine or comparator medications).Main outcomes and measuresIncident diagnosed drug overdoses were identified from inpatient and emergency department records within 6 months of treatment initiation. The propensity score-adjusted cumulative incidence of overdose and hazard ratios (HRs) were estimated with intention-to-treat (analyzed based on initial treatment) and as-treated analyses (added censoring at treatment discontinuation). Results were stratified by prior prescription opioid fill.ResultsThe cohort included 23 084 young people initiating benzodiazepine treatment (14 444 female participants [62.6%]; mean [SD] age, 23 [4.1] years) and 66 706 initiating a comparator treatment (38 446 female participants [57.6%]; mean [SD] age, 22 [4.4] years). Six months after treatment initiation, 9.7% (95% CI, 9.3%-10.1%) of benzodiazepine users and 12.3% (95% CI, 12.1%-12.6%) of the comparator group were still receiving treatment. The crude incidence of drug overdose at 6 months was 0.9% for benzodiazepine initiators and 0.8% for comparator treatment initiators. In adjusted analyses, an increased risk of drug overdose was associated with benzodiazepines vs comparator treatments (intention-to-treat analysis: HR, 1.25 [95% CI, 1.03-1.51]; as-treated analysis: HR, 1.44 [95% CI, 1.14-1.80]). This association was stronger among young people with a recent prescription opioid fill vs those without a recent prescription opioid fill (as-treated analysis: adjusted HR, 2.01 [95% CI, 1.24-3.25] vs adjusted HR, 1.31 [95% CI, 1.00-1.70]).Conclusions and relevanceThe findings of this study suggest that benzodiazepines, compared with alternative pharmacologic treatments for common sleep disorders, were associated with an increased risk of drug overdose among young people during the following 6-month period, especially among those with a recent opioid prescription. Drug overdose is an important safety consideration when treating young people with benzodiazepines.
| S-EPMC9682430 | biostudies-literature