Risk Of Drug Overdose Research Articles

T162 - Drug Overdose Risk Following Benzodiazepine Treatment in Young Adults With Depression or Anxiety Disorders

T162 - Drug Overdose Risk Following Benzodiazepine Treatment in Young Adults With Depression or Anxiety Disorders

Drug overdose risk with benzodiazepine treatment in young adults: Comparative analysis in privately and publicly insured individuals.

Benzodiazepines (BZDs) carry a risk for drug overdose and are prescribed alone or simultaneously with selective-serotonin reuptake inhibitors (SSRIs) for the treatment of anxiety and depression in young adults. We aimed to measure risks of drug overdose following BZD treatment initiation, and simultaneous BZD and SSRI initiation, compared with SSRI treatment alone in young adults with depression or anxiety. The cohort study used administrative databases covering privately (MarketScan, 1/1/2009-12/31/2018) and publicly (Medicaid, 1/1/2015-12/31/2016) insured young adults (18-29 years) in the United States. Those with depression or anxiety diagnoses newly initiating BZD or SSRI treatment (without BZD or SSRI prescriptions in prior year) were included. Simultaneous "BZD + SSRI" initiation was defined as starting BZD and SSRI treatment on the same day. The cohorts included 604 664 privately insured young adults (BZD = 22%, BZD + SSRI = 10%, SSRI = 68%) and 110 493 publicly insured young adults (BZD = 23%, BZD + SSRI = 5%, SSRI = 72%). Incident medically treated drug overdose events were identified from emergency department and inpatient encounters (ICD poisoning codes) within 6months of treatment initiation. Crude and propensity-score adjusted cumulative incidence and hazard ratios (HR) were estimated. Sub-analyses evaluated drug overdose intent. Adjusted HRs of drug overdose for BZD vs. SSRI treatment was 1.36 (95% confidence interval [CI]:1.23-1.51) in privately and 1.59 (95%CI:1.37-1.83) in publicly insured young adults. The adjusted HRs of drug overdose for BZD + SSRI treatment vs. SSRI treatment were 1.99 (95%CI:1.77-2.25) in privately and 1.98 (95%CI:1.47-2.68) in publicly insured young adults. Among young adults in the United States, initiating benzodiazepine treatment for anxiety and depression, alone or simultaneously with selective-serotonin reuptake inhibitors (SSRI), appears to have an increased risk of medically treated drug overdose compared with SSRI treatment alone. These associations were observed in publicly and privately insured individuals.

Understanding intentionality of fentanyl use and drug overdose risk: Findings from a mixed methods study of people who inject drugs in New York City.

As the proportion of drug overdose deaths involving fentanyl continues to increase in the US, monitoring exposure to and possible changes in intention to use fentanyl among people who use drugs (PWUD) is of great public health importance. This mixed methods study examines intentionality of fentanyl use among persons who inject drugs (PWID) in New York City during a period of unprecedently high rates of drug overdose mortality. Between October 2021 and December 2022, N=313 PWID were enrolled in a cross-sectional study that included a survey and urine toxicology screening. A subset of N=162 PWID also participated in an in-depth interview (IDI) examining drug use patterns, including fentanyl use and experiences with drug overdose. 83% of PWID were urine-toxicology positive for fentanyl, though only 18% reported recent intentional fentanyl use. Intentionality of fentanyl use was associated with being younger, white, increased drug use frequency, recent overdose (OD), recent stimulant use, among other characteristics. Qualitative findings suggest PWID tolerance to fentanyl may be increasing, which could result in an increased preference for fentanyl. Concern about overdose was common with nearly all PWID using overdose prevention strategies to avoid it. The findings from this study demonstrate a high prevalence of fentanyl use among PWID in NYC, despite an expressed preference for heroin. Our results suggest that the pervasiveness of fentanyl may be increasing fentanyl use and tolerance, which may contribute to an increased risk for drug overdose. Expanding access to existing evidence-based interventions such as naloxone and medications for opioid use disorder is necessary to reduce overdose mortality. Further, exploring the implementation of additional novel strategies to reduce the risk of drug overdose should be considered, including other forms of opioid maintenance treatment and expansion and government support for overdose prevention centers.

Prescription characteristics associated with drug overdose risk among adults prescribed benzodiazepines: a cohort study

BackgroundDrug overdose (OD) deaths in the U.S. continue to rise. After opioids, benzodiazepines (BZD) are the medication most commonly involved in prescription overdoses, yet OD risk factors among those prescribed BZD are not well understood. Our objective was to examine characteristics of BZD, opioid, and other psychotropic prescriptions associated with increased drug OD risk following a BZD prescription.MethodsWe completed a retrospective cohort study using a 20% sample of Medicare beneficiaries with prescription drug coverage. We identified patients with a BZD prescription (“index”) claim between 1 April 2016 and 31 December 2017. In the 6 months pre-index, those without and with BZD claims comprised incident and continuing cohorts, which were split by age (incident < 65 [n = 105,737], 65 + [n = 385,951]; continuing < 65 [n = 240,358], 65 + [n = 508,230]). Exposures of interest were: average daily dose and days prescribed of the index BZD; baseline BZD medication possession ratio (MPR) for the continuing cohort; co-prescribed opioids and psychotropics. Our primary outcome was a treated drug OD event (including accidental, intentional, undetermined, or adverse effect) within 30 days of the index BZD, examined using Cox proportional hazards.ResultsAmong incident and continuing BZD cohorts, 0.78% and 0.56% experienced an OD event. Compared to 14–30 days, a < 14-day fill corresponded to higher OD risk in incident (< 65 adjusted hazard ratio [aHR] 1.16 [95% CI 1.03–1.31]; 65 + : aHR 1.21 [CI 1.13–1.30]) and continuing (< 65: aHR 1.33 [CI 1.15–1.53]; 65 + : aHR 1.43 [CI 1.30–1.57]) cohorts. Among continuing users, lower baseline exposure (i.e., MPR < 0.5) was associated with increased OD risk for those < 65 (aHR 1.20 [CI 1.06–1.36]); 65 + (aHR 1.12 [CI 1.01–1.24]). Along with opioids, concurrent antipsychotic use and antiepileptic use were associated with elevated risk of OD in all 4 cohorts (e.g., aHRs for the continuing 65 + cohort: opioid, 1.73 [CI 1.58–1.90]; antipsychotic, 1.33 [CI 1.18–1.50]; antiepileptic, 1.18 [1.08–1.30]).ConclusionsIn both the incident and continuing cohorts, patients dispensed fewer days' supply were at increased OD risk; those in the continuing cohort with more limited baseline BZD exposure were also at elevated risk. Concurrent medication exposures including opioids, antipsychotics, and antiepileptics were associated with short-term elevated OD risk.

Risk of drug overdose with benzodiazepine use in young patients

Risk of drug overdose with benzodiazepine use in young patients

Association of Benzodiazepine Treatment for Sleep Disorders With Drug Overdose Risk Among Young People

Benzodiazepines are prescribed for the treatment of adolescent sleep disorders; however, benzodiazepine overdoses occur, often in combination with opioids. To 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. This 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. New use of benzodiazepine treatment or comparator pharmacologic treatments (defined as ≥1 year without a prescription for benzodiazepine or comparator medications). Incident 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. The 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]). The 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.

More Harm Than Public Health in Drug Policy? A Comment

Well-conceived drug-control policies could contribute importantly to economic and social development and public health. Unfortunately, the reality of drug policies in most countries is rather that they undermine public health by failing to protect people who use drugs from infectious disease and the risk of drug overdose. Drug laws and policies that mandate incarceration for minor, non-violent drug offences have profound health costs as the risk of infectious disease in prison is high, and too few prisons offer appropriate health services for people who use drugs. Overly zealous drug-control policies, moreover, have led to enormous human suffering, as many countries have restricted the use of opioids for the relief of pain associated with cancer and other conditions. Protection of the health of communities involved with the production of drug crops such as coca leaf and opium poppy has rarely figured in ‘alternative development’ programmes for these populations. A few countries have shown that intentionally health-focused drug-control policies can lessen some of these harms.

Towards evidence-based integration of services for HIV, non-communicable diseases and substance use: insights from modelling.

Towards evidence-based integration of services for HIV, non-communicable diseases and substance use: insights from modelling.

Unintentional Drug Overdoses in Virginia: Analysis of Syndromic and Death Data

Substance abuse results in considerable morbidity each year in the United States. The relationship between drug overdose emergency department visits and deaths that opiate use contributed to or caused in Virginia was assessed for 2012-2013 to determine if syndromic surveillance data can be used to provide a real-time and accurate picture of the population at risk for drug overdose. Drug overdose emergency department visits showed divergent demographics from opiate deaths with respect to sex and age distributions. This may indicate a shift in the population previously identified as at risk for drug use morbidity.

On the Role of Genetic Testing for Personalized Drug Overdose Management

Author Reply: We thank our colleagues for their interest in our study entitled “Opioid Receptor Polymorphism A118G Associated with Clinical Severity in a Drug Overdose Population.” Our results add to the growing literature over the past decade that implicate a handful of promising single nucleotide polymorphisms (SNPs) of the mu opioid receptor gene (OPRM1) as candidates for clinically relevant variability in baseline mesolimbic reward neurobiology (dopamine–opioid interaction), opioid sensitivity, and addiction [1]. Our findings warrant further research to understand the mechanisms underlying specific at-risk overdose populations. We completely concur that results of our pilot study, as with all such investigations, will require validation in larger populations, an effort which is currently being addressed at our institution. Confirming our results would have significant impact in the field of addiction to pave the way for personalized prescription practices not only for opioids, but for those at risk for drug overdose. Our data which demonstrated higher overdose severity in G allele subjects, not limited to opioid drugs, is likely due to dopamine–opioid interactions in the mesolimbic/striatal pathways relevant to reward and habit formation. Indeed, several lines of evidence have established significant disturbances of the opioid system in association with various drugs of abuse [2, 3]. We therefore chose not to limit the analysis to only opioids given the biologic plausibility of enhanced abuse and addiction behaviors which apply for all drugs, not limited to opioids. To address our colleagues’ suggestion to eliminate sympathomimetics, such as cocaine, from the analysis, we would argue that it is equally plausible that OPRM1 variants affect the same reward pathways for sympathomimetics, and thus arbitrary removal of these exposures would actually introduce, not eliminate, bias. A question was also raised as to whether the 118G allele confers resistance rather than increased susceptibility as suggested by the findings of our study. Consistent with the results of our study, multiple investigations have reported an association of the 118G allele with opioid abuse [4–6]. However, the mu opioid receptor is involved in multiple physiological functions, thus the 118G allele could be beneficial for some processes, but adverse for others. Our colleagues also question whether race/ethnicity may have introduced confounding into our analysis. To truly control for the effect of racial bias, it would be necessary to not only gather self-reported data, which is difficult to gather on critically ill patients with altered mental status due to overdose, but also it would be necessary to perform additional analyses such as ancestral informative markers (AIMs), which we did not have available at the time. The poor specificity of racial/ethnic variables in addiction research is often compounded by failure to measure social and environmental exposures that track with self-identified race in the USA, thereby masking important gene–environment effects. Missing these effects means missing an opportunity to disentangle the complex social, environmental, behavioral, and genetic factors that interact to create disease and determine treatment outcomes [7]. To account for this, future studies of OPRM1 variants in overdose populations should gather social and environmental variables as well as perform AIMs analysis.

P02-125 Choice of psychotropic drugs used for intentional drug overdose

Objectives:To assess with which frequency subjects with intentional overdose of psychotropic drugs ingest their own psychotropic drug treatment, and whether prescription of a drug may be a factor influencing the choice of drugs used for the IDO.Methods:Demographic characteristics, psychiatric history, and currently prescribed psychotropic drug treatment were collected for all the patients (n=1654) admitted to an emergency department (ED) for IDO with psychotropic drugs (anxiolytics, hypnotics, antidepressants, antipsychotics and mood stabilizers) over a period of 18 months.Results:Two-thirds of the patients ingested during the IDO at least one of their own prescribed psychotropic drugs. Compared with the subjects who had ingested psychotropic drugs not prescribed for them, they were more likely to have a history of psychiatric hospitalization (OR 4.2; 95%CI 3.1-5.5), of parasuicide (OR 2.5; 95%CI 1.9-3.3), to be a psychiatric outpatient (OR 3.9; 95%CI 3.0-5.1), and to present with a serious IDO (OR 2; 95%CI 1.4-2.9). Independently from age and psychiatric hospitalization history (i.e. the seriousness of psychiatric disorder), they ingested during the IDO more often antidepressants (OR 4.4; 95%CI 3.0-6.4), antipsychotics (OR 2.9; 95%CI 1.7-4.8) and mood stabilizers (OR 4.1; 95%CI 1.6-10.7). No association was found with prescription for overdose of benzodiazepine or paracetamol.Conclusion:Prescription of the psychotropic drugs plays an important role in the choice of the drugs ingested for the IDO. It might make potentially “dangerous” drugs available for the patient. Physicians have always to balance the benefit of the treatment against the risk of drug overdose.

Factors associated with choice of psychotropic drugs used for intentional drug overdose

Knowledge of the factors influencing the choice of drugs used for intentional drug overdose (IDO) may allow the reduction of IDO lethality. To assess with which frequency subjects with intentional overdose of psychotropic drugs ingest their own psychotropic drug treatment, and whether prescription of a drug may be a factor influencing the choice of drugs used for the IDO. Demographic characteristics, psychiatric history, and currently prescribed psychotropic drug treatment were collected for all the patients (n = 1,654) admitted to an emergency department (ED) for IDO with psychotropic drugs (anxiolytics, hypnotics, antidepressants, neuroleptics and mood stabilizers) over a period of 18 months. Drugs ingested for the IDO were compared in subjects who had ingested at least one psychotropic drug that was prescribed for them and subjects who had ingested psychotropic drugs not prescribed for them using multivariate logistic regression. Two-thirds of the patients ingested during the IDO at least one of their own prescribed psychotropic drugs. Compared with the subjects who had ingested psychotropic drugs not prescribed for them, they were more likely to have a history of psychiatric hospitalization (OR 4.2; 95%CI 3.1-5.5), of being a psychiatric outpatient (OR 3.9; 95%CI 3.0-5.1), of parasuicide (OR 2.5; 95%CI 1.9-3.3) and a serious IDO (OR 2; 95%CI 1.4-2.9). Independently from age and psychiatric hospitalization history, they ingested during the IDO more often antidepressants (OR 4.4; 95%CI 3.0-6.4), antipsychotics (OR 2.9; 95%CI 1.7-4.8) and mood stabilizers (OR 4.1; 95%CI 1.6-10.7). No association was found with prescription for overdose of hypnotic (OR 1.1; 95%CI 0.8-1.5), anxiolytic (OR 1.2; 95%CI 0.9-1.7) or paracetamol (OR 1.0; 95%CI 0.5-2.1). Prescription of the psychotropic drugs plays an important role in the choice of the drugs ingested for the IDO. It might make potentially "dangerous" drugs available for the patient. Physicians have always to balance the benefit of the treatment against the risk of drug overdose.

Patterns and economic effects of drug overdose mortality in Texas: 1980-1986.

Drug overdose mortality and its economic consequences are explored for ten different drug categories in this article. Data on drug overdose mortality in Texas for the years 1980-1986 are examined and a cost of mortality analysis is presented using the human capital methodology. In addition, mortality rates per 100,000 population are presented for each drug category. The results indicate that the cost of drug overdose mortality has more than doubled over the six-year period. The greatest growth in mortality cost has been for narcotics and cocaine, with commonly prescribed psychoactive drugs remaining fairly constant. The results suggest that men are at far greater risk of drug overdose than women with respect to illicit drugs. Women, however, appear to be at greater risk for overdose from commonly prescribed drugs.