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Gender and Prescription Opioid Misuse in the Emergency Department

2014; Wiley; Volume: 21; Issue: 12 Linguagem: Inglês

10.1111/acem.12547

1553-2712

Esther K. Choo, Carole Douriez, Traci C. Green,

Emergency and Acute Care Studies

To the best of the authors' knowledge, gender differences in nonmedical opioid presentations to the emergency department (ED) have not been studied. The objective was to explore gender differences in ED visits related to nonmedical prescription opioid use in a nationally representative sample. Data from the 2011 U.S. Department of Health and Human Services Substance Abuse and Mental Health Services Administration's Drug Abuse Warning Network (DAWN) were analyzed to compare visit characteristics between women and men. Logistic regression models were developed to examine the association between gender and specific drug presentations and clinical outcomes. There were an estimated 426,010 DAWN-defined visits involving prescription opioid use in 2011. The prevalence of drugs in opioid-involved visits was similar between women and men. Ingestion of another drug along with opioids was associated with increased odds of hospital admission for both women and men, and types of opioids ingested were similar between women and men. However, gender differences were noted in clinical outcomes, depending on the specific drug combination. Gender differences exist in ED presentations related to prescription opioids. Further research is needed to understand these differences and any implications for gender-specific emergency care and brief interventions. Según el conocimiento de los autores, las diferencias de género en las atenciones no médicas al Servicio de Urgencias (SU) no se han estudiado. El objetivo fue explorar las diferencias en función del género en las visitas relacionadas con el uso de opiáceos no prescritos por médicos en un muestra representativa nacional. Se analizaron los datos desde 2001 del Department of Health and Human Services Substance Abuse and Mental Health Services Administration's Drug Abuse Warning Network (DAWN) para comparar las características entre las visitas entre varones y mujeres. Se desarrollaron modelos de regresión logística para examinar la asociación entre el género y las atenciones específicas por drogas y los resultados clínicos. Hubo una estimación de 426.010 visitas definidas por DAWN involucradas con la prescripción de fármacos opiáceos en 2011. La prevalencia de fármacos en las visitas relacionadas con fármacos opiáceos fue similar entre las mujeres y los varones. La ingestión de otro fármaco junto con los fármacos opiáceos se asoció con un riesgo incrementado de ingreso hospitalario tanto para las mujeres como para los varones, y los tipos de fármacos opiáceos ingeridos fueron similares entre las mujeres y los varones. Sin embargo, hubo diferencias entre géneros en los resultados clínicos dependiendo de la combinación específica de fármacos. Las diferencias de género existen en la atenciones en el SU relacionadas con la prescripción de opiáceos. Se precisa de futuras investigaciones para comprender estas diferencias y cualquiera de sus implicaciones en la atención de urgencias específicas de género e intervenciones breves. Over the past decade, there has been a marked increase in prescription opioid misuse and abuse. In 2004, it was estimated that the number of emergency department (ED) visits involving the nonmedical use of prescription opioids was 144,644; in 2008 this number increased to 305,885.1 Nationally, there were an estimated 14,800 prescription opioid overdose deaths in 2008, representing an increase of greater than 370% from 1999.2 Various explanations have been proposed for the upswing, including changes in prescribing practices and lack of public awareness about the potential of opioids to cause addiction and death. The existing literature demonstrates great heterogeneity in all aspects of opioid use: motives for opioid use, medical needs of the user, the source of the drug, concurrent other drug use, and comorbidities. Gender has emerged as a distinguishing factor in the epidemiology of prescription opioid abuse.3-7 For example, although men still make up the majority of nonmedical users of prescription opioids, the rate of rise in fatal prescription opioids overdoses in women has been higher: deaths among women have increased by 400% since 1999, compared to 265% among men.8 This statistic—only partially understood—highlights the importance of further investigations into the phenomenon of prescription opioid use and how and why outcomes may be affected by gender. Studies have demonstrated gender differences influencing initiation and ongoing nonmedical use of prescription opioids, including high-risk times of consumption, routes of administration, and particularly motives for using prescription opioids.9 Men have been described as using opioids more often for pleasurable aspects or to enhance amusement, similar to the positive expectancies noted in male alcohol misuse. In contrast, women may engage in nonmedical use of opioids more often to deal with negative emotions and address interpersonal problems.3, 4, 6, 10, 11 Women are also more likely than men to use additional medications such as sedatives to enhance the therapeutic effects of prescription opioids12; co-ingestion is a known risk factor for mortality from prescription opioids. In addition, women are more likely than men to be prescribed prescription pain medications, are given higher doses, and use them for longer time periods than men.8 If gender is indeed a significant factor in opioid use and misuse, it may affect how and why women and men present to the ED, as well as the treatments and services they need once they engage with ED care providers. To date, gender patterns in ED presentation for nonmedical use of prescription opioids have not been described. Using the Drug Abuse Warning Network (DAWN) of the Substance Abuse and Mental Health Administration (SAMHSA), a nationally representative sample of drug-related ED visits, we sought to examine gender differences in prevalence of visits for nonmedical use of prescription opioids; drugs used in combination with opioids as a proxy for gender-based difference in use patterns; and outcomes of opioid-related ED visits, including disposition and mortality. This was a retrospective cohort study using SAMHSA's DAWN database. As this study used only existing, publically available, deidentified data, it was exempt from institutional review board review. DAWN collects data from a nationally representative sample of hospitals throughout the United States, including Alaska and Hawaii.13 Nonfederal, short-stay, general surgical and medical hospitals with a 24-hour ED are eligible for inclusion. This analysis used the 2011 data set, the last year DAWN was funded to collect ED visit data. For 2011, data were collected from 233 participating hospitals, and a total of 229,211 drug-related ED visits were identified; by applying poststratified weights to the data received from the participating sampled hospitals, the submitted cases were extrapolated to an estimate of 5,067,374 drug-related ED visits out of an estimated 126 million total ED visits. Of these drug-related visits, 2,462,948 were considered to involve drug misuse or abuse, with the balance involving adverse reactions and accidental ingestions. DAWN does not capture any other data on individual visits, including admission diagnoses, measures of illness severity, procedures needed, length of stay, or service of admission, except for psychiatric admissions. For this analysis, we selected out visits involving adults (≥18 years of age) and nonmedical use of pharmaceuticals and excluded those related to adverse reactions, accidental ingestions, or only involving illicit and/or alcohol use. The 3,300 individual drugs captured by DAWN in 2011 were reviewed by the study team to identify those falling into categories of prescription opioids, illicit drugs, antidepressants, or anxiolytics. Both single and combination prescription opioids were included in the first category. All drug names were reviewed by two authors (EKC and CD), and any unrecognized drugs were confirmed against a toxicology database. Alcohol was a predefined variable in the DAWN data set. We created individual variables to indicate if the prescription opioids involved in the visits were taken alone or in combination with other substances (primary outcomes). Other variables of interest extracted for this study included gender, age, race, and clinical disposition, including hospital admission or transfer, intensive care unit (ICU) admission, referral to outpatient detoxification, admission for inpatient detoxification or psychiatric care, and death. We calculated proportions and 95% confidence intervals (CIs) for demographic and drug use variables and compared differences between women and men using univariate (chi-square) analysis, defining as significant nonoverlapping 95% CIs. We identified the top three most frequently used drugs for women and men in each drug/drug combination category; however, in presenting this list, we did not include the nonspecific category "Narcotic analgesics NOS," which was at or near the top for all subgroups, and reported rankings of specifically named opiates only. We then developed logistic regression models to examine the associations between gender and specific drug presentations and clinical outcomes, adjusting for age and race. These were selected a priori, rather than through sequential or stepwise processes, based on evidence in the literature. Model variables were examined for evidence of collinearity. Model fit was evaluated using Hosmer-Lemeshow goodness-of-fit testing for sample survey data. We also examined interactions between gender and race; however, these did not have significant effects in any model. Adjusted odds ratios (aORs) for which the 95% CI did not cross the null value of 1 were considered statistically significant. For all analyses, we used "svy" commands in Stata to account for weights and clustering and obtain accurate point estimates, standard errors, CIs, and tests of hypothesis. Out of an estimation sample of 1,096,741 visits, DAWN captured 426,010 related to opioid misuse, indicating that 23.9% (95% CI = 21.3% to 26.5%) of drug-involved ED visits were for nonmedical use of prescription drugs, and 38.8% (95% CI = 34.4% to 43.2%) involved opioids. There were no significant differences between women and men with opioid use in the proportions of patients represented across age or race categories (Table 1). Visits by women and by men were equally likely to involve illicit drug use, including subsets of cocaine and heroin use and anxiolytics; however, women were more likely to present with antidepressant use, while men were more likely to present with alcohol co-ingestion (Table 1). There were no significant overall differences between women and men in clinical outcomes examined, including proportions referred to outpatient detoxification or admitted for detoxification or psychiatric reasons, hospital admission or transfer, ICU admission, or death (Table 1). More than 30% of both women and men required hospital admission, and of those, more than 20% required ICU admission. Death was a rare outcome for both genders. While "narcotic analgesic NOS" was one of the most frequently coded prescription opioids, when the agent was identifiable, the most commonly listed individual opioids were acetaminophen/hydrocodone (Vicodin), single-entity oxycodone, and acetaminophen/oxycodone (Percocet). The three most commonly reported specific opioids, by drug/drug combination category and gender, are shown in Table 2. In the gender-stratified multivariable analyses (Table 3), women who presented with prescription opioid misuse with either concurrent illicit drug use or antidepressant use were more likely to require general hospital admission. Among men, presentations for opioids with alcohol and with heroin increased the odds for general hospital admission. Opioids in combination with antidepressants were associated with ICU admission in both women and men, although for men, wide CIs for this outcome reflect the small numbers of male patients with this combination. Opioids in combination with anxiolytics were also associated with ICU admission. No studied drug combination was associated with increa-sed odds of death. In both women and men, using opioids alone, rather than in combination with alcohol or other drugs or medications, was associated with decreased odds of general hospital admission. Of note, several models evaluating association with ICU admission and death demonstrated poor fit, likely due to the small sample sizes for these outcomes (Table 3 and Data Supplements S1 and S2, available as supporting information in the online version of this paper). Previous literature has demonstrated a tremendous heterogeneity among opioid users in terms of patterns of use and the interactions between types of use and subgroups of gender, race/ethnicity, familial substance abuse, routes of administration, concurrent drug use, and comorbid psychiatric and medical disorders.10, 14-17 With the premise that understanding the needs of specific subgroups of users may help develop more effective screening and treatment approaches, we examined a gender-stratified, nationally representative population of opioid users seeking ED care. Opioid use in the study population was high, and men and women were equally represented among opioids users. Although men and women used similar types of prescription opioids in combination with alcohol, illicit drugs, and antidepressants, there were differences between them in clinical outcomes within drug combination categories. This may be due to patterns or amounts of drugs taken, polysubstance use, or different thresholds for seeking health care. The difference may also be biological: observed sex differences include greater susceptibility to adverse effects of drugs, which may also contribute to gender differences in hospital admission and ICU care involving these drug combinations. For both men and women, opioids taken alone posed similarly lower risks for need for hospitalization compared to when taken in combination with other substances, an intuitive finding that confirms the higher risk of co-ingestion observed in previous studies.18, 19 Further, the lower risk of single agent was similar between genders, even though the specific agent involved differed between men and women who presented with opioids alone. Among the drug combinations studied, ICU admission was associated with opioids and antidepressants for both women and men and with opioids and anxiolytics only for men. Although this study did not examine the characteristics of the nonopioid drugs involved in the ED visits, it may be that the long-acting formulations available for these drug categories played a role in the need for ICU-level care. There may be additional factors underlying the gender differences observed for opioids and anxiolytics, such as the quantities or formulations of anxiolytics taken by men who presented to the ED with this drug combination. Women in the DAWN data set were more likely to have opioid ingestions in combination with antidepressants and men more likely to use opioids with alcohol, consistent with previous literature that described gender-specific reasons for opioid use.20 We also found that these particular combinations were clinically severe (i.e., were associated with elevated odds of hospitalization) for each gender. Further study is needed to understand the explanation for this; it may be that social expectations or biases on the part of medical/behavioral health care providers make women more likely to have opioids and antidepressants prescribed together, prescribed in a way or used or metabolized by women in a way that creates higher risk for presentation to the ED and hospitalization. Similarly, alcohol and opioids may be a particularly dangerous combination in men, whether because of gender-determined differences in the way opioids and alcohol are taken together or less caution in screening for alcohol problems or prescribing opioids to men with histories of high-risk alcohol use. With ED visits for prescription opioid misuse still on the rise, our study adds to the literature supporting an important role for the ED in examining and preventing medication safety errors, improving safer prescribing of opioids, and educating patients about combinations and drug–drug interactions.21, 22 Our study underscores the importance of considering the patient's history of substance abuse and mental health conditions and current medication lists—such as referencing a prescription monitoring program—when making prescribing decisions, and of advising patients, particularly those treated with other medications, of the serious potential for addiction or death.23 Prior studies have characterized gender differences in prescription opioid misuse based on self-report. This study provides more objective data on opioid misuse among a subset of men and women who experienced clinically significant consequences of drug use and associated co-ingestions. While these data cannot elucidate the root cause of these differences, they provide impetus for a deeper, gender-specific understanding of the complex factors that may lead to serious morbidity from prescription opioids. The DAWN data were collected through retrospective chart review, and thus the determination of eligibility for an individual case was dependent on the quality and accuracy of clinical information captured in the patient chart. It is possible that biases on the part of clinicians could lead to overrepresentation of drug misuse for one gender or the other. Clinical information captured in DAWN is limited. Although we could observe drugs and drug combinations implicated in visits, we are not able to correlate these with clinical diagnoses, pain-related complaints, co-occurring medical or psychiatric issues, or other specific information that would enable us to more thoroughly evaluate potential confounders of the relationship between opioid use and gender. The data were confined to individuals 18 years and older; thus, findings may not generalize to younger populations presenting to the ED. Finally, in this exploratory analysis, we did not achieve good fit for some of the models examining drug combinations and the rarer outcomes of ICU admission and death. These associations merit further exploration in a larger dataset powered to examine these serious outcomes more closely. Emergency department visits related to prescription opioid misuse are numerous and often involve combinations with other substances. We found gender differences in these visits, especially in patterns of co-ingestions of other substances and associations between specific drug combinations and hospital admission. A better understanding of the gender factors involved in the initiation, misuse, treatment needs, and clinical outcomes may inform the development of gender-specific interventions and preventive measures. 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