Gender differences in diversion among non-medical users of prescription opioids and sedatives

Abstract

Background:

Non-medical use of prescription drugs is a major public health concern in the United States. Prescription opioids and sedatives are among the most widely abused drugs and their combined use can be lethal. Increasingly rigid prescribing guidelines may contribute to the changing context of opioid use and increase drug diversion.

Objective:

To examine gender differences in diversion of prescription opioids and sedatives among non-medical prescription opioid and sedative polysubstance users. We hypothesize that men will be more likely than women to engage in incoming diversion.

Methods:

Data from the Prescription Drug Abuse, Misuse, and Dependence Study, a cross-sectional study focused on prescription drug users, were analyzed. Non-medical use was defined as use of a drug that was not prescribed or use in a way other than prescribed. Individuals who reported past 12-month non-medical opioid and sedative use were included; diversion was defined as incoming (obtaining drugs from a source other than a health professional) and outgoing (giving away/selling/trading prescription drugs).

Results:

Among the 198 polysubstance users, 41.4% were female. Men were 2.85 times as likely as women to report incoming diversion (95% CI: 1.21–6.72). Women were more likely to obtain opioids from a healthcare professional; men were more likely to obtain sedatives from a roommate, coworker, or friend. Over half of men and women reported outgoing diversion opioids or sedatives.

Conclusion:

Drug diversion highlights an important point of intervention. Current prevention efforts that target prescribers should be expanded to include users and diversion activities; these interventions should be gender-specific.

Introduction

Non-medical use (NMU) of prescription drugs is a major public health concern in the United States (US) (1). NMU, also sometimes referred to as misuse, is defined in the literature as the use of a prescription drug other than prescribed or without a prescription. Approximately 20% of Americans over the age of 12 have misused prescription drugs at least once in their lifetime (1). NMU of prescription drugs increased with increasing prescribing of these drugs since the 1990s (1). The opioid epidemic in the US is a national public health crisis with prescription opioid related deaths quadrupling between 2000 and 2017 (2). In 2017 the US Department of Health and Human Services declared the opioid epidemic a public health emergency. Adverse health outcomes including addiction or overdose can follow NMU of prescription drugs, primarily NMU of opioids (1). In 2018, about 10.3 million individuals in the US reported misusing a prescription opioid (3). From 2016 to 2017, drug overdose deaths in the US increased 9.6%, from 19.8 per 100,000 to 21.7 per 100,000; of these, 67.8% of overdoses involved an opioid, mostly synthetic opioids (excluding methadone), including illicitly manufactured fentanyl (4,5). Opioid-involved overdose rates differ greatly by sex; in 2017, the rate was 20.4 per 100,000 among men compared to 9.4 per 100,000 among females (4).

Opioids and benzodiazepines are among the most widely abused prescription drugs and combined use of these drugs increases lethality (6). Prescription opioids are commonly used to treat acute and chronic pain while benzodiazepines (a sedative) are used to treat anxiety, insomnia, and seizures (7). Both act on the central nervous system. The combined use of prescription opioids and benzodiazepines can lead to adverse outcomes including cognitive impairment, suppressed breathing, and death (7,8) as well as increases in emergency room visits and hospital admissions (6,9). Among privately insured patients, the elimination of concurrent opioid and benzodiazepine use could reduce opioid related emergency room visits by 15% (9). Additionally, among US Medicare Part D beneficiaries, concurrent opioid and benzodiazepine was associated with five times the risk of an opioid-related overdose in the initial 90 days of prescription (10). In 2017, about 21% of the total opioid overdose deaths involved benzodiazepines (11).

Although some individuals may use both opioids and benzodiazepines to increase the potency of the drugs, others may use both drugs for medicinal purposes, unaware of the adverse effects (10,11). Using data from the National Ambulatory Medical Care Survey, Agarwal and Landon found that the number of single visits where opioids and benzodiazepines were both prescribed increased from 0.5% in 2003 to 2.0% in 2015 (12). Additionally, opioids were prescribed in 26.4% of visits involving a benzodiazepines (12). Conversely, benzodiazepines were prescribed in 19.2% of visits involving an opioid (12).

Given the increased use and concerns of adverse events related to the combined use of opioids and sedatives, it is important to know where these drugs are being obtained in addition to how they are being prescribed. Not all prescription drugs used non-medically come from a doctor or healthcare professional; they are diverted, both given away and received illicitly. In fact, opioids and benzodiazepines are the most commonly diverted drugs (13). Diversion is defined as the channeling of regulated prescription drugs from legal sources to individuals for whom they were not prescribed. Diversion can be further categorized as incoming, where individuals received drugs from a source other than a health care professional, and outgoing, defined as an individual selling, giving away, or trading their prescription drugs. The most common sources of diverted drugs are family or friends (14,15).

Gender differences have been noted in who is prescribed prescription opioids and sedatives. In 2018, 17.2% of females filled at least one prescription for an opioid compared to 12.8% of men (5).Women are more likely to be prescribed prescription opioids and sedatives than men (16,17). Women are almost 50% more likely than men to use an abusable prescription drug, even when demographics, health status, socioeconomic status, and diagnoses are controlled (16). These differences may be related to marital status, age, employment status, urbanicity, and access to care (16). However, gender differences in sources of acquisition of prescription opioids have not been widely studied among individuals who are using both opioids and sedatives non-medically.

In an online survey conducted in 2005 among undergraduate students, individuals who reported NMU of opioids most commonly obtained them from their parents or friends (15). Some gender differences were noted; among individuals who used opioids non-medically in the past year, parents were the single leading source of opioids for women while friends who were not in the same university were the single leading source for men (15). Additionally, a study conducted among drug offenders who reported illegal prescription drug involvement in Arizona found that men were more likely to obtain prescription drugs from friends and family, while women and older individuals were more likely to obtain their drugs from a healthcare establishment (18).

Cicero and colleagues (2011) examined diversion among two samples: one national sample of individuals undergoing opioid treatment and a sample of individuals in South Florida who reported non-medical opioid use (19). Among the individuals undergoing opioid treatment, women were more likely to obtain prescription opioids through doctor’s prescriptions, sharing, and theft, however, men were more likely to use a dealer (19). Younger individuals were more likely to obtain drugs through dealers or theft whereas older individuals were more likely to obtain drugs from a medical source (19). Gender differences in sources of opioid were not observed in the South Florida sample (19).

Identifying other points of prevention is an important component in the effort to reduce adverse health outcomes related to combined prescription opioid and sedative use. This analysis examined gender differences in sociodemographic characteristics, types of diversion, and sources of drugs used among non-medical users of both prescription opioids and sedatives. We hypothesized that men would be more likely than women to report receiving drugs illicitly, otherwise known as incoming diversion.

Methods

Population

Data from the Prescription Drug Abuse, Misuse, and Dependence Study, funded by the National Institute on Drug Abuse (PI: LB Cottler), a 2011 study examining prescription drug use and test-retest reliability of DSM-IV criteria for prescription drug use disorders, were analyzed to identify patterns of prescription opioid and sedative use. Individuals aged 18–65 years of age, who had used amphetamine/dextroamphetamine (Adderall), alprazolam (Xanax), hydrocodone/acetaminophen (Vicodin), or similar prescription drugs in the past 12 months, were recruited through newspaper advertisements and flyers posted in highly visible community settings such as grocery stores, school campuses, and medical offices in the St. Louis area.

The Prescription Drug Abuse, Misuse, and Dependence Study was approved and monitored by the Washington University St. Louis Institutional Review Board. Written informed consent was obtained from participants, and interviews were conducted by trained interviewers. Quality control measures were implemented during the study period, including recording and reviewing of interviews. Participants were compensated $20 for their time and effort. Participants were asked about prescription and illicit drugs; however, this analysis is focused on prescription opioids and sedatives. Participants were asked if they had used prescription opioids (codeine, propoxyphene (Darvon), meperidine (Demerol), hydromorphone hydrochloride (Dilaudid), methadone, morphine, aspirin and oxycodone hydrochloride (Percodan), pentazocine/tripelennamine (Talwin, T’s & blues), fentanyl, hydrocodone, oxycodone hydrochloride (OxyContin), tramadol (Ultram), or other narcotic pain pills) and sedatives (chlordiazepoxide (Librium), secobarbital (Seconal), diazepam (Valium), alprazolam (Xanax), zolpidem (Ambien), or other tranquilizers, or sedatives, or sleeping pills).

Among the 389 study participants who endorsed non-medical use of prescription opioids or sedatives, 151 (38.8%) reported NMU of prescription opioids only, 40 (10.3%) reported NMU of sedatives only, and 198 (50.9%) reported NMU of both opioids and sedatives. Our final analytical sample consisted of those who reported NMU of both opioids and sedatives in the past 12-months (n = 198).

Measures

In this analysis, gender was the primary variable of interest while diversion and sources of prescription opioids and sedatives were the primary outcomes. Participants specified their genders in the interview. NMU was defined as use of a drug that was not prescribed for the person or was used in a way other than prescribed. NMU was assessed by asking participants “How many days in the last 365 days did you use (DRUG CATEGORY: SEDATIVES, OPIOIDS), that were prescribed for you and used them exactly as prescribed?” and “How many days in the last 365 days did you use (DRUG CATEGORY: SEDATIVES, OPIOIDS) that were prescribed for you but used them in a way other than prescribed – like by using them more than prescribed or after your prescription ended or for a different reason?” Information on the use of someone else’s prescription opioid or sedatives was attained by asking participants “In the last 12 months, did you get (DRUG CATEGORY: SEDATIVES, OPIOIDS) from (SOURCE)?” Sources included a healthcare professional or prescription, a family member, spouse, or partner, a roommate, coworker or friend, or from a dealer. If participants reported receiving drugs in the past 12 months from sources other than a health professional or a prescription (i.e. family, friends, etc.), use was categorized as incoming diversion. Outgoing diversion was assessed by asking participants “in the last 12 months did you (sell/give away/trade) your (DRUG CATEGORY: SEDATIVES, OPIOIDS)?” If individuals responded yes for either prescription opioids or sedatives in the past 12 months, use was categorized outgoing diversion. Simultaneous use was assessed through the questions “in the last 12 months did you use sedatives with prescription opioids?” and “in the last 12 months did you use prescription opioids with sedatives?” Participants who responded yes to either were categorized as having past 12-month simultaneous use of prescription opioids and sedatives. Other sociodemographic variables included age (continuous), race (White, Black, other), employment status (employed full or part time, unemployed), and education (less than high school graduation, at least GED/high school diploma).

Analysis

Chi-square tests of independence and Fisher’s Exact Tests were used to determine differences in sociodemographic characteristics by gender. Diversion, drug source, and simultaneous use were assessed among men and women who reported past 12-month use of both opioids and sedatives. Logistic regression was used to quantify gender differences in significant variables in descriptive analyses. All data were analyzed using SAS software, version 9.4 SAS Institute Inc., Cary, NC, USA), with statistical significance set at p ≤ 0.05.

Results

Of the 198 participants reporting past 12-month non-medical use of both prescription opioids and sedatives, shown in Table 1, 58.6% were men. Compared to women, men reported more unemployment (78.5% vs 65.9%, p < .05) and incoming diversion (46.0% vs 30.9%, (p < .05). Over half of participants, regardless of gender, reported high rates of outgoing diversion (men: 62.1%; women: 69.7%). High rates of simultaneous use of opioids and sedatives were also reported among both men and women (68.5% and 75.0%, respectively). Among participants reporting NMU of both opioids and sedatives, women were more likely to get their opioids from a healthcare professional compared to men (66.2% vs 47.5%, p < .05). However, women were less likely to obtain their sedatives from a peer/friend than men (40.3% vs 66.3%, p < .01).

Table 1.

Sociodemographic characteristics and types of diversion among individuals reporting both non-medical prescription opioid and non-medical sedative use, by gender (n = 198).

	Men (n = 116; 58.6%)	Women (n = 82; 41.4%)	P-Value
Characteristics
Mean Age (±SD)	36.2(±12.2)	39.4(±12.8)	0.0840
Race			0.7773
Caucasian	52 (44.8%)	34 (41.5%)
Black	58 (50.0%)	42 (51.2%)
Other	6 (5.2%)	6 (7.3%)
Employment Status			0.0486
Employed	25 (21.6%)	28 (34.2%)
Unemployed	91 (78.5%)	54 (65.9%)
Highest Level of Education Completed
Less than high school graduation			0.5252
At least GED/high school diploma	33 (28.5%)	20 (24.4%)
	83 (71.6%)	62 (75.6%)
Any Incoming Diversion (n = 182)			0.0334
Yes	52 (46.0%)	25 (30.9%)
No	61 (54.0%)	56 (69.1%)
Any Outgoing Diversion (n = 194)			0.2969
Yes	59 (62.1%)	53 (69.7%)
No	36 (37.9%)	23 (47.3%)
Simultaneous Use of Rx opioid and sedative (n = 164)			0.3593
Yes	63 (68.5%)	54 (75.0%)
No	29 (31.5%)	18 (25.0%)
Obtaining of Opioid (n = 176) Last 12 months got opioid from a health professional or Rx			0.129
Yes	47 (47.5%)	51 (66.2%)
No	52 (52.5%)	26 (37.8%)
Last 12 months got opioid from a family member, spouse, partner			.0542
Yes	24 (24.2%)	29 (37.7%)
No	75 (75.8%)	48 (62.3%)
Last 12 months got opioid from roommate, coworker, friend			0.526
Yes	57 (57.6%)	33 (42.9%)
No	42 (42.4%)	44 (57.1%)
Last 12 months got opioid from a dealer			.3323
Yes
No	24 (14.2%)	14 (18.2%)
	75 (75.8%)	64 (81.8%)
Obtaining of Sedative (n = 170)
Last 12 months got sedative from a health professional or Rx			0.837
Yes	36 (36.7%)	36 (50.0%)
No	62 (63.3%)	36 (50.0%)
Last 12 months got sedative from a family member, spouse, partner			.2056
Yes	24 (24.5%)	24 (33.3%)
No	74 (75.5%)	48 (66.7%)
Last 12 months got sedative from roommate, coworker, friend			.0007
Yes	65 (66.3%)	29 (40.3%)
No	33 (33.7%)	43 (59.7%)
Last 12 months got sedative from a dealer			.0516
Yes	29 (29.6%)	12 (16.7%)
No	69 (70.4%)	60 (83.3%)

After adjusting for potential confounders including age, race, education, and employment status, shown in Table 2, men were 2.85 (95% CI: 1.21, 6.72) times as likely as women to report incoming diversion. After adjustment, men were about 75% less likely to obtain their prescription opioids from a healthcare professional than women (OR: 0.27, 95% CI: 0.11, 0.66). However, after adjustment, a peer/friend source was not more likely for men compared to women (OR: 1.87, 95% CI: 0.88, 3.98).

Table 2.

Odds ratios and 95% confidence intervals for the association between gender and incoming diversion, adjusted for age, race, education, and employment status among individuals reporting both non-medical prescription opioid and non-medical sedative use.

	OR (95% CI)
Any Incoming Diversion (n = 182)
Men	2.85 (1.21–6.72)
Women	ref.
Last 12 months got opioid from a health professional or Rx (n = 176)
Men	0.27 (0.11–0.66)
Women	ref.
Last 12 months got sedative from roommate, coworker, friend (n = 170)
Men	1.87 (0.88–3.98)
Women	ref.

Discussion

Over half of individuals reporting non-medical use of opioids or sedatives also reported simultaneous use of both drugs. Hwang and colleagues (20) found that from 2002 to 2014, the concomitant dispensing of opioids and benzodiazepines rose from 6.8% to 9.6%. More recently, the Centers for Medicare and Medicaid Services (CMS) reported that, in 2015, among 33.3% of Medicare Part D patients who filled a prescription for opioids, a prescription for benzodiazepines was concurrently filled (21). In a population of veterans, approximately 27% were concurrently prescribed opioids and benzodiazepines (22). Laboratory tests of 144,535 urine samples taken from individuals who had a prescription for at least one medication determined that 25% of patients tested positive for both opioids and benzodiazepines (23). Additionally, using data from the National Survey on Drug Use and Health from 2002–2014, Boggis and Feder found that 28% of adults who reported past year opioid misuse also reported misuse of tranquilizers, including benzodiazepines (24). This is concerning because the combination of prescription medications can interfere with the treatment of opioid overdose and result in adverse events such as suppressed breathing and death. Naloxone, an opioid antagonist, may not reverse suppressed breathing at the recommended doses when sedative and opioids are used together (6).

In 2016, the US Food and Drug Administration (FDA) implemented black box warnings, the highest level of warnings, for prescription opioids and benzodiazepines, recommending that healthcare providers stop prescribing opioids and benzodiazepines together (7). Moreover, the Center for Disease Control and Prevention (CDC) Guidelines for Prescription Opioids for Chronic Pain recommended the use of urine tests prior to opioid therapy to screen for the use of other drugs and annual testing thereafter (25).

Given changes in prescribing patterns, obtaining prescription drugs from health professionals may be more challenging for patients due to more stringent prescribing guidelines. Using claims data from the Blue Cross-Blue Shield Axis, Zhu and colleagues found that from July 2012 to December 2017, the monthly incidence of first time opioid prescriptions decreased by 54% (26). The number of providers who initiated opioid therapy in opioid-naive patients also declined (26). Additionally, using data from the IQVIA Xponent database which has outpatient records from about 59,400 retail pharmacies in all 50 states and the District of Columbia, Schieber and colleagues found that from January 2006 to December 2017, the number of opioids prescribed decreased (27). They also noted a decline in the prescribing rate for short-term, high-dosage, and long-acting prescriptions; however, the prescribing rate and mean duration for long-term prescriptions of opioids increased in this 12 year period (27). An additional study found among individuals who used benzodiazepines, that in 2010 the number of new opioid prescriptions stopped increasing and began to decline (28).

Because of these changes in prescribing, there is a changing context of opioid use. Drug diversion may be increasing, and may present a point of intervention. A systematic review by Hulme and colleagues (14) found that opioids and sedatives were more likely obtained free from a friend or family member or bought from a dealer or street market rather than from legitimate medical sources. The most common source of diverted drugs was a friend or family member (57%) and the next most common was a dealer or the street market (32%) (14). It is also important to note that as prescription opioids are more strictly regulated, heroin use is increasing (29,30). Opioid users are shifting to heroin, which is cheaper and more readily available, and the use of heroin as the initiating opioid of abuse is increasing (29,30).

Additionally, gender differences were observed. Men were more likely to report any incoming diversion compared to women, while more than half of all reported any outgoing diversion. Over half of women reported obtaining prescription from a healthcare professional compared to 47.5% of men. This is consistent with the current literature given that women are more likely to obtain prescription opioids and sedatives from healthcare providers (16,17).

Given the gender differences in incoming diversion and sources of prescription opioids and sedatives observed in these analyses, there may be a utility of implementing gender specific interventions. Women primarily get opioids from healthcare professionals; therefore, this is the best place to intervene and educate women on the dangers of sharing medications and how to properly dispose of them. In light of the high unemployment rates observed in this sample, especially among men, state unemployment offices may be a source of information about both incoming and outgoing diversion. The high unemployment rate also may result in no health insurance for some. This may fuel incoming diversion due to lack of insurance and the ability to go to a physician and receive their own prescription. Previous literature has documented motivations for misuse among adults in the United States. Among adults in 2015 who reported misuse of prescription pain relievers, pain relief was the most common reason for misuse (63.4%) (31). Among adults in 2015 who reported misuse of prescription tranquilizers, including sedatives, to relax or relieve tension was the most common reason for misuse (46.2%) (31). This suggests diversion may be mitigated through addressing physical and mental pain.

A high proportion of outgoing diversion was reported in our sample with nearly two thirds of men and over two thirds of women reporting that they sold, gave away, or traded their most used sedative or opioid. This may support the finding that individuals who use prescription drugs non-medically primarily obtain them from friends and family (14). This is also consistent with previous literature documenting that individuals who divert pharmaceutical drugs may not be aware of the dangers of diverting their medications and tend to report NMU of those drugs (14). Additionally, adults with recent opioid use do not report receiving instructions on storage and proper disposal of any leftover medication (32). Therefore, prevention efforts should be expanded to include individuals who may be sharing their prescribed drugs with others. Proper disposal of prescription medications which are no longer in use may reduce the diversion of opioid and sedative prescriptions. Disposal pouches offer a convenient, easy to use and acceptable disposal method (33).

Furthermore, there is an additional risk in obtaining prescription opioids and sedatives from sources other than a healthcare provider. Although users may aim to purchase or use opioids and sedatives obtained from other sources such as a dealer or street market, they might not always obtain the desired drug. Substandard and falsified medical products can be easily accessed through illegal street markets via unregulated websites, social media platforms, and smartphone applications (34). These medical products are often similar to the authentic product; however, the product may not contain the active ingredient or may be incorrectly formulated. Additionally, these products may contain toxic chemicals, bacteria, and unknown impurities which can be harmful (35). From 2016 to 2017, the largest increase in drug overdose deaths involved synthetic opioids (4). This increase was mostly driven by illicitly manufactured fentanyl (4), which can be obtained from these alternative markets.

Strengths and limitations

Previous studies have focused on how healthcare providers can intervene and eliminate the use of both prescription opioids and sedatives. In addition, the FDA has recommended that healthcare providers not prescribe opioids and sedatives to patients simultaneously, and the CDC has recommended that healthcare providers use urine tests to determine if a patient is currently using other medications and drugs. However, in this current study, we assessed other sources where non-medical users of prescription opioids and sedatives can obtain these medications. Our analyses found that these drugs may not always be obtained from a healthcare provider and these drugs are readily available for sale outside of medical facilities and in the medicine cabinets of friends and family members.

This study has limitations that should be noted. These analyses were conducted in a small sample size of 198 participants between the ages of 18 and 65 from the US Midwest and may not be applicable to adolescents and older adults. Furthermore, these results may not be generalizable to populations outside of the US Midwest. Nonetheless, this study still provides valuable information as it is important to examine trends among community-dwelling populations in addition to patient populations. Future studies should assess diversion trends over time in a larger sample, especially among the understudied population of older adults. However, it still adds to the literature on gender differences in sources of obtaining prescription opioids and sedatives, which has not been widely studied.

Conclusion

Polysubstance use, in general, is prevalent among drug users and more research is needed to understand polysubstance use in terms of patterns, prevalence, and consequences (36). Due to the potential adverse health outcomes associated with non-medical prescription opioid and sedative use, it is important to understand where non-medical users of these drugs are obtaining them. Additionally, this polysubstance should be considered in the face of a changing opioid context, where individuals are shifting toward heroin use and away from prescription opioid use. By doing so, we can highlight important intervention points and expand prevention efforts to all sources, rather than solely to prescribers. These interventions should be gender-specific, given that men are more likely to engage in incoming diversion compared to women.