## Abstract

Objectives. To understand the extent to which medication adherence was related to diversion of prescription analgesics.

Design. Cross-sectional analyses of data from the College Life Study, a prospective study of young adults.

Setting. Participants were originally sampled as incoming first-time first-year college students from one large public university in the Mid-Atlantic United States.

Participants. One hundred ninety-two young adults aged 21–26 who were prescribed an analgesic to treat acute pain in the past year.

Outcome Measure. Diversion of prescription analgesics. The study tested two competing hypotheses: 1) individuals who skip doses (under-users) are at greatest risk for diversion because they have leftover medication; and 2) individuals who over-use their prescriptions (over-users) are at greatest risk for diversion, perhaps because of a general propensity to engage in deviant behavior.

Results. Fifty-eight percent followed physician's instructions regarding their prescription analgesic medication; 27% under-used their prescribed medication and 16% over-used their prescribed medication. Twenty-seven percent of the total sample diverted their medication, with over-users being the most likely to divert (63%). Holding constant demographic characteristics and perceived harmfulness of nonmedical use, over-users were almost five times as likely as adherent users to divert analgesic medications (P < 0.05).

Conclusions. Further research is needed to better understand the relationship between adherence and diversion. If these findings are replicated, physicians who are involved in pain management for acute conditions among young adults should take steps to monitor adherence and reduce diversion of prescription analgesics.

## Introduction

Analgesic medications are one of the most commonly prescribed classes of drugs in the United States [1,2], with a total of 230.7 million prescriptions written in 2006 [3]. In the wake of pain management awareness initiatives and the “pain as the 5th vital sign” campaign, prescribing of both nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids (including strong opioids) to treat acute pain has increased over the past several decades [4]. An estimated 19% of the US population purchased at least one prescription analgesic medication in 2006 [3]. While these medications are generally highly effective for pain management, serious medical consequences have been noted [5–7], including overdose deaths [8–10]. Recent research suggests that prescription analgesics are the most commonly diverted class of medication [11], with one study showing that among college students prescribed an analgesic in the past year, 26% were approached to divert their medication [12]. In another recent study, 35% of college students had diverted a prescription analgesic in their lifetime [13].

It is plausible that diversion is related to the extent to which patients adhere to their prescribing physicians' instructions. Surprisingly little research has investigated the connection between medication adherence and diversion of prescription analgesics. Additionally, despite a growing body of literature examining adherence and misuse among chronic pain patients [14–19], little is known about medication adherence in patients with acute pain, especially among young adults—the age group at highest risk for nonmedical use of prescription analgesics [20].

The present study had two aims: 1) to understand the extent to which young adults followed physician instructions with regard to a prescription for analgesic medications; and 2) to describe the association between medication adherence and diversion. Prior research has demonstrated that non-adherence can take two forms: skipping doses (under-use) and taking more than prescribed (over-use). In this study, we tested two competing hypotheses: 1) individuals who skip doses are at greatest risk for diversion, as they would tend to have extra unused doses available; and 2) individuals who over-use their own prescriptions might be at greater risk for diversion because they might tend to engage in deviant behavior and perceive nonmedical use as less harmful than adherent users.

## Methods

### Parent Study Design

Data were derived from the College Life Study, an ongoing longitudinal prospective study of 1,253 young adults originally sampled as incoming first-year college students at a large public university in the Mid-Atlantic region of the United States. During summer orientation in 2004, students were recruited to participate in the study. Students who used an illicit drug or nonmedically used a prescription drug at least once during high school were deliberately oversampled. Sometime during their first year of college, they completed a 2-hour interview, which was repeated annually, regardless of continued college enrollment. Details of recruitment and interview procedures can be found elsewhere [21]. Interviews were administered by trained interviewers. The study was approved by the University Institutional Review Board, and a Federal Certificate of Confidentiality was obtained. Data for the present analyses are taken from interviews conducted during Years 5, 6, and 7. Incentive payments varied by assessment; at Year 5, participants received $70, plus a$20 bonus for on-time completion. The on-time completion bonus was increased to \$30 for Years 6 and 7.

### Participants

The analytic sample consisted of 192 individuals (ages 21–26), who, at one or more of the three annual assessments, reported that they had received a prescription for an analgesic medication sometime in the past year. Individuals with a past-year analgesic prescription at more than one time point were only counted once, using the first year in which they had a prescription. Of the 192 individuals, the majority (89%, n = 171) were prescribed opioid analgesics, 12 individuals (6%) were prescribed non-opioids (primarily NSAIDs), and nine individuals (5%) could not remember the name of their medication. All 192 individuals had acute pain conditions (e.g., surgeries [including dental procedures], broken bones, torn ligaments, muscle spasms); none had chronic pain conditions. A wide variety of medications were prescribed, the most common of which were hydrocodone/acetaminophen combinations and oxycodone/acetaminophen combinations. The sample was 50% male, 71% white, and did not differ demographically from participants not prescribed an analgesic.

### Measures

#### Demographics

Race was self-reported. Family income was approximated by the mean adjusted gross income for each participant's home ZIP code during their last year in high school [22].

#### Diversion

Participants were asked how many times in the past year they had shared, sold, and/or traded their prescription analgesic medication. Individuals who reported any of these behaviors were categorized as past-year diverters.

Participants were asked about the instructions their physician gave them regarding how to take their analgesic medication. Most were able to recall a specific amount (e.g., “one tablet”) and frequency (e.g., “every four to six hours”). Participants were then asked to describe their actual use. Adherence was defined as agreement between the physician's instructions and the individual's behavior. Individuals were divided into three adherence categories: 1) under-users, who took medication either less often than was prescribed, sporadically (e.g., when they remembered), or not at all; 2) adherent users, who took their medication as prescribed; and 3) over-users, who took their medication more often than prescribed.

#### Perceived Harmfulness of Nonmedical Use of Prescription Analgesics

At year 4, perceived harmfulness was assessed via a question adapted from the Monitoring the Future survey [23]: “How much do you think people risk harming themselves (physically or in other ways) by taking someone else's prescription pain relievers occasionally?” Responses were dichotomized into “moderate/great risk” and “no/slight risk.” Three individuals who responded “can't say/drug unfamiliar” were grouped into the latter category on the assumption that if they were unfamiliar with the drug, they were unlikely to believe it was harmful.

### Statistical Analysis

Fisher's exact tests were used to compare the prevalence of diversion among the three groups. Multivariate logistic regression analyses were performed to examine whether differences between groups remained statistically significant after adjusting for sex, race, family income, perceived harmfulness of nonmedical use, and type of analgesic (i.e., non-opioid, opioid analgesic). The nine individuals who did not know the type of analgesic that they were prescribed were dropped from the statistical model (i.e., it predicted “failure”[non-diversion] perfectly).

## Results

Over half of the sample met our criteria for adherent use of their prescription analgesics in the past year (58%, n = 111). The remaining 42% (n = 81) used their prescribed analgesic inconsistently with their physician's instructions, either by under-use (27%, n = 51) or over-use (16%, n = 30). The three groups were similar with respect to demographic characteristics and perceived harmfulness of nonmedical use (Table 1).

Table 1

Demographic characteristics by adherence grouping and logistic regression examining associations between diversion and adherence

 Total (n = 192) Under-Users (n = 51) Adherent Users (n = 111) Over-Users (n = 30) AOR (95% CI) Sex (N, % male) 95 (49.5) 21 (41.2) 48 (43.2) 26 (86.7) 1.67 (0.79–3.56) Race (N, % White) 137 (71.4) 32 (62.8) 81 (73.0) 24 (80.0) 0.94 (0.42–2.09) Family income (m, SD in ten thousands)† 8.0 (3.9) 7.8 (3.6) 8.2 (4.1) 7.2 (3.2) 0.90 (0.81–1.01) Perceived harmfulness of nonmedical use (N, %)‡ No/slight risk 49 (25.8) 13 (25.5) 26 (23.9) 10 (33.3) Reference category 2.01 (0.81–4.97) Moderate/great risk 141 (74.2) 38 (74.5) 83 (76.2) 20 (66.7) Type of analgesic prescribed Non-opioid 12 (6.3) 3 (5.9) 8 (7.2) 1 (3.3) Reference category 1.94 (0.39–9.79) Opioid 171 (89.1) 45 (88.2) 98 (88.3) 28 (93.3) Unknown§ 9 (4.7) 3 (5.9) 5 (4.5) 1 (3.3) Adherence Adherent user Reference category 0.62 (0.25–1.55) 4.99 (1.88–13.26)* Under-user Over-user
 Total (n = 192) Under-Users (n = 51) Adherent Users (n = 111) Over-Users (n = 30) AOR (95% CI) Sex (N, % male) 95 (49.5) 21 (41.2) 48 (43.2) 26 (86.7) 1.67 (0.79–3.56) Race (N, % White) 137 (71.4) 32 (62.8) 81 (73.0) 24 (80.0) 0.94 (0.42–2.09) Family income (m, SD in ten thousands)† 8.0 (3.9) 7.8 (3.6) 8.2 (4.1) 7.2 (3.2) 0.90 (0.81–1.01) Perceived harmfulness of nonmedical use (N, %)‡ No/slight risk 49 (25.8) 13 (25.5) 26 (23.9) 10 (33.3) Reference category 2.01 (0.81–4.97) Moderate/great risk 141 (74.2) 38 (74.5) 83 (76.2) 20 (66.7) Type of analgesic prescribed Non-opioid 12 (6.3) 3 (5.9) 8 (7.2) 1 (3.3) Reference category 1.94 (0.39–9.79) Opioid 171 (89.1) 45 (88.2) 98 (88.3) 28 (93.3) Unknown§ 9 (4.7) 3 (5.9) 5 (4.5) 1 (3.3) Adherence Adherent user Reference category 0.62 (0.25–1.55) 4.99 (1.88–13.26)* Under-user Over-user
*

Significantly associated with likelihood of diversion (P < 0.05).

Family income was measured via the mean adjusted gross income for each participant's home ZIP code during their last year in high school.

Two participants in the adherent users were missing data on perceived risk. n (%) for perceived risk for that group are out of 109 and 190.

§

Because having an unknown analgesic predicted failure of the logistic regression model perfectly (non-diversion), these cases were dropped from the model, reducing the N of the regression model by six observations.

AOR = adjusted odds ratio; CI = confidence interval; SD = standard deviation.

Overall, more than a quarter (27%, n = 51) of participants (29% of those prescribed opioids and 17% of those prescribed non-opioids) diverted their prescribed analgesic. As shown in Figure 1, over-users had the highest proportion of diverters (63%). Table 1 shows that, even after controlling for demographic characteristics, perceived harmfulness of nonmedical use, and type of analgesic prescribed, over-users were significantly more likely than adherent users to divert their analgesic medication (adjusted odds ratio [AOR] = 4.99, 95% confidence interval [CI] = 1.88–13.26; P = 0.001). Under-users did not statistically differ from adherent users with respect to their likelihood to divert. Over-users were more than eight times as likely as under-users to divert their medication (AOR = 8.03, 95% CI = 2.52–25.59; P < 0.001; data not shown in table).

Figure 1

Diversion of prescription analgesics by adherence grouping among young adults prescribed an analgesic medication in the past year (n = 192).

Figure 1

Diversion of prescription analgesics by adherence grouping among young adults prescribed an analgesic medication in the past year (n = 192).

## Discussion

The finding that 42% of the sample used their analgesic medication in a way that was inconsistent with their physician's instructions (27% under-used, 16% over-used) comports with prior evidence from chronic pain patients [18,24–26]. We found no support for our first hypothesis that under-users would be more likely to divert due to having extra unused doses. However, the second hypothesis was supported, with over-users almost five times as likely as adherent users and more than eight times as likely as under-users to share, sell, or trade their medication. Particularly, the concern is that these individuals had sufficient medication from the prescription to both over-use it and divert it.

### Limitations

The study results may not be generalizable to all young adult populations. Because data were obtained by self-report, the findings are subject to recall bias, although this problem was minimized by focusing on the individual's most recent analgesic prescription in the past year. To provide a more nuanced view of analgesic medication adherence, future studies should collect more detailed information about the exact number of pills prescribed and used. It would be helpful to know the final disposition of all unused doses. Even among under-users who are unlikely to divert their medication, unused doses that have not been properly disposed of provide an ongoing opportunity for nonmedical use by someone else via theft or other means. More detailed information regarding the outcome of these unused does in addition to how doses were diverted (e.g., sharing, selling, trading) and to whom would also be valuable.

### Implications

Additional research is warranted to better understand the relationships between medication adherence, diversion, and nonmedical use. Future research should investigate more details regarding adherence behavior, including history of adherence to physician instructions, the number of pills prescribed for various conditions, and patient attitudes regarding diversion.

The findings of this study should be tempered with caution because of the homogenous nature of the sample (young adults with acute pain) and the small sample size. If replicated, these results could have significant implications for clinical practice for physicians with young adult patients. Because many analgesic medications have addiction potential, it is important to balance necessary pain management with “judicious dosing,” as suggested by McLellan and Turner [1] to minimize the risk of diversion and subsequent nonmedical use. Given that dental pain/surgery were reported reasons for being prescribed an analgesic and wisdom tooth extraction is a common procedure for young adults, developing specific prescribing guidelines for dentists and oral surgeons to reduce diversion might be beneficial. Aside from serious concerns about the potential for diversion and nonmedical use, excessive dosing is at odds with efforts to control health care costs, which have become a national priority.

Prior research with adolescents and young adults has identified that individuals with a history of conduct problems and illicit drug involvement are at increased risk for diversion of prescription medications [13]; thus, close oversight, including follow-up visits [27], are recommended for individuals with these characteristics. However, these characteristics might not be identifiable to clinicians outside of psychiatric service settings. Therefore, monitoring for adherence to physician's instructions when given a prescription for opioid analgesics and cautioning against diversion in all patients might be necessary. Given that the prevalence of over-use was low among those prescribed a non-opioid analgesic, these drugs should be considered as an alternative to opioid analgesics in cases of acute pain to decrease the likelihood of over-use. Because of concerns regarding opioid use, prescribing of NSAID analgesics in all but severe pain cases is still advocated as the first course of action in treating acute pain, to be followed by prescription opioids if needed [28,29].

## Acknowledgments

This study was funded by the National Institute on Drug Abuse (R01DA14845, Dr. Arria, PI). Special thanks are extended to Emily Winick, the interviewing team, and the participants.

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Disclosure:
None of the authors has any financial disclosures to report.