Elsevier

Drug and Alcohol Dependence

Volume 178, 1 September 2017, Pages 223-230
Drug and Alcohol Dependence

Full length article
Prescribing of benzodiazepines and opioids to individuals with substance use disorders

https://doi.org/10.1016/j.drugalcdep.2017.05.014Get rights and content

Highlights

  • Many substance use disorder (SUD) patients receive benzodiazepine fills over a long period.

  • Co-occurring SUD and pain are associated with high rates of benzodiazepine fills.

  • Concomitant benzodiazepine and opioid dispensing are common in those with SUDs.

  • Females and whites are most likely to receive 5 plus benzodiazepine fills >7 days.

  • Benzodiazepine prescribers should seek out potentially dangerous polypharmacy.

Abstract

Background

Benzodiazepines are recommended for short-term use due to risk of dependence. This study examined characteristics associated with benzodiazepine and opioid dispensing of 7+ days in a Medicaid population with substance use disorder (SUD).

Methods

Using 2014 MarketScan® data, we performed zero-inflated negative binomial regression to ascertain characteristics associated with longer-term use of these medications.

Results

Nearly 14% of those with SUDs received 1+ fills of benzodiazepines of 7+ days. The highest rates were among those aged 45–64 (IRR = 2.38, p < 0.0001) and with non-alcohol SUDs (IRR = 1.12, p < 0.0001). Individuals with co-occurring psychiatric disorders, particularly anxiety and depression (IRR = 1.41, p < 0.0001), had high rates of benzodiazepine fills. Receiving a 7+ day oral opioid fill (IRR = 1.30, p < 0.0001) coincided with increased benzodiazepine dispensing. Similar results occurred for longer-term prescribing of opioids, with higher rates among those with non-alcohol SUDs (IRR = 1.23, p <  0.0001).

Conclusions

For many people with SUDs, receiving a benzodiazepine or opioid prescription of 7+ days is not a single occurrence; patients in our sample were more likely to receive 2+ fills than to receive one. Longer-term prescribing is most pronounced among those with co-occurring anxiety disorders. This suggests that anxiety in those with SUD should preferentially not be treated using benzodiazepines. Longer-term polypharmacy with benzodiazepines and opioids coincided. Overdoses among those using both drugs are growing and this study provides evidence that attention to the opioid epidemic should include attention to polypharmacy that includes benzodiazepines.

Introduction

Results of the 2015 National Survey on Drug Use and Health (NSDUH) indicated that approximately 20.8 million individuals aged 12 years and older (7.8%) met diagnostic criteria for a substance use disorder (SUD) during the past year (SAMHSA, 2016Substance Abuse Substance Abuse and Mental Health Services Administration [SAMHSA], 2016). A substantial proportion of individuals with a SUD also have a co-occurring mental health disorder. The 2015 NSDUH results indicate that 8.1 million (41.2%) adults aged 18 years or older with a SUD during the past year also had a mental illness (SAMHSA, 2016). It is important to treat both conditions properly in individuals with dual diagnoses (Minkoff, 2001, Minkoff, 2013, Perron et al., 2010, Wisdom et al., 2011).

Benzodiazepines are most commonly prescribed for the short-term treatment of anxiety disorders. Their appropriateness for managing symptoms of alcohol withdrawal is reflected in their labeling as approved by the U.S. Food and Drug Administration (FDA) (e.g., FDA, 2010, FDA, 2013). Benzodiazepines are not FDA-approved for managing any other withdrawal syndrome (FDA, 2017). According to American Psychiatric Association guidelines, however, benzodiazepines also have a role in the management of agitation due to intoxication with cocaine or other stimulants (American Psychiatric Association, 2010).

Benzodiazepines have a number of negative side effects and carry warnings regarding drug interactions, fetal harm, dependence, and withdrawal (FDA, 2011). According to the International Clinical Practice Guidelines, treatments involving benzodiazepines should be limited to 4 weeks (Peters et al., 2015). Benzodiazepines can produce both physical and psychological dependence (Hood et al., 2014, Uzun et al., 2010), and physical tolerance can develop after only 3–6 weeks of use (Hood et al., 2014). Benzodiazepines are associated with impaired memory and diminished emotional affect (Ashton, 2002), as well as cognitive impairment, delusions, falls, and other morbidities in older adults (American Geriatrics Society, 2015). The safety and effectiveness of these medications have not been established for long-term use or for patients with any form of SUD except alcohol withdrawal (Minkoff, 2001).

Accumulating evidence suggests that benzodiazepine exposure is particularly hazardous for persons with a SUD. Data from the National Institute on Drug Abuse show a 5-fold increase in the number of deaths from benzodiazepine overdose between 2001 and 2014 (National Institute on Drug Abuse, 2015), with benzodiazepines involved in 31% of opioid overdose deaths in 2011 (Chen et al., 2014), suggesting a particular danger associated with concomitant use of opioids and benzodiazepines. SAMHSA has reported increasing admissions for benzodiazepine abuse (SAMHSA, 2011) and noted a high association of benzodiazepine use disorder with opioid use disorder and comorbid psychiatric illness (SAMHSA, 2012). Prescribing benzodiazepines in the presence of known substance use disorder should be undertaken with care.

This study examined the number of outpatient benzodiazepine prescriptions dispensed for a greater than 7-day supply to individuals with a SUD diagnosis. We analyzed this occurrence with and without specific co-occurring psychiatric or pain disorders and looked at dispensing for those with different demographic characteristics. We also examined longer-term benzodiazepine fills with and without receipt of any antidepressant or of an oral opioid dosed in excess of 7 days. On the basis of those findings, we expanded our analysis to include a counterpart examination of predictors of oral opioid fills of 7+ days, including association with demographic and diagnostic variables, as well as receipt of either a longer-term fill of benzodiazepines or antidepressant dispensing. Our objective was to ascertain, among those with a SUD diagnosis, characteristics associated with longer-term use of benzodiazepines and opioids, including the extent to which such use co-occurs.

Section snippets

Data

We used the Truven Health Analytics MarketScan® Multi-State Medicaid Database for outpatient services and pharmaceutical claims for Medicaid enrollees from multiple states. We included all Medicaid enrollees in the MarketScan data in 2014 aged 13–64 years who had a SUD diagnosis (i.e., an alcohol disorder or any other nontobacco-related SUD). We excluded individuals who were dually eligible for Medicaid and Medicare and those who lacked information related to sex or age. After identifying

Descriptives

Of the 3,932,665 enrollees represented in the 2014 MarketScan Medicaid outpatient and pharmaceutical claims, 415,043 had a SUD-related diagnosis. After omitting 18,271 individuals who fell outside the age range of 13–64 years, an additional 59,677 individuals with dual Medicare and Medicaid coverage, and 2410 who were missing data on any of the variables, the sample for this study included 337,095 enrollees.

Table 1 provides frequencies for the sample by selected demographic, diagnostic, and

Discussion

Because benzodiazepines are useful for managing acute symptoms during alcohol withdrawal, they have a valuable role to play in that limited capacity for patients with alcohol use disorders. Benzodiazepines also can be an appropriate short-term treatment for anxiety. However, long-term use of benzodiazepines has not been demonstrated to be safe or effective, and use for those with a SUD, including those with co-occurring psychiatric disorders, subjects the patient to risk of iatrogenic addiction

Contributors

Dr. O’Brien oversaw and contributed to the study design and implementation, to review of the results, and to the preparation of the manuscript. Dr. Karnell contributed to review of the analytic results and to preparation of the manuscript. Ms. Gokhale and Mr. Pack conducted the study analyses. Drs. Campopiano and Zur assisted with the design, review of results, and manuscript preparation. All authors materially contributed to the preparation of the article and have approved the final article.

Role of funding source

This research was supported by the (Substance Abuse and Mental Health Services Administration SAMHSA), U.S. Department of Health and Human Services (HHS) (SAMHSA IDIQ prime contract HSS283200700029I, task order HHSS28342002T; and SAMHSA IDIQ prime contract HHSS283201200031I/HHSS28342002T, task order HHS83-12-3102). The opinions expressed in this article are those of the authors and not necessarily those of SAMHSA or HHS.

Conflict of interest

None.

Acknowledgments

We would like to acknowledge the contributions of Erika Crable and Paige Jackson at Truven Health Analytics.

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