Non-prescribed Benzodiazepines Research Articles

Clinical Outcomes of Benzodiazepine Prescribing for People Receiving Opioid Agonist Treatment: A Systematic Review of the Evidence

Many countries are experiencing an increased use of unregulated benzodiazepines in combination with opioids and other drugs, which contributes to drug-related harm. This descriptive review identifies and synthesises the outcomes of studies co-prescribing benzodiazepines and opioids. A systematic review was undertaken in Medline, CINAHL, PsychInfo, Embase, and the Cochrane databases covering publications from 1 January 1991 to 18 November 2021. Inclusion criteria were peer reviewed, English language studies of adults prescribed opioid agonist treatment (OAT) and a concurrent benzodiazepine, and reporting outcome data. Of the 4370 titles screened, 18 papers were included. The main outcomes identified covered all-cause mortality (ACM) (n = 5); overdose death (n = 3); retention in treatment (n = 7); and hospitalisation/emergency department encounters (n = 2). Other outcomes included QTc interval, cognitive function, illicit drug use, and mental health. The prescription of benzodiazepines alongside OAT increased the ACM by 75–90%, while evidence on overdose death was less robust but indicative of increased risk (40–334%). There was an indicative positive effect on treatment retention, with increased retention in those prescribed a benzodiazepine with OAT compared to those not prescribed or taking non-prescribed benzodiazepines. In conclusion, methodologically robust epidemiological studies found increased ACM and overdose death but possibly improved retention. However confounders (e.g., psychiatric comorbidity) exist, so a trial is recommended.

Treating Benzodiazepine Withdrawal in a Bridge Clinic.

Benzodiazepine-involved overdose deaths are rising, driven by increasing use of nonprescribed benzodiazepine pills. For patients who wish to stop nonprescribed benzodiazepine use, rapid inpatient tapers are typically the only option to treat benzodiazepine withdrawal. Substance use disorder bridge clinics can provide the high-touch care needed to manage outpatient benzodiazepine tapers in patients at high risk due to other substance use disorders. Describe the implementation and short-term outcomes of an outpatient benzodiazepine taper protocol to treat benzodiazepine withdrawal in a substance use disorder bridge clinic. The clinical team developed a 4- to 6-week intensive outpatient taper protocol using diazepam. Patients with benzodiazepine use disorder were eligible if they had benzodiazepine withdrawal, lacked a prescriber, wanted to stop benzodiazepines completely, and agreed to daily visits. For patients who initiated a taper between April 2021 and December 2022, we evaluated the proportion of patients who completed a taper (i.e., tapered to a last prescribed dose of diazepam 10 mg/d or less); likelihood of remaining on the taper over time; and seizure, overdose, or death documented at the study institution during or within 1 month of taper completion or discontinuation. Other secondary outcomes included HIV testing and prevention, hepatitis C testing, and referrals to recovery coaching or psychiatry. Fifty-four patients initiated a total of 60 benzodiazepine tapers. The population was mostly male (61%) and non-Hispanic White (85%). Nearly all patients had opioid use disorder (96%), and most (80%) were taking methadone or buprenorphine for opioid use disorder before starting the taper. Patients reported using multiple substances in addition to benzodiazepines, most commonly fentanyl (75%), followed by cocaine (41%) and methamphetamine (21%). Fourteen patients (23%) completed a taper with a median duration of 34 days (IQR 27.8-43.5). Most tapers were stopped when the patient was lost to follow-up (57%), or the team recommended inpatient care (18%). Two patients had a seizure, and 4 had a presumed opioid-involved overdose during or within 1 month after the last taper visit, all individuals who did not complete a taper. No deaths occurred during or within 1 month of taper completion or discontinuation. Challenges included frequent loss to follow-up in the setting of other unstable substance use. Patients received other high-priority care during the taper including HIV testing (32%), PrEP initiation (6.7%), hepatitis C testing (30%), and referrals to recovery coaches (18%) and psychiatry (6.7%). Managing benzodiazepine withdrawal with a 4- to 6-week intensive outpatient taper in patients with benzodiazepine and opioid use disorders is challenging. More work is needed to refine patient selection, balance safety risks with feasibility, and study long-term, patient-centered outcomes.

Trends in co-prescribed opioids and benzodiazepines, non-prescribed opioids and benzodiazepines, and schedule-I drugs in the United States, 2013 to 2019

Concurrent opioid and benzodiazepine users are at increased risk of overdose death, compared to opioid-only users.The objective of this study was to understand recent time trends in opioid and benzodiazepine concurrent use, misuse, and schedule-I drug use, and how these differ by age, sex and geographic region. Commercial, United States medical insurance claims data and urine drug test results from 2013 to 2019 were used to study the outcomes of concurrent use (n = 756,258), schedule-I drug use (n = 746,672) and prescription misuse (n = 452,523). Drug use outcomes were studied at quarterly time points for each year.Data analysis included joinpoint regression models to estimate quarterly drug use rates, determined by positive urine tests for corresponding drug categories, and was conducted from November 2021 through January 2022. Concurrent use decreased from 19.3% to 9.8%, misuse generally decreased from 75.6% to 55.1%, and schedule-I use increased from 8.9% to 13.8%, from 2013 to 2019. Concurrent use decreased at greater rates after 2016, after the Centers for Disease Control and Food and Drug Administration guidelines against concurrent use were released, while schedule-I use increased, notably after the 2014 hydrocodone reschedule. This indicates a potential shift from prescription use to non-prescribed drug use, where most affected groups included males, younger individuals, and those residing in Northeastern regions.Study results support public health initiatives focused on policy that increases access to multimodal pain management and substance use disorder management programs—critical steps in preventing patients from seeking non-prescribed drugs for self- medicating due to pain or addiction.

Increased risk of non-fatal overdose associated with non-prescribed benzodiazepine use in Scotland, UK.

Drug-related deaths (DRDs) in Scotland increased for seven years in a row between 2014 and 2020, consolidating Scotland's place at the top of the United Kingdom and European drug-related mortality charts. One of the defining features of this recent and rapid rise has been the role of benzodiazepines, which are now involved in the majority of all DRDs. These deaths are linked to use of non-prescribed, benzodiazepine-type novel psychoactive substances (NPS) which have been identified by the United Nations as a global threat to public health. This study aimed to estimate the prevalence and determinants of non-prescribed benzodiazepine use and its association with recent non-fatal overdose among a national sample of people who inject drugs (PWID). Data from the 2019-20 Needle Exchange Surveillance Initiative (NESI) was analysed using logistic regression. NESI is a voluntary, anonymous, biennial, cross-sectional, bio-behavioural survey of PWID attending community-based services providing injecting equipment in mainland Scotland. Prevalence of non-prescribed benzodiazepine use in the past six months was 52% and significantly associated with age (aOR 0.97, 0.96-0.98), frequent incarceration (aOR 1.29, 1.07-1.57), recent public injecting (aOR 3.25, 2.33-4.55), a recent methadone prescription (aOR 1.87, 1.51-2.33), and a history of benzodiazepine prescription (aOR 1.92, 1.47-2.52). In addition, non-prescribed benzodiazepine use was significantly associated with non-fatal overdose in the past year among PWID (aOR 2.47, 1.90-3.21). This study found a high prevalence of non-prescribed benzodiazepine use among a national sample of PWID in Scotland. Prevalence was highest among populations known to be at increased risk of drug-related death and use was strongly associated with overdose. These novel findings highlight the scale of the non-prescribed benzodiazepine issue Scotland faces, and the urgency required to expand its harm reduction infrastructure to address this unique element of its overdose crisis.

Real or fake? Sourcing and marketing of non-prescribed benzodiazepines amongst two samples of people who regularly use illicit drugs in Australia.

There is concern around non-prescribed benzodiazepine use, particularly with increasing detections of counterfeit products containing high-risk novel compounds. The aims of this study were to investigate how and which non-prescribed benzodiazepines are being sourced; forms, appearance and packaging; and awareness of risks associated with non-prescribed benzodiazepines. Data were collected from a sample of Australians who inject drugs or use ecstasy and/or other illicit stimulants on a monthly or more frequent basis, and who reported past 6-month use of non-prescribed benzodiazepines (n = 235 and n = 250, respectively). Data were collected on source, diversion from a known/trusted prescription, product name and aesthetic characteristics for the last non-prescribed benzodiazepine obtained. Amongst participants who injected drugs, 71% reported that their last non-prescribed benzodiazepines were diverted from a known/trusted prescription, compared to 59% of participants who used ecstasy/other stimulants. Sourcing via cryptomarkets was rare. Across both samples, the majority reported last obtaining substances sold/marketed as diazepam or alprazolam. Participants sourcing via non-diverted means were twice as likely to obtain alprazolam. Known sourcing of novel compounds was rare. Amongst participants who used ecstasy/other stimulants, 36% reported confidence in the content/dose of non-prescribed benzodiazepines even when the source is unknown. Most participants obtained substances sold as classic/registered benzodiazepines, mostly via diverted prescriptions, with a substantial minority potentially unaware of counterfeits circulating. While diverted use undeniably presents risks, tightening of prescriptions in Australia could inadvertently lead to greater supply of novel benzodiazepines as seen internationally, reinforcing prioritisation of demand and harm reduction strategies.

Benzodiazepine analysis by an improved LC-MS/MS method illustrates usage patterns in Washington State

BackgroundThe standard approach for benzodiazepine detection often includes immunoassay followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The illicit use of non-prescribed benzodiazepines has been trending up nationally. MethodsWe developed and validated an improved LC-MS/MS assay for benzodiazepine detection in urine. We expanded the testing panel by adding five drugs to the previous panel of ten. We determined the prevalence of individual benzodiazepines in our patient population. Immunoassay results were compared with LC-MS/MS to evaluate assay performance. ResultsClonazepam and alprazolam were the most common benzodiazepines present. Etizolam and flualprazolam were also prevalent in Washington State. Compared with the LC-MS/MS assay, the immunoassay had variable cross-reactivity, which explained false negative and false positive immunoassay results. The inclusion of new drugs in the LC-MS/MS panel significantly reduced the incidence of immunoassay results interpreted as falsely positive. ConclusionNew illicit benzodiazepines have emerged regionally and nationally. The inclusion of novel drugs in LC-MS/MS assay was helpful in properly characterizing the epidemiology of benzodiazepine use in our patient population. This information will lead to better assay result interpretations and patient care, and our experiences provide a roadmap for other clinical laboratories looking to expand their testing menu or transition to new instrumentation.

Consensus-Based Guidance on Opioid Management in Individuals With Advanced Cancer-Related Pain and Opioid Misuse or Use Disorder

Opioid misuse and opioid use disorder (OUD) are important comorbidities in people with advanced cancer and cancer-related pain, but there is a lack of consensus on treatment. To develop consensus among palliative care and addiction specialists on the appropriateness of various opioid management strategies in individuals with advanced cancer-related pain and opioid misuse or OUD. For this qualitative study, using ExpertLens, an online platform and methodology for conducting modified Delphi panels, between August and October 2020, we conducted 2 modified Delphi panels to understand the perspectives of palliative and addiction clinicians on 3 common clinical scenarios varying by prognosis (weeks to months vs months to years). Of the 129 invited palliative or addiction medicine specialists, 120 participated in at least 1 round. A total of 84 participated in all 3 rounds. Consensus was investigated for 3 clinical scenarios: (1) a patient with a history of an untreated opioid use disorder, (2) a patient taking more opioid than prescribed, and (3) a patient using nonprescribed benzodiazepines. Participants were mostly women (47 [62%]), White (94 (78 [65%]), and held MD/DO degrees (115 [96%]). For a patient with untreated OUD, regardless of prognosis, it was deemed appropriate to begin treatment with buprenorphine/naloxone and inappropriate to refer to a methadone clinic. Beginning split-dose methadone was deemed appropriate for patients with shorter prognoses and of uncertain appropriateness for those with longer prognoses. Beginning a full opioid agonist was deemed of uncertain appropriateness for those with a short prognosis and inappropriate for those with a longer prognosis. Regardless of prognosis, for a patient with no medical history of OUD taking more opioids than prescribed, it was deemed appropriate to increase monitoring, inappropriate to taper opioids, and of uncertain appropriateness to increase the patient's opioids or transition to buprenorphine/naloxone. For a patient with a urine drug test positive for non-prescribed benzodiazepines, regardless of prognosis, it was deemed appropriate to increase monitoring, inappropriate to taper opioids and prescribe buprenorphine/naloxone. The findings of this qualitative study provide urgently needed consensus-based guidance for clinicians and highlight critical research and policy gaps.

“The idea is to help people achieve greater success and liberty”: A qualitative study of expanded methadone take-home access in opioid use disorder treatment

Background: Prior to the COVID-19 pandemic, the United States (US) was already facing an epidemic of opioid overdose deaths. Overdose deaths continued to surge during the pandemic. To limit COVID-19 spread and to avoid disruptions in access to medications for opioid use disorder (MOUD), including buprenorphine and methadone, US federal and state agencies granted unprecedented exemptions to existing MOUD guidelines for Opioid Treatment Programs (OTPs), including loosening criteria for unsupervised take-home doses. We conducted a qualitative study to evaluate the impact of these policy changes on MOUD treatment experiences for providers and patients at an OTP in California. Methods: We interviewed 10 providers (including two physicians, five social worker associates, and three nurse practitioners) and 20 patients receiving MOUD. We transcribed, coded, and analyzed all interviews to identify emergent themes. Results: Patient participants were middle-aged (median age 51 years) and were predominantly men (53%). Providers discussed clinical decision-making processes and experiences providing take-homes. Implementation of expanded take-home policies was cautious. Providers reported making individualized decisions, using patient factors to decide if benefits outweighed risks of overdose and misuse. Decision-making factors included patient drug use, overdose risk, housing status, and vulnerability to COVID-19. New patient groups started receiving take-homes and providers noted few adverse events. Patients who received take-homes reported increased autonomy and treatment flexibility, which in turn increased likelihood of treatment stabilization and engagement. Patients who remained ineligible for take-homes, usually due to ongoing non-prescribed opioid or benzodiazepine use, desired greater transparency and shared decision-making. Conclusion: Federal exemptions in response to COVID-19 led to the unprecedented expansion of access to MOUD take-homes within OTPs. Providers and patients perceived benefits to expanding access to take-homes and experienced few adverse outcomes, suggesting expanded take-home policies should remain post-COVID-19. Future studies should explore whether these findings are generalizable to other OTPs and assess larger samples to quantify patient-level outcomes resulting from expanded take-home policies.

Predictors of postdischarge follow-up attendance among hospitalized dermatology patients: Disparities and potential interventions

Predictors of postdischarge follow-up attendance among hospitalized dermatology patients: Disparities and potential interventions

Psychiatric disorders in a population of deceased drug users

Purpose To estimate the prevalence of psychiatric morbidity and dual diagnosis in a population of decedents with positive drug toxicology and evaluate changes over time between 2001–2002 and 2011–2012. Materials and methods A total of 520 autopsied drug users with positive toxicology were included in the study from 2001 to 2002 and from 2011 to 2012. Materials included autopsy reports, toxicological screening during autopsy and data from the Danish national health registers, including psychiatric diagnoses from psychiatric hospitals and ambulatory functions, dispensed prescription use from pharmacies and registered treatment for drug use disorders. Results In 2001–2002, 63.3% of the decedents had only positive toxicology, 22.5% also had psychiatric morbidity, and 14.2% had a dual diagnosis. In 2011–2012, 56.4% had only positive toxicology, 26.1% also had psychiatric morbidity, and 17.5% had a dual diagnosis. None of the changes were significant. Decedents with only positive toxicology became older at time of death over time; decedents with psychiatric morbidity and a dual diagnosis did not. The prevalence of nonprescribed psychotropic medication, methadone and benzodiazepines increased. Conclusion Decedents with psychiatric morbidity and dual diagnosis did not increase their lifespan over a 10-year period. Decedents with only positive toxicology increasingly consumed nonprescribed psychotropic medication and may have suffered from undiagnosed psychiatric disorders. The prevalence of prescribed and nonprescribed benzodiazepines and methadone increased and may have contributed to premature mortality.

Predictors of pharmacologic therapy for neonatal opioid withdrawal syndrome: a retrospective analysis of a statewide database.

Identify factors associated with the need for pharmacologic therapy (PT) among opioid exposed newborn (OENs). Retrospective analysis of a statewide database of OENs from 2017 through 2019. Multivariable mixed-effects logistic regression modeled the association of maternal characteristics, infant characteristics, and family engagement practices on the receipt of PT. Of 2098 OENs, 44.8% required PT for NOWS. Higher odds of PT were associated with in-utero exposure to medication treatment for opioid use disorder (MOUD) and non-prescribed opioids in addition to MOUD; nicotine, benzodiazepines, SSRIs; male; out-born infants and mother's ineligibility to provide breast-milk. Lower odds were associated with increasing birth year, skin-to-skin (STS) care, and rooming-in. Male, out-born infants exposed to MOUD with additional non-prescribed opioids, nicotine, benzodiazepines and SSSRIs with mothers ineligible to provide breast-milk were more likely to require PT, while modifiable care practices including STS care, and rooming-in decreased the likelihood of PT.

The Opioid Epidemic Within the COVID-19 Pandemic: Drug Testing in 2020.

The convergence of the opioid epidemic and the coronavirus disease 2019 (COVID-19) pandemic has created new health care challenges. The authors analyzed changes in clinical drug testing patterns and results at a national clinical laboratory, comparing data obtained before and during the pandemic. Testing for prescription and illicit drugs declined rapidly during the pandemic, with weekly test volumes falling by approximately 70% from the baseline period to the trough (the week beginning March 29) before rising in subsequent weeks. Among individuals tested, positivity increased by 35% for non-prescribed fentanyl and 44% for heroin during the pandemic. Positivity for non-prescribed fentanyl increased significantly among patients positive for other drugs: by 89% for specimens positive for amphetamines; 48% for benzodiazepines; 34% for cocaine; and 39% for opiates (P < 0.01 for all comparisons). These findings suggest significant increases in dangerous drug combinations. Positivity for non-prescribed use of many other drugs remained consistent or declined for some drugs, relative to pre-pandemic patterns. Models adjusting for potential confounding variables, including medication-assisted treatment and treatment at a substance use disorder facility indicated that the risk for non-prescribed fentanyl positivity rose by more than 50% during the pandemic. In summary, these findings demonstrate decreased drug testing overall, with increased positivity for high-risk drugs and dangerous drug combinations. The convergence of the drug abuse epidemic and COVID-19 pandemic has led to an increased need for health care and public health resources dedicated to supporting vulnerable patients and addressing the underlying causes of these disturbing trends.

The Cyclical and Evolving Nature of Methamphetamine Use: An Evaluation of Near Real-time Urine Drug Test Results.

Objective:To determine methamphetamine positivity and copositivity with other drugs in urine drug test (UDT) results geographically through time.Methods:This cross-sectional study of UDT results from January 1, 2014, through December 31, 2019, included patient specimens submitted by health care professionals across the United States. The analysis used LC-MS/MS to detect cocaine, heroin, alcohol, marijuana and nonprescribed methamphetamine, fentanyl, methadone, buprenorphine, benzodiazepines, and other opioids. Logistic regression was used to evaluate association of demographic features and model yearly methamphetamine detection patterns across US census divisions. Odds ratios (OR) from logistic modeling were used to evaluate the impact of methamphetamine positivity on the spatio-temporal detection patterns of additional nonprescribed or illicit drugs.Results:The probability of being positive for methamphetamine increased nationally from 0.010 [0.010–0.011] in 2014 to 0.044 [0.042–0.046] in 2019, a 340% increase after correction for demographic covariates. The highest predicted positivity rate was in male patients, 25- to 34-years-old, from the West North Central division and from substance use disorder treatment centers. Nationally, copositivity ORs for fentanyl, heroin, and other opioids with methamphetamine were highest in 2019. Increases in ORs from 2014 through 2019 were statistically significant for heroin (P = 0.024) and fentanyl (P = 0.0085). Copositivity ORs for methamphetamine and other substances varied by census division.Conclusions:The probability of being positive for methamphetamine in UDT increased nationwide between 2014 and 2019. Not all census divisions are increasing at the same rate. Copositivity with additional substances is increasing in some census divisions, which further increases the risk of overdose and poor treatment outcomes.

Patterns and correlates of prescribed and non-prescribed pregabalin use among a sample of people who inject drugs in Australia.

Pregabalin is a gamma-aminobutyric acid analogue registered and subsidised for the treatment of neuropathic pain in Australia. Despite pre-clinical evidence of low abuse potential, there are increasing reports of extramedical use and overdose deaths involving pregabalin. This study aimed to describe patterns of pregabalin use among an Australian sample of people who inject drugs (PWID) and identify sociodemographic, substance use and mental/physical health correlates of prescribed and non-prescribed use. Data were obtained from the 2018 Illicit Drug Reporting System, comprising a cross-sectional sample of 905 PWID recruited from Australian capital cities. Multinomial logistic regression was used to identify correlates of past 6-month prescribed and non-prescribed pregabalin use. One-quarter (25%) of participants reported any past 6-month pregabalin use, with 10% reporting prescribed use and 15% non-prescribed use. Past 6-month use of prescribed benzodiazepines and non-prescribed pharmaceutical opioids were associated with both prescribed and non-prescribed pregabalin use compared to no recent pregabalin use. Pain/discomfort on the day of interview was significantly associated with prescribed pregabalin use. Recent use of non-prescribed benzodiazepines and illicit stimulants and past year non-fatal overdose were significantly associated with non-prescribed pregabalin use (compared to no recent pregabalin use). Pregabalin use was relatively common among an Australian sample of PWID. Benzodiazepine and pharmaceutical opioid use were positively correlated with both prescribed and non-prescribed pregabalin use, suggesting that education campaigns regarding the risks of harm associated with concomitant use of these substances are warranted (targeting both health professionals and consumers).

Alprazolam use among a sample of Australians who inject drugs: Trends up to six years post regulatory changes

IntroductionAlprazolam is a high potency triazolobenzodiazepine that is associated with a disproportionate amount of harm compared to other benzodiazepines. In Australia, amid growing concerns of extra-medical use and harms, alprazolam was up-scheduled from Schedule 4 (prescription only) to Schedule 8 (controlled drug) on 1 February 2014, with further restrictions introduced on 1 February 2017. This study aims to examine the impact of these regulatory changes among cross-sectional samples of people who inject drugs (PWID), from 2011–2019. MethodsData were obtained from the 2011–2019 Illicit Drug Reporting System, comprising cross-sectional samples of PWID recruited annually from Australian capital cities (approximately ~900 per year). ResultsBy 2019, the proportion of PWID who reported past six-month use of non-prescribed (17%) and prescribed (4%) alprazolam had halved compared to 2011 (39% and 13%, respectively), with no evidence of an increase in use of other sedative substances. Following the up-scheduling of alprazolam in 2014, there was an increase in the median last price paid for 2 mg of diverted alprazolam ($5AUD pre-rescheduling versus $7AUD post rescheduling), with 61% of those able to answer reporting that diverted alprazolam had become ‘more difficult’ to obtain post versus pre-rescheduling. The correlates associated with non-prescribed alprazolam use remained relatively consistent pre- and post-regulatory change, with past-month criminal activity, past six-month opioid agonist therapy and past six-month use of non-prescribed other benzodiazepines associated with non-prescribed alprazolam use in both the 2013 and 2018 samples. ConclusionsRegulatory changes appear to have resulted in sustained reductions in alprazolam use amongst our annual cross-sectional sentinel samples of PWID, although a considerable minority (17%) continued to report non-prescribed use in 2019. To achieve further reductions in non-prescribed use and associated harms, these regulatory changes need to be coupled with other interventions, such as direct consumer engagement and harm reduction messaging. Our findings suggest that people receiving opioid agonist therapy remain a key target population for such interventions.

Nonmedical Benzodiazepine Use in Adolescents: Indirect Effects of Internalizing and Externalizing Symptoms

Benzodiazepines (BZDs) are a substance commonly misused in adolescence. A significant risk factor for the nonmedical use of BZDs is sex, whereby girls are more likely to misuse such drugs. However, very few studies have examined the mental health correlates of adolescents who engage in the nonmedical use of BZDs. The current study examines whether internalizing or externalizing symptoms explain the relationship between sex and nonmedical BZD use. Self-reported questionnaires were collected in 2018 from 6986 American high-school students between the ages of 12 and 19 years. Analyses were conducted using MPlus. A total of 5.3% (n = 367) adolescents reported using non-prescribed BZDs in the past year. Girls were significantly more likely to report BZD misuse than boys. Indirect effects emerged for both internalizing and externalizing symptoms in the association between sex and nonmedical BZD use. Our results suggest that nonmedical BZD use in adolescence may be indicative of increased mental health and behavioral problems.

Physician Renewal of Chronically Prescribed Controlled Substances Based on Urine Drug Test Results.

Objective: The effect of specific urine drug testing (UDT) results on physician prescribing habits has not been well described. The primary objective was to report renewal rates of chronically prescribed controlled substances based on types of inconsistent UDT results. Methods: We conducted a retrospective chart review over a 5-month period comparing prescription renewals rates for patients with consistent versus inconsistent UDTs. Inconsistent UDTs were defined by prescribed drug not detected or the presence of heroin, cocaine, nonprescribed opioids, nonprescribed benzodiazepines, or marijuana. Results: Of the 474 UDTs reviewed, 214 (45.1%) were inconsistent. The most common findings among inconsistent UDTs, including overlapping results, were prescribed drug not detected (26.8%) and the presence of marijuana (20.7%), nonprescribed opioids (9.9%), and nonprescribed benzodiazepines (6.1%). In contrast, cocaine (5.5%) and heroin (0.4%) were less likely to be found on UDTs for this population. The relative risk (RR) of prescription renewal was 0.64 (95% CI 0.57-0.71) for inconsistent UDTs versus consistent UDTs. Within the inconsistent UDTs, the renewal rates when marijuana (79.6%) or nonprescribed opioids or benzodiazepines (63.6%) were present were much higher than when heroin or cocaine were present (0.0%; P < .001). Patients whose prescribed controlled substance was not detected had a 55.8% renewal rate. Conclusions: Prescription renewal rates were high when patient UDTs contained nonprescribed marijuana, opioids, and benzodiazepines, or when the prescribed drug was not detected. Prescription renewal rates were low when illicit drugs, such as heroin and cocaine, were detected.

Evaluating the Impact of Prescribed Versus Nonprescribed Benzodiazepine Use in Methadone Maintenance Therapy: Results From a Population-based Retrospective Cohort Study.

Objectives:Benzodiazepine (BZD) use is common in patients who are engaged in methadone as a treatment for opioid use disorder. BZD prescribing is generally discouraged for this patient population due to the increased risk of BZD dependence and BZD use disorder, medication-assisted treatment (MAT) discontinuation, and opioid-overdose death. However, some patients have concurrent mental health disorders, where BZD use may be clinically indicated. This study evaluates the impact of prescribed BZD on MAT outcomes.Methods:Linking urine drug screening data (UDS) and prescribing information from single-payer health records, we conducted a retrospective Kaplan–Meier analysis between patients using prescribed and nonprescribed BZD with methadone treatment retention as the primary outcome. Data are from a network of 52 outpatient clinics in Ontario, Canada, between January 1, 2006 and June 30, 2013.Results:We identified 3692 patients initiating methadone-assisted treatment for the first time; 76% were BZD−/UDS− (no BZD prescription and <30% screens positive for BZD); 13% were BZD+/UDS−; 6% BZD−/UDS+; and 6% BZD+/UDS+. Using 1-year treatment retention as a primary outcome, patients using nonprescribed BZD (BZD−/UDS+) were twice as likely (adjusted odds ratio 0.38, 95% confidence interval 0.27–0.53) to discontinue treatment as those not using BZD (BZD−/UDS−), or those using BZD in a prescribed manner (BZD+/UDS+).Conclusions:Our findings suggest that prescribed BZD can be used during methadone MAT without impacting a patient's retention in MAT, but nonprescribed BZD use is predictive of treatment discontinuation. Importantly, we urge both the physician and patient to seek alternative clinical options to BZD prescribing, due to the potential for developing physical dependence (and BZD use disorder) to BZD and the risks of negative interactions with opioids.

Concurrent Use of Opioids and Benzodiazepines: Evaluation of Prescription Drug Monitoring by a United States Laboratory.

Objectives:Recently, more than 63% of the 52,404 drug overdose deaths in the United States involved heroin and opioid pain medications. More than 30% of opioid-related deaths also involved benzodiazepines. Previous studies examining the extent of concurrent opioid and benzodiazepine use have relied on prescription data. To gain fuller insight into the extent of the concurrent use problem, we analyzed opioid and benzodiazepine prescription patterns in the context of drug testing results.Methods:All specimens from patients that were prescribed at least 1 drug and were tested for both opioids and benzodiazepines by a national reference laboratory were included. This resulted in an analytical set of 231,228 sets of test results from 144,535 patients with diverse demographic factors being tested in a variety of health care settings.Results:Laboratory test results indicated concurrent use of opioids and benzodiazepines in over 25% of patients. In 52% of test results with evidence of concurrent use, 1 drug class was prescribed and the other was non-prescribed. Nearly 1 in 5 specimens (19%) testing positive for prescribed opioids also tested positive for non-prescribed benzodiazepines. Over 15% of specimens with prescribed benzodiazepines also demonstrated non-prescribed opioid use.Conclusions:The extent of concurrent use of benzodiazepines and opioids, particularly non-prescribed use, suggests the need for more effective clinician assessment and intervention. The results support the Centers for Disease Control and Prevention opioid prescribing guidelines that drug testing occur before and periodically throughout opioid use and suggest that this testing should be extended to patients prescribed benzodiazepines as well.

(227) Medication Adherence Monitoring in Patients Prescribed Buprenorphine/Naloxone

We sought to assess the relationship between the frequency of urine drug monitoring (UDM) and adherence to prescribed buprenorphine/naloxone therapy, and use of illicit substances, non-prescribed opiates or benzodiazepines. Patients prescribed buprenorphine/naloxone were included if they had ≥2 urine samples (separated by ≥6 months) assessed between 2013 and 2016. Baseline and final samples were classified as positive or negative for: buprenorphine, and for any illicit substance, for non-prescribed opiates/synthetic opioids, and for benzodiazepines. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated using multiple logistic regression analysis with the following independent variables: gender, age decade, primary payor, geographic region, year tested, buprenorphine dose, and frequency of UDM. Because data were obtained from a de-identified database, this study was not submitted for IRB review. For 6,900 patients in the analysis, the rate of negative urines for buprenorphine was lower in the final urine compared to the baseline urines (10% vs 8%) and for the final sample, patients with ≥1 sample/month were significantly less likely to be negative for buprenorphine than those with 1 sample/3 months (10% vs 6%; aOR, 0.53; 95% CI, 0.41-0.70 for 1/month vs 1/3 months). A non-prescribed opiate was detected in 16% and 11% of first and last samples respectively, with the largest decline observed in those with the most frequent UDM testing (23% vs. 11%). A non-prescribed benzodiazepine was detected in 19% and 16% of first and last samples respectively, with the largest decline observed in those with the most frequent UDM testing (27% vs. 19%). Frequent urine drug monitoring may have the potential to increase adherence to prescribed buprenorphine/naloxone and decrease the use of non-prescribed opiates and benzodiazepines.