Quantitative testing of buprenorphine and norbuprenorphine to identify urine sample spiking during office-based opioid treatment

Background: Patients may spike urine samples with buprenorphine during office-based opioid treatment to simulate adherence to prescribed buprenorphine, potentially to conceal diversion of medications. However, routine immunoassay screens do not detect instances of spiking, as these would simply result in a positive result. The aim of this study was to report on the experience of using quantitative urine testing for buprenorphine and norbuprenorphine to facilitate the identification of urine spiking. Methods: This is a retrospective chart review of 168 consecutive patients enrolled in outpatient buprenorphine treatment at an urban academic medical setting between May 2013 and August 2014. All urine samples submitted were subjected to quantitative urine toxicology testing for buprenorphine and norbuprenorphine. Norbuprenorphine-to-buprenorphine ratio of less than 0.02 were further examined for possible spiking. Demographic and clinical variables were also extracted from medical records. Clinical and demographic variables of those who did and did not spike their urines were compared. Statistically significant variables from the univariate testing were entered as predictors of spiking in a regression analysis. Results: A total of 168 patients were included, submitting a total of 2275 urine samples. Patients provided on average 13.6 (SD = 9.9) samples, and were in treatment for an average 153.1 days (SD = 142.2). In total, 8 samples (0.35%) from 8 patients (4.8%) were deemed to be spiked. All of the samples suspected of spiking contained buprenorphine levels greater than 2000 ng/mL, with a mean norbuprenorphine level of 11.9 ng/mL. Spiked samples were submitted by 6 patients (75.0%) during the intensive outpatient (IOP) phase of treatment, 2 patients (25.0%) during the weekly phase, and none from the monthly phase. Regression analysis indicated that history of intravenous drug use and submission of cocaine-positive urine samples at baseline were significant predictors of urine spiking. Conclusions: Even though only a small number of patients were identified to have spiked their urine samples, quantitative testing may help identify urine spiking during office-based opioid treatment with buprenorphine.     

Psychiatry residents’ and fellows’ confidence and knowledge in interpreting urine drug testing results related to opioids

Background: Prior studies have suggested that physicians and residents may not have sufficient knowledge to appropriately interpret urine drug tests (UDTs) in patients who are prescribed opioids or using illicit substances. Therefore, the aim of this study was to survey psychiatry residents and fellows about their confidence and knowledge in interpreting UDTs in patients with chronic pain or receiving office-based opioid treatment. Methods: All psychiatry residency and fellowship program directors in the New England states were approached to recruit their trainees to participate in an anonymous online survey including a 7-item knowledge test. Results: A total of 93 residents and fellows completed the survey. Only a minority (24.7%) reported any prior training in UDT interpretation. A majority (62.6%) felt confident about interpreting UDTs. The mean total score for the knowledge test was 3.5 (SD =1.1, range: 1–6). There were no significant differences in total score by confidence in UDT interpretation (3.7 vs. 3.4, t?=??1.17, nonsignificant [NS]), nor by prior training in UDT interpretation (3.8 vs. 3.5, t?=??1.22, NS). Conclusions: Psychiatry residents and fellows infrequently receive training in UDT interpretation, score poorly on the knowledge test, and their confidence in UDT interpretation does not reflect their knowledge. Future research should evaluate educational interventions that improve UDT interpretation among psychiatry residents and fellows.     

Urine naloxone concentration at different phases of buprenorphine maintenance treatment

In spite of the benefits of buprenorphine‐naloxone co‐formulation (BNX) in opioid maintenance treatment, the naloxone component has not prevented parenteral use of BNX. Current laboratory methods are not sufficient to differentiate between therapeutic and illicit use of buprenorphine, and little is known about urine naloxone concentrations. Measurement of urine naloxone, together with buprenorphine and norbuprenorphine, might help to determine the naloxone source and administration route. A liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method was developed and validated for this purpose. Naloxone, buprenorphine, and norbuprenorphine total concentrations were measured in urine samples from opioid‐dependent patients before and during stable and unstable phases of maintenance treatment with BNX. The limit of quantification in urine was 1.0 µg/L for naloxone, buprenorphine and norbuprenorphine. Before treatment, all samples contained buprenorphine but the median naloxone concentration was 0 µg/L. During the maintenance treatment with BNX all urine samples were positive for naloxone, buprenorphine and norbuprenorphine. The naloxone concentration at a stable phase of treatment (median 60 µg/L, range 5–200 µg/L) was not different from the naloxone concentration at an unstable phase (70 µg/L, 10–1700 µg/L). Applying an upper limit of 200 µg/L to the sample, the median naloxone/buprenorphine ratio was higher in the high than in the low naloxone concentration group (0.9 vs 0.3, respectively). This study suggests that naloxone in urine can act as an indicator of compliance with BNX. Parenteral use of BNX was associated with a high naloxone/buprenorphine ratio. Negative naloxone with positive buprenorphine suggests the use/abuse of buprenorphine alone. Copyright © 2013 John Wiley & Sons, Ltd.     

Integrating injectable opioid agonist treatment into a drug treatment court program: A case study

Background: A substantial proportion of individuals involved with the North American criminal justice system are convicted for drug-related activities. Drug treatment court (DTC) programs were developed as an alternative to incarceration for drug-related offences and aim to prioritize addiction treatment and improve health and social outcomes; however, only a fraction of DTC participants have access to first-line medications for opioid use disorder (OUD). Further, despite emerging evidence for the efficacy of injectable opioid agonist therapy (OAT) in treating individuals with severe OUD where past treatment attempts with first-line therapies have been unsuccessful, this treatment has never, to our knowledge, been implemented in correctional settings. Case: An individual in their 50s with a history of severe OUD, multiple interactions with the criminal justice system, and prior unsuccessful treatment attempts with methadone was initiated on injectable treatment with diacetylmorphine. The patient received 300?mg of diacetylmorphine witnessed 3 times daily at a supervised injection clinic. During a 1.5-year stabilization phase, the patient’s illicit opioid use significantly reduced. They subsequently enrolled in a DTC program for drug-related charges preceding initiation on injectable OAT and remained on this therapy during 16 months in DTC. Following graduation from DTC, the patient continued to receive treatment and returned to gainful employment in the community, with no further charges or episodes of incarceration. Discussion: This case describes the successful completion of a DTC program by an individual prescribed injectable OAT for severe OUD. The patient’s treatment plan played an integral role in DTC graduation and long-term adherence, leading to improved health and social outcomes, including cessation of illicit drug use, enhanced quality of life, and improved social functioning. The case highlights the potential benefits of a stepped and integrated approach to addiction treatment in DTC programs.     

Feasibility of collaborative care treatment of opioid use disorders with buprenorphine during pregnancy

Background: Medication-assisted treatment with buprenorphine or methadone is recommended for pregnant patients with opioid use disorders (OUDs) to minimize adverse maternal and neonatal outcomes. Collaborative care approaches have been successfully utilized with office-based opioid treatment with buprenorphine in primary care settings, but research is significantly limited in the obstetric setting. Our aim with this study is to demonstrate the feasibility of a collaborative care model for pregnant patients with opioid use disorder. Methods: This is a case series of 16 pregnancies in 14 women initiated on office-based opioid treatment with buprenorphine in a perinatal mental health service embedded in 2 obstetric clinics. Patients are treated by a psychiatrist alongside their prenatal care provider and followed for up to 6 months postpartum and referred to ongoing substance abuse treatment to a community prescriber. Results: The average age of the patients was 30.3 years, and an average gestational age of 23.6 weeks at the time of referral. Treatment continued until delivery in 15 (93.8%) pregnancies, with an average duration of treatment of 14.5 weeks. The majority (60%) had a cesarean delivery. Twelve (80%) infants were admitted to the Neonatal Intensive Care Unit (NICU) for monitoring or treatment of neonatal abstinence syndrome, 14 (87.5%) patients continued or resumed treatment with buprenorphine postpartum at the time of discharge from our program, and 13 (81.3%) were referred to a community prescriber. Conclusions: A collaborative care approach to buprenorphine treatment is feasible during pregnancy. Further research is needed to improve the treatment of OUD during pregnancy.     

Randomized pilot trial of Web-based cognitive-behavioral therapy adapted for use in office-based buprenorphine maintenance

Background: Despite the clear success of office-based buprenorphine treatment in increasing availability of effective treatment for opioid use disorder, constraints on its effectiveness include high attrition and limited high-quality behavioral care in many areas. Web-based interventions may be a novel strategy for providing evidence-based behavioral care to individuals receiving office-based buprenorphine maintenance. This report describes modification and initial pilot testing of Web-based training in cognitive-behavioral therapy (CBT4CBT) specifically for use with individuals in office-based buprenorphine. Methods: Twelve-week randomized pilot trial evaluating effects of CBT4CBT-Buprenophine in retaining participants and reducing drug use with respect to standard office-based buprenorphine alone was carried out. Twenty individuals meeting DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th Edition) criteria for current opioid use disorder were randomized to standard buprenorphine treatment or buprenorphine plus access to CBT4CBT-Buprenorphine. Results: There were promising findings regarding rates of urine toxicology screens negative for opioids (91% versus 64%; P?=?.05, effect size d?=?0.88) and all drugs (82% versus 30%; P?=?.004, d?=?1.2). Individuals randomized to CBT4CBT-Buprenorphine completed a mean of 82.6 (SD?=?4.4) days of treatment (of a possible 84) compared with 68.6 (SD?=?32.6) for those assigned to standard buprenorphine treatment. Conclusions: Although preliminary and limited by the small sample size, this trial suggests the feasibility and promise of validated, Web-based interventions, tailored for this specific patient population, for improving outcomes in office-based buprenorphine.     

High‐dose buprenorphine for treatment of high potency opioid use disorder

A 29‐year‐old woman presented to detox for treatment of an opioid use disorder with illicit fentanyl. While in detox, she was started on opioid agonist treatment with buprenorphine/naloxone. Unfortunately, she continued to have withdrawal symptoms despite being optimised to a dose of 32 mg. She was given additional PRNs of buprenorphine/naloxone to a total daily dose of 40 mg, which helped to alleviate her symptoms of withdrawal and cravings. She was stabilised on buprenorphine/naloxone 40 mg daily without any side effects and was discharged to a rehabilitation centre.     

Enzymatic assays for detecting lactose and sucrose in urine to reveal intravenous drug abuse with emphasis on buprenorphine

Buprenorphine and methadone are commonly used medications for opioid maintenance treatment (OMT), using sublingual and oral administration, respectively. Although beneficial for OMT, these drugs can also be abused by intravenous administration. In intravenous abuse cases, the adjuvants lactose and sucrose are excreted in urine without hydrolysis to monosaccharides, since there are no disaccharidases in the blood. We validated enzymatic methods for the analysis of lactose and sucrose in urine. The analytical performance of both assays was considered appropriate for detecting intravenous drug abuse. The principle was proven by analyzing 93 postmortem (PM) urine samples for lactose, following comprehensive toxicological drug screening. In addition, 32 clinical urine samples from potential drug abusers were analyzed to assess the effect of PM changes on the assay. The mean level of lactose was low in clinical samples and relatively low in PM samples in which no drugs were found. Markedly elevated levels were seen in many of the buprenorphine positive samples, suggesting intravenous administration. Enzymatic methods could provide a simple and cost effective way to assess the intravenous administration of OMT drugs or drugs of abuse. Very high levels of glucose in urine may interfere with the assays. Furthermore, other causes for elevated urine disaccharides, such as hypolactasia and increased intestinal permeability, need to be considered in the interpretation of the results. Copyright © 2016 John Wiley & Sons, Ltd.     

Consideration of opioid agonist treatment in a pregnant adolescent: A case report and literature review

Abstract

Background: Opioid use greatly increases the risk of overdose death, as well as contracting human immunodeficiency virus (HIV) and hepatitis. Opioid agonist treatment is recommended for pregnant women who are dependent on opioids. However, there is a dearth of studies on the use of opioid agonist treatment in pregnant teenagers. Case: Ms. A, a 15?year-old G1PO in foster care, presented to our tertiary women’s hospital requesting opioid agonist treatment for use of pill opioids. She reported nasal inhalation of 5–6 opioid tablets daily, with recent attempts to self-taper using nonprescribed buprenorphine since learning of her pregnancy. Last reported opioid use was >24?hours prior to admission. Urine drug testing was positive only for opioids (negative for buprenorphine and methadone). She did not exhibit significant withdrawal symptoms while hospitalized. The psychiatric treatment team recommended deferring opioid agonist treatment and pursuing outpatient substance use treatment. Unfortunately, Ms. A did not attend outpatient treatment and was lost to follow up. Discussion: Based upon our experience and review of the studies regarding opioid use disorder (OUD) and perinatal and adolescent opioid use, we recommend that pregnant adolescents with OUD be referred to opioid agonist treatment with buprenorphine or methadone. Studies specifically addressing opioid agonist treatment in pregnant teenagers are needed.     

A comparison of buprenorphine induction strategies: patient-centered home-based inductions versus standard-of-care office-based inductions

Although novel buprenorphine induction strategies are emerging, they have been inadequately studied. To examine our newly developed patient-centered home-based inductions, we conducted a subgroup analysis of 79 opioid-dependent individuals who had buprenorphine inductions at an urban community health center. Participants chose their induction strategy. Standard-of-care office-based inductions were physician driven, with multiple assessments, and observed, and the patient-centered home-based inductions emphasized patient self-management and included a "kit" for induction at home. We conducted interviews and extracted medical records. Using mixed nonlinear models, we examined associations between induction strategy and opioid use and any drug use. Compared with those with standard-of-care office-based inductions, participants with patient-centered home-based inductions had no significant differences in opioid use (adjusted odds ratio [AOR] = 0.63, 95% confidence interval [CI] = 0.13-2.97) but greater reductions in any drug use (AOR = 0.05, 95% CI = 0.01-0.37). Taking into account the limitations of our observational cohort study design, we conclude that participants with patient-centered home-based inductions had similar reductions in opioid use and greater reductions in any drug use than those with standard-of-care office-based inductions. It is essential that new induction strategies be based on existing models or theories and be well studied.     

Alcohol and Drug Use and Aberrant Drug-Related Behavior Among Patients on Chronic Opioid Therapy

Objective: To better identify individuals on chronic opioid therapy (COT) at high risk for aberrant-drug related behavior (ADRB). We examine whether patients with low level alcohol and drug use have similar characteristics to those with alcohol and drug disorders. We then examined the relationship of alcohol and drug use to ADRBs among COT patients. Methods: The sample was 972 randomly selected COT patients (age 21–80 years old) from a large health system in Northern California, USA, and interviewed in 2009. Logistic regression models were used to model the dependent variables of: alcohol use, illicit drug use, alcohol disorders, illicit drug disorders, and ADRBs. Results: The odds of daily/weekly alcohol use were lower for those with a high daily opioid dose (120+ mg/day vs. <20 mg/day) (OR = 0.32, p < 0.010). Illicit drug disorders were associated with depression (OR = 2.31, p < .001) and being on a high daily opioid dose (OR = 5.51, p < .01). Participants with illicit drug use had higher odds of giving (OR = 2.57, p < 0.01) and receiving opioids from friends or family (OR = 3.25, p < 0.001), but disorder diagnoses were not associated with ADRBs. Conclusions: Findings reinforce that illicit drug use should be of high concern to clinicians prescribing opioids, and suggest it should be considered separately from alcohol use and alcohol disorders in the evaluation of ADRBs. Frequent alcohol use is low, but not uncommon, and suggests a need to discuss specific issues regarding safe use of opioids among persons who use alcohol that may differ from their risk of drug use.     

Effect of buprenorphine dose on treatment outcome

The goal of this meta-analysis is to provide evidence based information about proper dosing for buprenorphine maintenance treatment to improve treatment outcome. To be selected for the review and inclusion in the meta-analysis, articles had to be randomized, controlled, or double-blind clinical trials, with buprenorphine as the study drug; the length of buprenorphine maintenance treatment had to be 3 weeks or longer; doses of buprenorphine had to be clearly stated; outcome measures had to include retention rates in buprenorphine treatment; outcome measures had to include illicit opioid use based on analytical determination of drugs of abuse in urine samples as outcome variables; and outcome measures had to include illicit cocaine use based on analytical determination of drugs of abuse in urine samples as outcome variables. Twenty-nine articles were excluded because they did not meet the inclusion criteria. The authors present the results of 21 articles that met inclusion criteria. The higher buprenorphine dose (16-32 mg per day) predicted better retention in treatment compared with the lower dose (less than 16 mg per day) (P = .009, R(2) adjusted = 0.40), and the positive urine drug screens for opiates predicted dropping out of treatment (P = .019, R(2) Adjusted = 0.40). Retention in treatment predicted less illicit opioid use (P = .033, R(2) Adjusted = 0.36), and the positive urine drug screens for cocaine predicted more illicit opioid use (P = .021, R(2) Adjusted = 0.36). Strong evidence exists based on 21 randomized clinical trials that the higher buprenorphine dose may improve retention in buprenorphine maintenance treatment.     

Lacking evidence for the association between frequent urine drug screening and health outcomes of persons on opioid agonist therapy

BackgroundOpioid agonist therapy (OAT) is a first-line treatment for opioid use disorder (OUD); however, the efficacy and role of urine drug screening (UDS) in OAT has received little research attention. Prior evidence suggests that UDS frequency reflects philosophy and practice context rather than differences in patient characteristics or clinical need. Therefore, we reviewed the literature on the effect of and recommendations for the frequency of UDS on health outcomes for persons with OUD who receive OAT.MethodsWe searched Medline and EMBASE for articles published from 1995-2017. Search results underwent double, independent review with discrepancies resolved through discussion with a third reviewer, when necessary. Additional articles were identified through snowball searching, hand searching (Google Scholar), and expert consultation. The Cochrane tool was used to assess risk of bias.ResultsOf the 60 potentially eligible articles reviewed, only one three-arm randomized open-label trial, comparing weekly and monthly UDS testing with take-home OAT doses, met our inclusion criteria.ConclusionsOur review identified an urgent gap in research evidence underpinning an area of clinical importance and that is routinely reported by patients as an area of concern.     

Demystifying buprenorphine misuse: Has fear of diversion gotten in the way of addressing the opioid crisis?

Buprenorphine is considered one of the most effective treatments for opioid use disorder and significantly reduces risk of overdose death. However, concerns about its diversion and misuse have often taken center stage in public discourse and in the design of practices and policies regarding its use. This has been to the detriment of many vulnerable patient populations, especially those involved in the criminal justice system. Policies that restrict access to buprenorphine in criminal justice and other settings due to concerns of diversion do not accurately reflect the relative risks and safety profile associated with it, creating unnecessary barriers that drive an illicit market of this much-needed medication. Although proper regulation of all controlled medications should be a priority, in most instances the benefits of buprenorphine highly outweigh its risks. In the midst of a national crisis, efforts should be focused on expanding, and not restricting, access to this lifesaving treatment.     

Drug test results as a predictor of retention among patients using buprenorphine in a comprehensive outpatient treatment program

The study examined the relationship between continued non-medical drug use and treatment retention for patients receiving buprenorphine maintenance treatment in a comprehensive addiction treatment program. The participants were 106 newly admitted patients and 103 continuing patients in treatment for an average of 9.4 months at the start of the study. Retrospective chart reviews were used to determine for each group whether the use of illicit, non-prescribed drugs during a 3-month baseline period was associated with lowered rates of treatment retention over the following 14 months. The New Admissions group was divided into 4 subgroups based on the percentage of urine drug tests that were positive during baseline: 0, 1–33, 34–67, or 68–100%. Because only 16 (15%) of the continuing patients had positive drug tests during baseline, the continuing group was divided into just 2 subgroups—no positives and any positives. Newly admitted patients testing positive for drugs more than 33% of the time were significantly more likely than those with less frequent or no positive tests to withdraw from treatment within 2 months. Continuing patients with at least 1 positive drug test left treatment 6 months sooner, on average, than those with no positive tests and were twice as likely to leave without completing continuing care (87 to 42%). Non-prescribed drug use during buprenorphine maintenance treatment is strongly correlated with lowered retention and risk of early treatment termination for new and continuing patients. Actions taken to monitor and reduce drug use during buprenorphine maintenance treatment may improve retention and enhance long-term recovery outcomes.     

Utility of sweat patch testing for drug use monitoring in outpatient treatment for opiate dependence

We evaluated the utility of sweat testing for monitoring of drug use in outpatient clinical settings and compared sweat toxicology with urine toxicology and self-reported drug use during a randomized clinical trial of the efficacy of buprenorphine for treatment of opioid dependence in primary care settings. All study participants (N = 63) were opiate-dependent, treatment-seeking volunteers. The results based on toxicology tests obtained from 188 properly worn and unadulterated patches (out of 536 applied) show that the level of agreement between positive sweat test results and positive urine results was 33% for opiates and 92% for cocaine. The findings of this study, that there is a low acceptability of sweat patch testing by patients (only 54.3% were brought back attached to the skin) and that weekly sweat testing is less sensitive than weekly urine testing in detecting opiate use, suggest limited utility of sweat patch testing in outpatient clinical settings.     

A Comparison of Random and Post-Accident Urine Opiate and Opioid Tests

Opioid use is associated with poor reaction time, attention, balance and memory posing a potential threat to workplace safety. The purpose of this study is to determine if there is a statistical association between opiate/opioid use and work related accidents as measured by urine drug tests by comparing the proportion of opiate/opioid laboratory positive urine specimens for postaccident verses random samples. The prevalence of laboratory positive opiate/opioid tests, the odds ratio, Fisher's exact probability test and the population attributable risk were calculated for each comparison. This study found a statistically significant difference for opiate/opioid results favoring the post-accident group.