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Background: Urine drug tests (UDTs) are recommended to monitor patients treated for opioid use disorder in primary care. The aims are to (1) estimate the frequency of self-report and UDT results of opioid and cocaine use and (2) evaluate the association between treatment time with non-disclosure of opioid or cocaine use and having a positive UDT., Methods: We conducted a retrospective review of patients enrolled in a primary care-based buprenorphine program between January 2011-April 2013. We describe three clinical visits types: no disclosure of opioid/cocaine use and positive UDT; disclosure of opioid or cocaine use and a negative or positive UDT; and no disclosure of opioid or cocaine use and a negative UDT. We fit generalized estimating equations logistic regression models to evaluate whether treatment time is associated with non-disclosure of opioids or cocaine use and a positive UDT., Results: Among all UDT results (n = 1755) from 130 patients, 10% were positive for illicit opioids and 4% for cocaine. Among UDTs with illicit opioid or cocaine positive results, in 57% and 76% of these scenarios, the patient did not disclose. The odds of non-disclosure and having a positive UDT was higher in the first 180 days for opioids and 90 days for cocaine., Conclusion: Among primary care patients treated with buprenorphine, a small but substantial percentage of UDTs were cocaine or opioid positive. As treatment time increased, non-disclosure was less common but persisted even after six months. Among primary care patients treated with buprenorphine, UDTs contribute information to optimize clinical care., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Urine adulteration is a concern among patients treated for opioid use disorder. Quantitative urine testing for buprenorphine (B) and norbuprenorphine (NB), and the appropriate interpretation of B and NB levels, can facilitate constructive conversations with patients that may lead to modifications in the treatment plan, and strengthening of the patient-provider relationship., Case Summary: Three cases are presented in which discordant urine B and NB levels were recognized. Each patient was submerging buprenorphine/naloxone strips in their urine to mask ongoing illicit drug use. The authors used an approach to addressing intentional adulteration of urine samples that adheres to the principles of harm-reduction, the centrality of the patient-provider relationship, and the acknowledgment that ongoing illicit drug use and subsequent dishonesty about disclosure may be common among persons with substance use disorders. Each of the three patients ultimately endorsed diluting their urine, which allowed for strengthening of the patient-provider relationship and modifications to their treatment plans. Two of the three patients stabilized and achieved abstinence, while the third was eventually referred to a methadone treatment program., Conclusion: Providers should routinely monitor B and NB levels, rather than qualitative screening alone, and discordant levels should elicit a timely conversation with the patient. The authors use of a nonjudgmental approach to address urine adulteration, including giving patients an opportunity to reflect on potential solutions, has been effective at helping patients and providers to reestablish a therapeutic alliance and maintain retention in treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: This study examined whether starting buprenorphine treatment prior to prison and after release from prison would be associated with better drug treatment outcomes and whether males and females responded differently to the combination of in-prison treatment and post-release service setting., Methods: Study design was a 2 (In-Prison Treatment: Condition: Buprenorphine Treatment: vs. Counseling Only)×2 [Post-Release Service Setting Condition: Opioid Treatment: Program (OTP) vs. Community Health Center (CHC)]×2 (Gender) factorial design. The trial was conducted between September 2008 and July 2012. Follow-up assessments were completed in 2014. Participants were recruited from two Baltimore pre-release prisons (one for men and one for women). Adult pre-release prisoners who were heroin-dependent during the year prior to incarceration were eligible. Post-release assessments were conducted at 1, 3, 6, and 12-month following prison release., Results: Participants (N=211) in the in-prison treatment condition effect had a higher mean number of days of community buprenorphine treatment compared to the condition in which participants initiated medication after release (P=0.005). However, there were no statistically significant hypothesized effects for the in-prison treatment condition in terms of: days of heroin use and crime, and opioid and cocaine positive urine screening test results (all Ps>0.14) and no statistically significant hypothesized gender effects (all Ps>0.18)., Conclusions: Although initiating buprenorphine treatment in prison compared to after-release was associated with more days receiving buprenorphine treatment in the designated community treatment program during the 12-months post-release assessment, it was not associated with superior outcomes in terms of heroin and cocaine use and criminal behavior., Competing Interests: This study was supported by an unrestricted, unsolicited investigator initiated request from Reckitt Benckiser Pharmaceuticals, Inc. (provided study drug only) who had no role in study design; collection, analysis and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. The authors alone are responsible for the content and writing of this manuscript. Drs. Gordon, Kinlock, and Fitzgerald received funding from Alkermes on a prior study. Dr. Schwartz did a one-time consultation for Reckitt-Benckiser on behalf of his employer (the Friends Research Institute). Dr. O’Grady has in the past received funding for his time from Reckitt-Benckiser. Dr. Vocci has consulted with and received other funding (meals, travel expenses) from the following companies: Braeburn Pharmaceuticals, Demerx, Indivior, Pinney Associates. He has received travel and meal expenses from Intratab Labs Inc., and received consulting fees from Alkermes and Usona Institute. All of Dr. Vocci’s consulting fees go to his employer, Friends Research Institute, Inc., (Copyright © 2017 Elsevier B.V. All rights reserved.)

During a 12-week intervention, opioid dependent participants (N = 120) maintained on thrice-a-week (M, W, F) buprenorphine plus therapist and computer-based counseling were randomized to receive: (a) medication contingencies (MC = thrice weekly dosing schedule vs. daily attendance and single-day 50% dose reduction imposed upon submission of an opioid and/or cocaine positive urine sample); (b) voucher contingency (VC = escalating schedule for opioid and/or cocaine negative samples with reset for drug-positive samples); or (c) standard care (SC), with no programmed consequences for urinalysis results. VC resulted in better 12-week retention (85%) compared to MC (58%; p = 0.009), but neither differed from SC (76% retained). After adjusting for baseline differences in employment, and compared to SC, the MC group achieved 1.5 more continuous weeks of combined opioid/cocaine abstinence (p = 0.030), while the VC group had 2 more total weeks of abstinence (p = 0.048). Drug use results suggest that both the interventions were efficacious, with effects primarily in opioid rather than cocaine test results. Findings should be interpreted in light of the greater attrition associated with medication-based contingencies versus the greater monetary costs of voucher-based contingencies., (2009 APA, all rights reserved.)

Naltrexone treatment has demonstrated some advantages for special populations of heroin addicted individuals, but patients' compliance seems to be very poor, with a low adherence and low retention rate. Kappa-opioid system overdrive seems to contribute to opioid protracted abstinence syndrome, with dysphoria and psychosomatic symptoms during naltrexone treatment. The objective of this observational study was to determine the effectiveness of a functional k antagonist in improving naltrexone treatment outcome. A partial mu agonist/kappa antagonist (buprenorphine) and a mu antagonist (naltrexone) were combined during a 12 weeks protocol, theoretically leaving k antagonism as the major medication effect. Sixty patients were submitted to outpatient rapid detoxification utilizing buprenorphine and opioid antagonists. Starting on the fifth day, 30 patients (group A) received naltrexone alone. Alternatively, 30 patients (group B) received naltrexone (50mg oral dose) plus buprenorphine (4 mg sublingual) for the 12 weeks of the observational study. The endpoints of the study were: retention in treatment, negative urinalyses, changes in psychological symptoms (Symptom Checklist-90 Revised: SCL-90) and craving scores (visual analysis scale (VAS)). Thirty-four subjects (56.67%) completed the 12 weeks study. Twenty-one patients (35.0%) had all urine samples negative for opiates and cocaine. nine subjects (15.0%) had urine samples negative for cocaine and opiates for the last 4 weeks of the study. five subjects (8.3%) continued to use cocaine during the 12 weeks of the study. No significant change in pupillary diameter after buprenorphine administration was evidenced during clinical observations from baseline across the weekly measurements. Retention rates in group A (naltrexone) and group B (naltrexone + buprenorphine) at week 12 were respectively 40% (12 patients) and 73.33% (22 patients), with a significant difference in favour of group B (p= 0.018). Patients treated with naltrexone in combination with buprenorphine (B patients) showed a significantly lower rate of positive urines for morphine (4.45%) and cocaine metabolites (9.09%) than those treated with naltrexone alone (A) (25%, morphine; 33.33% cocaine) (p< 0.05; p< 0.05). Irritability, depression, tiredness, psychosomatic symptoms and craving scores decreased significantly less in Group A patients than in group B patients. The dysfunction of opioid system with kappa receptors hyper-activation provoked by heroin exposure, probably underlying dysphoric and psychosomatic symptoms during naltrexone treatment, seems to be counteracted, at least in part, by buprenorphine. The combination of buprenorphine and naltrexone may significantly improve the outcome of opioid antagonists treatment in terms of retention, negative urinalyses, and reduced dysphoria, mood symptoms and craving.

We evaluated the influence of psychotherapy attendance on treatment outcome in 90 dually (cocaine and heroin) dependent outpatients who completed 70 days of a controlled clinical trial of sublingual buprenorphine (16 mg, 8 mg, or 2 mg daily, or 16 mg every other day) plus weekly individual standardized interpersonal cognitive psychotherapy. Treatment outcome was evaluated by quantitative urine benzoylecgonine (BZE) and morphine levels (log-transformed), performed three times per week. Repeated-measures linear regression was used to assess the effects of psychotherapy attendance (percent of visits kept), medication group, and study week on urine drug metabolite levels. Mean psychotherapy attendance was 71% of scheduled visits. Higher psychotherapy attendance was associated with lower urine BZE levels, and this association grew more pronounced as the study progressed (p=0.04). The inverse relationship between psychotherapy attendance and urine morphine levels varied by medication group, being most pronounced for subjects receiving 16 mg every other day (p=0.02). These results suggest that psychotherapy can improve the outcome of buprenorphine maintenance treatment for patients with dual (cocaine and opioid) dependence.

Background: Buprenorphine is a partial mu-opiate agonist and kappa-opiate antagonist with established efficacy in the treatment of opiate dependence. Its efficacy for cocaine dependence is uncertain. This study evaluated buprenorphine for the treatment of concomitant cocaine and opiate dependence., Methods: Two hundred outpatients currently dependent on both cocaine and opiates were randomly assigned to double-blind groups receiving a sublingual solution of buprenorphine (2, 8, or 16 mg daily, or 16 mg on alternate days, or placebo), plus weekly individual drug abuse counseling, for 13 weeks. The chief outcome measures were urine concentrations of opiate and cocaine metabolites (quantitative) and proportion of urine samples positive for opiates or cocaine (qualitative). Group differences were assessed by use of mixed regression modeling., Results: The target dose of buprenorphine was achieved in 179 subjects. Subjects receiving 8 or 16 mg buprenorphine daily showed statistically significant decreases in urine morphine levels (P =.0135 for 8 mg and P <.001 for 16 mg) or benzoylecgonine concentrations (P =.0277 for 8 mg and P =.006 for 16 mg) during the maintenance phase of the study. For the 16-mg group, mean benzoylecgonine concentrations fell from 3715 ng/mL during baseline to 186 ng/mL during the withdrawal phase; mean morphine concentrations fell from 3311 ng/mL during baseline to 263 ng/mL during withdrawal. For the 8-mg group, mean benzoylecgonine concentrations fell from 6761 ng/mL during baseline to 676 ng/mL during withdrawal; mean morphine concentrations fell from 3890 ng/mL during baseline to 661 ng/mL during withdrawal. Qualitative urinalysis showed a similar pattern of results. Subjects receiving the highest dose showed concomitant decreases in both urine morphine and benzoylecgonine concentrations. There were no significant group differences in treatment retention or adverse events., Conclusions: A sublingual buprenorphine solution at 16 mg daily is well tolerated and effective in reducing concomitant opiate and cocaine use. The therapeutic effect on cocaine use appears independent of that on opiate use.

Depression is common among patients who abuse both opiates and cocaine, and its treatment has had mixed success. This study compares buprenorphine-maintained patients with lifetime major depressive disorder (MDD, N = 53) with those never depressed (ND, N = 96) on cocaine and opiate-free urines during a 12-week outpatient double-blind, placebo-controlled, randomized clinical trial. The 149 subjects were assigned to four groups: 1) desipramine (DMI) + contingency management (CM); 2) DMI + noncontingency management (NCM); 3) placebo + CM; and 4) placebo + NCM. Depression assessments included Hamilton Depression Rating Scale, Center for Epidemiological Studies Depression Inventory, and Structured Clinical Interview for DSM-IV interview for diagnosis of lifetime MDD. Urine toxicologies were performed thrice weekly and the CES-D was performed monthly. The MDD group had a larger proportion of females (45% vs 21%, P = 0.02) and were more likely to be married (13.2% vs 7.3%, P = 0.02) than the ND group. Treatment retention did not vary by depression status. Hierarchical Linear Modeling found that depressive symptoms decreased comparably across the four treatment groups. Although participation in CM improved drug-free urines more for patients with MDD than for the ND group (Z = 2.44, P = 0.01), treatment with DMI was significantly more efficacious for the ND group than for the MDD group (Z = -2.89, P = 0.003). These results suggest that patients with MDD may respond better to behavioral treatments such as CM than to desipramine plus buprenorphine. The ND cocaine-abusing, opiate-dependent patients may be more responsive to the anticraving effects of DMI.

Co-dependence on opiates and cocaine occurs in about 60% of patients entering methadone treatment and has a poor prognosis. However, we recently found that desipramine (DMI) could be combined with buprenorphine to significantly reduce combined opiate and cocaine use among these dually dependent patients. Furthermore, contingency management (CM) has been quite potent in reducing cocaine abuse during methadone maintenance. To test the efficacy of combining CM with these medications we designed a 12-week, randomized, double blind, four cell trial evaluating DMI (150 mg/day) or placebo plus CM or a non-contingent voucher control in 160 cocaine abusers maintained on buprenorphine (median 16 mg daily). Cocaine-free and combined opiate and cocaine-free urines increased more rapidly over time in those treated with either DMI or CM, and those receiving both interventions had more drug-free urines (50%) than the other three treatment groups (25-29%). Self reported opiate and cocaine use and depressive and opioid withdrawal symptoms showed no differences among the groups and symptom levels did not correlate with urine toxicology results. Lower DMI plasma levels (average 125 ng/ml) were associated with greater cocaine-free urines. DMI and CM had independent and additive effects in facilitating cocaine-free urines in buprenorphine maintained patients. The antidepressant appeared to enhance responsiveness to CM reinforcement.

This study examined the usefulness of baseline cocaine urine toxicology results and self-reported days of cocaine use in predicting treatment response in cocaine- and opioid-dependent subjects. Ninety-nine male and 52 female subjects, maintained on buprenorphine, participated in a 24-week, randomized, double-blind, four-cell trial that evaluated desipramine (150 mg/d) or placebo plus contingency management or a noncontingent voucher control. Out of 151, 102 (67%) subjects had cocaine-positive and 49 (32%) cocaine-negative urines at the beginning of treatment. For the previous 30 days before study participation, 91 (60%) subjects reported using cocaine 15 or less days (low baseline cocaine use) and 60 (40%) subjects reported more than 15 days (high baseline cocaine use). By using the treatment effectiveness score (TES) as the outcome measure, a negative urine for cocaine at baseline predicted a better outcome during a 24-week trial for cocaine and opioid use. There also was a significant interaction between baseline cocaine urine results and desipramine response with the urine cocaine-negative group showing greater desipramine response than placebo for opioid and cocaine use. Self-reported cocaine use at baseline did not show significant predictive power for TES scores during the clinical trial. These results suggest that baseline cocaine urine results should be considered as stratifying variables in clinical trials for cocaine dependence.