Opioid reinforcement in heroin-dependent volunteers during outpatient buprenorphine maintenance.

This study examined the reinforcing effects of hydromorphone (HYD) (0, 4, 8, and 16 mg/70 kg i.m.) in heroin-dependent outpatient volunteers maintained on buprenorphine (BUP) at doses of 2, 4, and 8 mg, each for 2 weeks. Following a week of maintenance at each dose, volunteers received injections of one of the four HYD doses under double-blind conditions. Eight volunteers (abstainers) were heroin-free during HYD test weeks, whereas six volunteers remained heroin-positive (nonabstainers). Among abstainers, HYD had minimal reinforcing value, whereas in nonabstainers there were marked dose-related increases in HYD reinforcing value, which were not attenuated by increasing doses of BUP. A similar pattern was found for HYD subjective agonist effects. Heroin craving among nonabstainers was significantly higher compared with abstainers, and was reduced in a dose-related manner by HYD. Although BUP and HYD produced dose-related miosis, abstinence status had no differential effect. In summary, BUP effects on opioid reinforcement were consistent from outpatient setting (heroin abstinence) to laboratory setting (decreased HYD reinforcement), supporting the validity of this laboratory model.     

Treatment of heroin-dependent poly-drug abusers with contingency management and buprenorphine maintenance

This study targeted poly-drug (cocaine plus heroin) abstinence among buprenorphine-maintained participants with a 12-week voucher-based reinforcement therapy (VBRT) phase versus a yoked control condition. Baseline levels of cocaine and heroin use were significant predictors of treatment outcome, regardless of treatment assignment. Overall, there were no significant group differences on treatment outcome. However, among the subsample that produced one or more poly-drug-free urine results, VBRT participants had significantly increased cocaine-but not heroin and poly-drug-abstinence, although all results were in the predicted direction. Results suggest that for those who achieve poly-drug abstinence, VBRT may enhance treatment outcome. However, improved interventions, perhaps targeting single-drug abstinence, increasing reinforcement magnitude, or both, may be necessary to promote initial poly-drug abstinence in this population.     

Preference for brand-name buprenorphine is related to severity of addiction among outpatients in opioid maintenance treatment

As a form of opioid maintenance treatment, high-dose buprenorphine is increasingly being used in the United States. On the French market since 1996, it is the most commonly prescribed and frequently employed opioid maintenance treatment. For unknown reasons, the brand-name form is used far more often than the generic form (76–24%). The objective was to show that the patients' levels of addiction were differentiated according to the form of buprenorphine currently being used and to their previous experience of a different form. An observational study in 9 sites throughout France used self-assessment questionnaires filled out in retail pharmacies by all patients to whom their prescribed buprenorphine treatment was being delivered. The 151 canvassed pharmacies solicited 879 patients, of whom 724 completed the questionnaires. Participants were statistically similar to non-participants. The patients using the brand-name form subsequent to experience with the generic form exhibited a more elevated addiction severity index and a higher dosage than brand-name form users with no experience of a different form. Compared to generic users, their doses were higher, their was addiction more severe, and their alcohol consumption was more excessive; they were also more likely to make daily use of psychotropic substances. However, the level of misuse or illicit consumption was similar between these groups. Preferring the brand-name buprenorphine form to the generic form is associated with a higher level of severe addiction, a more frequent need for daily psychotropics, and excessive drinking; but the study was unable to show a causal link.     

Short-term buprenorphine maintenance: treatment outcome

Fifty-two heroin addicts were inducted onto buprenorphine under the care of psychiatric residents in a setting modeled on office practice. Subjects were maintained on a protocol of six weeks of 16 mg daily dosing, then tapered to zero dose up to week 16, and maintained on placebo through week 18. Of 44 subjects who continued after the first induction dose, 11 terminated during maintenance, 17 during taper; and 16 while on zero dose. Twice weekly urine toxicologies showed significant successive declines in samples positive for heroin use across these three periods: 70%, 41%, and 20%, respectively. Among historical variables, only prior AA attendance distinguished subjects who achieved zero dose from those who did not. A comparison with recent studies suggests that relatively inexperienced office-based physicians can maintain patients on buprenorphine at a level comparable to that reported for research clinic settings, but with comparable rates of heroin abstinence. These findings are discussed in light of potential options for office-based opioid maintenance.     

Methadone maintenance treatment: a primer for physicians.

The doctor-patient interaction in the methadone maintenance treatment clinic is qualitatively different from general medical settings. The patient presents with a specific request for treatment of opioid dependence, most often having already selected the methadone treatment modality, and the initial contact is centered around obtaining methadone. Addiction and needle use increase susceptibility to life-threatening illnesses, such as syphilis, endocarditis, tuberculosis, and AIDS. The physician is working with counselors, nurses, therapists and 12-Step programs, incorporating the best of the medical, psychodynamic, behavioral, and recovery models into treatment. Federal and state governments also control and regulate methadone treatment. Given this complex picture, the basic techniques of methadone maintenance treatment are reviewed, including the intake examination, the annual examination, dose adjustment, withdrawal from methadone maintenance, management of pregnant patients, dual diagnosis patients, and severely ill or medically disabled patients.     

Trauma treatment for veterans in buprenorphine maintenance treatment for opioid use disorder

IntroductionOpioid use disorder (OUD) rates are high among veterans. PTSD is also prevalent among veterans; those with comorbidity have worse outcomes than those without comorbidity. This study assessed buprenorphine retention rates in veterans initiating OUD treatment, comparing veterans without PTSD to veterans with PTSD who were receiving versus not receiving concurrent trauma treatment.MethodsThis retrospective chart review examined consecutive referrals to buprenorphine maintenance (N = 140). PTSD diagnosis was identified by chart review and retention was defined as continuous buprenorphine maintenance 6-months post-admission. Logistic regression analyses compared buprenorphine retention for veterans without PTSD and PTSD-diagnosed veterans who received concurrent trauma treatment to a reference group of PTSD-diagnosed veterans who did not receive trauma treatment. Models adjusted for opioid type, age, and service-connected status.ResultsSixty-seven (47.9%) buprenorphine-seeking veterans carried a PTSD diagnosis; only 31.3% (n = 21) received trauma treatment while in buprenorphine maintenance, with 11.9% (n = 8) receiving evidence-based psychotherapy for PTSD. Among PTSD-diagnosed veterans who received trauma treatment, 90.5% (n = 19/21) were in buprenorphine maintenance at 6-months, compared to 23.9% (n = 11/46) of PTSD-diagnosed veterans without trauma treatment, and 46.6% (n = 34/73) of veterans without PTSD. In the full model, veterans with trauma treatment had 43.36 times greater odds of remaining in buprenorphine treatment than the reference group.ConclusionsMost PTSD-diagnosed veterans in buprenorphine treatment were not receiving trauma treatment. Those receiving concurrent trauma treatment had better retention, suggesting OUD and trauma can be simultaneously addressed. Future clinical trials should investigate trauma-focused treatment for veterans with comorbid PTSD who are seeking buprenorphine for OUD.     

丁丙诺啡维持治疗海洛因依赖119例疗效观察

目的：观察丁丙诺啡维持治疗海洛因依赖的疗效,为进一步推广提供依据。方法：119例海洛因依赖者采用丁丙诺啡舌下片维持治疗（BMT）,维持治疗期间进行不良反应监测和生命质量量表评定。结果：119例海洛因依赖者1个月、6个月、12个月的维持率分别为42例（35．3%）、36例（30．2%）、34例（28．6%）。维持治疗期间不良反应轻,无肝肾功能损害。维持治疗前后,患者生命质量评分比较差异有统计学意义（P〈0．05）。结论：丁丙诺啡维持治疗能够显著改善海洛因依赖者的生命质量,不良反应轻,有助于提高脱毒后的操守率,值得推广应用。     

Well-being, psychosocial factors, and side-effects among heroin-dependent inpatients after detoxification using buprenorphine versus clonidine

Previous studies comparing buprenorphine and clonidine provided little information about subjective factors associated with the effective management of opioid withdrawal. This study sought to compare detoxification programs using these medications with regard to side-effects and related distress, general well-being, perceived self-efficacy and social support. A total of 200 treatment-seeking heroin-dependent patients, aged 18-50, were randomly assigned to buprenorphine or clonidine inpatient withdrawal treatments over 10days followed by 11days of relapse prevention measures. A semi-structured interview and a battery of self-rating scales assessing parameters of the interest were administered to the patients who completed the 10-day detoxification protocol with buprenorphine (n=90) and clonidine (n=50). Chi-square statistics and analysis of covariance were performed to examine between-group differences. Compared with patients treated with clonidine, patients who received buprenorphine developed significantly less side-effects and related distress, and had higher senses of well-being, self-efficacy and social support. The findings suggest that buprenorphine is preferable for inpatient detoxification due to its side-effects profile and positive effects on well-being and psychosocial variables. These early benefits of buprenorphine could enable consequent maintenance treatment.     

丁丙诺啡辅助美沙酮维持治疗疗效观察

目的：探讨丁丙诺啡辅助美沙酮维持治疗效果。方法：对云南省曲靖市麒麟区美沙酮维持治疗的患者因客观原因不能进行美沙酮治疗给予丁丙诺啡替代治疗情况进行分析。结果：治疗组比对照组分别高22．5％和19．16％，降低脱失，脱失率低15％，能杜绝使用其他非法药（毒）品。结论：在维持患者因客观原因不能服用美沙酮时，丁丙诺啡辅助治疗能显著提高患者的依从性、提高尿吗啡阴性率。     

Methadone and buprenorphine for the management of opioid dependence in pregnancy

This article provides an overview and discussion of the collective maternal, fetal and neonatal outcome research on women maintained on methadone or buprenorphine during pregnancy. Its focus is on an assessment of the comparative effectiveness of methadone and buprenorphine pharmacotherapy, with particular attention given to recent findings from the literature. Recommendations for clinical practice are outlined, and directions for future research are presented. Findings from comparative studies of methadone and buprenorphine underscore the efficacy of both medications in preventing relapse to illicit opioid use in the treatment of opioid-dependent pregnant patients, as well as the simplicity of induction onto methadone and patient retention while receiving such therapy. Fetal monitoring suggests that buprenorphine results in less fetal cardiac and movement suppression than does methadone. The clinical implications of these findings need future exploration. For the neonate, evidence from studies using a wide range of designs, including retrospective chart reviews, prospective observational studies, and randomized clinical trials, show consistent results, with prenatal exposure to buprenorphine resulting in less severe neonatal abstinence syndrome relative to methadone. Any medication given to pregnant women should be prescribed only after considering the risk?:?benefit ratio for the maternal-fetal dyad. Medication choices for each opioid-dependent patient during pregnancy need to be made on a patient-by-patient basis, taking into consideration the patient's opioid dependence history, previous and current treatment experiences, medical circumstances and treatment preferences. Moreover, for a full remission of opioid addiction to be sustainable, both post-partum and across the lifespan, treatment providers must not rely solely on medication to treat their patients but should also utilize women-specific comprehensive treatment models that address the underlying multifaceted complexities of their patient's lives.     

美沙酮维持治疗中转诊患者服药依从性调查分析

目的：了解美沙酮维持治疗（methadone maintenance treatment,MMI）过程中转诊患者服药依从性情况。方法：收集从其他MMT门诊转入我门诊的160例转诊患者的基本资料,对其能否继续治疗、尿检情况、转入日及转回日至首次服药间隔时间天数等分析。结果：转入后未能继续治疗者33例（20.63％）,其中长转者占4例（2.50％）,临转者占29例（18.13％）;转入后能继续治疗者转入日、转回日至首次服药平均间隔时间分别为3.86±0.53天和3.55±0.41天;转入、转回首次尿检阳性率分别为83.70％和63.50％。结论：MMT中转诊患者服药依从性相对较低,存在转诊后脱失、尿吗啡检测阳性率偏高、转诊后缺服药现象明显等需待完善情况。     

Cessation of methadone maintenance treatment using buprenorphine: transfer from methadone to buprenorphine and subsequent buprenorphine reductions

BACKGROUND: Buprenorphine is used in the treatment of opioid dependence. Due to its pharmacology, the transfer from methadone to buprenorphine may precipitate withdrawal symptoms. METHODS: Methadone maintained patients with clinical indicators of stability who were seeking withdrawal from methadone were recruited from three Australian states. Patients on methadone doses between 30 and 40 mg were randomised to transfer to buprenorphine by a fixed dose (transfer at 30 mg methadone) or by a variable dose induction (transfer when 'uncomfortable'). A third group of patients with methadone doses less than 30 mg were transferred to buprenorphine at their entry methadone dose. Fifty-one patients were inducted onto buprenorphine using the same dosing protocol with the first dose of 4 mg buprenorphine. Following stabilisation on buprenorphine, patients gradually reduced the buprenorphine dose to 0 mg. Withdrawal severity and drug use was monitored. RESULTS: There were no significant difference between the transfer at 30 mg and transfer when 'uncomfortable' dosing protocols in severity of withdrawal on transfer from methadone to buprenorphine. Those on doses less than 30 mg reported significantly less withdrawal discomfort at transfer. All but one patient stabilised on buprenorphine. Thirty-eight of the 51 patients inducted onto buprenorphine reached 0 mg. CONCLUSIONS: Transfer from methadone to buprenorphine can safely occur from doses of around 30 mg of methadone. Buprenorphine dose reductions were well tolerated. Thirty-one percent of patients were not using heroin or methadone at 1-month follow-up.     

Effects of buprenorphine maintenance dose on mu-opioid receptor availability, plasma concentrations, and antagonist blockade in heroin-dependent volunteers.

The clinical effectiveness of opioid maintenance for heroin dependence is believed to result from a medication's ability to decrease mu-opioid receptor (muOR) availability thereby replacing agonist effects, alleviating withdrawal symptoms and attenuating heroin effects. We empirically tested this hypothesis in five heroin-dependent volunteers who were successively maintained on 32, 16, 2, and 0 mg daily buprenorphine (BUP) tablet doses. We predicted and confirmed that higher BUP doses would decrease in vivo muOR availability (measured with PET and [(11)C]carfentanil), increase plasma levels of BUP and its metabolite nor-BUP, and decrease withdrawal symptoms and hydromorphone (HYD) responses. Relative to placebo, BUP significantly decreased mean (+/-SEM) whole-brain muOR availability 41+/-8, 80+/-2, and 84+/-2% at 2, 16, and 32 mg, respectively. Regions of interest (ROIs) (prefrontal cortex, anterior cingulate, thalamus, amygdala, nucleus accumbens, caudate) showed similar dose-dependent effects. Changes in muOR availability varied across ROIs (prefrontal cortex, 47% vs amygdala, 27%) at BUP 2 mg, but were more homogeneous across ROIs at BUP 32 mg (94-98%; except thalamus, 88%). Relative to placebo (0 ng/ml), peak plasma levels of BUP and nor-BUP were comparable and dose-dependent (0.5-1, 5-6, and 13-14 ng/ml at 2, 16, and 32 mg, respectively). muOR availability decreases were negatively correlated with BUP plasma level and positively correlated with questionnaire-based opioid withdrawal symptoms and attenuation of HYD symptoms. These findings suggest that high-dose BUP maintenance produces near-maximal muOR occupation, muOR availability correlates well with plasma levels, and BUP-related opioid symptoms and antagonist blockade exhibit concentration-effect relationships.     

Methadone maintenance treatment: outcomes from the Otago methadone programme

AIM: To provide information on methadone treatment outcomes for opiate-dependent individuals. METHODS: Questionnaires and random urine tests were completed for 112 Otago clients comparing outcomes before and during methadone maintenance treatment. RESULTS: Treatment retention rates were high, with 86% of clients remaining on the programme six months or more. The number of clients on benefits reduced by almost 30% during treatment, with employment rates doubling from 19% to 40% (including attendance at educational programmes). For the 89 clients injecting opiates daily at initial presentation, 64% reported no opiate use in the three months prior to review. Of the remaining 36%, opiate use reduced significantly. Rates of sharing injecting equipment reduced by almost 90%. Almost 50% of cannabis users reduced their use from daily to less than daily use. Clients reporting no current use of illicit benzodiazepines increased by 85%. Heavy binge drinking weekly or more reduced by almost 75%. Use of other illicit drugs reduced by almost 90%. Drug-related convictions reduced by almost 60%, while accidental drug overdoses reduced by over 90%. CONCLUSION: The widespread benefits of methadone maintenance treatment demonstrated underline the importance of making quality methadone programmes readily accessible within the health system. Currently, there are long waiting lists and many individuals cannot gain access to active treatment. We believe the health system urgently needs to look at expanding existing services and/or establishing private methadone clinics similar to those in New South Wales.     

Methadone maintenance improves cognitive performance after two months of treatment

Methadone maintenance (MM) has received little scientific attention regarding neurocognitive effects. The present study examined cognitive function in 17 opiate-dependent subjects at baseline and after 2 months of MM treatment. Subjects demonstrated significant improvements from baseline on measures of verbal learning and memory, visuospatial memory, and psychomotor speed and reduced frequency of drug use (Addiction Severity Index) relative to baseline, although the total percentage of urine samples positive for additional illicit substances was slightly increased. No effect of illicit drug use was observed when the sample was stratified by urine toxicology results, suggesting that improvements in cognition were not associated with additional illicit drug use. Results suggest that opiate-dependent subjects exhibit significant improvement in cognitive function after MM treatment. Future investigations are needed to confirm these findings.     

Methadone maintenance program for AIDS-affected opiate addicts

To slow the spread of AIDS, it may be important for substance abuse treatment programs to give priority admission to patients who are HIV-infected and infectious. A new program is described that provides methadone maintenance treatment to opiate addicts who are "AIDS affected"--heroin addicts diagnosed with AIDS, AIDS-related complex (ARC), or other significant symptoms of HIV infection. The program aims to protect the health of patients and to protect the general public by slowing the spread of the human immunodeficiency virus (HIV). This article describes the program's history and goals, its referral and patient admission process, methods of assessment and treatment planning, medical care, counseling procedures, tolerance for misbehavior, philosophy toward eventual detoxification, and procedures that maintain confidentiality.     

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.