Craving predicts opioid use in opioid-dependent patients initiating buprenorphine treatment: A longitudinal study

Background: Few studies have assessed associations between craving and subsequent opioid use. We prospectively evaluated the relative utility of two craving questionnaires to predict opioid use among opioid-dependent patients in outpatient treatment. Method: Opioid-dependent patients (n?=?147) initiating buprenorphine treatment were assessed every two weeks for 3 months. Craving was measured using the: (1) Desires for Drug Questionnaire (DDQ) and (2) Penn Alcohol-Craving Scale adapted for opioid craving (PCS). Multi-level logistic regression models estimated the effects of craving on the likelihood of opioid use. Craving assessed at time t was entered as a time-varying predictor of opioid use at time t?+?1. Results: Craving scores plateaued at approximately 2 weeks after initiation of buprenorphine. In adjusted regression models, a 1-point increase in PCS scores (on a 7-point scale) was associated with a significant increase in the odds of opioid use at the subsequent assessment (OR?=?1.27, 95% CI 1.08; 1.49, p?p?p?>?0.05) or DDQ control (OR?=?0.97, 95%CI 0.85; 1.11, p?>?0.05) scores. Conclusion: Self-reported craving for opioids was modestly associated with subsequent relapse to opioid use among a cohort of patients treated with buprenorphine. Assessment of craving may provide clinical utility in predicting relapse among treated opioid-dependent patients.     

Brief vs. Extended Buprenorphine Detoxification in a Community Treatment Program: Engagement and Short-Term Outcomes

Background: Despite evidence supporting the efficacy of buprenorphine relative to established detoxification agents such as clonidine, little research has examined: 1) how best to implement buprenorphine detoxification in outpatient settings; and 2) whether extending the length of buprenorphine detoxification improves treatment engagement and outcomes. Objectives: The current study examined the impact on 1) successful detoxification completion; 2) transition to longer-term treatment; and 3) treatment engagement of two different length opioid detoxifications using buprenorphine. Methods: The study compared data obtained from two consecutive studies of early treatment engagement strategies. In one study (n = 364), opioid-addicted participants entered treatment through a Brief (5-day) buprenorphine detoxification. In the other study (n = 146), participants entered treatment through an Extended (i.e., 30-day) buprenorphine detoxification. Results: Results indicated a greater likelihood of successful completion and of transition among participants who received the Extended as compared to the Brief detoxification. Extended detoxification participants attended more counseling sessions and submitted fewer drug-positive urine specimens during the first 30 days of treatment, inclusive of detoxification, than did Brief detoxification participants. Conclusions: Results demonstrate that longer periods of detoxification improve participant engagement in treatment and early treatment outcomes. Scientific Significance: Current findings demonstrate the feasibility of implementing an extended buprenorphine detoxification within a community-based treatment clinic.     

Buprenorphine withdrawal syndrome in newborns: a report of 13 cases

Aims To assess neonatal abstinence syndrome (NAS) and neurodevelopmental outcome in infants born to addicted mothers under buprenorphine substitution therapy. Setting District general hospital, Angoulême, France. Methods Retrospective case records study of infants admitted to the neonatal intensive care unit (NICU) and/or special care baby unit (SCBU) from January 1994 to December 2000 for surveillance and/or treatment of buprenorphine NAS. Results Thirteen infants were born to addicted mothers under buprenorphine maintenance therapy during the study period. Eight were male and five were female; mean birth term and weight were 39 weeks gestation and 3000 g, respectively. Apgar scores were within normal limits; four infants were small for gestational age, none was dysmorphologic and none was extracted for fetal distress. NAS occurred in 11 cases (85%) and required treatment in 10 cases. Morphine chlorhydrate 0.5 mg/kg/day was administered in divided doses to seven children and gave better results than paregoric alone or in combination with diazepam. Upon follow‐up, seven children presented transient lower limbs hypertonia, jerky movements and jitteriness that lasted 3–9 months. The overall milestones acquisitions were within normal limits. Conclusion Buprenorphine substitution seems to be safe during pregnancy, and has had no teratogenic effects reported to date. It induces NAS of variable intensity that is less prolonged in comparison to methadone; the neurodevelopmental outcome of exposed children is normal in the majority of cases, although some presented with transient motor abnormalities that resolved completely in 85% of those recruited to our study.     

Puffy hand syndrome due to drug addiction: a case-control study of the pathogenesis

AIM: We studied the pathogenesis of puffy hand syndrome of intravenous drug use. We hypothesized that injections of high-dose sublingual buprenorphine, instead of the recommended sublingual administration, could play an important role in lymphatic obstruction and destruction. DESIGN AND PARTICIPANTS: We set up a case-control study in substitution centres, recruiting intravenous drug addicts with and without puffy hands, respectively. The subjects were asked to answer anonymously a questionnaire of 40 items comprising social and demographic status, history of illicit drugs use, buprenorphine misuse and injection practices. FINDINGS: We included 33 cases and 33 controls, mean age of 34 years. They were past heroin users, mainly methadone-substituted. In multivariate analysis, sex (women) (OR = 8.9, P = 0.03), injections in the hands (OR = 5.9, P = 0.03), injections in the feet (OR = 6.5, P = 0.01) and the absence of tourniquet (OR = 7.0, p = 0.02) were significant risk factors for puffy hand syndrome. In 69.7% of the cases and 59.4% of the controls, respectively, there was a high-dose sublingual buprenorphine misuse, although it appeared not to be a significant risk factor for puffy hand syndrome. CONCLUSIONS: Injection practices are likely to cause puffy hands syndrome, but buprenorphine misuse should not be considered as a significant risk factor. However, intravenous drug users must still be warned of local and systemic complications of intravenous drug misuse.     

Buprenorphine for Pain Relief in a Patient with Drug Abuse

Abstract

Buprenorphine is a mixed opioid agonistlantagonist which appears to produce less physical dependence and respiratory depression than typical μ-agonist opioids. These effects suggest its use for analgesia for drug abusers. However, buprenorphine may precipitate withdrawal from other opioids. The present case illustrates the utility of buprenorphine and describes a method to transfer a patient from a μ-agonist to buprenorphine without precipitating withdrawal or interrupting analgesia.     

An injection depot formulation of buprenorphine: extended bio-delivery and effects

AIM: Buprenorphine is an effective medication for treatment of opioid dependence. An injectable depot formulation of buprenorphine has been developed using biodegradable polymer microcapsule technology. This formulation may offer effective treatment of opioid dependence and enhance treatment delivery while minimizing risks of patient non-adherence or illicit diversion of the medication. This report provides a characterization of the bio-delivery of this injectable depot in humans and of the relationship of drug blood levels to pharmacodynamic indices. METHOD AND PARTICIPANTS: The data are from two studies in which 11 opioid-dependent volunteers each received a single depot injection containing 58 mg of buprenorphine, and include previously unreported detailed plasma concentration data over a 6-week time-course following depot administration and examination of their relationship to pharmacodynamic indices. FINDINGS: Mean plasma buprenorphine increased gradually following depot administration, peaked at 2-3 days with a mean concentration of 1.25 ng/ml and then decreased gradually, approaching undetectable levels (< 0.10 ng/mL) by 6 weeks. There was substantial between-subject consistency in several aspects of buprenorphine bio-delivery, including time to first detectable blood level (4 hours), peak blood level (2 days) and undetectable blood level (6-6.5 weeks). In contrast, there was marked between-subject variability in the magnitude of peak buprenorphine concentrations, ranging from 0.17 to 3.47 ng/ml. Extent of opioid blockade was tested by weekly opioid challenges with 3 mg subcutaneous hydromorphone; subjective response and pupillary constriction were related inversely to both buprenorphine and norbuprenorphine plasma concentrations (r=0.84-0.95). CONCLUSION: The data document that this depot formulation provides effective buprenorphine delivery for several weeks and that effects persist even at fairly low buprenorphine plasma concentrations. Suggestions are offered for further research needed to develop this formulation for clinical use as a detoxification and/or maintenance pharmacotherapy for opioid dependence.     

Quality Measurement in Wonderland: The Curious Case of a Dialysis Readmissions Measure

The standardized readmission ratio is a new quality measure for dialysis facilities that will affect public reporting and payment beginning in 2017. Like all quality measures affecting public reporting and payment, the standardized readmission ratio was vetted by a process that included a technical expert panel convened by the US Centers for Medicare and Medicaid Services, and, then, the National Quality Forum. Unlike previous measures, standardized readmission ratio followed a tortuous path that exposed problems in the development and endorsement process. Although it is acknowledged that processes in the dialysis facility can be improved to decrease readmissions, multiple objections to the implementation of the standardized readmission ratio measure existed. This review discusses the standardized readmission ratio measure and issues related to quality metric development that are important for the nephrology community to consider.     

Treatment outcomes among a cohort of African American buprenorphine patients: Follow-up at 12 months

Background: Although buprenorphine/naloxone (bup/nal) is well-established as a safe and effective treatment for opioid use disorders (OUDs), there are few studies reporting 12-month outcomes of patients receiving bup/nal in formerly drug-free outpatient programs. Objectives: To examine 12-month outcomes by bup/nal treatment enrollment status among a cohort of African American patients enrolled in a clinical trial. Methods: This analysis builds upon a randomized trial of 300 opioid-dependent African American bup/nal patients in two outpatient programs in Baltimore, MD. A subset of participants (N = 133, n = 47 female) were tracked for a 12-month follow-up interview. Results: The participants receiving bup/nal at 12 months had significantly fewer opioid-positive urine screens (44% v. 73%) and days of self-reported heroin use (M [SE] = 1.13 [.34] v. 7.12 [1.44]) than the out-of-bup/nal-treatment group (both ps ≤ .001). Similarly, those receiving bup/nal reported significantly fewer days of cocaine use (M [SE] = 0.85 [0.23] v. 2.88[0.75]) and alcohol use (M [SE] = 1.44 [0.38] v. 3.69 [1.04]; both ps<.05). There were no significant differences related to criminal activity, quality of life, and most ASI composite scores. Models adjusting for the baseline value, prior treatment experience, and assigned study condition largely confirmed these findings, except that participants in treatment had fewer days of crime and higher psychological quality of life scores compared to those out-of-treatment. Conclusions: Those receiving bup/nal at 12 months had significantly lower rates of illicit opioid use than those who were not. Approaches to improve bup/nal treatment retention and reengagement of patients with OUD are needed.     

Buprenorphine versus methadone maintenance treatment in an ambulant setting: a health-related quality of life assessment

Background To compare the effects on quality of life (QOL) of oral methadone with sublingual buprenorphine. Methods We performed an open‐label, non‐randomized, two‐site (methadone–buprenorphine) study. During 6 months we assessed the quality of life status of 53 opioid‐dependent patients admitted to a methadone or buprenorphine maintenance programme using the German version (Berlin Quality of Life Profile) of the Lancashire Quality of Life Profile. Physical symptoms were measured using the Opioid Withdrawal Scale. Five hundred and thirty urine screening tests were carried out randomly to detect additional consumption. Results Sixty‐seven opioid‐dependent subjects (38 on methadone and 29 on buprenorphine) were enrolled in the study, and 53 completed it (30 subjects treated with buprenorphine and 23 subjects with racemic methadone). The subjects were comparable on all baseline measures. At the first follow‐up (week 8), the buprenorphine‐maintained group showed significantly less additional consumption of opioids (P = 0.013) compared with the methadone group. Patients retained in the buprenorphine or methadone programme (week 24) showed no significant differences in all quality of life scores. At the end of the study period, the buprenorphine‐maintained group showed significantly less additional consumption of opioids (P = 0.001) and cocaine (P = 0.018) compared with the methadone group. The outcome measures for withdrawal symptoms after 24 weeks of treatment with buprenorphine showed slight advantages in stomach cramps, fatigue or tiredness, feelings of coldness and heart pounding. Conclusions These results suggest that buprenorphine treatment is as effective as methadone regarding effects on quality of life and withdrawal symptoms. Buprenorphine has the potential to reduce the harm caused by drug abuse. Further research is needed to determine if buprenorphine is more effective than methadone in particular subgroups of patients.     

A multi-center randomized trial of buprenorphine-naloxone versus clonidine for opioid detoxification: findings from the National Institute on Drug Abuse Clinical Trials Network

AIMS: The clinical effectiveness of buprenorphine-naloxone (bup-nx) and clonidine for opioid detoxification in in-patient and out-patient community treatment programs was investigated in the first studies of the National Institute of Drug Abuse Clinical Trials Network. DESIGN: Diagnostic and Statistical Manual version IV (DSM IV)-diagnosed opioid-dependent individuals seeking short-term treatment were randomly assigned, in a 2 : 1 ratio favoring bup-nx, to a 13-day detoxification using bup-nx or clonidine. METHODS: A total of 113 in-patients (77 bup-nx, 36 clonidine) and 231 out-patients (157 bup-nx, 74 clonidine) participated. Supportive interventions included appropriate ancillary medications and standard counseling procedures guided by a self-help handbook. The criterion for treatment success was defined as the proportion of participants in each condition who were both retained in the study for the entire duration and provided an opioid-free urine sample on the last day of clinic attendance. Secondary outcome measures included use of ancillary medications, number of side effects reported and withdrawal and craving ratings. FINDINGS: A total of 59 of the 77 (77%) in-patients assigned to the bup-nx condition achieved the treatment success criterion compared to eight of the 36 (22%) assigned to clonidine, whereas 46 of the 157 (29%) out-patients assigned to the bup-nx condition achieved the treatment success criterion, compared to four of the 74 (5%) assigned to clonidine. CONCLUSION: The benefits of bup-nx for opioid detoxification are supported and illustrate important ways in which clinical research can be conducted in community treatment programs.     

Evaluation of an injection depot formulation of buprenorphine: placebo comparison

AIMS: Buprenorphine is a mu-opioid partial agonist that is marketed in a sublingual formulation as a treatment for opioid dependence. A microcapsule depot sustained-release formulation has been developed which may offer effective treatment of opioid dependence while also minimizing risks of illicit diversion or patient non-compliance. The present study examined the efficacy of depot buprenorphine in suppressing the opioid withdrawal syndrome and in attenuating the effects of exogenous opioid challenge. DESIGN: A placebo-controlled, double-blind, randomized trial. SETTING: A closed residential research facility. PARTICIPANTS: A total of 15 opioid-dependent participants were enrolled into the 6-week study. INTERVENTION: Fifteen participants were randomized to receive a single subcutaneous depot injection containing buprenorphine (58 mg) or placebo. Two participants, both of whom received placebo, terminated participation after depot administration. Thirteen participants (six buprenorphine, seven placebo) completed the 6-week study and were assessed throughout the study for signs and symptoms of opioid withdrawal and for response to weekly subcutaneous challenges with 3 mg hydromorphone. MEASUREMENT: Subjective, physiological and observer-rated indices of opioid withdrawal and opioid agonist effects. FINDINGS: Depot buprenorphine provided more effective relief from opioid withdrawal than placebo, as evidenced by significantly fewer buprenorphine participants requiring supplemental medications for withdrawal suppression after depot administration compared to participants receiving placebo. In the weekly hydromorphone challenge sessions, depot buprenorphine significantly reduced opioid response on measures of subjective effects and pupillary diameter. CONCLUSIONS: Results from this double-blind, placebo-controlled study indicate that depot buprenorphine is effective in providing both withdrawal suppression and opioid blockade. Future studies examining additional doses and repeated dosing regimens with depot buprenorphine are warranted.