Buprenorphine-maintained Patients Research Articles

0693 Rest-activity rhythm in Methadone and Buprenorphine-maintained patients

Abstract Introduction Opioid use disorder (OUD) is a chronic relapsing disorder with a high overdose death rate. In OUD, sleep and circadian disruptions are highly prevalent, interfere with retention in opioid maintenance treatment (OMT) and increase relapse. Growing evidence suggests a link between sleep/circadian disruptions and dopaminergic (DA) signaling which accounts for addictive properties of drugs of abuse. The current study investigated rest-activity rhythm in Methadone and Buprenorphine-maintained patients and how it relates to DA changes in patients. Methods To access rest-activity rhythm, twenty-five OUD patients (9 Females; age 44.34±11.97; 60% White, 32% Black; 18 Methadone; 7 Buprenorphine) and thirty-four age, sex, race and BMI-matched healthy controls wore wrist accelerometers for one-week and completed questionnaires for sleep and chronotype. Among OUD patients, sixteen of them completed [11C]NNC112 and [11C]raclopride PET scans for the assessments of D1R and D2R availability, respectively. Negative mood was accessed as secondary outcomes. Results Our preliminary data showed that compared to healthy participants, OUD patients undergoing OMT reported greater sleep problems and showed greater sleep irregularity measured by actigraphy, but no differences in other parameters such as sleep duration, rhythm timing or physical activity. Among patients, greater eveningness and irregularity were associated with higher level of negative mood including depression and anxiety. There is a tendency of a positive correlation between later phase and greater D1 receptor availability and a negative association between sleep irregularity and D2 receptor availability. Conclusion Our finding suggests that a link between altered rest-activity rhythm and DA signaling in OUD patients. Circadian/sleep interventions that regulate rest-activity rhythm might benefit mood improvement and promote OUD recovery by normalizing DA transmission. Support (if any)

Reductions in tobacco use in naltrexone, relative to buprenorphine-maintained individuals with opioid use disorder: Secondary analysis from the National Drug Abuse Treatment Clinical Trials Network

BackgroundSmoking prevalence in individuals with opioid use disorder (OUD) is over 80%. Research suggests that opioid use significantly increases smoking, which could account for the strikingly low smoking-cessation rates observed in both methadone- and buprenorphine-maintained patients, even with the use of first-line smoking-cessation interventions. If opioids present a barrier to smoking-cessation, then better smoking outcomes should be observed in OUD patients treated with extended-release naltrexone (XR-NTX, an opioid antagonist) compared to those receiving buprenorphine (BUP-NX, a partial opioid agonist). MethodsThe current study is a secondary analysis of a 24-week, multi-site, open-label, randomized clinical trial conducted within the National Drug Abuse Treatment Clinical Trials Network comparing the effectiveness of XR-NTX vs. BUP-NX for adults with OUD. Longitudinal mixed effects models were used to determine if there was a significant reduction in cigarette use among daily smokers successfully inducted to treatment (n = 373) and a subset of those who completed treatment (n = 169). ResultsAmong daily smokers inducted onto OUD medication, those in the XR-NTX group smoked fewer cigarettes per day (M = 11.36, SE = 0.62) relative to smokers in the BUP-NX group (M = 13.33, SE = 0.58) across all study visits, (b (SE) = −1.97 (0.55), p < .01). Results were similar for the treatment completers. ConclusionsOUD patients treated with XR-NTX reduced cigarette use more than those treated with BUP-NX, suggesting that XR-NTX in combination with other smoking cessation interventions might be a better choice for OUD smokers interested in reducing their tobacco use.

Assessment of Subjective Sleep Problems in Men With Opioid Dependence Maintained on Buprenorphine.

To assess the rates of sleep disturbances in male patients with opioid dependence maintained on buprenorphine and to assess the factors associated with sleep disturbances in this population. Observational, cross-sectional study. Male patients with opioid dependence aged 18 years and older, and started on buprenorphine at least 6 months before were screened. Those with history of comorbid psychiatric illnesses (except sleep disorders), on any other substance in high-risk category (based on WHO-Alcohol Smoking Substance Involvement Screening Test (ASSIST)), or on any other psychotropic medications (in addition to OAT with buprenorphine) were excluded. Sleep was assessed using the Pittsburgh Sleep Quality Index (PSQI), Sleep-50, and Epworth Sleepiness Scale (ESS). Each participant was interviewed in a single session lasting 60 minutes. One hundred six participants were included. Their mean age was 41.1 (SD 14.3) years. The participants had been on OAT with buprenorphine for a median duration of 60 months (IQR 17-120), with excellent adherence rate in past 1 month. The mean current dose of buprenorphine was 10.2 (SD 3.8) mg per day. The mean subjective total sleep time was 403.5 minutes (SD 94.8) and the median sleep latency was 35 minutes (IQR 18.8-62.5). The mean PSQI score was 6.6 (SD 3.4). Nearly 63% (n = 67) participants had PSQI scores more than 5 (PSQI > 5) suggesting sleep problems. Sociodemographic, substance use, and treatment variables were compared between participants who scored more than 5 and those who scored less than 5 on PSQI. No significant difference was found between the 2 groups. Substantial proportion of male patients with opioid dependence maintained on buprenorphine have sleep problems. The sleep problems in buprenorphine-maintained patients seem to be independent of substance use and treatment-related attributes.

(289) Conditioned Pain Modulation in Buprenorphine-Maintained Patients with Opioid Use Disorder

The number of persons on buprenorphine maintenance for opioid use disorder (OUD) is rising and these patients often have chronic pain. It is not clear whether the endogenous analgesic system, which is often dysregulated in chronic pain patients, is affected by buprenorphine maintenance. Conditioned pain modulation (CPM) can evaluate endogenous analgesia; CPM is tested by applying a primary noxious stimulus alone and then simultaneously with a conditioning noxious stimulus on a remote body part. An efficient CPM results in an increase in primary pain threshold in the presence of the conditioning stimulus. A less efficient CPM is pro-nociceptive and results in lower primary pain threshold in the presence of the conditioning stimulus. This study assessed CPM in persons without chronic pain maintained on buprenorphine. CPM was tested by measuring pressure pain threshold at baseline and while undergoing a cold pressor test. Further, this study examined whether adjunct hydromorphone and/or buprenorphine, compared to placebo, effected CPM. Participants (N=13) with OUD who were maintained on 12mg or 16mg buprenorphine performed three study sessions, at least one week apart, where they underwent CPM at baseline and after cumulative doses of 32mg IV hydromorphone, 32mg IV buprenorphine, or placebo. Thirty-one percent of participants displayed less efficient CPM in at least one session prior to drug administration based on lower pressure pain threshold during cold-pressor testing compared to baseline. There were no significant differences in the proportion of individuals with less efficient CPM following 32mg IV hydromorphone (69%), 32mg buprenorphine (54%), or placebo (62%) (p=0.779). Results suggest that some buprenorphine-maintained individuals experience less efficient CPM. High doses of hydromorphone or buprenorphine did not improve CPM compared to placebo. Non-opioid analgesic strategies should be developed to address chronic pain in persons maintained on buprenorphine. Study medications provided by Indivior, Inc.

Frequency and correlates of sleep disturbance in methadone and buprenorphine-maintained patients

BackgroundOpioid use disorder (OUD) is a significant public health problem, and opioid maintenance treatment (OMT) on methadone or buprenorphine is a common approach. This study characterized sleep impairment in patients maintained on methadone or buprenorphine, and evaluated its association with psychiatric and medical comorbidities. MethodsParticipants (N=185) maintained on methadone (N=125) or buprenorphine (N=60) for OUD completed the Medical Outcomes Study Sleep Scale (MOS) to provide a point-prevalence assessment of sleep impairment. Measures of lifetime problems and current functioning were also examined and compared as both a function of OMT and level of sleep impairment. ResultsParticipants reported high levels of sleep impairment on the MOS, including not getting the amount of sleep they needed (42.9%), not sleeping enough to feel rested (39.6%) and trouble falling asleep (23.3%) or falling back asleep after waking (25.8%). Few differences were observed between OMT groups, and psychiatric dysfunction emerged as the most robust predictor of sleep impairment ratings. Patients with sleep impairment, independent of OMT medications, also reported current opioid withdrawal, psychiatric impairment, negative affect, and pain. ConclusionsResults demonstrate substantial and clinically-significant impairments in sleep that are associated with a variety of current problems that could impact OMT outcomes and decrease quality of life. Outcomes support the development of methods to improve sleep in OMT patients, and to examine the degree to which sleep improvements may be associated with improvements in mood and other health-related measures.

Study protocol of the ESUB-MG cluster randomized trial: a pragmatic trial assessing the implementation of urine drug screening in general practice for buprenorphine maintained patients.

BackgroundIn addiction care, urine drug screening tests are recommended to assess psychoactive substances use. While intrinsic diagnostic value of these tests is demonstrated, the consequences of carrying out these tests on opiate maintenance treatment (OMT) have not been established. The main objective will be to assess the impact of on-site urine drug screening tests (OS-UDS) in general practice compared to routine medical care on OMT retention at 6 months in opioid-dependent patients initiating buprenorphine.Methods/DesignThe ESUB-MG study uses a pragmatic, cluster randomized controlled trial design. General Practitioners (GPs) regularly managing patients treated with buprenorphine and consenting for participating will be invited to participate. GPs will be randomly assigned to one of two groups for 6 to 24 months: (a) control group (usual care: standard medical strategy for assessing drug use); (b) interventional group (including 1/ a training session on practice and interpretation of OS-UDS; 2/ the supply of OS-UDS at GPs’ medical offices; 3/ performing an OS-UDS before the first prescription of buprénorphine). GPs will have to include 1 to 10 patients aged 18 years-old or more, consulting for starting treatment by buprenorphine, not opposed to participate. The primary outcome will be OMT retention at 6 months.DiscussionThis randomized interventional trial should bring sufficient level of evidence to assess effectiveness of performing OS-UDS in general practice for patients treated by buprenorphine. Training GPs to drug tests and supplying them in their office should lead to an improvement of opioid-addicted patients’ care through helping decision.Trials registrationNCT02345655 (first registration May 14, 2014)

Characterizing pain and associated coping strategies in methadone and buprenorphine-maintained patients

BackgroundChronic pain is common among patients receiving opioid maintenance treatment (OMT) for opioid use disorder. To aid development of treatment recommendations for coexisting pain and opioid use disorder, it is necessary to characterize pain treatment needs and assess whether needs differ as a function of OMT medication. MethodsA point-prevalence survey assessing pain and engagement in coping strategies was administered to 179 methadone and buprenorphine-maintained patients. ResultsForty-two percent of participants were categorized as having chronic pain. Methadone patients had greater severity of pain relative to buprenorphine patients, though both groups reported high levels of interference with daily activities, and participants with pain attended the emergency room more frequently relative to participants without pain. Only 2 coping strategies were being utilized by more than 50% of participants (over-the-counter medication, prayer). ConclusionsResults indicate that pain among OMT patients is common, severe, and of significant impairment. Methadone patients reported greater severity pain, particularly worse pain in the past 24h, though interference from pain in daily activities did not vary as a function of OMT. Most participants with pain were utilizing few evidenced-based pain coping strategies. Increasing OMT patient access to additional pain treatment strategies is an opportunity for immediate intervention, and similarities across OMT type suggest interventions do not need to be customized to methadone vs. buprenorphine patients.

Chronic pain and coping strategies within methadone and buprenorphine-maintained patients

Chronic pain and coping strategies within methadone and buprenorphine-maintained patients

10-years outcome of methadone- and buprenorphine-maintained patients. Mortality, quality of life and substance use

self-efficacy in a variety of contexts, and negatively associatedwith the number of marijuana-related problems, but was not significantly associated with past 30-day use of marijuana. Conclusions: Clinicians andeducators coulduse this list of harm reduction strategies to identify clients who might benefit from encouragement and training to employ specific strategies in highrisk situations, and to assess changes in confidence to engage in specific harm reduction techniques as an outcome of public health education. Financial support: N/A.

Factors Affecting Norbuprenorphine Level in Monitoring Clinical Outcome for Buprenorphine-maintained Patients

Results: The multiple regression analysis of the predictable variables for positive urine drug screen (UDS) before and after the level showed that norbuprenorphine level (P = 0.018 before and P = 0.02 after the level) and the primary drug of addiction (P = 0.047 before and P = 0.01 after the level) are significantly associated with positive UDS for opiates before and after the level (R = 0.06 and R = 0.09, respectively). The multiple regression analysis of the predictable variables for norbuprenorphine level showed that age (P = 0.01), race (P = 0.006), hepatitis C status, (P = 0.006), primary drug of addiction (P = 0.0001), and buprenorphine dose (P = 0.0003) are significantly associated with higher levels of norbuprenorphine (R = 0.70). The positive UDS for cocaine (P = 0.02) before the level is significantly associated with lower norbuprenorphine level (R = 0.70).

Rifampin, but not rifabutin, may produce opiate withdrawal in buprenorphine-maintained patients

BackgroundThis series of studies examines the pharmacokinetic/pharmacodynamic interactions between buprenorphine, an opioid partial agonist increasingly used in treatment of opioid dependence, and rifampin, a medication used as a first line treatment for tuberculosis; or rifabutin, an alternative antituberculosis medication. MethodsOpioid-dependent individuals on stable doses of buprenorphine/naloxone underwent two, 24-h blood sampling studies: (1) for buprenorphine pharmacokinetics and (2) following 15 days of rifampin 600mg daily or rifabutin 300mg daily for buprenorphine and rifampin or rifabutin pharmacokinetics. ResultsRifampin administration produced significant reduction in plasma buprenorphine concentrations (70% reduction in mean area under the curve (AUC); p=<0.001) and onset of opiate withdrawal symptoms in 50% of participants (p=0.02). While rifabutin administration to buprenorphine-maintained subjects resulted in a significant decrease in buprenorphine plasma concentrations (35% decrease in AUC; p<0.001) no opiate withdrawal was seen. Compared with historical control data, buprenorphine had no significant effect on rifampin pharmacokinetics, but was associated with 22% lower rifabutin mean AUC (p=0.009), although rifabutin and its active metabolite concentrations remained in the therapeutic range. ConclusionsRifampin is a more potent inducer of buprenorphine metabolism than rifabutin with pharmacokinetic and pharmacodynamic adverse consequences. Those patients requiring rifampin treatment for tuberculosis and receiving buprenorphine therapy are likely to require an increase in buprenorphine dose to prevent withdrawal symptoms. Rifabutin administration was associated with decreases in buprenorphine plasma concentrations, but no clinically significant adverse events were observed.

P03-234 - Cognitive functions in buprenorphine maintained patients versus abstinent heroin abusers on naltrexone hydrochloride therapy

IntroductionMethadone and buprenorphine are among the most widely employed pharmacological treatments currently available for opioid addiction. Cognitive effects of buprenorphine in abstinent heroin abusers are nevertheless far from being understood.MethodsNeuropsychological performance of 18 buprenorphine-maintained patients (BMP) was evaluated relative to that of 32 currently abstinent heroin abusers on naltrexone hydrochloride therapy (FHAN), and 34 non-drug dependent controls. The three groups were demographically balanced. Clinical groups reported histories of similar patterns of drug use and had increased periods of abstinence from any illicit substance use including heroin.ResultsThe BMP group performed poorer than controls on the RAVLT (encoding and delayed recall of verbal information), CTT (conceptual flexibility, executive functions) and the RBANS figure copy (visual perception) and delayed recall of visual information. There were no significant differences in any of the cognitive measures between the BMP and FHAN groups or between the FHAN group and controls. Furthermore, there were no differences in the percentage of abnormal cases between the two patient groups.ConclusionOverall, results suggest that treatment with naltrexone in abstinent heroin abusers may result in less impairment of cognitive functions compared to treatment with buprenorphine. These findings are relevant for improved prognosis and treatment strategies in opioid dependence.

Neuropsychological functioning in buprenorphine maintained patients versus abstinent heroin abusers on naltrexone hydrochloride therapy

Methadone and buprenorphine are among the most widely employed pharmacological treatments currently available for opioid addiction. Cognitive effects of buprenorphine in abstinent heroin abusers are nevertheless far from being understood. Neuropsychological performance of 18 buprenorphine-maintained patients (BMP) was evaluated relative to that of 32 currently abstinent heroin abusers on naltrexone hydrochloride therapy (FHAN), and 34 non-drug dependent controls. The three groups were demographically balanced. Clinical groups reported histories of similar patterns of drug use and had increased periods of abstinence from any illicit substance use including heroin. The BMP group performed poorer than controls on the RAVLT (encoding and delayed recall of verbal information), CTT (conceptual flexibility, executive functions) and the RBANS figure copy (visual perception) and delayed recall of visual information. There were no significant differences in any of the cognitive measures between the BMP and FHAN groups or between the FHAN group and controls. Furthermore, the non-differing percentage of abnormal cases between the two patient groups led us to infer that treatment with either BPM or FHAN is not accompanied by qualitative differences in the cognitive profiles of these patients. Overall, results suggest that treatment with naltrexone in abstinent heroin abusers may result in less impairment of cognitive functions compared to treatment with buprenorphine. These findings are relevant for improved prognosis and treatment strategies in opioid dependence.

The barriers to smoking cessation in Swiss methadone and buprenorphine-maintained patients

BackgroundSmoking rates in methadone-maintained patients are almost three times higher than in the general population and remain elevated and stable. Due to the various negative health effects of smoking, nicotine dependence contributes to the high mortality in this patient group. The purpose of the current study was to investigate Swiss methadone and buprenorphine-maintained patients' willingness to stop smoking and to clarify further smoking cessation procedures.MethodsSubstance abuse history, nicotine dependence, and readiness to stop smoking were assessed in a sample of 103 opiate-dependent patients in the metropolitan area of Zurich, Switzerland. Patients were asked to document their smoking patterns and readiness to quit.ResultsOnly a small number of patients were willing to quit smoking cigarettes (10.7%) and, even though bupropione or nicotine replacement therapy was included in the fixed daily treatment care, only one patient received nicotine replacement therapy for smoking cessation. A diagnosis of depression in patients' clinical records was associated with readiness to stop smoking. No significant associations were found between readiness to quit smoking and age, methadone treatment characteristics, and presence of co-dependencies.ConclusionThe current prescription level of best medicine for nicotine dependence in Swiss methadone and buprenorphine-maintained patients is far from adequate. Possible explanations and treatment-relevant implications are discussed.

Pharmacodynamics of diazepam co-administered with methadone or buprenorphine under high dose conditions in opioid dependent patients

Background Benzodiazepine abuse is common among methadone- and buprenorphine-maintained patients; however interactions between these drugs under high dose conditions have not been adequately examined under controlled conditions. Objective To investigate the effects of co-administering diazepam with methadone or buprenorphine under high dose conditions. Design Double-blind, randomly ordered, 2 × 2 cross-over design in which the effects of diazepam dose (0 mg versus 40 mg) and opioid dose (100% versus 150% normal dose) were examined over four sessions in methadone- and buprenorphine-maintained patients. Participants Four methadone- and seven buprenorphine-prescribed patients without concurrent dependence on other substances or significant medical co-morbidity. Measures Physiological (pulse rate, blood pressure, pupil size, respiratory rate and peripheral SpO 2), subjective (ARCI, VAS ratings) and performance (reaction time, cancellation task and Digit Symbol Substitution Test, DSST) measures were taken prior to and for 6 h post-dosing. Results High dose diazepam was associated with time-dependent increases in the intensity of subjective drug effects (strength of drug effect, sedation) and decreases in psychological performance (reaction time, DSST) for both methadone and buprenorphine patients. These effects were generally independent of the opioid dose administered. High dose opioid administration (150% normal dose) was associated with reductions in overall SpO 2 levels and performance (reaction time, DSST) in the methadone patients, but had virtually no impact on pharmacodynamic responses in the buprenorphine group. Conclusion High dose diazepam significantly alters subjective drug responses and psychological performance in patients maintained on methadone and buprenorphine.

Buprenorphine for Postoperative Pain Following General Surgery in a Buprenorphine-Maintained Patient

Back to table of contents Previous article Next article Letters to the EditorFull AccessBuprenorphine for Postoperative Pain Following General Surgery in a Buprenorphine-Maintained PatientSARAH W. BOOK M.D.HUGH MYRICK M.D.ROBERT MALCOLM M.D.,ERIC C. STRAIN M.D.,SARAH W. BOOK M.D.Search for more papers by this authorHUGH MYRICK M.D.Search for more papers by this authorROBERT MALCOLM M.D.Search for more papers by this author,ERIC C. STRAIN M.D.Search for more papers by this author,Published Online:1 Jun 2007AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To The Editor: Office-based, long-term buprenorphine is a growing treatment for opioid dependence (1) . Patients with opioid dependence may require treatment for pain during their opioid therapy, and such treatment can be complicated. Recently suggested recommendations for the treatment of acute pain in a buprenorphine-maintained individual include the following four options: using concomitant short-term opioid analgesics, dividing the daily buprenorphine dose, replacing the buprenorphine with another opioid analgesic, or replacing the buprenorphine with methadone and then adding an opioid analgesic (2) . We present a case of postoperative pain control in a buprenorphine-maintained patient, using supplemental doses of sublingual buprenorphine for pain management. The patient was a 32-year-old woman with opioid dependence who had been successfully maintained on sublingual buprenorphine/naloxone 24/6 mg daily for 6 months, up to and including the day she underwent surgical removal of breast implants under general anesthesia. The patient was seen in an outpatient addiction treatment clinic (by Dr. Book) and prescribed buprenorphine/naloxone 2/0.5 mg tablets for postoperative pain control, with instructions to take one to two sublingual tablets every 4 to 6 hours for pain. On her first and second postoperative days at home, she reported taking 12/3 mg every 6 hours to relieve pain, in addition to her 24/6 mg per day baseline dose, for a total daily dose of 72/18 mg of buprenorphine/naloxone. She was able to successfully and comfortably taper her dose by postoperative day 11 to her baseline dose of 24/6 mg. The patient did not report taking other analgesics, including nonsteroidals. Although this individual case was limited by self-report, self-titration, and lack of control, the off-label use of supplemental doses of sublingual buprenorphine for acute postoperative pain in a buprenorphine-maintained individual is a novel approach. Buprenorphine is a partial m agonist shown to have a ceiling to analgesic effects in preclinical studies. Indeed, the bell-shaped dose-response curve of buprenorphine suggests that high doses may produce diminishing analgesic effects (3 , 4) . However, this was not the case for our patient, who had adequate pain control, with total daily doses of up to 72/18 mg following surgery that typically may require 60 mg per day of oxycodone. Furthermore, because no other respiratory depressants were used, this high dose of buprenorphine could safely be used as an outpatient dose. These findings suggest that the time-limited, off-label use of supplemental doses of sublingual buprenorphine may be an effective fifth option for management of acute pain in selected buprenorphine-maintained patients. Charleston, S.C.Baltimore, Md.Drs. Book and Malcolm have received honoraria from Reckitt Benckiser. Dr. Strain has received speaker’s honorarium and travel funds from Reckitt Benckiser. Dr. Myrick reports no competing interests.

Influence of Peak and Trough Levels of Opioid Maintenance Therapy on Driving Aptitude

To evaluate driving aptitude and traffic-relevant performance at peak and trough medication levels in opioid-dependent patients receiving maintenance therapy with either buprenorphine (mean: 13.4 mg) or methadone (52.7 mg) and a medication-free control group, the Addiction Clinic at Medical University Vienna conducted a prospective, open-label trial where 40 opioid-dependent patients maintained either on buprenorphine or methadone were assessed regarding their traffic-relevant performance. Using the standardized Act and React Testsystem (ART) 2020 Standard test battery, traffic-relevant performance was analysed 1.5 h (peak level) and 20 h (trough level) after administration of opioid maintenance therapy. Results showed that patients at trough level had a significantly higher percentage of incorrect reactions (p = 0.03) and more simple errors (p = 0.02) than patients at peak level as well as methadone-maintained patients at peak level tended to perform less well than buprenorphine-maintained patients in some of the test items, e.g. methadone-maintained patients at trough level had a higher number of delayed reactions in the RST3 phase 2 test (p = 0.09) and answered fewer questions correctly in the visual structuring ability test (p = 0.04). This investigation indicates that opioid-maintained patients did not differ significantly at peak vs.trough level in the majority of the investigated items and that both substances do not appear to affect traffic-relevant performance dimensions when given as a maintenance therapy in a population where concomitant consumption would be excluded.

Opioid plasma concentrations in methadone‐and buprenorphine‐maintained patients

This is the first trial to compare the relationship of opioid plasma concentrations in methadone-versus buprenorphine-maintained subjects. Sixty subjects (19 females and 41 males) seeking treatment who met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for opioid dependence were recruited and treated at the Drug Addiction Outpatient Clinic at the University of Vienna. Of these, 44 (11 female and 33 male) were included in the analyses of plasma concentrations. Subjects received either daily sublingual buprenorphine (2 mg or 8 mg tablets; maximum daily dose: 8 mg) or oral methadone (racemic R-/S-methadone) and were maintained on a stable dose after an induction period of 2 weeks. Mean dose and mean plasma concentrations were correlated on an individual and collective basis. Correlation was 0.51 for buprenorphine, whereas the score for methadone was 0.69. Intra-individual variation was much higher for buprenorphine (p<0.0001), while the concentration-to-dose ratio was very small. Based on the differences of the pharmacokinetics of blood plasma of the two agents, we tried to explain the differences in the acceptance of treatment, which was significantly lower in the buprenorphine-maintained group. No such differences could be evaluated between completers and dropouts in buprenorphine-maintained subjects, neither concerning withdrawal scores nor dose, plasma concentration, concentration-to-dose ratios or intra-individual variation.

Counseling Requirements for Buprenorphine Maintenance in Primary Care

Objective: This preliminary study was conducted to establish the minimal counseling requirements for buprenorphine maintenance in primary care settings. A brief, nurse-administered, medically focused counseling approach for buprenorphinemaintained patients, Medical Management (MM), was designed by the authors. To evaluate preliminary feasibility and efficacy of MM prior to using it in a primary care setting, we evaluated it in a methadone maintenance program. Method: Fourteen opioid dependent patients were treated for 12 weeks with thrice-weekly buprenorphine plus either MM provided thrice weekly (5–10 minutes) by an RN, or MM plus individual Drug Counseling (MM+DC). DC was provided weekly (45 minutes) by a Ph.D.-level psychologist or a Certified Alcohol and Drug Counselor. Results: Seven of the 7 MM and 6 of the 7 MM+DC patients completed all 12 weeks of the study. Rates of opioid-positive urine toxicology tests averaged 72% for MM and 54% for MM+DC. Two of the 7 MM and 4 of the 7 MM+DC patients achieved ≥3 consecutive weeks of opioid-negative urine toxicology tests. None of these differences reached statistical significance. Conclusions: These preliminary findings demonstrate the feasibility and efficacy of MM and suggest, as with methadone, that DC may be a necessary component of buprenorphine treatment of opioid dependence. Therefore, providers of office- or primary care-based buprenorphine maintenance may need to incorporate aspects of drug counseling.

Maintenance Therapy with Synthetic Opioids and Driving Aptitude

Aims: To assess the influence of methadone and buprenorphine maintenance treatment on the driving aptitude of opioid-dependent patients. Design: Prospective, open label, outpatient maintenance, single-blind (investigator) study. Participants and Setting: Thirty opioid-dependent patients maintained on either methadone or buprenorphine were recruited from the drug-addiction outpatient clinic in Vienna. Measurements: The traffic-relevant performance dimensions of the participants were assessed 22 h after receiving synthetic opioid maintenance therapy, by a series of seven tests constituting the Act & React Test System (ART) 2020 Standard test battery, developed by the Austrian Road Safety Board (ARSB). To test for additional consumption of illicit substances, blood and urine samples were taken at the beginning of the tests. Findings: The patient group only differed from control subjects in two of the ART 2020 Standard tests. During a task to test the subject’s attention under monotonous circumstances (Q1 test), patients had a significantly greater number of reactions (p = 0.027) and a significantly higher percentage of incorrect reactions than control subjects. When driving in a dynamic environment (DR2 test) patients had a significantly longer mean decision time (p = 0.029) and mean reaction time (p = 0.009) compared with control subjects. Interestingly, when separated into treatment groups, the mean decision and reaction times of buprenorphine-maintained patients in the DR2 test did not differ from controls, whereas patients maintained on methadone showed significantly prolonged mean decision (p = 0.009) and reaction times (p = 0.004). In this same test, patients who had consumed additional illicit drugs had a longer mean reaction time compared with control subjects (p = 0.036). Conclusion: The synthetic opioid-maintained subjects investigated in the current study did not differ significantly in comparison to healthy controls in the majority of the ART 2020 Standard tests.