High-dose Buprenorphine Research Articles

The Pregnancy Recovery Center: A women-centered treatment program for pregnant and postpartum women with opioid use disorder

ObjectiveTo evaluate the impact of women-centered substance abuse treatment programming on outcomes among pregnant women with opioid use disorder (OUD). MethodsWe compared two retrospective cohorts of pregnant women with OUD on buprenorphine maintenance therapy who delivered an infant at the University of Pittsburgh from 2014 to 2016. Cohort 1 was composed of pregnant women who received women-centered OUD treatment services through the Pregnancy Recovery Program (PRC) and Cohort 2 was composed of pregnant women who received buprenorphine at OUD programs without women-centered services (non-PRC). Women-centered outcomes were defined as a) pregnancy-specific buprenorphine dosing, b) prenatal and postpartum care attendance, c) breastfeeding and d) highly effective contraception utilization. Chi-square and t-tests were used to compare outcomes between PRC and non-PRC patients. ResultsAmong 248 pregnant women with OUD, 71 (28.6%) were PRC and 177 (71.4%) were non-PRC patients. PRC patients were significantly more likely to initiate buprenorphine during vs. prior to their pregnancy (81.4% vs. 44.2%; p < .01) and have a higher buprenorphine dose at the time of delivery (16.0 mg vs. 14.1 mg; p = .02) compared to non-PRC patients. Likewise, PRC patients were significantly more likely to attend their postpartum visit (67.9% vs. 52.6%; p = .05) and receive a long-acting reversible contraceptive (LARC) method (23.9% vs. 13.0%, p = .03) after delivery compared to non-PRC patients. Finally, PRC patients had a smaller percent decrease in the rate of breastfeeding during their delivery hospitalization (−14.7% vs. −37.1%). ConclusionsIncorporating women-centered services into OUD treatment programming may improve gender-specific outcomes among women with OUD.

Influence of a single dose of buprenorphine on rabbit (Oryctolagus cuniculus) gastrointestinal motility

ObjectiveTo establish a noninvasive imaging protocol for rabbit gastrointestinal transit evaluation. To assess the effect of a single injection of buprenorphine on the digestive transit of rabbits via this new technique. Study designProspective, parallel study. AnimalsFifteen specific pathogen-free male New Zealand White rabbits weighing 2.68 ± 0.28 kg. MethodsA 10 mL kg–1 barium meal was administered and the rabbits were subjected to serial radiographic and ultrasound examinations without treatment and 1 week later following a single intramuscular dose of 100 μg kg–1 of buprenorphine. Radiographic data from the stomach and caecum were collected and assigned a retention score ranging from 0 (no barium) to 3 (large amount of barium). The resulting scores and pyloric and duodenal contraction counts were analysed using a mixed linear model and are expressed as least square mean (lsm) ± standard error. Transit was estimated based on the apparition time of faeces in the pelvic area and analysed using a Wilcoxon test. A p < 0.05 was considered significant. ResultsBuprenorphine treatment induced a higher lsm number of pyloric (1.73 ± 0.19 versus 0.78 ± 0.19, p < 0.01) and lsm duodenal contractions (17.35 ± 1.04 versus 13.44 ± 1.04, p < 0.01). Buprenorphine administration decreased the lsm barium retention score in the stomach (2.44 ± 0.05 versus 2.64 ± 0.05, p < 0.01), but had no effect on the lsm barium retention score in the caecum. The time to apparition of faeces in the pelvic area was not influenced by buprenorphine administration (p = 0.66). Conclusions and clinical relevanceA single high dose of buprenorphine appears to have no adverse effect on gastrointestinal motility in healthy rabbits.

Efficacy of buprenorphine and clonidine in opioid detoxification: A hospital- based study.

Background:The need for effective and accepted method for opioid detoxification is ever increasing. Sublingual buprenorphine and oral clonidine have been effective in opioid detoxification. As often, there is a great variation in the dosage of buprenorphine and clonidine prescribed by the clinicians; hence, there is a felt need to find an effective dosage for a favorable outcome of opioid detoxification.Objective:The objective of this study was to compare the effectiveness of different doses of sublingual buprenorphine and clonidine in opioid detoxification.Materials and Methods:A total of 100 patients with the diagnosis of opioid dependence as per the international classification of diseases-10 criteria were recruited for this study. Participants were assigned randomly into four groups – low-dose clonidine, high-dose clonidine, low-dose sublingual buprenorphine, and high sublingual dose buprenorphine using a computer-generated random number table, resulting in 25, 26, 23, and 26 patients in each group, respectively.Results:The four groups had comparable scores on all the items of “stages of change readiness and treatment eagerness scale” for the assessment of motivation at baseline. Progressive decrease in withdrawal score was seen in all the groups on “clinical opiate withdrawal scale” and “subjective opiate withdrawal scale.”Conclusion:From the current study, we can infer that both low and high doses of buprenorphine and clonidine are comparable regarding controlling withdrawal.

A cross-national analysis of the association between years of implementation of opioid substitution treatments and drug-related deaths in Europe from 1995 to 2013.

Data at the individual-level provide evidence that opioid substitution treatment (OST) programs protect against mortality for opioid dependent populations. Prior research has not examined the merits of national implementation of opioid substitution programs for reducing mortality at the country-level. This study elucidates longitudinal associations between country-level implementation of opioid substitution treatment programs on mortality rates of drug related deaths (DRD) from 1995 to 2013 in 30 European nations. Cases of DRD were measured using National Definitions for each country from official sources of data. Preliminary analysis of dispersion of cases of DRD using means and variances justified use of the negative binomial regression model with a population offset. Year and country-level fixed effects negative binomial regression models investigated the association between years of implementation of methadone maintenance therapy (MMT), OST in prison, and high dose buprenorphine treatment (HDBT) implementation and mortality rates from drug related deaths after adjusting for unemployment rates, heroin seizures and per capita expenditures on health. Beta coefficients were converted to Incidence Rate Ratios (IRR) and standard errors bootstrapped using non-parametric methods to adjust for bias (SDbs). The mean mortality rate of DRD was 1.81 from 1995 to 2013. In adjusted models, each additional year of MMT (IRR=.61, SD=.04, p<.001; SDbs=.08, p<.001), prison OST (IRR=.90, SD=.01, p<.001; SDbs=.02, p<.001), and HDBT (IRR=.09, SD=.02, p<.001; SDbs=.02, p<.01) was significantly associated with lower rates of DRDs after adjusting for country and year fixed effects. Implementation of OST programs in the general population and in prison settings may have protected against mortality from drug use at the country-level in Europe from 1995 to 2013.

Ultrarapid Influence of Buprenorphine on Major Depression in Opioid-Dependent Patients: A Double Blind, Randomized Clinical Trial

ABSTRACTObjective: To examine the impact of different doses of buprenorphine on depression symptoms in opioid dependent inpatient over a three-day interval, using a randomized clinical trial design (RCT). Design: Patients were randomized and assigned to three groups. Participants: Forty males who were admitted to an inpatient psychiatric unit and who fulfilled the DSM-5 criteria for both opioid dependence and major depressive disorder. Intervention: Patients randomly received 32 mg, 64 mg, or 96 mg of buprenorphine as a single high dose. Out of 40 patients, 11 (27.5%) received 32 mg, 14 (35%) received 64 mg and 15 (37.5%) received 96 mg of buprenorphine. We conducted medical precautional measures, including cardiovascular and respiratory monitoring. Measurements: Depression was measured by the Beck Depression Inventory (BDI). All patients completed the three-day treatment duration. The results showed a significant reduction in depression symptoms within each of the three groups (p = 0.00), although there was no significant difference in depression outcome across the groups (p = 0.90). Conclusions: The results suggest that a single high dose of buprenorphine could provide a safe, simple and speedy means of depression improvement. A single high dose of buprenorphine can be used as medication that supplies a fast and maintained treatment for major depressive disorder in patients who are opioid dependent. Placebo-controlled trials of longer periods and larger sample sizes are needed to test ability and safety, as well as the physiological and psychological impact of extended exposure to this drug.

Anxiety Treatment of Opioid Dependent Patients with Buprenorphine: A Randomized, Double-blind, Clinical Trial.

Objective:The objective of this study is to examine the impact of vary doses of buprenorphine on anxiety symptoms in opioid-dependent inpatients over a 7 days period, using a randomized controlled trial design.Design:Patients were randomized to three groups.Patients and Methods:Fourteen men who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for both opioid use disorder and generalized anxiety disorder and were seeking for treatment.Intervention:Patients obtain dosages of 32 mg or 64 mg or 96 mg of buprenorphine as a single dose only and were treated in a psychiatric inpatient unit. Of 14 subjects; 5 (35.7%) obtained 32 mg, 4 (28.6%) obtained 64 mg, and 5 (35.7%) obtained 96 mg of buprenorphine.Measurements:Administering daily Hamilton Anxiety Rating Scale and interview.Results:All the patients ended the 7-day treatment time. The results showed a significant reduction in anxiety symptoms within each of the three groups (P = 0.00), but no difference in outcome between the groups (P = 0.605).Conclusions:The outcome suggests a single high dose of buprenorphine can supply a speedy, safe, simple, and suitable means of anxiety treatment. The single high dose of buprenorphine could be a novel mechanism medication that provides a rapid and sustained improvement for generalized anxiety disorder in opioid dependent patients. Placebo-controlled trials of longer duration are needed to evaluate ability, safety, and psychological and physiological influence of extended exposure to this medication.

Buprenorphine in the Treatment of Severe Major Depression with Severe Suicidal Temptations

Administration of high dose of buprenorphine is associated with rapid-acting anti-depressive and ant-suicidal effects.

Opiate withdrawal syndrome in buprenorphine abusers admitted to a rehabilitation center in Tunisia.

Illicit use of high dosage buprenorphine has been well documented in several countries, including Tunisia. The aim of this survey is to assess the buprenorphine withdrawal syndrome time course, and how it may be affected by the population characteristics among subjects admitted to a rehabilitation center in Tunisia. A prospective research has permitted study of the socio-demographic characteristics and assessment of buprenorphine withdrawal syndrome among 32 subjects admitted for buprenorphine dependence by using the clinical opiate withdrawal scale. An ANOVA was conducted to examine the effect of different factors on the withdrawal scores. 32 subjects were included. Among them 30 were males, 27 had been injecting buprenorphine, 16 were poly-drug abusers and 2 had a history of mental disorders. Buprenorphine withdrawal syndrome was of a mild intensity and had a delayed onset. Withdrawal mean scores varied between 0 and 9, and maximum values were reached at day 21. These scores varied significantly over time (p<0,001). The sex v time interaction and the mode of consumption of buprenorphine had significant effects on the withdrawal scores (p<0,001). The poly-drug consumption and the history of mental disorders did not have any significant effect on the withdrawal scores. This study has permitted description of buprenorphine withdrawal syndrome among patients going through a detoxification treatment at a rehabilitation center. Understanding this syndrome would help elaborate effective and suitable buprenorphine dependence management plans.

Three high doses of buprenorphine in the treatment of prolonged and severe opium dependence: a new access

Background: Heavy and prolonged opium dependence is a progressing problem in the East. For the treatment of opium dependence, buprenorphine can be prescribed less frequently than daily due to its long half-life.Objective: To administered three high doses buprenorphine instead of daily use to reduce probability of buprenorphine dependence.Results: The prescription of three high doses of 32, 96 and 72 mg buprenorphine was tolerated conveniently. Administration of high doses of buprenorphine completely improved opium withdrawal symptoms.Discussion: The current work indicated that few high doses of buprenorphine, could be adequate and satisfactory for the improvement of heavy and prolonged opium dependence.Conclusions: We came to this result that administration of high dose buprenorphine looks to be convenient, acceptable and tolerable. More research studies should be of interest as high buprenorphine doses are getting more general clinically. We concluded that three doses of 32, 72 and 96 mg buprenorphine, could be adequate for the improvement of severe opium use disorder.

Diminution de la prévalence du docteur shopping de la buprénorphine entre 2004 et 2014 en France

The opioid maintenance treatments (OMT) are widely misused and diverted in many countries. Doctor shopping represented the main way to obtain high quantities of opioids in abuse/diversion. The aim of this study was to assess the trends in the prevalence of doctor shopping for high dosage buprenorphine (HDB) and methadone (MTD) from 2004to 2014by using the French Health Insurance claims. This was a cross-sectional study of patients treated by OMT (High Dosage Buprenorphine or Methadone) between 2004and 2014from a representative sample of the French Health Insurance claims. Doctor shopping was defined as at least 1day of overlapping prescriptions, written by at least 2different prescribers and filled in at least 3different pharmacies. HDB patients were more likely men (77.9% in 2014) with a mean age ranged from 33.4±7.6years in 2004to 39.5±9.3years in 2014, P<0.001. MTD patients were also more likely men (73.9% in 2014) with a mean age ranged from 33.5±6.9years in 2004to 37.1±8.5years in 2014, P<0.001. In 2014, 35% of HDB patients and 36% of MTD patients presented a long-term disease which was most frequently a mental health disorders. The prevalence of doctor shopping for HDB decreased from 2004to 2014 (12.6% versus 3.9%, P<0.001). The prevalence of doctor shopping for MTD was very low during the period study (0.2% to 0.5%). Overall, the prevalence of doctor shopping was higher for HDB than for MTD whatever the year (P<0.001) of the study. Doctor shopping for HDB decreased significantly during the last decade while doctor shopping for MTD remained nearly inexistent even if it could be underestimated because of dispensations in specialized centers and in hospitals not comprised in the insurance claims. The low rates of doctor shopping reported in these last years could result from the guidelines for good practices in OMT use made in 2004and the adjustments of ANSM (French National Agency for Medicines and Health Products Safety) for HDB best use made in 2011.

Caractéristiques des sujets sous traitement de substitution vus en médecine générale d’après l’enquête nationale OPEMA 2013

The objective of the study is to describe the characteristics of subjects under opiate maintenance treatment by general practionners (GPs). Data analysis from observatory for pharmacodependency in ambulatory medicine survey (observation des pharmacodépendances en médecine ambulatoire [OPEMA]) program in 2013 of the subjects under high dosage buprenorphine (HDB) and methadone prescribed or obtained illegally reported by GPs in France. Survey concerned consumers with 862, 433 and 429 of high dosage buprenorphine and respectively methadone. The average age is 39±9 years respectively, and 36±8 years; over 70% are male; 55% have paid employment and over 30% report social benefits; 9% are in temporary housing. In both groups, more than 50% have anxiety and depression; over 25% have associated somatic disorders and digestive diseases, respiratory, pain is the most common. Almost 99% use oral route; nearly 100% have a daily consumption and about 20% of the alcohol concomitantly; 24% of HDB use benzodiazepines and 18% of the methadone group (P=0.06); 33% of the population using methadone consume illicit psychoactive substances and 21% for HDB population (P<0.0001), in particular cannabis (P<0.0001). Heroin and cocaine are also consumed. The population consuming opiate maintenance treatments shows social, somatic and psychiatric vulnerability. Misuse associated forms and consumption of other psychoactive substances and illegal drugs are observed. Despite the complexity of management of these patients, general practitioners have a major role to play.

Incidence of high dosage buprenorphine and methadone shopping behavior in a retrospective cohort of opioid-maintained patients in France

BackgroundOpioid Substitution Treatment (OST) misuse and diversion have significantly increased worldwide. Obtaining OST prescriptions from multiple prescribers, known as doctor shopping, is a way in which opioids may be diverted. ObjectivesThe aim of this study was to assess the incidence of OST (high dosage buprenorphine (HDB) and methadone (MTD)) shopping behavior and identify associated risk factors, and its impact on mortality. MethodsA retrospective cohort of patients treated by OST between April 1, 2004 and December 31, 2012 from a sample of the French Health Insurance database was established. Doctor shopping was defined as ≥1day of overlapping prescriptions written by ≥2 different prescribers and filled in ≥3 different pharmacies. ResultsA total of 2043 patients were enrolled, 1450HDB and 593 MTD. The one-year incidence of shopping behavior was 8.4% (95% CI: 7.0–10.1) in HDB group and 0% in MTD group, compared to 0.2% (95% CI: 0.1–0.2) for diuretics. On multivariate analysis, factors associated with HDB shopping behavior were: male gender HR: 1.74 (95% CI: 1.20–2.54); low-income status HR: 2.95 (95% CI: 2.07–4.44); mental health disorders HR: 1.43 (95% CI: 1.06–1.94); concurrent hypnotics use HR: 1.90 (95% CI: 1.39–2.61); concurrent use of weak opioids HR: 1.48 (95% CI: 1.09–1.99) and morphine HR: 1.69 (95% CI: 1.02–2.80). HDB shoppers had a higher, yet non-significant risk of death (HR: 1.56 (95% CI: 0.64–3.81)) than non HDB shoppers. ConclusionShopping behavior was only found in high dosage buprenorphine patients and concerned almost one out ten patients.

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

ABSTRACTAs 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.

Instant Detoxification of Heroin with High Dose of Buprenorphine

Instant Detoxification of Heroin with High Dose of Buprenorphine

Treatment of Chronic Methadone Dependence with Buprenorphine

Background: Methadone abuse is a puzzle. Objective: To uncover the achievement of a single high dose of 64 mg of buprenorphine for the remedy of methadone dependency. Results: 64 mg of buprenorphine as a single administration can be sufficient for the treatment of methadone dependent patient. Discussion: Our study indicates that buprenorphine 64 mg as a single dose only, can be sufficient for the treatment of methadone withdrawal symptoms. So, this work may be a substantial addition to the literature. Conclusions: We can conclude that a single high dose of buprenorphine may be enough for the treatment of methadone withdrawal symptoms.

Quick Opium Detoxification With 100 mg of Buprenorphine

Background: Dependency to opium is a worldwide problem. Objective: To merit the competency of a single high dose of buprenorphine in opium detoxification. Results: Administration of 100 mg of buprenorphine as a single dose is very effective in the opium detoxification. Discussion: Our study suggests that administration of 100 mg of sublingual buprenorphine as a high single dose is quite practical in opium detoxification. Hence, this experience could be a factual addition to the literature. Conclusions: We infer that a single high dose of buprenorphine efficaciously treats opium withdrawal symptoms.

The Effect of a Payer-Mandated Decrease in Buprenorphine Dose on Aberrant Drug Tests and Treatment Retention Among Patients with Opioid Dependence

BackgroundThe optimal dose for office-based buprenorphine therapy is not known. This study reports on the effect of a change in payer policy, in which the insurer of a subset of patients in an office-based practice imposed a maximum sublingual buprenorphine dose of 16mg/day, thereby forcing those patients on higher daily doses to decrease their dose. This situation created conditions for a natural experiment, in which treatment outcomes for patients experiencing this dose decrease could be compared to patients with other insurance who were not challenged with a dose decrease. MethodsSubjects were 297 patients with opioid use disorder in a primary care practice who were prescribed buprenorphine continuously for at least 3months. Medical records were retrospectively reviewed for urine drug test results and treatment retention. Rates of aberrant urine drug tests were calculated in the period before the dose decrease and compared to rate after it with patients serving as their own controls. Comparison groups were formed from patients with the same insurance on buprenorphine doses of 16mg/day or lower, patients with different insurance on 16mg/day or lower, and patients with different insurance on greater than 16mg/day. Rates of aberrant drug tests and treatment retention of patients on 16mg/day or less of buprenorphine were compared to that of patients on higher daily doses. ResultsThe rate of aberrant urine drug tests among patients who experienced a dose decrease rose from 27.5% to 34.2% (p=0.043). No comparison group showed any significant change in aberrant drug test rates. Moreover, all groups who were prescribed buprenorphine doses greater than 16mg/day displayed lower rates of aberrant urine drug tests than groups prescribed lower doses. Retention in treatment was also highest among those prescribed greater than 16mg/day (100% vs. 86.8%, 90.1%, and 84.4% p=0.010). DiscussionAn imposed buprenorphine dose decrease was associated with an increase in aberrant drug tests. Patients in a control group with higher buprenorphine doses had greater retention in treatment. These findings suggest that buprenorphine doses greater than 16mg/day are more effective for some patients and that dose limits at this level or lower are harmful.

Triple dosing with high doses of buprenorphine: Withdrawal and plasma concentrations.

In maintenance treatment for opiate addiction, buprenorphine can be administered less frequently than daily due to its long half-life. To examine the plasma concentration of buprenorphine and norbuprenorphine for 72 hours after a dose of 72 mg and to objectively and subjectively evaluate the correlations between concentrations and withdrawal levels. Patients in maintenance treatment with buprenorphine with a daily dose of 24 mg were given a triple dose of 72 mg (n = 9), in an outpatient setting. Blood samples were drawn, and withdrawal symptoms were evaluated objectively and subjectively every 24 hours over 72 hours. Urine and blood toxicology samples were obtained. The triple dose was generally accepted well with low subjective and objective withdrawal scores. However, two patients aborted the study on day 3 and reported withdrawal symptoms. Benzodiazepine use was confirmed in one while the other likely used unauthorized buprenorphine. Administration of buprenorphine in three times the daily dose seems acceptable, also in the higher daily maintenance doses (here, 24 mg) used in many clinical settings. Two patients did not tolerate the regimen but, partly due to the outpatient setting, the reasons why are unclear. Further research should be of interest as high buprenorphine doses are becoming more common clinically.

Pharmacokinetic and pharmacodynamic evaluation of high doses of buprenorphine delivered via high-concentration formulations in cats.

To evaluate the potential benefits of high-dose buprenorphine formulations for analgesia in cats, serial and crossover studies were undertaken to investigate their pharmacokinetics and thermal antinociceptive effects. Twelve healthy adult domestic shorthair cats (6.0 ± 1.1 kg body weight) were studied. Aqueous solutions of buprenorphine hydrochloride at 0, 0.02, 0.06, 0.12 and 0.24 mg/kg body weight and formulations containing 0, 0.3, 0.6 and 1.2 mg/ml with and without preservatives were given subcutaneously. Blood samples were taken and thermal threshold (TT) measured prior to and at regular time points up to 72 h after dosing. Descriptive statistics and analyses of variance were applied as appropriate. Baseline TT was 47.6 ± 4.1°C, which increased in all groups treated with all buprenorphine dosages and formulations. After doses of 0.12 mg/kg and above, TT was significantly higher than baseline at most time points from 1-30 h post-treatment. The time to maximum effect (Tmax) ranged between 0.25 and 2.00 h; and plasma concentrations associated with maximum antinociceptive effect (Cmax) were 1.01-1.72 ng/ml after the 0.02 mg/kg dose, 1.4-4.9 ng/ml after the 0.06 mg/kg dose, 4.6-51.4 ng/ml after the 0.12 mg/kg dose and 5.3-22.3 ng/ml after the 0.24 mg/kg dose. The range of estimates for the buprenorphine elimination half-life were as follows: 0.02 mg/kg = 1.35-5.33 h; 0.06 mg/kg = 16.1-31.2 h; 0.12 mg/kg = 10.1-34.0 h; and 0.24 = mg/kg 16.1-31.6 h. The mean 'plasma concentration for the offset of analgesia' was 2.3 ± 2.0 ng/ml. No adverse effects were seen. The addition of preservatives to a high-concentration buprenorphine formulation had no impact on antinociception nor any side effects. Aqueous high-concentration buprenorphine formulations administered at 0.12 or 0.24 mg/kg have potential for clinical use in cats, providing prolonged antinociception in a single subcutaneous injection of minimal dose volume.

Commentary on Burns et al. (2015): retention in buprenorphine treatment.

Commentary on Burns et al. (2015): retention in buprenorphine treatment.