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- Does Buprenorphine/Naloxone Therapy Prolong Ventricular Repolarization During Sleep? [JOURNAL ARTICLE]
- Chest 2014 Oct 1; 146(4_MeetingAbstracts):955A.
Sleep Posters IISESSION TYPE: Original Investigation PosterPRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PMPURPOSE: The mortality rates associated with opioid use have increased dramatically, especially with methadone. Opioids cause central sleep apnea and may adversely affect myocardial repolarization leading to lethal ventricular arrhythmias. Buprenorphine, a semisynthetic partial μ-opioid agonist in combination with naloxone, has become increasingly prescribed because of its reputed protective ceiling effect regarding respiratory suppression. However, buprenorphine/naloxone has recently been shown to produce serious breathing disturbances during sleep and data concerning electrocardiographic effects during sleep do not exist. We hypothesized that buprenorphine/naloxone could prolong repolarization during sleep.METHODS: Single lead (II) ECG previously obtained from overnight polysomnography recordings of 20 consecutive patients receiving buprenorphine/naloxone for detoxification therapy and without other cardiac or medication risk factors for delayed ventricular repolarization were analyzed. Four data points randomly selected for each parameter were blindly obtained during stages Wake, N1, N2 and Rapid Eye-Movement Sleep for the following intervals: RR, PR, QRS, Tp-e, QT, and corrected QTc using Bazett's formula. Data was compared with normal appropriate age, BMI, and gender matched controls that had also previously undergone polysomnography. Independent sample t-tests were used for comparison.There were no significant differences between the buprenorphine/naloxone and control groups in demographics or parameters that reflect delayed ventricular repolarization. For the buprenorphine/naloxone group, the mean (SD) for QT, QTc and Tp-e measured 392.9 (36.6), 418.30 (24.0) and 81.5 (14.0) msec respectively compared to the control group which measured 388.8 (30.6), 425.8 (26.2), and 79.8 (12.1) msec.CONCLUSIONS: Statistically significant abnormal electrocardiographic markers of delayed ventricular repolarization due to buprenorphine/naloxone were not observed. However, the prevalence of this effect based upon other studies may be small. Therefore, the possibility of adverse cardiac effects due to buprenorphine/naloxone cannot be excluded. Further studies with larger numbers are needed.Due to the association of opioids with central sleep apnea and increased mortality rates, it is important to further study buprenorphine/naloxone's effect on myocardial repolarization to help provide crucial information to physicians for prescription considerations.The following authors have nothing to disclose: Hana Kazbour, Jonathan Harrison, Summer Brown, Frank Yanowitz, Gregory Snow, Amanda McDonald, Donna Ferrell, Rustin Simmons, Tom Nuttall, Robert FarneyNo Product/Research Disclosure Information.
- Primary Care-Based Buprenorphine Taper vs Maintenance Therapy for Prescription Opioid Dependence: A Randomized Clinical Trial. [JOURNAL ARTICLE]
- JAMA Intern Med 2014 Oct 20.
Prescription opioid dependence is increasing and creates a significant public health burden, but primary care physicians lack evidence-based guidelines to decide between tapering doses followed by discontinuation of buprenorphine hydrochloride and naloxone hydrochloride therapy (hereinafter referred to as buprenorphine therapy) or ongoing maintenance therapy.To determine the efficacy of buprenorphine taper vs ongoing maintenance therapy in primary care-based treatment for prescription opioid dependence.We conducted a 14-week randomized clinical trial that enrolled 113 patients with prescription opioid dependence from February 17, 2009, through February 1, 2013, in a single primary care site.Patients were randomized to buprenorphine taper (taper condition) or ongoing buprenorphine maintenance therapy (maintenance condition). The buprenorphine taper was initiated after 6 weeks of stabilization, lasted for 3 weeks, and included medications for opioid withdrawal, after which patients were offered naltrexone treatment. The maintenance group received ongoing buprenorphine therapy. All patients received physician and nurse support and drug counseling.Illicit opioid use via results of urinanalysis and patient report, treatment retention, and reinitiation of buprenorphine therapy (taper group only).During the trial, the mean percentage of urine samples negative for opioids was lower for patients in the taper group (35.2% [95% CI, 26.2%-44.2%]) compared with those in the maintenance group (53.2% [95% CI, 44.3%-62.0%]). Patients in the taper group reported more days per week of illicit opioid use than those in the maintenance group once they were no longer receiving buprenorphine (mean use, 1.27 [95% CI, 0.60-1.94] vs 0.47 [95% CI, 0.19-0.74] days). Patients in the taper group had fewer maximum consecutive weeks of opioid abstinence compared with those in the maintenance group (mean abstinence, 2.70 [95% CI, 1.72-3.75] vs 5.20 [95% CI, 4.16-6.20] weeks). Patients in the taper group were less likely to complete the trial (6 of 57 [11%] vs 37 of 56 [66%]; P < .001). Sixteen patients in the taper group reinitiated buprenorphine treatment after the taper owing to relapse.Tapering is less efficacious than ongoing maintenance treatment in patients with prescription opioid dependence who receive buprenorphine therapy in primary care.clinicaltrials.gov Identifier: NCT00555425.
- Modeling Longitudinal Changes in Buprenorphine Treatment Outcome for Opioid Dependence. [JOURNAL ARTICLE]
- Pharmacopsychiatry 2014 Oct 16.
Introduction: The present analysis describes the longitudinal change in buprenorphine treatment outcome. It also examines several participant characteristics to predict response to buprenorphine. Methods: Participants (n=501, age>15 years) received buprenorphine/naloxone treatment for 4 weeks, and then were randomly assigned to undergo dose tapering over either 7 days or 28 days. An empirical model was developed to describe the longitudinal changes in treatment outcome. Several patient characteristics were also examined as possible factors influencing treatment outcome. Results: We have developed a model that captures the general behavior of the longitudinal change in the probability of having an opioid-negative urine sample following buprenorphine treatment. The model captures both the initial increase (i. e., initial response) and the subsequent decrease (i. e., relapse to opioid) in the likelihood of providing an opioid-negative urine sample. Characteristics associated with successful buprenorphine treatment outcome include: having a negative urine test for drugs, having alcohol problems [assessed using alcohol domain of addiction severity index (ASI-alcohol)] at screening, being older, and receiving low cumulative buprenorphine dose. However, ASI-alcohol values were generally low which make the application of the proposed alcohol effect for patients with more severe alcohol problems questionable. Conclusions: A novel approach for analyzing buprenorphine treatment outcome is presented in this manuscript. This approach describes the longitudinal change in the probability of providing an opioid-free urine sample instead of considering opioid use outcome at a single time point. Additionally, this model successfully describes relapse to opioid. Finally, several patient characteristics are identified as predictors of treatment outcome.
- Combined Abuse of Clonidine and Amitriptyline in a Patient on Buprenorphine Maintenance Treatment. [JOURNAL ARTICLE]
- J Addict Med 2014 Oct 13.
Buprenorphine/naloxone maintenance therapy is often prescribed in primary care to treat opioid dependence. Previous reports have described concomitant abuse of opioids and clonidine. In this case, a primary care patient on buprenorphine/naloxone maintenance therapy demonstrating altered mental status, hallucinations, falls, and rebound hypertension was found to be concomitantly abusing clonidine and amitryptyline, which share metabolic pathways with buprenorphine. Clinicians should be aware of patients' combining amitryptyline, clonidine, and gabapentin with buprenorphine to achieve a mood altering state, avoid co-prescribing them if possible, and maintain communication with pharmacies and other providers when they are prescribed.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
- Buprenorphine/Naloxone Dose and Pain Intensity Among Individuals Initiating Treatment for Opioid Use Disorder. [JOURNAL ARTICLE]
- J Subst Abuse Treat 2014 Sep 26.
Opioid use disorder and pain often co-occur, complicating the treatment of each condition. Owing to its partial agonist properties, buprenorphine/naloxone (BUP/NX) may confer advantages over full agonist opioids for treatment of both conditions. The optimal dose of BUP/NX for comorbid pain is not known. We examined dose and other factors associated with pain intensity among patients initiating BUP/NX for opioid use disorder.We studied 1106 patients initiating BUP/NX treatment for opioid use disorder from 2003 to 2010. Information on pain level, diagnoses, and treatment were extracted from medical records. Eligible patients had at least one self-reported pain intensity numerical rating score (NRS) within 30days before BUP/NX initiation (baseline) and at least one between 15 and 90days after BUP/NX initiation (during treatment). The primary outcome was NRS decrease (2 or greater) from baseline to during treatment. We used generalized estimating equations to model odds of the primary outcome with BUP/NX dose as the independent variable of interest in the subset of patients with a baseline NRS≥2.The sample was 94% male and 73% White. Mean age was 50. Psychiatric and non-opioid substance use comorbidities were common. The following demographic and clinical correlates were associated with a decrease in pain intensity: age 18-29 (compared to 30-39 and 40-49); absence of PTSD diagnosis and absence of a chronic pain diagnosis. BUP/NX dose was not associated with decreased pain intensity in bivariate or multivariable analysis.BUP/NX maintenance treatment was generally consistent with improvements in pain intensity; however, factors other than BUP/NX dose contribute to improved pain intensity among those initiating the medication.
- Neonatal abstinence syndrome: essentials for the practitioner. [Journal Article, Review]
- J Pediatr Pharmacol Ther 2014 Jul; 19(3):147-55.
The incidence of neonatal abstinence syndrome (NAS) has increased dramatically during the past 15 years, likely due to an increase in antepartum maternal opiate use. Optimal care of these patients is still controversial because of the available published literature lacking sufficient sample size, placebo control, and comparative pharmacologic trials. Primary treatment for NAS consists of opioid replacement therapy with either morphine or methadone. Paregoric and tincture of opium have been abandoned because of relative safety concerns. Buprenorphine is emerging as a treatment option with promising initial experience. Adjunctive agents should be considered for infants failing treatment with opioid monotherapy. Traditionally, phenobarbital has been used as adjunctive therapy; however, results of clonidine as adjunctive therapy for NAS appear to be beneficial. Future directions for research in NAS should include validating a simplified scoring tool, conducting comparative studies, exploring home management options, and optimizing management through pharmacogenomics.
- Comparative prices of diverted buprenorphine/naloxone and buprenorphine in a UK prison setting: A cross-sectional survey of drug using prisoners. [JOURNAL ARTICLE]
- Drug Alcohol Depend 2014 Sep 30.
There is evidence regarding the abuse potential of buprenorphine in prison settings. There is also emerging evidence from community settings that buprenorphine/naloxone is less amenable to abuse than the single preparation buprenorphine hydrochloride as evidenced by cost-differentials of diverted medication. This study sought to explore cost-differentials within a prison setting of diverted buprenorphine/naloxone medication relative to either single preparation buprenorphine hydrochloride or methadone.Cross-sectional survey in one remand prison.A total of 85 prisoners participated in the survey. Prisoners estimated buprenorphine to have a significantly (p<0.001) higher cost than buprenorphine/naloxone both inside and outside of prison. This finding was supported when the analysis was restricted to both the prisoners with a longer-term experience of taking opioid substitution drugs during their current prison stay and those with a longer-term experience prior to reception.Consideration should be given to the recommendation that buprenorphine/naloxone medication is the prescribed buprenorphine preparation of choice for clinicians offering opiate substitution therapy to prisoners, pending developments of buprenorphine preparations that have less abuse potential than sublingual preparations.
- Safety studies of post-surgical buprenorphine therapy for mice. [JOURNAL ARTICLE]
- Lab Anim 2014 Oct 10.
The use of appropriate analgesia in laboratory mice may be suboptimal because of concerns about adverse events (AE). Target Animal Safety trials were conducted to determine the safety of an extended-release suspension of buprenorphine. Drug or control suspensions were injected subcutaneously in surgically-treated BALB/c mice anesthetized with ketamine-xylazine to mimic post-operative conditions in which the compound might commonly be administered. Single and repeat five-fold (5×) excesses of the 3.25 mg/kg intended dose were used to provoke potential AE. Trials included prospective measurements of weight changes, blood chemistry, hematology, and histopathology. Clinical and histopathology findings were similar in drug-treated and control mice in a four-day trial using a single 16.25 mg/kg, 5× overdose of the drug. In a 12-day trial, which used a total buprenorphine dose of 48.75 mg/kg, clinical and histopathology values were also similar in control and drug-treated female mice. In the male arm of the repeat-overdose trial, two of eight mice died on the morning of day 12, three days following the third 16.25 mg/kg overdose administration. Histopathology did not reveal a cause of death. In a 14-month trial using a single 3.25 mg/kg dose of the drug, no significant findings identified potential AE. These findings indicate a high tolerance to an extended-release buprenorphine suspension administered post-operatively in mice with appropriate husbandry.
- Geographic variability in HIV and injection drug use in Ukraine: Implications for integration and expansion of drug treatment and HIV care. [JOURNAL ARTICLE]
- Int J Drug Policy 2014 Sep 16.
Ukraine has the highest HIV burden of any European country with much of the current HIV epidemic concentrated among people who inject drugs (PWIDs) and their sexual partners. Opiate substitution therapy (OST) is limited in Ukraine and expansion of OST is urgently needed to help stem the tide of the HIV epidemic.We accessed publicly available data in Ukraine in order to explore geographic variability with respect to prevalence of HIV, PWIDs and OST programmes.The regions of Ukraine with the largest number of opioid dependent persons (the south and eastern portions of the country) correspond to the regions with the highest HIV prevalence and HIV incidence. The number of opioid PWIDs per 100,000 population as well as the number of all OST treatment slots per 100,000 varied significantly across the three HIV prevalence categories. Overall, the proportion of individuals receiving either methadone maintenance therapy (MMT) or buprenorphine maintenance therapy (BMT) was quite low: average across categories: 7.3% and 0.4%, respectively. Additionally, less than half of OST patients receiving MMT or BMT were HIV positive patients.There is significant geographic variability in both numbers of HIV positive individuals and numbers of PWIDs across Ukraine, however, there may be a more concentrated epidemic among PWIDs in many regions of the country. Scale up of addiction treatment for PWID, especially OST, can have a significant impact on preventing injection related morbidity, such as HIV and HCV infection. Ukraine can learn from the mistakes other nations have made in denying critical treatment opportunities to PWID.