Showing papers on "Buprenorphine published in 2014"

Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence

Abstract: Methadone is widely used as a replacement for illicit opioid use such as heroin in medically-supported opioid substitution maintenance programmes. Two other drugs have been used to help reduce illicit opioid use, specifically buprenorphine and LAAM (levo-alpha-acetylmethadol). LAAM is not used in current clinical practice. Buprenorphine is currently used and can reduce illicit opioid use compared with placebo, although it is less effective than methadone. Buprenorphine is an opioid drug that is not as potent as heroin and methadone, although the effects of buprenorphine may last longer. Buprenorphine can be taken once every two days. The trials include different formulations of buprenorphine: sublingual solution, sublingual tablets, combined buprenorphine/naloxone sublingual tablet and an implant. Key results The review of trials found that buprenorphine at high doses (16 mg) can reduce illicit opioid use effectively compared with placebo, and buprenorphine at any dose studied retains people in treatment better than placebo. Buprenorphine appears to be less effective than methadone in retaining people in treatment, if prescribed in a flexible dose regimen or at a fixed and low dose (2 - 6 mg per day). Buprenorphine prescribed at fixed doses (above 7 mg per day) was not different from methadone prescribed at fixed doses (40 mg or more per day) in retaining people in treatment or in suppression of illicit opioid use.

Treatment retention among patients randomized to buprenorphine/naloxone compared to methadone in a multi-site trial.

Abstract: Aims To examine patient and medication characteristics associated with retention and continued illicit opioid use in methadone (MET) versus buprenorphine/naloxone (BUP) treatment for opioid dependence.

Mindfulness-Oriented Recovery Enhancement for Chronic Pain and Prescription Opioid Misuse: Results from an Early Stage Randomized Controlled Trial

Abstract: Prescription opioid misuse is an emerging public health concern with significant health and psychological risks. Though opioid analgesic therapy for chronic pain is often efficacious, and most patients take medicine as prescribed, some individuals exhibit addictive tendencies toward opioids (Fishbain, Cole, Lewis, Rosomoff, & Rosomoff, 2007). Opioid addiction among chronic pain patients involves cognitive, affective, and behavioral dysregulation that, when coupled with persistent or worsening pain, may result in significant functional impairment and suffering (Hojsted, Nielsen, Guldstrand, Frich, & Sjogren, 2010). Opioid addiction may be presaged by the occurrence of opioid misuse behaviors, such as dose escalation or use of prescribed opioids to self-medicate negative emotions and stress (Butler et al., 2007); these medication-misusing behaviors are common, with more than one-in-ten chronic pain patients exhibiting signs of opioid misuse (Fishbain et al., 2007). Although opioid agents with lower addiction liability like buprenorphine can effectively substitute for unauthorized opioid use (Ling et al., 2002), extant treatments for opioid addiction are typically ineffective in the absence of ongoing maintenance pharmacotherapy (Weiss et al., 2011). Further, persons seeking treatment for chronic pain respond especially poorly to motivational and behavioral addiction treatments (Larson et al., 2007). Current best practices for persons with chronic pain who are at risk for prescription opioid misuse and addiction (e.g., Jamison, Serraillier, & Michner, 2011; Oliver et al., 2012) include frequent opioid adherence monitoring, opioid treatment agreements and compliance training, and cognitive-behavioral substance misuse counseling (Jamison et al., 2010). Yet, new interventions are needed to effectively address the maladaptive cognitive-affective processes and appetitive responses elicited by pain, stress, and drug-related cues that undergird the risk chain from chronic pain to opioid misuse and addiction. This risk chain initiates from prolonged use of opioids, which produces physical dependence via neuroadaptations resulting in tolerance, withdrawal, and, in some cases, opioid-induced hyperalgesia (Chu, Angst, & Clark, 2008). Heightened pain sensitivity, when coupled with tolerance to the analgesic effects of opioids, can result in increased opioid craving (Ren, Shi, Epstein, Wang, & Lu, 2009) and consumption (Martell et al., 2007), and can elicit negative emotions that feed back to magnify pain perception. This process may result in appraisal of pain sensations as threatening and perseveration on the affective components of pain (Garland, 2012). Consequently, opioids are often misused to self-medicate (Khantzian, 1997; Kirsh, Jass, Bennett, Hagen, & Passik, 2007) the negative affective states and autonomic arousal that cause, co-occur with, or result from pain (Janig, 1995; Martenson, Cetas, & Heinricher, 2009). As with pain, stress and negative affect can become internal cues associated with past opioid use episodes that elicit the habit of opioid use, particularly among opioid misusers who take opioids to cope with emotional distress. Concomitantly, the habitual drive to engage in prescription opioid misuse (including unauthorized dose escalation) involves implicit neurocognitive operations that promote craving and aberrant drug taking (Goldstein et al., 2009; Stacy & Wiers, 2010) by biasing attention towards opioid-related cues (e.g., the sight of a pill bottle) (Garland, Froeliger, Passik, & Howard, 2012). Theory suggests that addiction occurs when the appetitive motivation to obtain natural rewards is re-organized around seeking drug-induced reward and the desire to alleviate dysphoria stemming from withdrawal and aversive experiences (e.g., pain and stress) (Alcaro & Panksepp, 2011; Koob & Le Moal, 2008). In that regard, decreased responsiveness to natural reinforcers has been observed among opiate dependent individuals and is robustly predictive of future opiate consumption (Lubman et al., 2009; Lubman, Allen, Peters, & Deakin, 2007, 2008). Hence, the problem of co-occurring chronic pain and prescription opioid misuse may involve a cycle of behavioral escalation where nociception and stress amplify pain and provoke recurrent self-medication with opioids, which in turn biases attention towards opioid-related cues that come to elicit the habit of opioid use despite ever diminishing analgesia and increasing dysphoria (Garland, Froeliger, Zeidan, Partin, & Howard, 2013). Despite such risks, opioids remain medically necessary for many individuals experiencing prolonged and intractable pain. Thus, therapeutic interventions are needed to target comorbid pain and opioid misuse. Though cognitive-behavioral therapy (CBT) has been shown to produce therapeutic reductions in pain (Williams, Eccleston, & Morley, 2012) and opioid misuse (Jamison et al., 2010) in isolation, there is scant research on psychological treatments that simultaneously address symptoms of co-occurring chronic pain and opioid misuse. To that end, we conducted an early-stage randomized controlled trial of Mindfulness-Oriented Recovery Enhancement (MORE) (Garland, 2013), a novel multimodal intervention that integrates mindfulness training, cognitive reappraisal skills, and positive emotion regulation into a therapeutic approach designed to modify attentional biases, habit behavior, affective dysregulation, and autonomic stress responses underlying the feedback loop between chronic pain, craving, and opioid misuse behaviors. Each of these three intervention components has been shown to be beneficial in isolation. Mindfulness training leads to reductions in pain (Gaylord et al., 2011; Kabat-Zinn et al., 1992; Rosenzweig et al., 2010; Zeidan et al., 2011) that are mediated by increased nonreactivity to aversive mental experiences and reinterpretation of affectively-laden pain sensations as innocuous sensory signals (Garland, Gaylord, Palsson, Faurot, Mann, & Whitehead, 2012). Moreover, mindfulness training produces salutary effects on emotional distress (Grossman, Niemann, Schmidt, & Walach, 2004; Hofmann, Sawyer, Witt, & Oh, 2010) and addiction-related factors (Bowen et al., 2009; Garland, Froeliger, & Howard, 2013), including attentional bias and autonomic cue-reactivity (Garland, Gaylord, Boettiger, & Howard, 2010). Similarly, cognitive reappraisal has been shown to significantly decrease negative emotions and downregulate stress physiology (Ochsner & Gross, 2005), as well as reduce substance craving (Kober et al., 2011). In complementary fashion, positive emotion regulatory strategies (e.g., savoring pleasant events) may upregulate positive affect, reduce anhedonia, and promote psychological resilience (Garland, Fredrickson, Kring, Johnson, Meyer, & Penn, 2010). MORE, which was originally tested as a treatment for alcohol dependence (Garland, Gaylord et al., 2010), capitalizes on the synergy of these three treatment components by integrating them into a multimodal intervention. The aim of this study was to evaluate the feasibility of developing a clinical trial comparing acute (pre-post) and longer-term (3-month follow-up) efficacy of MORE with that of a conventional support group (SG) in reducing chronic pain and prescription opioid misuse. The study employed an active control condition which attempted to control for non-specific therapeutic factors such as social interaction and support. We hypothesized that participation in MORE would be associated with significantly greater reductions in pain severity, pain interference, stress symptoms, and desire for opioids than would participation in a SG. We also hypothesized that compared to SG participants, a significantly greater proportion of individuals completing MORE who met clinical criteria for prescription opioid use disorder before treatment would no longer meet opioid use disorder criteria following treatment. Insofar as clinicians in the field must often make dichotomous diagnostic judgments in practice and may need to ascertain the extent to which a disorder can be rendered subclinical following treatment (cf., Eftekhari et al., 2013), we were interested in whether MORE could reduce symptoms below the clinical threshold for opioid use disorder. Lastly, although MORE was designed to target a wide array of cognitive, affective, and autonomic mechanisms as detailed above, in the present study we tested the effects of the intervention on a focused set of mediators selected for their direct relevance to primary study outcomes. Because emotional reactivity and maladaptive appraisals of pain and stress undergird the risk chain linking chronic pain and opioid misuse, we hypothesized that the therapeutic effects of MORE on pain severity and opioid use disorder status would be associated with increased nonreactivity, cognitive reappraisal, and reinterpretation of pain sensations as innocuous sensory information.

Buprenorphine Treatment for Hospitalized, Opioid-Dependent Patients: A Randomized Clinical Trial

Abstract: Importance Buprenorphine opioid agonist treatment (OAT) has established efficacy for treating opioid dependency among persons seeking addiction treatment. However, effectiveness for out-of-treatment, hospitalized patients is not known. Objective To determine whether buprenorphine administration during medical hospitalization and linkage to office-based buprenorphine OAT after discharge increase entry into office-based OAT, increase sustained engagement in OAT, and decrease illicit opioid use at 6 months after hospitalization. Design, Setting, and Participants From August 1, 2009, through October 31, 2012, a total of 663 hospitalized, opioid-dependent patients in a general medical hospital were identified. Of these, 369 did not meet eligibility criteria. A total of 145 eligible patients consented to participation in the randomized clinical trial. Of these, 139 completed the baseline interview and were assigned to the detoxification (n = 67) or linkage (n = 72) group. Interventions Five-day buprenorphine detoxification protocol or buprenorphine induction, intrahospital dose stabilization, and postdischarge transition to maintenance buprenorphine OAT affiliated with the hospital’s primary care clinic (linkage). Main Outcomes and Measures Entry and sustained engagement with buprenorphine OAT at 1, 3, and 6 months (medical record verified) and prior 30-day use of illicit opioids (self-report). Results During follow-up, linkage participants were more likely to enter buprenorphine OAT than those in the detoxification group (52 [72.2%] vs 8 [11.9%], P P = .007). Compared with those in the detoxification group, participants randomized to the linkage group reported less illicit opioid use in the 30 days before the 6-month interview (incidence rate ratio, 0.60; 95% CI, 0.46-0.73; P Conclusions and Relevance Compared with an inpatient detoxification protocol, initiation of and linkage to buprenorphine treatment is an effective means for engaging medically hospitalized patients who are not seeking addiction treatment and reduces illicit opioid use 6 months after hospitalization. However, maintaining engagement in treatment remains a challenge. Trial Registration clinicaltrials.gov Identifier:NCT00987961

Barriers to Primary Care Physicians Prescribing Buprenorphine

Abstract: PURPOSE Despite the efficacy of buprenorphine-naloxone for the treatment of opioid use disorders, few physicians in Washington State use this clinical tool. To address the acute need for this service, a Rural Opioid Addiction Management Project trained 120 Washington physicians in 2010–2011 to use buprenorphine. We conducted this study to determine what proportion of those trained physicians began prescribing this treatment and identify barriers to incorporating this approach into outpatient practice. METHODS We interviewed 92 of 120 physicians (77%), obtaining demographic information, current prescribing status, clinic characteristics, and barriers to prescribing buprenorphine. Residents and 7 physicians who were prescribing buprenorphine at the time of the course were excluded from the study. We analyzed the responses of the 78 remaining respondents. RESULTS Almost all respondents reported positive attitudes toward buprenorphine, but only 22 (28%) reported prescribing buprenorphine. Most (95%, n = 21) new prescribers were family physicians. Physicians who prescribed buprenorphine were more likely to have partners who had received a waiver to prescribe buprenorphine. A lack of institutional support was associated with not prescribing the medication (P = .04). A lack of mental health and psychosocial support was the most frequently cited barrier by both those who prescribe and who do not prescribe buprenorphine. CONCLUSION Interventions before and after training are needed to increase the number of physicians who offer buprenorphine for treatment of addiction. Targeting physicians in clinics that agree in advance to institute services, coupled with technical assistance after they have completed their training, their clinical teams, and their administrations is likely to help more physicians become active providers of this highly effective outpatient treatment.

A review of buprenorphine diversion and misuse: the current evidence base and experiences from around the world.

Abstract: Outpatient opioid addiction treatment with sublingual buprenorphine pharmacotherapy has rapidly expanded in the United States and abroad, and, with this increase in medication availability, there have been increasing concerns about its diversion, misuse, and related harms. This narrative review defines the behaviors of diversion and misuse, examines how the pharmacology of buprenorphine alone and in combination with naloxone influence its abuse liability, and describes the epidemiological data on buprenorphine diversion and intravenous misuse, risk factors for its intravenous misuse, and the unintended consequences of misuse and diversion. Physician practices to prevent, screen for, and therapeutically respond to these behaviors, which are a form of medication nonadherence, are discussed, and gaps in knowledge are identified. Outpatient opioid addiction treatment with sublingual buprenorphine pharmacotherapy experiences from other countries that have varied health care systems, public policies, and access to addiction treatment are shared to make clear that diversion and misuse occur across the world in various contexts, for many different reasons, and are not limited to buprenorphine. Comparisons are made with other opioids with known abuse liability and medications with no known abuse. The objective was to facilitate understanding of diversion and misuse so that all factors influencing their expression (patient and provider characteristics and public policy) can be appreciated within a framework that also recognizes the benefits of addiction treatment. With this comprehensive perspective, further careful work can help determine how to minimize these behaviors without eroding the current benefits realized through improved addiction treatment access and expansion.

Assessment of the trends in medical use and misuse of opioid analgesics from 2004 to 2011.

Abstract: Background The epidemic of medical use and abuse of opioid analgesics is linked to the economic burden of opioid-related abuse and fatalities in the United States. Multiple studies have estimated the extent to which prescription opioid analgesics contribute to the national drug abuse problem; studies also assessing the trends in medical use and abuse of opioid analgesics have confirmed the relationship between increasing medical use of opioids and increasing fatalities.The available data is limited until 2002. Study design Retrospective analysis of data from 2004 to 2011 from 2 databases: Automation of Reports and Consolidated Orders System (ARCOS) for opioid use data and Drug Abuse Warning Network (DAWN) for drug misuse data. Objective To determine the proportion of drug abuse related to opioid analgesics and the various trends in the medical use and abuse of 8 opioid analgesics commonly used to treat pain: buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, and oxycodone. Methods The data obtained from DAWN is a nationally representative sample of hospital emergency department admissions resulting from drug abuse. Main outcome measure was the identification of trends in the medical use and misuse of opioid analgesics from 2004 to 2011. Results From 2004 to 2011, there was an increase in the medical use of all opioids except for a 20% decrease in codeine. The abuse of all opioids including codeine increased during this period. Increases in medical use ranged from 2,318% for buprenorphine to 35% for fentanyl, including 140% for hydromorphone, 117% for oxycodone, 73% for hydrocodone, 64% for morphine, and 37% for methadone. The misuse increased 384% for buprenorphine with available data from 2006 to 2011, whereas from 2004 to 2011, it increased 438% for hydromorphone, 263% for oxycodone, 146% for morphine, 107% for hydrocodone, 104% for fentanyl, 82% for methadone, and 39% for codeine. Comparison of opioid use showed an overall increase of 1,448% from 1996 to 2011, with increases of 690% from 1996 to 2004 and 100% from 2004 to 2011. In contrast, misuse increased more dramatically: 4,680% from 1996 to 2011, with increases of 1,372% from 1996 through 2004 and 245% from 2004 to 2011. The number of patients seeking rehabilitation for substance abuse also increased 187% for opioids, whereas it increased 87% for heroin, 40% for marijuana, and decreased 7% for cocaine. Limitations Limitations of this assessment include the lack of data from 2003, lack of data available on meperidine, and that the aggregate data systems used in the study did not identify specific formulations or commercial products. Conclusion The present trend of continued increase in the medical use of opioid analgesics appears to contribute to increases in misuse, resulting in multiple health consequences.

Association of opioid agonist therapy with lower incidence of hepatitis C virus infection in young adult injection drug users.

Abstract: Importance Injection drug use is the primary mode of transmission for hepatitis C virus (HCV) infection. Prior studies suggest opioid agonist therapy may reduce the incidence of HCV infection among injection drug users; however, little is known about the effects of this therapy in younger users. Objective To evaluate whether opioid agonist therapy was associated with a lower incidence of HCV infection in a cohort of young adult injection drug users. Design, Setting, and Participants Observational cohort study conducted from January 3, 2000, through August 21, 2013, with quarterly interviews and blood sampling. We recruited young adult (younger than 30 years) injection drug users who were negative for anti-HCV antibody and/or HCV RNA. Exposures Substance use treatment within the past 3 months, including non–opioid agonist forms of treatment, opioid agonist (methadone hydrochloride or buprenorphine hydrochloride) detoxification or maintenance therapy, or no treatment. Main Outcomes and Measures Incident HCV infection documented with a new positive result for HCV RNA and/or HCV antibodies. Cumulative incidence rates (95% CI) of HCV infection were calculated assuming a Poisson distribution. Cox proportional hazards regression models were fit adjusting for age, sex, race, years of injection drug use, homelessness, and incarceration. Results Baseline characteristics of the sample (n = 552) included median age of 23 (interquartile range, 20-26) years; 31.9% female; 73.1% white; 39.7% who did not graduate from high school; and 69.2% who were homeless. During the observation period of 680 person-years, 171 incident cases of HCV infection occurred (incidence rate, 25.1 [95% CI, 21.6-29.2] per 100 person-years). The rate ratio was significantly lower for participants who reported recent maintenance opioid agonist therapy (0.31 [95% CI, 0.14-0.65]; P = .001) but not for those who reported recent non–opioid agonist forms of treatment (0.63 [95% CI, 0.37-1.08]; P = .09) or opioid agonist detoxification (1.45 [95% CI, 0.80-2.69]; P = .23). After adjustment for other covariates, maintenance opioid agonist therapy was associated with lower relative hazards for acquiring HCV infection over time (adjusted hazard ratio, 0.39 [95% CI, 0.18-0.87]; P = .02). Conclusions and Relevance In this cohort of young adult injection drug users, recent maintenance opioid agonist therapy was associated with a lower incidence of HCV infection. Maintenance treatment with methadone or buprenorphine for opioid use disorders may be an important strategy to prevent the spread of HCV infection among young injection drug users.

Medication-Assisted Treatment With Buprenorphine: Assessing the Evidence

Abstract: In 2002, buprenorphine and buprenorphine-naloxone became the first medications to be approved under a new federal law that permits long-term opioid treatment in settings other than opioid treatment clinics. In short order, buprenorphine has established a reputation as an effective alternative to methadone maintenance treatment with a key advantage: availability. In this literature review, the authors describes research evidence for buprenorphine treatment, including no fewer than 16 adequately designed randomized controlled trials indicating its positive impact on treatment retention and illicit opioid use.

Safety, tolerability, and clinical effect of low-dose buprenorphine for treatment-resistant depression in midlife and older adults.

Abstract: Objective Describe the clinical effect and safety of low-dose buprenorphine, a kappa-opioid receptor antagonist, for treatment-resistant depression (TRD) in mid-life and older adults.

Review of the assessment and management of neonatal abstinence syndrome

Abstract: Neonatal abstinence syndrome (NAS) secondary to in-utero opioid exposure is an increasing problem. Variability in assessment and treatment of NAS has been attributed to the lack of high-quality evidence to guide management of exposed neonates. This systematic review examines available evidence for NAS assessment tools, nonpharmacologic interventions, and pharmacologic management of opioid-exposed infants. There is limited data on the inter-observer reliability of NAS assessment tools due to lack of a standardized approach. In addition, most scales were developed prior to the prevalent use of prescribed prenatal concomitant medications, which can complicate NAS assessment. Nonpharmacologic interventions, particularly breastfeeding, may decrease NAS severity. Opioid medications such as morphine or methadone are recommended as first-line therapy, with phenobarbital or clonidine as second-line adjunctive therapy. Further research is needed to determine best practices for assessment, nonpharmacologic intervention, and pharmacologic management of infants with NAS in order to improve outcomes.

Primary care-based buprenorphine taper vs maintenance therapy for prescription opioid dependence: a randomized clinical trial.

Abstract: Importance 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. Objective To determine the efficacy of buprenorphine taper vs ongoing maintenance therapy in primary care–based treatment for prescription opioid dependence. Design, Setting, and Participants 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. Interventions 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. Main Outcomes and Measures Illicit opioid use via results of urinanalysis and patient report, treatment retention, and reinitiation of buprenorphine therapy (taper group only). Results 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 Conclusions and Relevance Tapering is less efficacious than ongoing maintenance treatment in patients with prescription opioid dependence who receive buprenorphine therapy in primary care. Trial Registration clinicaltrials.gov Identifier:NCT00555425

Prenatal Buprenorphine Versus Methadone Exposure and Neonatal Outcomes: Systematic Review and Meta-Analysis

Abstract: Increasing rates of maternal opioid use during pregnancy and neonatal withdrawal, termed neonatal abstinence syndrome (NAS), are public health concerns. Prenatal buprenorphine maintenance treatment (BMT) versus methadone maintenance treatment (MMT) may improve neonatal outcomes, but associations vary. To summarize evidence, we used a random-effects meta-analysis model and estimated summary measures of BMT versus MMT on several outcomes. Sensitivity analyses evaluated confounding, publication bias, and heterogeneity. Subjects were 515 neonates whose mothers received BMT and 855 neonates whose mothers received MMT and who were born from 1996 to 2012 and who were included in 12 studies. The unadjusted NAS treatment risk was lower (risk ratio=0.90, 95% confidence interval (CI): 0.81, 0.98) and mean length of hospital stay shorter (-7.23 days, 95% CI: -10.64, -3.83) in BMT-exposed versus MMT-exposed neonates. In treated neonates, NAS treatment duration was shorter (-8.46 days, 95% CI: -14.48, -2.44) and morphine dose lower (-3.60 mg, 95% CI: -7.26, 0.07) in those exposed to BMT. BMT-exposed neonates had higher mean gestational age and greater weight, length, and head circumference at birth. Fewer women treated with BMT used illicit opioids near delivery (risk ratio=0.44, 95% CI: 0.28, 0.70). Simulations suggested that confounding by indication could account for some of the observed differences. Prenatal BMT versus MMT may improve neonatal outcomes, but bias may contribute to this protective association. Further evidence is needed to guide treatment choices.

The response of agitated behavior to pain management in persons with dementia.

Abstract: Objectives Behavioral disturbances and pain are common in nursing home (NH) patients with dementia. An association between pain and increased agitation has been suggested, and recently a significant reduction of agitation has been demonstrated by pain treatment in patients with moderate to severe dementia. We now examined which specific agitated behaviors respond to individualized pain treatment. Design Cluster randomized clinical trial. Setting 60 clusters (i.e., clusters defined as single independent NH units) in 18 NHs within five municipalities of Western Norway. Participants 352 patients with moderate to severe dementia and clinically significant behavioral disturbances. Intervention The control group received usual treatment and care. According to a predefined scheme for 8 weeks, all patients in the intervention group received individual daily pain treatment with acetaminophen, extended release morphine, buprenorphine transdermal patch, and/or pregabaline. Measurements Cohen-Mansfield Agitation Inventory subscales and items. Results Analyses demonstrated that Factor 3 (Verbally agitated behaviors) showed the largest significant difference (DF = 1204.0, t = −4.308, p Conclusion We found that verbal agitation behaviors such as complaining, negativism, repetitious sentences and questions, constant request for attention, and cursing or verbal aggression responded to pain treatment. In addition, restlessness and pacing were sensible to analgesics. Such behaviors should therefore lead to an assessment of pain, and pain treatment. Further studies comparing how pain treatment should be balanced against other strategies including psychotropic drugs are needed.

It's MORe exciting than mu: crosstalk between mu opioid receptors and glutamatergic transmission in the mesolimbic dopamine system.

Abstract: Opioids selective for the G-protein coupled mu opioid receptor (MOR) produce potent analgesia and euphoria. Heroin, a synthetic opioid, is considered one of the most addictive substances, and the recent exponential rise in opioid addiction and overdose deaths has made treatment development a national public health priority. Existing medications (methadone, buprenorphine, and naltrexone), when combined with psychosocial therapies, have proven efficacy in reducing aspects of opioid addiction. Unfortunately, these medications have critical limitations including those associated with opioid agonist therapies (e.g., sustained physiological dependence and opioid withdrawal leading to high relapse rates upon discontinuation), nonadherence to daily dosing, and non-renewal of monthly injection with extended-release naltrexone. Furthermore, current medications fail to ameliorate key aspects of addiction such as powerful conditioned associations that trigger relapse (e.g., cues, stress, the drug itself). Thus, there is a need for developing novel treatments that target neural processes corrupted with chronic opioid use. This requires a basic understanding of molecular and cellular mechanisms underlying effects of opioids on synaptic transmission and plasticity within reward-related neural circuits. The focus of this review is to discuss how crosstalk between MOR-associated G-protein signaling and glutamatergic neurotransmission leads to immediate and long-term effects on emotional states (e.g., euphoria, depression) and motivated behavior (e.g., drug-seeking, relapse). Our goal is to integrate findings on how opioids modulate synaptic release of glutamate and postsynaptic transmission via AMPA and NMDA receptors in the nucleus accumbens (NAc) and ventral tegmental area (VTA) with the clinical (neurobehavioral) progression of opioid dependence, as well as to identify gaps in knowledge that can be addressed in future studies.

Adding an Internet-delivered treatment to an efficacious treatment package for opioid dependence.

Abstract: Objective To examine the benefit of adding an Internet-delivered behavior therapy to a buprenorphine medication program and voucher-based motivational incentives Method A block-randomized, unblinded, parallel, 12-week treatment trial was conducted with 170 opioid-dependent adult patients (mean age = 343 years; 541% male; 953% White) Participants received an Internet-based community reinforcement approach intervention plus contingency management (CRA+) and buprenorphine or contingency management alone (CM-alone) plus buprenorphine The primary outcomes, measured over the course of treatment, were longest continuous abstinence, total abstinence, and days retained in treatment Results Compared to those receiving CM-alone, CRA+ recipients exhibited, on average, 97 total days more of abstinence (95% confidence interval [CI = 23, 172]) and had a reduced hazard of dropping out of treatment (hazard ratio = 047; 95% CI [026, 085]) Prior treatment for opioid dependence significantly moderated the additional improvement of CRA+ for longest continuous days of abstinence Conclusions These results provide further evidence that an Internet-based CRA+ treatment is efficacious and adds clinical benefits to a contingency management/medication based program for opioid dependence

Reductions in prescription opioid diversion following recent legislative interventions in Florida

Abstract: PURPOSE: Florida has been at the center of the nation's ongoing prescription opioid epidemic, with largely unregulated pain clinics and lax prescribing oversight cited as significant contributors to the opioid problem in the state METHODS: In an effort to mitigate prescription opioid abuse and diversion in Florida, legislative interventions were implemented during 2010 and 2011, which included two primary elements: (i) comprehensive legislation to better regulate the operation of pain clinics; and (ii) a statewide prescription drug monitoring program to promote safer prescribing practices Using systematic longitudinal data collected on a quarterly basis from law enforcement agencies across Florida, this report examined changes in prescription opioid diversion rates following implementation of these regulatory initiatives Quarterly diversion rates for buprenorphine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, and tramadol were calculated, and subsequently, hierarchical linear models were fit to test for differences in diversion rates over the 15 quarter period of interest RESULTS: Significant declines in diversion rates were observed for oxycodone, methadone, and morphine; hydrocodone displayed a marginally significant decline CONCLUSIONS: This study documented reductions in statewide opioid diversion rates following implementation of Florida's pain clinic and prescription drug monitoring program legislative interventions Although these initial findings appear promising, continued surveillance of diversion is clearly warranted Copyright © 2013 John Wiley & Sons, Ltd Language: en

The opioid system and brain development: effects of methadone on the oligodendrocyte lineage and the early stages of myelination.

Abstract: Oligodendrocytes express opioid receptors throughout development, but the role of the opioid system in myelination remains poorly understood. This is a significant problem as opioid use and abuse continue to increase in two particular populations: pregnant addicts (in whom drug effects could target early myelination in the fetus and newborn) and adolescents and young adults (in whom late myelination of 'higher-order' regions takes place). Maintenance treatments for opioid addicts include the long-lasting opioids methadone and buprenorphine. Similar to our previous findings on the effects of buprenorphine, we have now found that early myelination in the developing rat brain is also altered by perinatal exposure to therapeutic doses of methadone. Pups exposed to this drug exhibited elevated brain levels of the 4 major splicing variants of myelin basic protein, myelin proteolipid protein, and myelin-oligodendrocyte glycoprotein. Consistent with the enrichment and function of these proteins in mature myelin, analysis of the corpus callosum in these young animals also indicated an elevated number of axons with already highly compacted myelin sheaths. Moreover, studies in cultured cells showed that methadone exerts direct effects at specific stages of the oligodendrocyte lineage, stimulating the proliferation of progenitor cells while on the other hand accelerating the maturation of the more differentiated but still immature preoligodendrocytes. While the long-term effects of these observations remain unknown, accelerated or increased oligodendrocyte maturation and myelination could both disrupt the complex sequence of synchronized events leading to normal connectivity in the developing brain. Together with our previous observations on the effects of buprenorphine, the present findings further underscore a crucial function of the endogenous opioid system in the control of oligodendrocyte development and the timing of myelination. Interference with these regulatory systems by opioid use or maintenance treatments could disrupt the normal process of brain maturation at critical stages of myelin formation.

Phantom Limb Pain: A Systematic Neuroanatomical-Based Review of Pharmacologic Treatment

Abstract: Objective Review the current evidence-based pharmacotherapy for phantom limb pain (PLP) in the context of the current understanding of the pathophysiology of this condition. Design We conducted a systematic review of original research papers specifically investigating the pharmacologic treatment of PLP. Literature was sourced from PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL). Studies with animals, “neuropathic” but not “phantom limb” pain, or without pain scores and/or functional measures as primary outcomes were excluded. A level of evidence 1–4 was ascribed to individual treatments. These levels included meta-analysis or systematic reviews (level 1), one or more well-powered randomized, controlled trials (level 2), retrospective studies, open-label trials, pilot studies (level 3), and anecdotes, case reports, or clinical experience (level 4). Results We found level 2 evidence for gabapentin, both oral (PO) and intravenous (IV) morphine, tramadol, intramuscular (IM) botulinum toxin, IV and epidural Ketamine, level 3 evidence for amitriptyline, dextromethorphan, topiramate, IV calcitonin, PO memantine, continuous perineural catheter analgesia with ropivacaine, and level 4 evidence for methadone, intrathecal (IT) buprenorphine, IT and epidural fentanyl, duloxetine, fluoxetine, mirtazapine, clonazepam, milnacipran, capsaicin, and pregabalin. Conclusions Currently, the best evidence (level 2) exists for the use of IV ketamine and IV morphine for the short-term perioperative treatment of PLP and PO morphine for an intermediate to long-term treatment effect (8 weeks to 1 year). Level 2 evidence is mixed for the efficacy of perioperative epidural anesthesia with morphine and bupivacaine for short to long-term pain relief (perioperatively up to 1 year) as well as for the use of gabapentin for pain relief of intermediate duration (6 weeks).

Buprenorphine–Naloxone Therapy in Pain Management

Abstract: Buprenorphine-naloxone (bup/nal in 4:1 ratio; Suboxone; Reckitt Benckiser Pharmaceuticals Incorporation, Richmond, VA) is approved by the Food and Drug Administration for outpatient office-based addiction treatment. In the past few years, bup/nal has been increasingly prescribed off-label for chronic pain management. The current data suggest that bup/nal may provide pain relief in patients with chronic pain with opioid dependence or addiction. However, the unique pharmacological profile of bup/nal confers it to be a weak analgesic that is unlikely to provide adequate pain relief for patients without opioid dependence or addiction. Possible mechanisms of pain relief by bup/nal therapy in opioid-dependent patients with chronic pain may include reversal of opioid-induced hyperalgesia and improvement in opioid tolerance and addiction. Additional studies are needed to assess the implication of bup/nal therapy in clinical anesthesia and perioperative pain management.

Sexual Dysfunction in Patients with Alcohol and Opioid Dependence

Abstract: There are limited numbers of studies which have evaluated the sexual dysfunction (SD) in patients with alcohol and opioids dependence. This article reviews the existing literature. Electronic searches were carried out using the PubMed, Google Scholar, and ScienceDirect to locate the relevant literature. Subjects addicted to heroin or on methadone maintenance treatment (MMT) or buprenorphine maintenance treatment (BMT) show higher rates of SD in comparison to the general population. SD rates have ranged 34-85% for heroin addicts, 14-81% for MMT, 36-83% for BMT, and 90% for naltrexone maintenance. The rates of SD in alcohol-dependent population have ranged 40-95.2%, with rates being consistently much higher in alcohol-dependent population than in the healthy controls or social drinkers. The common SDs reported have been erectile dysfunction followed by premature ejaculation, retarded ejaculation and decreased sexual desire among men, and dyspareunia and vaginal dryness among women. This review suggests that long-term use of alcohol and opioids are associated with SD in almost all domains of sexual functioning. There is a need to increase the awareness of clinicians about this association as many times SD in patients with substance abuse lead to poor treatment compliance and relapse. Further, there is a need to carry out more number of studies to understand the relationship in a better way.

Changes in prevalence of prescription opioid abuse after introduction of an abuse-deterrent opioid formulation

Abstract: Objective The reformulation of oxycodone hydrochloride controlled-release (CR) tablets in August 2010 created a natural experiment at a national scale, providing an opportunity to evaluate patterns of abuse of prescription opioids and other drugs before and after introduction of this abuse-deterrent formulation (ADF). Design Observational, cross-sectional study Setting Sentinel sample of adults assessed for substance abuse treatment within the NAVIPPRO® surveillance system Subjects Two hundred thirty-two thousand and eight hundred seventy-four adults at 437 facilities during January 1, 2008 through December 31, 2011. Methods Time-series analysis using logistic regression to estimate quarterly prevalence of past 30-day abuse (adjusted for covariates and prescription volume) and changes in abuse pre-and post-ADF introduction. Results Increases in abuse prevalence occurred for all prescription opioids as a class and for extended-release (ER) opioids. Significantly greater abuse of ER oxymorphone and buprenorphine occurred in the post-ADF period (relative risk [RR] = 2.91, 95% confidence interval [CI] = 2.59–3.27 and RR = 1.85, 95% CI = 1.74–1.96). Increases in abuse for these two compounds were significant among groups who reported abuse via preferential routes of administration (oral only, snorting only, injection only) post-ADF introduction. Conclusions Replacement of a widely prescribed opioid formulation known for its abuse potential alone may have had little impact on overall rates of prescription opioids as a class. However, changes in abuse levels of certain opioids coinciding with ADF introduction suggest possible switching of abuse among this study sample to specific long-acting opioid analgesics. Additional follow-up studies will be important to monitor changing abuse patterns and their public health impact as new opioid formulations are developed and introduced to market.