Non-analgesic effects of opioids: opioids and the endocrine system.

Science.gov (United States)

Elliott, Jennifer A; Opper, Susan E; Agarwal, Sonali; Fibuch, Eugene E

2012-01-01

Opioids are among the oldest known and most widely used analgesics. The application of opioids has expanded over the last few decades, especially in the treatment of chronic non-malignant pain. This upsurge in opioid use has been accompanied by the increasingly recognized occurrence of opioid-associated endocrinopathy. This may arise after exposure to enteral, parenteral, or neuraxial opioids. Opioid-associated endocrinopathy consists primarily of hypothalamic-pituitary-gonadal axis or hypothalamic-pituitary-adrenal axis dysfunction and may manifest with symptoms of hypogonadism, adrenal dysfunction, and other hormonal disturbances. Additionally, opioid related endocrine dysfunction may be coupled with such disorders as osteoporosis and mood disturbances including depression. Undesirable changes in pain sensitivity such as opioid-induced hyperalgesia, and reduced potency of opioid analgesia may also be potential consequences of chronic opioid consumption. Few studies to date have been able to establish what degree of opioid exposure, in terms of dose or duration of therapy, may predispose patients to opioid-associated endocrinopathy. This article will review the currently available literature concerning opioid-associated endocrinopathy and will provide recommendations for the evaluation, monitoring, and management of opioid-associated endocrinopathy and its other accompanying undesired effects.

Screening for current opioid misuse and associated risk factors among patients with chronic nonalcoholic pancreatitis pain.

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Barth, Kelly S; Balliet, Wendy; Pelic, Christine M; Madan, Alok; Malcolm, Robert; Adams, David; Morgan, Katherine; Owczarski, Stefanie; Borckardt, Jeffrey J

2014-08-01

The objective of this study is to assess clinical variables that may be associated with risk for opioid misuse in individuals with chronic pancreatitis. This study utilized a descriptive, quasi-experimental, cross sectional design. Three hundred seven individuals with nonalcoholic chronic pancreatitis engaged in chronic opioid therapy for pain presented to an outpatient specialty clinic at an academic medical center. Participants completed the Current Opioid Misuse Measure (COMM), Brief Pain Inventory (BPI), Short Form (SF)-12 Quality of Life Measure, Center for Epidemiological Studies 10-item Depression Scale (CESD), and a single item asking about current alcohol use. Mean scores on the CESD, COMM, BPI, SF-12, and factors associated with opioid misuse measures from regression analyses were the outcome measures. Mean scores on the CESD, COMM, BPI pain-on-average item, and the SF-12 physical and psychological quality of life factors (t scores) were 11.2 (standard deviation [SD] = 6.7), 8.5 (SD = 7.3), 4.8 (SD = 2.8), 39.7 (SD = 7.0), and 45 (SD = 9.0), respectively. Descriptive analyses revealed that 55% of participants scored above the clinical cutoff for depression on the CESD, and 39% scored above the cutoff for opioid misuse concerns on the COMM. Regression analyses identified several factors associated with higher opioid misuse measure scores, including increased depressive symptoms from the CESD (β = 0.38, P factors accounted for 37% of the variance in current opioid misuse scores. Depression, quality of life, pain intensity and alcohol use may be good candidate variables for prospective studies to determine clinical risk factors for opioid misuse among patients with pancreatitis. Wiley Periodicals, Inc.

Opioid dependence and substitution therapy: thymoquinone as potential novel supplement therapy for better outcome for methadone maintenance therapy substitution therapy

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Adnan, Liyana Hazwani Mohd; Bakar, Nor Hidayah Abu; Mohamad, Nasir

2014-01-01

Methadone is widely being used for opioid substitution therapy. However, the administration of methadone to opioid dependent individual is frequently accompanied by withdrawal syndrome and chemical dependency develops. Other than that, it is also difficult to retain patients in the treatment programme making their retention rates are decreasing over time. This article is written to higlights the potential use of prophetic medicines, Nigella sativa, as a supplement for opioid dependent receiving methadone. It focuses on the potential role of N. sativa and its major active compound, Thymoquinone (TQ) as a calcium channel blocking agent to reduce withdrawal syndrome and opioid dependency. PMID:25859295

Provider confidence in opioid prescribing and chronic pain management: results of the Opioid Therapy Provider Survey

Science.gov (United States)

Pearson, Amy CS; Moman, Rajat N; Moeschler, Susan M; Eldrige, Jason S; Hooten, W Michael

2017-01-01

Introduction Many providers report lack of confidence in managing patients with chronic pain. Thus, the primary aim of this study was to investigate the associations of provider confidence in managing chronic pain with their practice behaviors and demographics. Materials and methods The primary outcome measure was the results of the Opioid Therapy Provider Survey, which was administered to clinicians attending a pain-focused continuing medical education conference. Nonparametric correlations were assessed using Spearman’s rho. Results Of the respondents, 55.0% were women, 92.8% were white, and 56.5% were physicians. Primary care providers accounted for 56.5% of the total respondents. The majority of respondents (60.8%) did not feel confident managing patients with chronic pain. Provider confidence in managing chronic pain was positively correlated with 1) following an opioid therapy protocol (P=0.001), 2) the perceived ability to identify patients at risk for opioid misuse (P=0.006), and 3) using a consistent practice-based approach to improve their comfort level with prescribing opioids (Pcorrelated with the perception that treating pain patients was a “problem in my practice” (P=0.005). Conclusion In this study, the majority of providers did not feel confident managing chronic pain. However, provider confidence was associated with a protocolized and consistent practice-based approach toward managing opioids and the perceived ability to identify patients at risk for opioid misuse. Future studies should investigate whether provider confidence is associated with measurable competence in managing chronic pain and explore approaches to enhance appropriate levels of confidence in caring for patients with chronic pain. PMID:28652805

Oral cryotherapy reduces mucositis and opioid use after myeloablative therapy--a randomized controlled trial.

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Svanberg, Anncarin; Birgegård, Gunnar; Ohrn, Kerstin

2007-10-01

Mucositis is a major complication in myeloablative therapy, which often necessitates advanced pharmacological pain treatment, including i.v. opioids. Attempts to prevent oral mucositis have included oral cryotherapy, which has been shown to reduce mucositis, but there is a lack of knowledge concerning the effect of oral cryotherapy on opioid use by reducing the mucositis for patients treated with myeloablative therapy before bone marrow transplantation (BMT). The aim of the present study was to evaluate if oral cryotherapy could delay or alleviate the development of mucositis and thereby reduce the number of days with i.v. opioids among patients who receive myeloablative therapy before BMT. Eighty patients 18 years and older, scheduled for BMT, were included consecutively and randomised to oral cryotherapy or standard oral care. A stratified randomisation was used with regard to type of transplantation. Intensity of pain, severity of mucositis and use of opioids were recorded using pain visual analogue scale (VAS) scores, mucositis index scores and medical and nursing charts. This study showed that patients receiving oral cryotherapy had less pronounced mucositis and significantly fewer days with i.v. opioids than the control group. In the autologous setting, cryotherapy patients also needed significantly lower total dose of opioids. Oral cryotherapy is an effective and well-tolerated therapy to alleviate mucositis and consequently reduce the number of days with i.v. opioids among patients treated with myeloablative therapy before BMT.

Opioid dependence and substitution therapy: thymoquinone as potential novel supplement therapy for better outcome for methadone maintenance therapy substitution therapy

Directory of Open Access Journals (Sweden)

Liyana Hazwani Mohd Adnan

2015-12-01

Full Text Available Methadone is widely being used for opioid substitution therapy. However, the administration of methadone to opioid dependent individual is frequently accompanied by withdrawal syndrome and chemical dependency develops. Other than that, it is also difficult to retain patients in the treatment programme making their retention rates are decreasing over time. This article is written to higlights the potential use of prophetic medicines, Nigella sativa, as a supplement for opioid dependent receiving methadone. It focuses on the potential role of N. sativa and its major active compound, Thymoquinone (TQ as a calcium channel blocking agent to reduce withdrawal syndrome and opioid dependency.

Role of the informed consent, from mesotherapy to opioid therapy.

Science.gov (United States)

Mammucari, M; Lazzari, M; Maggiori, E; Gafforio, P; Tufaro, G; Baffini, S; Maggiori, S; Palombo, E; de Meo, B; Sabato, A F

2014-01-01

Informed consent is part of a process of communication useful to obtain an agreement (conscious, voluntary and free) between doctors and patients. Mesotherapy is based on the introduction of drugs by intradermal route in order to obtain a dose-sparing effect with respect to deeper administration. Opioids are the most appropriate therapy for patients who do not respond to other therapies. Proper communication between doctor and patient, including an explanation of the potential benefits, limitations and risks (even mild), is recommended both in clinical practice and research. Active participation of the patient has the advantage of better control of adverse events, both of mesotherapy and opioid-based therapy. This information-education process returns to the fundamental concept of "first do no harm" and set a "therapeutic partnership" with patients.

The prescription opioid epidemic: an overview for anesthesiologists.

Science.gov (United States)

Alam, Asim; Juurlink, David N

2016-01-01

The objectives for preparing this article were to review the historical context and epidemiology surrounding the North American prescription opioid crisis, to summarize the evidence regarding the benefits and harms of long-term opioid therapy for non-cancer pain, and to outline ways in which anesthesiologists may help ameliorate the problem. We searched PubMed, Google Scholar, and EMBASE™ for relevant articles using various search terms, including pain, opioid epidemic, history of opioid use, perioperative care, and addiction. Related citations were further explored and searched depending on the specific subtopic of interest. In the 1980s and early 1990s, opioids were infrequently used for the treatment of chronic pain. Thereafter, however, physicians were gradually inculcated with the message that long-term opioid therapy was a safe and effective treatment option for patients with chronic non-cancer pain. Pharmaceutical companies supported this growing movement and employed aggressive and sometimes misleading marketing strategies for new opioid formulations. As a result, the practice of prescribing opioids flourished in the late 1990s. The surge in prescribing opioids was accompanied by a marked increase in opioid-related morbidity and mortality. This change in practice transpired despite the absence of randomized trials showing clinically significant benefit from the long-term use of opioids. Subsequently, however, a large and growing body of evidence has emerged quantifying the harms associated with long-term opioid therapy. Anesthesiologists widely prescribe opioids for acute and chronic pain; yet, as a group, they may be largely unaware of the current state of this growing epidemic and what role they can play to rectify this problem. Anesthesiologists are well positioned to take a leadership role in the management of postoperative discharge opioid therapy in an effort to curb the overutilization of opioids. Furthermore, anesthesiologists who regularly

Healthcare resource use and costs of opioid-induced constipation among non-cancer and cancer patients on opioid therapy

DEFF Research Database (Denmark)

Søndergaard, Jens; Christensen, Helene Nordahl; Ibsen, Rikke

2017-01-01

-based cohort study including patients ≥18 years of age initiating ≥4 weeks opioid therapy (1998–2012) in Denmark. A measure of OIC was constructed based on data from Danish national health registries, and defined as ≥1 diagnosis of constipation, diverticulitis, mega colon, ileus/subileus, abdominal pain....../acute abdomen or haemorrhoids and/or ≥2 subsequent prescription issues of laxatives. Total healthcare resource utilization and costs (including pharmacy dispense, inpatient-, outpatient-, emergency room- and primary care) were estimated according to OIC status, opioid treatment dosage and length, gender, age...... characteristics of non-cancer OIC patients showed a higher frequency of strong opioid treatment (69% versus 41%), long-term opioid treatment (1189 days versus 584 days), advanced age (73 years versus 61 years), and cardiovascular disease (31% versus 19%) compared to those without OIC (P 

Risk Factors for Opioid-Use Disorder and Overdose.

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Webster, Lynn R

2017-11-01

Opioid analgesics are recognized as a legitimate medical therapy for selected patients with severe chronic pain that does not respond to other therapies. However, opioids are associated with risks for patients and society that include misuse, abuse, diversion, addiction, and overdose deaths. Therapeutic success depends on proper candidate selection, assessment before administering opioid therapy, and close monitoring throughout the course of treatment. Risk assessment and prevention include knowledge of patient factors that may contribute to misuse, abuse, addiction, suicide, and respiratory depression. Risk factors for opioid misuse or addiction include past or current substance abuse, untreated psychiatric disorders, younger age, and social or family environments that encourage misuse. Opioid mortality prevalence is higher in people who are middle aged and have substance abuse and psychiatric comorbidities. Suicides are probably undercounted or frequently misclassified in reports of opioid-related poisoning deaths. Greater understanding and better assessment are needed of the risk associated with suicide risk in patients with pain. Clinical tools and an evolving evidence base are available to assist clinicians with identifying patients whose risk factors put them at risk for adverse outcomes with opioids.

Pain Management in the Opioid-Dependent Pregnant Woman.

Science.gov (United States)

Safley, Rebecca R; Swietlikowski, Jamie

Opioid dependence is an epidemic in the United States, and the percentage of pregnant women who are opioid dependent has increased dramatically in the last decade. Pain management, already a concern for intrapartum and postpartum care, is complicated in the context of opioid dependence. This clinical review surveys the literature on pain management in opioid-dependent pregnant women to summarize current consensus and evidence to guide clinical practice. Points of consensus for pain management in opioid-dependent pregnant women include continual opioid maintenance therapy throughout the pregnancy and the postpartum period; adequate management of acute pain; the contraindication of opioid agonist-antagonists for pain management; and the need for interdisciplinary teams using a multimodal approach to provide optimal care to opioid-dependent pregnant women.

Opioid pharmaceuticals and addiction: the issues, and research directions seeking solutions.

Science.gov (United States)

Walwyn, Wendy M; Miotto, Karen A; Evans, Christopher J

2010-05-01

There are few pharmaceuticals superior to opiates for the treatment of pain. However, with concerns of addiction, withdrawal and questionable efficacy for all types of pain, these compounds are far from a magical panacea for pain-relief. As it is unlikely that other classes of compounds will supersede the opioids in the very near future, it is important to both optimize current opioid therapies and curb the astounding diversion of opioids from their intended analgesic use to non-medical abuse. In optimizing opioid therapeutics it is necessary to enhance the clinical awareness of the benefits of treating pain and combine this with aggressive strategies to reduce diversion for non-medical use. At the heart of the issue of opioid misuse is the role of opioid systems in the reward circuitry, and the adaptive processes associated with repetitive opioid use that manifest during withdrawal. Emerging pharmacological insights of opioid receptors will be reviewed that provide future hope for developing opioid-based analgesics with reduced addictive properties and perhaps, reduced opponent processes. In addition, with the increased understanding of nociceptive circuitry and the molecules involved in transmitting pain, new therapeutic targets have become evident that may result in effective analgesics either alone or in combination with current opioid therapies.

Emerging therapies for patients with symptoms of opioid-induced bowel dysfunction

Directory of Open Access Journals (Sweden)

Leppert W

2015-04-01

Full Text Available Wojciech Leppert Chair and Department of Palliative Medicine, Poznan University of Medical Sciences, Poznan, Poland Abstract: Opioid-induced bowel dysfunction (OIBD comprises gastrointestinal (GI symptoms, including dry mouth, nausea, vomiting, gastric stasis, bloating, abdominal pain, and opioid-induced constipation, which significantly impair patients’ quality of life and may lead to undertreatment of pain. Traditional laxatives are often prescribed for OIBD symptoms, although they display limited efficacy and exert adverse effects. Other strategies include prokinetics and change of opioids or their administration route. However, these approaches do not address underlying causes of OIBD associated with opioid effects on mostly peripheral opioid receptors located in the GI tract. Targeted management of OIBD comprises purely peripherally acting opioid receptor antagonists and a combination of opioid receptor agonist and antagonist. Methylnaltrexone induces laxation in 50%–60% of patients with advanced diseases and OIBD who do not respond to traditional oral laxatives without inducing opioid withdrawal symptoms with similar response (45%–50% after an oral administration of naloxegol. A combination of prolonged-release oxycodone with prolonged-release naloxone (OXN in one tablet (a ratio of 2:1 provides analgesia with limited negative effect on the bowel function, as oxycodone displays high oral bioavailability and naloxone demonstrates local antagonist effect on opioid receptors in the GI tract and is totally inactivated in the liver. OXN in daily doses of up to 80 mg/40 mg provides equally effective analgesia with improved bowel function compared to oxycodone administered alone in patients with chronic non-malignant and cancer-related pain. OIBD is a common complication of long-term opioid therapy and may lead to quality of life deterioration and undertreatment of pain. Thus, a complex assessment and management that addresses underlying

Evaluation of the Tolerability of Switching Patients on Chronic Full ?-Opioid Agonist Therapy to Buccal Buprenorphine

OpenAIRE

Webster, Lynn; Gruener, Daniel; Kirby, Todd; Xiang, Qinfang; Tzanis, Evan; Finn, Andrew

2016-01-01

Objective?Assess whether patients with chronic pain receiving 80 to 220?mg oral morphine sulfate equivalent of a full ?-opioid agonist could be transitioned to buccal buprenorphine at approximately 50% of their full dose without inducing opioid withdrawal or sacrificing analgesic efficacy. Methods.?A randomized, double-blind, double-dummy, active-controlled, two-period crossover study in adult patients receiving around-the-clock full opioid agonist therapy and confirmed to be opioid dependent...

Pain Therapy Guided by Purpose and Perspective in Light of the Opioid Epidemic

Directory of Open Access Journals (Sweden)

Amie L. Severino

2018-04-01

Full Text Available Prescription opioid misuse is an ongoing and escalating epidemic. Although these pharmacological agents are highly effective analgesics prescribed for different types of pain, opioids also induce euphoria, leading to increasing diversion and misuse. Opioid use and related mortalities have developed in spite of initial claims that OxyContin, one of the first opioids prescribed in the USA, was not addictive in the presence of pain. These claims allayed the fears of clinicians and contributed to an increase in the number of prescriptions, quantity of drugs manufactured, and the unforeseen diversion of these drugs for non-medical uses. Understanding the history of opioid drug development, the widespread marketing campaign for opioids, the immense financial incentive behind the treatment of pain, and vulnerable socioeconomic and physical demographics for opioid misuse give perspective on the current epidemic as an American-born problem that has expanded to global significance. In light of the current worldwide opioid epidemic, it is imperative that novel opioids are developed to treat pain without inducing the euphoria that fosters physical dependence and addiction. We describe insights from preclinical findings on the properties of opioid drugs that offer insights into improving abuse-deterrent formulations. One finding is that the ability of some agonists to activate one pathway over another, or agonist bias, can predict whether several novel opioid compounds bear promise in treating pain without causing reward among other off-target effects. In addition, we outline how the pharmacokinetic profile of each opioid contributes to their potential for misuse and discuss the emergence of mixed agonists as a promising pipeline of opioid-based analgesics. These insights from preclinical findings can be used to more effectively identify opioids that treat pain without causing physical dependence and subsequent opioid abuse.

Pain Therapy Guided by Purpose and Perspective in Light of the Opioid Epidemic

Science.gov (United States)

Severino, Amie L.; Shadfar, Arash; Hakimian, Joshua K.; Crane, Oliver; Singh, Ganeev; Heinzerling, Keith; Walwyn, Wendy M.

2018-01-01

Prescription opioid misuse is an ongoing and escalating epidemic. Although these pharmacological agents are highly effective analgesics prescribed for different types of pain, opioids also induce euphoria, leading to increasing diversion and misuse. Opioid use and related mortalities have developed in spite of initial claims that OxyContin, one of the first opioids prescribed in the USA, was not addictive in the presence of pain. These claims allayed the fears of clinicians and contributed to an increase in the number of prescriptions, quantity of drugs manufactured, and the unforeseen diversion of these drugs for non-medical uses. Understanding the history of opioid drug development, the widespread marketing campaign for opioids, the immense financial incentive behind the treatment of pain, and vulnerable socioeconomic and physical demographics for opioid misuse give perspective on the current epidemic as an American-born problem that has expanded to global significance. In light of the current worldwide opioid epidemic, it is imperative that novel opioids are developed to treat pain without inducing the euphoria that fosters physical dependence and addiction. We describe insights from preclinical findings on the properties of opioid drugs that offer insights into improving abuse-deterrent formulations. One finding is that the ability of some agonists to activate one pathway over another, or agonist bias, can predict whether several novel opioid compounds bear promise in treating pain without causing reward among other off-target effects. In addition, we outline how the pharmacokinetic profile of each opioid contributes to their potential for misuse and discuss the emergence of mixed agonists as a promising pipeline of opioid-based analgesics. These insights from preclinical findings can be used to more effectively identify opioids that treat pain without causing physical dependence and subsequent opioid abuse. PMID:29740351

77 FR 75177 - Impact of Approved Drug Labeling on Chronic Opioid Therapy; Public Hearing; Request for Comments

Science.gov (United States)

2012-12-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1172] Impact of Approved Drug Labeling on Chronic Opioid Therapy; Public Hearing; Request for Comments AGENCY... impact the entire class of opioid drugs or a large subcategory thereof (e.g., ER/LA opioids), such as the...

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

Science.gov (United States)

Tsui, Judith I; Evans, Jennifer L; Lum, Paula J; Hahn, Judith A; Page, Kimberly

2014-12-01

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. To evaluate whether opioid agonist therapy was associated with a lower incidence of HCV infection in a cohort of young adult injection drug users. 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. 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. 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. 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

Opioid rotation with extended-release opioids: where should we begin?

Directory of Open Access Journals (Sweden)

Nalamachu S

2011-12-01

Full Text Available Srinivas NalamachuInternational Clinical Research Institute and Pain Management Institute, Overland Park, KS, USAAbstract: Opioid rotation is a common and necessary clinical practice in the management of chronic non-cancer pain to improve therapeutic efficacy with the lowest opioid dose. When dose escalations fail to achieve adequate analgesia or are associated with intolerable side effects, a trial of a new opioid should be considered. Much of the scientific rationale of opioid rotation is based on the wide interindividual variability in sensitivity to opioid analgesics and the novel patient response observed when introducing an opioid-tolerant patient to a new opioid. This article discusses patient indicators for opioid rotation, the conversion process between opioid medications, and additional practical considerations for increasing the effectiveness of opioid therapy during a trial of a new opioid. A Patient vignette that demonstrates a step-wise approach to opioid rotation is also presented.Keywords: extended-release opioids, chronic pain, opioid rotation

Long-term outcomes from the National Drug Abuse Treatment Clinical Trials Network Prescription Opioid Addiction Treatment Study.

Science.gov (United States)

Weiss, Roger D; Potter, Jennifer Sharpe; Griffin, Margaret L; Provost, Scott E; Fitzmaurice, Garrett M; McDermott, Katherine A; Srisarajivakul, Emily N; Dodd, Dorian R; Dreifuss, Jessica A; McHugh, R Kathryn; Carroll, Kathleen M

2015-05-01

Despite the growing prevalence of prescription opioid dependence, longitudinal studies have not examined long-term treatment response. The current study examined outcomes over 42 months in the Prescription Opioid Addiction Treatment Study (POATS). POATS was a multi-site clinical trial lasting up to 9 months, examining different durations of buprenorphine-naloxone plus standard medical management for prescription opioid dependence, with participants randomized to receive or not receive additional opioid drug counseling. A subset of participants (N=375 of 653) enrolled in a follow-up study. Telephone interviews were administered approximately 18, 30, and 42 months after main-trial enrollment. Comparison of baseline characteristics by follow-up participation suggested few differences. At Month 42, much improvement was seen: 31.7% were abstinent from opioids and not on agonist therapy; 29.4% were receiving opioid agonist therapy, but met no symptom criteria for current opioid dependence; 7.5% were using illicit opioids while on agonist therapy; and the remaining 31.4% were using opioids without agonist therapy. Participants reporting a lifetime history of heroin use at baseline were more likely to meet DSM-IV criteria for opioid dependence at Month 42 (OR=4.56, 95% CI=1.29-16.04, popioid abstinence. Eight percent (n=27/338) used heroin for the first time during follow-up; 10.1% reported first-time injection heroin use. Long-term outcomes for those dependent on prescription opioids demonstrated clear improvement from baseline. However, a subset exhibited a worsening course, by initiating heroin use and/or injection opioid use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Prescription Opioids

Science.gov (United States)

... therapy in a primary care setting struggles with opioid addiction. 4,5,6 Once addicted, it can be ... of drug overdose deaths involving methadone and other opioid analgesics in West Virginia. Addiction 2009;104(9):1541-8. Dunn KM, Saunders ...

Development of a brief tool for monitoring aberrant behaviours among patients receiving long-term opioid therapy: The Opioid-Related Behaviours In Treatment (ORBIT) scale.

Science.gov (United States)

Larance, Briony; Bruno, Raimondo; Lintzeris, Nicholas; Degenhardt, Louisa; Black, Emma; Brown, Amanda; Nielsen, Suzanne; Dunlop, Adrian; Holland, Rohan; Cohen, Milton; Mattick, Richard P

2016-02-01

Early identification of problems is essential in minimising the unintended consequences of opioid therapy. This study aimed to develop a brief scale that identifies and quantifies recent aberrant behaviour among diverse patient populations receiving long-term opioid treatment. 40 scale items were generated via literature review and expert panel (N=19) and tested in surveys of: (i) N=41 key experts, and (ii) N=426 patients prescribed opioids >3 months (222 pain patients and 204 opioid substitution therapy (OST) patients). We employed item and scale psychometrics (exploratory factor analyses, confirmatory factor analyses and item-response theory statistics) to refine items to a brief scale. Following removal of problematic items (poor retest-reliability or wording, semantic redundancy, differential item functioning, collinearity or rarity) iterative factor analytic procedures identified a 10-item unifactorial scale with good model fit in the total sample (N=426; CFI=0.981, TLI=0.975, RMSEA=0.057), and among pain (CFI=0.969, TLI=0.960, RMSEA=0.062) and OST subgroups (CFI=0.989, TFI=0.986, RMSEA=0.051). The 10 items provided good discrimination between groups, demonstrated acceptable test-retest reliability (ICC 0.80, 95% CI 0.60-0.89; Cronbach's alpha=0.89), were moderately correlated with related constructs, including opioid dependence (SDS), depression and stress (DASS subscales) and Social Relationships and Environment domains of the WHO-QoL, and had strong face validity among advising clinicians. The Opioid-Related Behaviours In Treatment (ORBIT) scale is brief, reliable and validated for use in diverse patient groups receiving opioids. The ORBIT has potential applications as a checklist to prompt clinical discussions and as a tool to quantify aberrant behaviour and assess change over time. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Non-analgesic effects of opioids: management of opioid-induced constipation by peripheral opioid receptor antagonists: prevention or withdrawal?

Science.gov (United States)

Holzer, Peter

2012-01-01

The therapeutic action of opioid analgesics is compromised by peripheral adverse effects among which opioid-induced constipation (OIC) is the most disabling, with a prevalence reported to vary between 15 and 90 %. Although OIC is usually treated with laxatives, there is insufficient clinical evidence that laxatives are efficacious in this indication. In contrast, there is ample evidence from double- blind, randomized and placebo-controlled trials that peripheral opioid receptor antagonists (PORAs) counteract OIC. This specific treatment modality is currently based on subcutaneous methylnaltrexone for the interruption of OIC in patients with advanced illness, and a fixed combination of oral prolonged-release naloxone with prolonged-release oxycodone for the prevention of OIC in the treatment of non-cancer and cancer pain. Both drugs counteract OIC while the analgesic effect of opioids remains unabated. The clinical studies show that more than 50 % of the patients with constipation under opioid therapy may benefit from the use of PORAs, while PORA-resistant patients are likely to suffer from non-opioid-induced constipation, the prevalence of which increases with age. While the addition of naloxone to oxycodone seems to act by preventing OIC, the intermittent dosing of methylnaltrexone every other day seems to stimulate defaecation by provoking an intestinal withdrawal response. The availability of PORAs provides a novel opportunity to specifically control OIC and other peripheral adverse effects of opioid analgesics (e.g., urinary retention and pruritus). The continuous dosing of a PORA has the advantage of few adverse effects, while intermittent dosing of a PORA can be associated with abdominal cramp-like pain.

Are peripheral opioid antagonists the solution to opioid side effects?

LENUS (Irish Health Repository)

Bates, John J

2012-02-03

Opioid medication is the mainstay of therapy for severe acute and chronic pain. Unfortunately, the side effects of these medications can affect patient comfort and safety, thus limiting their proven therapeutic potential. Whereas the main analgesic effects of opioids are centrally mediated, many of the common side effects are mediated via peripheral receptors. Novel peripheral opioid antagonists have been recently introduced that can block the peripheral actions of opioids without affecting centrally mediated analgesia. We review the clinical and experimental evidence of their efficacy in ameliorating opioid side effects and consider what further information might be useful in defining their role. IMPLICATIONS: The major analgesic effects of opioid medication are mediated within the brain and spinal cord. Many of the side effects of opioids are caused by activation of receptors outside these areas. Recently developed peripherally restricted opioid antagonists have the ability to block many opioid side effects without affecting analgesia.

Attitudes toward opioid substitution therapy and pre-incarceration HIV transmission behaviors among HIV-infected prisoners in Malaysia: implications for secondary prevention.

Science.gov (United States)

Bachireddy, Chethan; Bazazi, Alexander R; Kavasery, Ravi; Govindasamy, Sumathi; Kamarulzaman, Adeeba; Altice, Frederick L

2011-07-01

Pre-incarceration HIV transmission behaviors and current attitudes toward opioid substitution therapy (OST) among HIV-infected male prisoners in Malaysia have important implications for secondary HIV prevention efforts. In June 2007, 102 HIV-infected male prisoners within 6 months of community-release were anonymously surveyed in Kota Bharu, Malaysia. Nearly all subjects (95%) met criteria for opioid dependence. Overall, 66% of participants reported sharing needles, and 37% reported unprotected sex in the 30 days prior to incarceration. During this period, 77% reported injection drug use, with 71% injecting daily and 65% injecting more than one substance. Injection of buprenorphine (28%), benzodiazepines (28%) and methamphetamines (49%) was reported. Nearly all (97%) of those reporting unprotected sex did so with someone not known to be HIV-infected. While 51% believed that opioid substitution therapy (OST) would be helpful, only 33% believed they needed it to prevent relapse after prison release. Most participants (70%) expressed interest in learning more about OST. Those reporting the highest injection risks were more likely to believe OST would be helpful (pMalaysia is crucial to reduce community HIV transmission after release. Effectively reducing HIV risk associated with opioid injection will require OST expansion, including social marketing to improve its acceptability and careful monitoring. Access to sterile injection equipment, particularly for non-opioid injectors, and behavioral interventions that reduce sexual risk will also be required. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Drug-induced GABA transporter currents enhance GABA release to induce opioid withdrawal behaviors.

Science.gov (United States)

Bagley, Elena E; Hacker, Jennifer; Chefer, Vladimir I; Mallet, Christophe; McNally, Gavan P; Chieng, Billy C H; Perroud, Julie; Shippenberg, Toni S; Christie, MacDonald J

2011-10-30

Neurotransmitter transporters can affect neuronal excitability indirectly via modulation of neurotransmitter concentrations or directly via transporter currents. A physiological or pathophysiological role for transporter currents has not been described. We found that GABA transporter 1 (GAT-1) cation currents directly increased GABAergic neuronal excitability and synaptic GABA release in the periaqueductal gray (PAG) during opioid withdrawal in rodents. In contrast, GAT-1 did not indirectly alter GABA receptor responses via modulation of extracellular GABA concentrations. Notably, we found that GAT-1-induced increases in GABAergic activity contributed to many PAG-mediated signs of opioid withdrawal. Together, these data support the hypothesis that GAT-1 activity directly produces opioid withdrawal signs through direct hyperexcitation of GABAergic PAG neurons and nerve terminals, which presumably enhances GABAergic inhibition of PAG output neurons. These data provide, to the best of our knowledge, the first evidence that dysregulation of a neurotransmitter transporter current is important for the maladaptive plasticity that underlies opiate withdrawal.

Development of an integrated cognitive behavioral therapy for anxiety and opioid use disorder: Study protocol and methods.

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McHugh, R Kathryn; Votaw, Victoria R; Barlow, David H; Fitzmaurice, Garrett M; Greenfield, Shelly F; Weiss, Roger D

2017-09-01

Opioid use disorder is a highly disabling psychiatric disorder, and is associated with both significant functional disruption and risk for negative health outcomes such as infectious disease and fatal overdose. Even among those who receive evidence-based pharmacotherapy for opioid use disorder, many drop out of treatment or relapse, highlighting the importance of novel treatment strategies for this population. Over 60% of those with opioid use disorder also meet diagnostic criteria for an anxiety disorder; however, efficacious treatments for this common co-occurrence have not be established. This manuscript describes the rationale and methods for a behavioral treatment development study designed to develop and test an integrated cognitive-behavioral therapy for those with co-occurring opioid use disorder and anxiety disorders. The aims of the study are (1) to develop and pilot test a new manualized cognitive behavioral therapy for co-occurring opioid use disorder and anxiety disorders, (2) to test the efficacy of this treatment relative to an active comparison treatment that targets opioid use disorder alone, and (3) to investigate the role of stress reactivity in both prognosis and recovery from opioid use disorder and anxiety disorders. Our overarching aim is to investigate whether this new treatment improves both anxiety and opioid use disorder outcomes relative to standard treatment. Identifying optimal treatment strategies for this population are needed to improve outcomes among those with this highly disabling and life-threatening disorder. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of craving for opioid in opioid-dependent individuals and people under methadone maintenance treatment

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Azita Chehri

2014-02-01

Full Text Available Background: Methadone Maintenance Therapy (MMT is the most important treatment for opioid -dependency recurrence. The aim of this study was to compare the craving level in opioid-dependent individuals and people under methadone maintenance therapy. Methods: In this case – control study, 120 men with opioid dependency were selected through cluster sampling method. They were divided into two groups, 60 people in opioid-dependent group and 60 people in MMT group. Both groups were matched for age, sex, marital status, education, duration of opioid dependency and method of consumption. Then, they completed INCAS Substance Abuse Profile (ISAP, opiate withdrawal symptoms checklist, self–report of craving, Desire for Drug Questionnaire (DDQ, Obsessive Compulsive Drug Use Scale (OCDUS and visual cue-induced craving questionnaire. Data were analyzed by SPSS 15 using t-test and ANOVA. Results: Mean craving for drug significantly was lower in MMT group comparing opioid-dependent group (P<0.01. Conclusion: Methadone Maintenance Therapy decreased the craving for drugs and substances This can have an important role in relapse prevention.

Opioid Therapy for Chronic Pain: Overview of the 2017 US Department of Veterans Affairs and US Department of Defense Clinical Practice Guideline.

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Rosenberg, Jack M; Bilka, Brandon M; Wilson, Sara M; Spevak, Christopher

2018-05-01

The US Department of Veterans Affairs (VA) and US Department of Defense (DoD) revised the 2010 clinical practice guideline (CPG) for the management of opioid therapy for chronic pain, considering the specific needs of the VA and DoD and new evidence regarding prescribing opioid medication for non-end-of-life-related chronic pain. This paper summarizes the major recommendations and compares them with the US Centers for Disease Control and Prevention (CDC) guideline for prescribing opioids. This Opioid Therapy CPG was developed for VA-DoD service members, veterans, and their families. The VA/DoD Evidence-Based Practice Work Group convened a VA/DoD guideline renewal development effort and conformed to the guidelines established by the VA/DoD Joint Executive Council (JEC) and VA/DoD Health Executive Council (HEC). The panel developed questions, searched and evaluated the literature, developed recommendations using GRADE methodology, and developed algorithms. Passage of the CARA Act by Congress compelled consideration and comparison with the CDC opioid therapy guideline mid-development. There were 18 recommendations made. This article focuses on guideline development and key recommendations with CDC comparisons taken from four major areas, including: initiation and continuation of opioids;type, dose, follow-up, and taper of opioids;risk mitigation;acute pain. Guideline development and recommendations are presented. There was substantial overlap with the CDC opioid guideline. Additionally, there were items particularly relevant to the VA-DoD, including risk mitigation, suicide prevention, and preventing opioid use disorder in young patients. Our guideline highlights avoiding opioid therapy longer than 90 days as a critical juncture.

Use of electroanalgesia and laser therapies as alternatives to opioids for acute and chronic pain management [version 1; referees: 2 approved

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Paul F. White

2017-12-01

Full Text Available The use of opioid analgesics for postoperative pain management has contributed to the global opioid epidemic. It was recently reported that prescription opioid analgesic use often continued after major joint replacement surgery even though patients were no longer experiencing joint pain. The use of epidural local analgesia for perioperative pain management was not found to be protective against persistent opioid use in a large cohort of opioid-naïve patients undergoing abdominal surgery. In a retrospective study involving over 390,000 outpatients more than 66 years of age who underwent minor ambulatory surgery procedures, patients receiving a prescription opioid analgesic within 7 days of discharge were 44% more likely to continue using opioids 1 year after surgery. In a review of 11 million patients undergoing elective surgery from 2002 to 2011, both opioid overdoses and opioid dependence were found to be increasing over time. Opioid-dependent surgical patients were more likely to experience postoperative pulmonary complications, require longer hospital stays, and increase costs to the health-care system. The Centers for Disease Control and Prevention emphasized the importance of finding alternatives to opioid medication for treating pain. In the new clinical practice guidelines for back pain, the authors endorsed the use of non-pharmacologic therapies. However, one of the more widely used non-pharmacologic treatments for chronic pain (namely radiofrequency ablation therapy was recently reported to have no clinical benefit. Therefore, this clinical commentary will review evidence in the peer-reviewed literature supporting the use of electroanalgesia and laser therapies for treating acute pain, cervical (neck pain, low back pain, persistent post-surgical pain after spine surgery (“failed back syndrome”, major joint replacements, and abdominal surgery as well as other common chronic pain syndromes (for example, myofascial pain, peripheral

Medicaid Coverage for Methadone Maintenance and Use of Opioid Agonist Therapy in Specialty Addiction Treatment.

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Saloner, Brendan; Stoller, Kenneth B; Barry, Colleen L

2016-06-01

This study examined differences in opioid agonist therapy (OAT) utilization among Medicaid-enrolled adults receiving public-sector opioid use disorder treatment in states with Medicaid coverage of methadone maintenance, states with block grant funding only, and states without public coverage of methadone. Person-level treatment admission data, which included information on reason for treatment and use of OAT from 36 states were linked to state-level Medicaid policies collected in a 50-state survey. Probabilities of OAT use among Medicaid enrollees in opioid addiction treatment were calculated, with adjustment for demographic characteristics and patterns of substance use. In adjusted analysis, 45.0% of Medicaid-enrolled individuals in opioid addiction treatment in states with Medicaid coverage for methadone maintenance used OAT, compared with 30.1% in states with block grant coverage only and 17.0% in states with no coverage. Differences were widest in nonintensive outpatient settings. Medicaid methadone maintenance coverage is critical for encouraging OAT among individuals with opioid use disorders.

Functional Family Therapy (FFT) for Young People in Treatment for Non-opioid Drug Use:

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Filges, Trine; Andersen, Ditte; Jørgensen, Anne-Marie Klint

2015-01-01

The main aim of this review is to evaluate the current evidence on the effects of FFT on drug abuse reduction for young people in treatment for non-opioid drug use.......The main aim of this review is to evaluate the current evidence on the effects of FFT on drug abuse reduction for young people in treatment for non-opioid drug use....

Nonopioid substance use disorders and opioid dose predict therapeutic opioid addiction.

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Huffman, Kelly L; Shella, Elizabeth R; Sweis, Giries; Griffith, Sandra D; Scheman, Judith; Covington, Edward C

2015-02-01

Limited research examines the risk of therapeutic opioid addiction (TOA) in patients with chronic noncancer pain. This study examined TOA among 199 patients undergoing long-term opioid therapy at the time of admission to a pain rehabilitation program. It was hypothesized that nonopioid substance use disorders and opioid dosage would predict TOA. Daily mean opioid dose was 132.85 mg ± 175.39. Patients with nonopioid substance use disorders had 28 times the odds (odds ratio [OR] = 28.58; 95% confidence interval [CI] = 10.86, 75.27) of having TOA. Each 50-mg increase in opioid dose nearly doubled the odds of TOA (OR = 1.73; 95% CI = 1.29, 2.32). A 100-mg increase was associated with a 3-fold increase in odds (OR = 3.00; 95% CI = 1.67, 5.41). Receiver operating characteristic analysis revealed that opioid dose was a moderately accurate predictor (area under the curve = .75; 95% CI = .68, .82) of TOA. The sensitivity (.70) and specificity (.68) of opioid dose in predicting TOA was maximized at 76.10 mg; in addition, 46.00 mg yielded 80% sensitivity in identifying TOA. These results underscore the importance of obtaining a substance use history prior to prescribing and suggest a low screening threshold for TOA in patients who use opioids in the absence of improvement in pain or functional impairment. This article examines TOA in patients with chronic noncancer pain undergoing long-term opioid therapy. Results suggest that patients should be screened for nonopioid substance use disorders prior to prescribing. In the absence of improvement in pain or function, there is a low threshold (∼50 mg daily opioid dose) for addiction screening. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

Cognitive-Behavioural Therapies for Young People in Outpatient Treatment for Non-Opioid Drug Use:

DEFF Research Database (Denmark)

Filges, Trine; Knudsen, Anne-Sofie Due; Svendsen, Majken

2015-01-01

), Multidimensional Family Therapy (MDFT), and Psychoeducational Therapy (PET)). RESULTS Our main objective was to evaluate the current evidence on the effect of CBT on abstinence and drug use reduction for young people in outpatient treatment for non-opioid drug use. Seven randomised trials, involving 953......, and PET ) with respect to reduction in young people’s drug use. The evidence drawn from this systematic review is based on seven included studies analysed in two separate analyses, depending on whether the intervention was CBT with an add-on component such as motivational interviewing (four studies......) or CBT without an add-on component (three studies). The seven studies are very different in terms of their findings regarding the effects of CBT interventions compared to other interventions (ACRA, CBOP (+ACC), DHPE, FFT, IT, MDFT, and PET ) on young people’s drug use. Therefore, the overall conclusion...

Management of opioid addiction with buprenorphine: French history and current management

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Poloméni P

2014-03-01

pathophysiologic mechanisms of the disease, better knowledge of the pharmacology of opioid substitution treatments, and clear definition of short-, medium- and long-term treatment objectives. Data related to the management of opioid addiction by general practitioners in France have been published in 2005. Since then, the context has changed, other drugs were launched on the market such as generics of buprenorphine, methadone capsule, and Suboxone. Thus, an update seems necessary. This paper provides a description of opioid addiction management objectives and treatment modalities for general practitioners, based on currently available knowledge. Keywords: opioid addiction, withdrawal, opioid substitution treatment, buprenorphine, naloxone, general medicine

The US Opioid Crisis: Current Federal and State Legal Issues.

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Soelberg, Cobin D; Brown, Raeford E; Du Vivier, Derick; Meyer, John E; Ramachandran, Banu K

2017-11-01

The United States is in the midst of a devastating opioid misuse epidemic leading to over 33,000 deaths per year from both prescription and illegal opioids. Roughly half of these deaths are attributable to prescription opioids. Federal and state governments have only recently begun to grasp the magnitude of this public health crisis. In 2016, the Centers for Disease Control and Prevention released their Guidelines for Prescribing Opioids for Chronic Pain. While not comprehensive in scope, these guidelines attempt to control and regulate opioid prescribing. Other federal agencies involved with the federal regulatory effort include the Food and Drug Administration (FDA), the Drug Enforcement Agency (DEA), and the Department of Justice. Each federal agency has a unique role in helping to stem the burgeoning opioid misuse epidemic. The DEA, working with the Department of Justice, has enforcement power to prosecute pill mills and physicians for illegal prescribing. The DEA could also implement use of prescription drug monitoring programs (PDMPs), currently administered at the state level, and use of electronic prescribing for schedule II and III medications. The FDA has authority to approve new and safer formulations of immediate- and long-acting opioid medications. More importantly, the FDA can also ask pharmaceutical companies to cease manufacturing a drug. Additionally, state agencies play a critical role in reducing overdose deaths, protecting the public safety, and promoting the medically appropriate treatment of pain. One of the states' primary roles is the regulation of practice of medicine and the insurance industry within their borders. Utilizing this authority, states can both educate physicians about the dangers of opioids and make physician licensure dependent on registering and using PDMPs when prescribing controlled substances. Almost every state has implemented a PDMP to some degree; however, in addition to mandating their use, increased interstate

Opioid Analgesics and Nicotine: More Than Blowing Smoke.

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Yoon, Jin H; Lane, Scott D; Weaver, Michael F

2015-09-01

Practitioners are highly likely to encounter patients with concurrent use of nicotine products and opioid analgesics. Smokers present with more severe and extended chronic pain outcomes and have a higher frequency of prescription opioid use. Current tobacco smoking is a strong predictor of risk for nonmedical use of prescription opioids. Opioid and nicotinic-cholinergic neurotransmitter systems interact in important ways to modulate opioid and nicotine effects: dopamine release induced by nicotine is dependent on facilitation by the opioid system, and the nicotinic-acetylcholine system modulates self-administration of several classes of abused drugs-including opioids. Nicotine can serve as a prime for the use of other drugs, which in the case of the opioid system may be bidirectional. Opioids and compounds in tobacco, including nicotine, are metabolized by the cytochrome P450 enzyme system, but the metabolism of opioids and tobacco products can be complicated. Accordingly, drug interactions are possible but not always clear. Because of these issues, asking about nicotine use in patients taking opioids for pain is recommended. When assessing patient tobacco use, practitioners should also obtain information on products other than cigarettes, such as cigars, pipes, smokeless tobacco, and electronic nicotine delivery systems (ENDS, or e-cigarettes). There are multiple forms of behavioral therapy and pharmacotherapy available to assist patients with smoking cessation, and opioid agonist maintenance and pain clinics represent underutilized opportunities for nicotine intervention programs.

The impact of opioids on the endocrine system.

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Katz, Nathaniel; Mazer, Norman A

2009-02-01

Opioids have been used for medicinal and analgesic purposes for centuries. However, their negative effects on the endocrine system, which have been known for some times, are barely discussed in modern medicine. Therefore, we conducted a systematic review of the impact of opioids on the endocrine system. A review of the English language literature on preclinical and clinical studies of any type on the influence of opioids on the endocrine system was conducted. Preliminary recommendations for monitoring and managing these problems were provided. Long-term opioid therapy for either addiction or chronic pain often induces hypogonadism owing to central suppression of hypothalamic secretion of gonadotropin-releasing hormone. Symptoms of opioid-induced hypogonadism include loss of libido, infertility, fatigue, depression, anxiety, loss of muscle strength and mass, osteoporosis, and compression fractures in both men and women; impotence in men; and menstrual irregularities and galactorrhea in women. In view of the increased use of opioids for chronic pain, it has become increasingly important to monitor patients taking opioids and manage endocrine complications. Therefore, patients on opioid therapy should be routinely screened for such symptoms and for laboratory abnormalities in sex hormones. Opioid-induced hypogonadism seems to be a common complication of therapeutic or illicit opioid use. Patients on long-term opioid therapy should be prospectively monitored, and in cases of opioid-induced hypogonadism, we recommend nonopioid pain management, opioid rotation, or sex hormone supplementation after careful consideration of the risks and benefits.

Static magnetic therapy does not decrease pain or opioid requirements: a randomized double-blind trial.

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Cepeda, M Soledad; Carr, Daniel B; Sarquis, Tony; Miranda, Nelcy; Garcia, Ricardo J; Zarate, Camilo

2007-02-01

A growing multibillion dollar industry markets magnetic necklaces, bracelets, bands, insoles, back braces, mattresses, etc., for pain relief, although there is little evidence for their efficacy. We sought to evaluate the effect of magnetic therapy on pain intensity and opioid requirements in patients with postoperative pain. We designed a randomized, double-blind, controlled trial. One-hundred-sixty-five patients older than 12 yr of age were randomized to magnetic (n = 81) or sham therapy (n = 84) upon reporting moderate-to-severe pain in the postanesthesia care unit. Devices were placed over the surgical incision and left in place for 2 h. Patients rated their pain intensity on a 0-10 scale every 10 min and received incremental doses of morphine until pain intensity was Magnetic therapy lacks efficacy in controlling acute postoperative pain intensity levels or opioid requirements and should not be recommended for pain relief in this setting.

Management of constipation in palliative care patients undergoing opioid therapy: is polyethylene glycol an option?

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Wirz, Stefan; Klaschik, Eberhard

2005-01-01

This study assessed the efficacy of laxative use for treatment of constipation in patients receiving opioid therapy, with special attention to polyethylene glycol 3350/electrolyte solution (PEG-ES). Computerized data from 206 patients were analyzed using descriptive statistics. Subgroups were analyzed using confirmatory statistics. Constipation occurred in 42.7 percent of patients. Laxatives were administered to 74.3 percent of these patients using a standardized step scheme, with good results in 78.4 percent. As a therapy for constipation, the combined administration of PEG-ES, sodium picosulphate, and liquid paraffin proved most effective, although statistical analysis yielded no significance. Early use of PEG-ES using a step scheme holds promise for treatment of opioid-related constipation in palliative care patients, although further investigation is warranted.

Pain, opioids, and sleep: implications for restless legs syndrome treatment.

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Trenkwalder, Claudia; Zieglgänsberger, Walter; Ahmedzai, Sam H; Högl, Birgit

2017-03-01

oxycodone in RLS, opioids have been considered an efficacious off-label therapy in patients with severe RLS. A recent trial has proved the efficacy of a combination of prolonged release oxycodone/naloxone in patients with severe RLS as second-line therapy, with a mean dosage of 10/5 mg twice daily (mean difference of International Restless Legs Syndrome Study Group Rating Scale (IRLS) score between groups at 12 weeks: 8.15), and has now been licensed as the first opioid therapy in Europe. The current results from both short- and long-term trials and studies with opioids encourage optimism in alleviating RLS symptoms in patients with severe RLS, or possibly during or after augmentation. Copyright © 2016 Elsevier B.V. All rights reserved.

Long-term opioid therapy in Denmark

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Birke, H; Ekholm, Ola; Sjøgren, P

2017-01-01

significantly associated with initiation of L-TOT in individuals with CNCP at baseline. During follow-up, L-TOT in CNCP patients increased the likelihood of negative changes in pain interference with work (OR 9.2; 95% CI 1.9-43.6) and in moderate activities (OR 3.7; 95% CI 1.1-12.6). The analysis of all......,145). A nationally representative subsample of individuals (n = 2015) completed the self-administered questionnaire in both 2000 and 2013. Collected information included chronic pain (≥6 months), health behaviour, self-rated health, pain interference with work activities and physical activities. Long-term users were...... individuals indicated a dose-response relationship between longer treatment duration and the risk of experiencing negative changes. CONCLUSIONS: Individuals on L-TOT seemed not to achieve the key goals of opioid therapy: pain relief, improved quality of life and functional capacity. SIGNIFICANCE: Long...

Treating opioid dependence. Growing implications for primary care.

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Krantz, Mori J; Mehler, Philip S

2004-02-09

Almost 3 million Americans have abused heroin. The most effective treatment for this concerning epidemic is opioid replacement therapy. Although, from a historical perspective, acceptance of this therapy has been slow, growing evidence supports its efficacy. There are 3 approved medications for opioid maintenance therapy: methadone hydrochloride, levomethadyl acetate, and buprenorphine hydrochloride. Each has unique characteristics that determine its suitability for an individual patient. Cardiac arrhythmias have been reported with methadone and levomethadyl, but not with buprenorphine. Due to concerns about cardiac risk, levomethadyl use has declined and the product may ultimately be discontinued. These recent safety concerns, specifics about opioid detoxification and maintenance, and new federal initiatives were studied. Opioid detoxification has a role in both preventing acute withdrawal and maintaining long-term abstinence. Although only a minority of eligible patients are engaged in treatment, opioid maintenance therapy appears to offer the greatest public health benefits. There is growing interest in expanding treatment into primary care, allowing opioid addiction to be managed like other chronic illnesses. This model has gained wide acceptance in Europe and is now being implemented in the United States. The recent Drug Addiction Treatment Act enables qualified physicians to treat opioid-dependent patients with buprenorphine in an office-based setting. Mainstreaming opioid addiction treatment has many advantages; its success will depend on resolution of ethical and delivery system issues as well as improved and expanded training of physicians in addiction medicine.

The evolution of chronic opioid therapy and recognizing addiction.

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Daum, Akiva M; Berkowitz, Oren; Renner, John A

2015-05-01

Chronic pain is one of the most common complaints in the United States. Opioids have become a frequently prescribed treatment for patients with chronic nonmalignant pain. Concurrently, opioid use disorders have risen to epidemic levels. Studies investigating iatrogenic opioid addiction have been of limited quality. Aberrant drug-related behaviors may be warning signs of impending addiction. Proper screening and close monitoring are essential for managing patients on opioids for chronic nonmalignant pain.

Incidence of iatrogenic opioid dependence or abuse in patients with pain who were exposed to opioid analgesic therapy: a systematic review and meta-analysis.

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Higgins, C; Smith, B H; Matthews, K

2018-06-01

The prevalence and incidence of chronic conditions, such as pain and opioid dependence, have implications for policy development, resource allocation, and healthcare delivery. The primary objective of the current review was to estimate the incidence of iatrogenic opioid dependence or abuse after treatment with opioid analgesics. Systematic electronic searches utilised six research databases (Embase, Medline, PubMed, Cinahl Plus, Web of Science, OpenGrey). A 'grey' literature search and a reference search of included articles were also undertaken. The PICOS framework was used to develop search strategies and the findings are reported in accordance with the PRISMA Statement. After eligibility reviews of 6164 articles, 12 studies (involving 310 408 participants) were retained for inclusion in the meta-analyses. A random effects model (DerSimonian-Laird method) generated a pooled incidence of opioid dependence or abuse of 4.7%. There was little within-study risk of bias and no significant publication bias; however, substantial heterogeneity was found among study effects (99.78%). Sensitivity analyses indicated that the diagnostic criteria selected for identifying opioid dependence or abuse (Diagnostic Statistical Manual (DSM-IV) vs International Classification of Diseases (ICD-9)) accounted for 20% and duration of exposure to opioid analgesics accounted for 18% of variance in study effects. Longer-term opioid analgesic exposure, and prescription of strong rather than weak opioids, were associated with a significantly lower incidence of opioid dependence or abuse. The incidence of iatrogenic opioid dependence or abuse was 4.7% of those prescribed opioids for pain. Further research is required to confirm the potential for our findings to inform prevention of this serious adverse event. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Effectiveness of Mindfulness-Based Group Therapy Compared to the Usual Opioid Dependence Treatment.

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Imani, Saeed; Atef Vahid, Mohammad Kazem; Gharraee, Banafsheh; Noroozi, Alireza; Habibi, Mojtaba; Bowen, Sarah

2015-06-01

This study investigated the effectiveness of mindfulness-based group therapy (MBGT) compared to the usual opioid dependence treatment (TAU).Thirty outpatients meeting the DSM-IV-TR criteria for opioid dependence from Iranian National Center for Addiction Studies (INCAS) were randomly assigned into experimental (Mindfulness-Based Group Therapy) and control groups (the Usual Treatment).The experimental group undertook eight weeks of intervention, but the control group received the usual treatment according to the INCAS program. The Five Factor Mindfulness Questionnaire (FFMQ) and the Addiction Sevier Index (ASI) were administered at pre-treatment and post-treatment assessment periods. Thirteen patients from the experimental group and 15 from the control group completed post-test assessments. The results of MANCOVA revealed an increase in mean scores in observing, describing, acting with awareness, non-judging, non-reacting, and decrease in mean scores of alcohol and opium in MBGT patient group. The effectiveness of MBGT, compared to the usual treatment, was discussed in this paper as a selective protocol in the health care setting for substance use disorders.

Effectiveness of Mindfulness-Based Group Therapy Compared to the Usual Opioid Dependence Treatment

Directory of Open Access Journals (Sweden)

Saeed Imani

2015-11-01

Full Text Available  Objective: This study investigated the effectiveness of mindfulness-based group therapy (MBGT compared to the usual opioid dependence treatment (TAU.Thirty outpatients meeting the DSM-IV-TR criteria for opioid dependence from Iranian National Center for Addiction Studies (INCAS were randomly assigned into experimental (Mindfulness-Based Group Therapy and control groups (the Usual Treatment.The experimental group undertook eight weeks of intervention, but the control group received the usual treatment according to the INCAS program.  Methods:The Five Factor Mindfulness Questionnaire (FFMQ and the Addiction Sevier Index (ASI were administered at pre-treatment and post-treatment assessment periods. Thirteen patients from the experimental group and 15 from the control group completed post-test assessments. Results:The results of MANCOVA revealed an increase in mean scores in observing, describing, acting with awareness, non-judging, non-reacting, and decrease in mean scores of alcohol and opium in MBGT patient group. Conclusion:The effectiveness of MBGT, compared to the usual treatment, was discussed in this paper as a selective protocol in the health care setting for substance use disorders.

Physician Introduction to Opioids for Pain Among Patients with Opioid Dependence and Depressive Symptoms

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Tsui, Judith I.; Herman, Debra S.; Kettavong, Malyna; Alford, Daniel; Anderson, Bradley J.; Stein, Michael D.

2011-01-01

This study determined the frequency of reporting being introduced to opioids by a physician among opioid dependent patients. Cross-sectional analyses were performed using baseline data from a cohort of opioid addicts seeking treatment with buprenorphine. The primary outcome was response to the question: “Who introduced you to opiates?” Covariates included sociodemographics, depression, pain, current and prior substance use. Of 140 participants, 29% reported that they had been introduced to opioids by a physician. Of those who were introduced to opioids by a physician, all indicated that they had initially used opioids for pain, versus only 11% of those who did not report being introduced to opioids by a physician (p<0.01). There was no difference in current pain (78% vs. 85%, p=0.29), however participants who were introduced to opioids by a physician were more likely to have chronic pain (63% vs. 43%, p=0.04). A substantial proportion of individuals with opioid dependence seeking treatment may have been introduced to opioids by a physician. PMID:20727704

Role of Urine Drug Testing in the Current Opioid Epidemic.

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Mahajan, Gagan

2017-12-01

While the evidence for urine drug testing for patients on chronic opioid therapy is weak, the guidelines created by numerous medical societies and state and federal regulatory agencies recommend that it be included as one of the tools used to monitor patients for compliance with chronic opioid therapy. To get the most comprehensive results, clinicians should order both an immunoassay screen and confirmatory urine drug test. The immunoassay screen, which can be performed as an in-office point-of-care test or as a laboratory-based test, is a cheap and convenient study to order. Limitations of an immunoassay screen, however, include having a high threshold of detectability and only providing qualitative information about a select number of drug classes. Because of these restrictions, clinicians should understand that immunoassay screens have high false-positive and false-negative rates. Despite these limitations, though, the results can assist the clinician with making preliminary treatment decisions. In comparison, a confirmatory urine drug test, which can only be performed as a laboratory-based test, has a lower threshold of detectability and provides both qualitative and quantitative information. A urine drug test's greater degree of specificity allows for a relatively low false-negative and false-positive rate in contrast to an immunoassay screen. Like any other diagnostic test, an immunoassay screen and a confirmatory urine drug test both possess limitations. Clinicians must keep this in mind when interpreting an unexpected test result and consult with their laboratory when in doubt about the meaning of the test result to avoid making erroneous decisions that negatively impact both the patient and clinician.

Trends in opioid agonist therapy in the Veterans Health Administration: is supply keeping up with demand?

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Oliva, Elizabeth M; Trafton, Jodie A; Harris, Alex H S; Gordon, Adam J

2013-03-01

Opioid agonist therapy (OAT) through addiction specialty clinic settings (clinic-based OAT) using methadone or buprenorphine or office-based settings using buprenorphine (office-based OAT) is an evidence-based treatment for opioid dependence. The low number of clinic-based OATs available to veterans (N = 53) presents a barrier to OAT access; thus, the expansion in office-based OAT has been encouraged. To examine trends in office-based OAT utilization over time and whether availability of office-based OAT improved the proportion of veterans with opioid use disorders treated with OAT. We examined Veterans Health Administration (VHA) administrative data for evidence of buprenorphine prescribing and clinic-based OAT clinic stops from October 2003 through September 2010 [fiscal years (FY) 2004-2010]. The number of patients receiving buprenorphine increased from 300 at 27 facilities in FY2004 to 6147 at 118 facilities in FY2010. During this time, the number of patients diagnosed with an opioid use disorder increased by 45%; however, the proportion of opioid use disorder patients receiving OAT remained relatively stable, ranging from 25% to 27%. Office-based OAT utilization and the number of opioid use disorder veterans treated with OAT are increasing at the same rate over time, suggesting that office-based OAT is being used to meet the growing need for OAT care. Although office-based OAT is increasingly being used within the VHA and may be one way the VHA is keeping up with the demand for OAT, more research is needed to understand how to engage a greater proportion of opioid use disorder patients in treatment.

Evaluation of the acceptability and usability of a decision support system to encourage safe and effective use of opioid therapy for chronic, noncancer pain by primary care providers.

Science.gov (United States)

Trafton, Jodie; Martins, Susana; Michel, Martha; Lewis, Eleanor; Wang, Dan; Combs, Ann; Scates, Naquell; Tu, Samson; Goldstein, Mary K

2010-04-01

To develop and evaluate a clinical decision support system (CDSS) named Assessment and Treatment in Healthcare: Evidenced-Based Automation (ATHENA)-Opioid Therapy, which encourages safe and effective use of opioid therapy for chronic, noncancer pain. CDSS development and iterative evaluation using the analysis, design, development, implementation, and evaluation process including simulation-based and in-clinic assessments of usability for providers followed by targeted system revisions. Volunteers provided detailed feedback to guide improvements in the graphical user interface, and content and design changes to increase clinical usefulness, understandability, clinical workflow fit, and ease of completing guideline recommended practices. Revisions based on feedback increased CDSS usability ratings over time. Practice concerns outside the scope of the CDSS were also identified. Usability testing optimized the CDSS to better address barriers such as lack of provider education, confusion in dosing calculations and titration schedules, access to relevant patient information, provider discontinuity, documentation, and access to validated assessment tools. It also highlighted barriers to good clinical practice that are difficult to address with CDSS technology in its current conceptualization. For example, clinicians indicated that constraints on time and competing priorities in primary care, discomfort in patient-provider communications, and lack of evidence to guide opioid prescribing decisions impeded their ability to provide effective, guideline-adherent pain management. Iterative testing was essential for designing a highly usable and acceptable CDSS; however, identified barriers may limit the impact of the ATHENA-Opioid Therapy system and other CDSS on clinical practices and outcomes unless CDSS are paired with parallel initiatives to address these issues.

The opioid epidemic and national guidelines for opioid therapy for chronic noncancer pain: a perspective from different continents

Directory of Open Access Journals (Sweden)

Winfried Häuser

2017-06-01

Conclusion:. Implementation of opioid prescribing guidelines should ensure that physicians prescribe opioids only for appropriate indications in limited doses for selected patients and advice patients on their safe use. These measures could contribute to reduce prescription opioid misuse/abuse and deaths.

Using behavioral economics to predict opioid use during prescription opioid dependence treatment.

Science.gov (United States)

Worley, Matthew J; Shoptaw, Steven J; Bickel, Warren K; Ling, Walter

2015-03-01

Research grounded in behavioral economics has previously linked addictive behavior to disrupted decision-making and reward-processing, but these principles have not been examined in prescription opioid addiction, which is currently a major public health problem. This study examined whether pre-treatment drug reinforcement value predicted opioid use during outpatient treatment of prescription opioid addiction. Secondary analyses examined participants with prescription opioid dependence who received 12 weeks of buprenorphine-naloxone and counseling in a multi-site clinical trial (N=353). Baseline measures assessed opioid source and indices of drug reinforcement value, including the total amount and proportion of income spent on drugs. Weekly urine drug screens measured opioid use. Obtaining opioids from doctors was associated with lower pre-treatment drug spending, while obtaining opioids from dealers/patients was associated with greater spending. Controlling for demographics, opioid use history, and opioid source frequency, patients who spent a greater total amount (OR=1.30, peconomic resources to drugs, reflects propensity for continued opioid use during treatment among individuals with prescription opioid addiction. Future studies should examine disrupted decision-making and reward-processing in prescription opioid users more directly and test whether reinforcer pathology can be remediated in this population. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Reasons for opioid use among patients with dependence on prescription opioids: the role of chronic pain.

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Weiss, Roger D; Potter, Jennifer Sharpe; Griffin, Margaret L; McHugh, R Kathryn; Haller, Deborah; Jacobs, Petra; Gardin, John; Fischer, Dan; Rosen, Kristen D

2014-08-01

The number of individuals seeking treatment for prescription opioid dependence has increased dramatically, fostering a need for research on this population. The aim of this study was to examine reasons for prescription opioid use among 653 participants with and without chronic pain, enrolled in the Prescription Opioid Addiction Treatment Study, a randomized controlled trial of treatment for prescription opioid dependence. Participants identified initial and current reasons for opioid use. Participants with chronic pain were more likely to report pain as their primary initial reason for use; avoiding withdrawal was rated as the most important reason for current use in both groups. Participants with chronic pain rated using opioids to cope with physical pain as more important, and using opioids in response to social interactions and craving as less important, than those without chronic pain. Results highlight the importance of physical pain as a reason for opioid use among patients with chronic pain. Copyright © 2014 Elsevier Inc. All rights reserved.

Comorbid Post-Traumatic Stress Disorder and Opioid Dependence.

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Patel, Rikinkumar S; Elmaadawi, Ahmed; Nasr, Suhayl; Haskin, John

2017-09-03

Post-traumatic stress disorder (PTSD) is predominant amongst individuals addicted to opioids and obscures the course of illness and the treatment outcome. We report the case of a patient with major depressive disorder and opioid dependence, who experienced post-traumatic stress disorder symptoms during a recent visit to the inpatient unit. The similarity of symptoms between post-traumatic stress disorder and opioid dependence is so high that, sometimes, it is a challenge to differentiate between these conditions. Since opioid withdrawal symptoms mimic hyper vigilance, this results in an exaggeration of the response of patients with post-traumatic stress disorder. This comorbidity is associated with worse health outcomes, as its pathophysiology involves a common neurobiological circuit. Opioid substitution therapy and psychotherapeutic medications in combination with evidence-based cognitive behavioral therapy devised for individuals with comorbid post-traumatic stress disorder and opioid dependence may improve treatment outcomes in this population. Therefore, we conclude that the screening for post-traumatic stress disorder in the opioid-abusing population is crucial. To understand the underlying mechanisms for this comorbidity and to improve the treatment response, further research should be encouraged.

European Pain Federation position paper on appropriate opioid use in chronic pain management

DEFF Research Database (Denmark)

O'Brien, T; Christrup, L L; Drewes, A M

2017-01-01

rests with the primary care physician and other non-specialist opioid prescribers. There is much confusing and conflicting information available to non-specialist prescribers regarding opioid therapy and a great deal of unjustified fear is generated. Opioid therapy should only be initiated by competent...

Buprenorphine-naloxone therapy in pain management.

Science.gov (United States)

Chen, Kelly Yan; Chen, Lucy; Mao, Jianren

2014-05-01

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.

Rational use and interpretation of urine drug testing in chronic opioid therapy.

Science.gov (United States)

Reisfield, Gary M; Salazar, Elaine; Bertholf, Roger L

2007-01-01

Urine drug testing (UDT) has become an essential feature of pain management, as physicians seek to verify adherence to prescribed opioid regimens and to detect the use of illicit or unauthorized licit drugs. Results of urine drug tests have important consequences in regard to therapeutic decisions and the trust between physician and patient. However, reliance on UDT to confirm adherence can be problematic if the results are not interpreted correctly, and evidence suggests that many physicians lack an adequate understanding of the complexities of UDT and the factors that can affect test results. These factors include metabolic conversion between drugs, genetic variations in drug metabolism, the sensitivity and specificity of the analytical method for a particular drug or metabolite, and the effects of intentional and unintentional interferants. In this review, we focus on the technical features and limitations of analytical methods used for detecting drugs or their metabolites in urine, the statistical constructs that are pertinent to ordering UDT and interpreting test results, and the application of these concepts to the clinical monitoring of patients maintained on chronic opioid therapy.

Non-opioid anesthetic drug abuse among anesthesia care providers: a narrative review.

Science.gov (United States)

Zuleta-Alarcón, Alix; Coffman, John C; Soghomonyan, Suren; Papadimos, Thomas J; Bergese, Sergio D; Moran, Kenneth R

2017-02-01

The objective of this narrative review is to provide an overview of the problem of non-opioid anesthetic drug abuse among anesthesia care providers (ACPs) and to describe current approaches to screening, therapy, and rehabilitation of ACPs suffering from non-opioid anesthetic drug abuse. We first performed a search of all literature available on PubMed prior to April 11, 2016. The search was limited to articles published in Spanish and English, and the following key words were used: anesthesiology, anesthesia personnel, AND substance-related disorders. We also searched Ovid MEDLINE ® databases from 1946-April 11, 2016 using the following search terms: anesthesiology OR anesthesia, OR nurse anesthetist OR anesthesia care provider OR perioperative nursing AND substance-related disorders. Despite an increased awareness of drug abuse among ACPs and improvements in preventive measures, the problem of non-opioid anesthetic drug abuse remains significant. While opioids are the most commonly abused anesthesia medications among ACPs, the abuse of non-opioid anesthetics is a significant cause of morbidity, mortality, and professional demise. Early detection, effective therapy, and long-term follow-up help ACPs cope more effectively with the problem and, when possible, resume their professional activities. There is insufficient evidence to determine the ability of ACPs to return safely to anesthesia practice after rehabilitation, though awareness of the issue and ongoing treatment are necessary to minimize patient risk from potentially related clinical errors.

An opioid-based pain control program for head and neck cancer patients undergoing chemoradiation therapy achieves a high completion rate of radiation

International Nuclear Information System (INIS)

Kato, Kengo; Matsuura, Kazuto; Zenda, Sadamoto

2011-01-01

Appropriate supportive care is essential for intensive chemoradiation therapy (CRT), and pain management is an important supportive care for CRT for head and neck cancer. We developed an opioid-based pain control program for head and neck cancer patients undergoing CRT, and assessed its efficacy and safety. 110 head and neck cancer patients undergoing platinum-based concomitant CRT were enrolled from 10 cancer centers or university hospitals. Their pain caused by CRT was managed with a four-step opioid-based pain control program, and adverse events and usage of opioid were analyzed. 101 suitable cases of 110 patients were analyzed. 53% of cases suffered grade 3-4 mucositis. The rate of completion of radiotherapy was 99% and the rate of unplanned breaks in radiotherapy was 13%. The usage rate of opioid was 83% and the rate of compliance with the pain control program was 92%. The median maximum quantity of morphine used per day was 35 mg. No patient had to stop the opioid program or radiotherapy due to adverse effects of opioids. An opioid-based pain control program for head and neck cancer patients undergoing CRT achieves a high completion rate of radiation. (author)

Pharmacist's role in dispensing opioids for acute and chronic pain.

Science.gov (United States)

Marlowe, Karen F; Geiler, Richard

2012-10-01

Pain continues to be a serious health care concern in the United States. Patients with chronic pain experience the impact of the disease throughout their lives including their social interactions, family relationships, and in many cases economic productivity. Multiple surveys have found that many pharmacists hold misconceptions regarding opioids, pain disease states, and their understandings of current regulations. Multiple barriers affect the ability of pharmacists to deliver care to patients' prescribed opioid therapy. Inadequate communication between health care professionals and patients is one of the hurdles, which prevents quality care. Increased communication between health care providers including access to health information is one step, which is crucial to improving provision of pharmacotherapy. Finally, the quality of educational opportunities relative to opioids and pain management specifically for pharmacists needs to be increased, and consideration needs to be given for making appropriate pain management education mandatory.

The effectiveness of telemedicine-delivered opioid agonist therapy in a supervised clinical setting.

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Eibl, Joseph K; Gauthier, Graham; Pellegrini, David; Daiter, Jeffery; Varenbut, Michael; Hogenbirk, John C; Marsh, David C

2017-07-01

Opioid use disorder has been declared a public health crisis across North America and opioid agonist therapy (OAT) is the standard of care for these patients. Despite the increasing adoption of telemedicine as a delivery method for OAT, its effectiveness has not yet been evaluated against traditional in-person treatment. This study compared treatment outcomes for in-person versus telemedicine-delivered OAT. We conducted a non-randomized cohort comparison study using an administrative database for patients who commenced OAT between 2011 and 2012 across 58 clinic sites in the province of Ontario, Canada. Patients were stratified by primary treatment modality as being: in-person (telemedicine), mixed (25-75% by telemedicine), or via telemedicine (>75% appointments by telemedicine). The primary outcome was continuous retention in treatment as defined by one year of uninterrupted therapy, based on pharmacy dosing records. A total of 3733 OAT initiating patients were identified. Patients treated via telemedicine were more likely to be retained in therapy than patients treated in-person (n=1590; aOR=1.27; 95% CI 1.14-1.41; pTelemedicine patients demonstrated a retention rate of 50% at one year whereas in-person patients were retained at a rate of 39%. The mixed group also had higher likelihood of retention than the in-person group (n=418; aOR=1.26; 95% CI 1.08-1.47; p=0.001) and had a retention rate of 47% at one year. Telemedicine may be an effective alternative to delivering in person OAT, and it has the potential to expand access to care in rural, remote, and urban regions. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Opioid therapy in non-cancer chronic pain patients: Trends and efficacy in different types of pain, patients age and gender

Directory of Open Access Journals (Sweden)

Yasin S AlMakadma

2013-01-01

Full Text Available Background: In both developing and developed countries, chronic pain remains a real issue and a true disease that affects up to 42% of the population in some areas. Opioids are widely used for the management of chronic pain with variations in prescribing practices, indications and observed efficacy. Aim: to analyze trends in opioids prescribing and patient response in chronic non-cancer pain conditions. Methods: Retrospective study of 1500 casenotes of patients suffering variable non-cancer chronic pain conditions. Detailed review of those cases who were managed using opioids. Statistical analysis using "SOFA" software set. Results: The prevalence of opioids prescribing in patients suffering this condition was thus around 35% (n=526. Women older than 50 years were more likely than men to have a chronic pain condition and to be given opioid therapy for 1 year or more. Opioid efficacy on neuropathic and mixed types of pain was found to be significant with relatively low rate of drop-out and limited side-effects that are not life threatening. Overall, patients stopped or changed their opioid medication due to inefficacy in only 12.7% of cases. Conclusions: The simple fact of having pain is itself a source of self-reported disability regardless of the actual physiological or pathological mechanism. Policy makers should be aware of the huge impact of chronic pain disease and of its serious effects on social and economical well-being. In developing countries, chronic pain could represent a real challenge for all parties. Multimodal management, including opioids, appears crucial for the approach of this disease.

Impact of opioid therapy on gonadal hormones: focus on buprenorphine.

Science.gov (United States)

Varma, Anjali; Sapra, Mamta; Iranmanesh, Ali

2018-02-17

Objective The USA is in the midst of an opioid crisis. Understanding the impact of opioids and commonly used treatments for opioid dependence is essential for clinicians and researchers in order to educate and treat the nation's growing population with opioid use disorders. As a relatively new treatment for opioid dependence, buprenorphine is gaining popularity to the extent of becoming not only a preferred approach to the maintenance of opiate addiction, but also an option for chronic pain management. The purpose of this report is to review the available evidence on the endocrine effects of buprenorphine, particularly as it relates to the hypothalamic-pituitary-gonadal (HPG) axis, which is controversial and not fully defined. Method We conducted a Pubmed search (2000-2017) for human studies in the English language for articles that were available as full length regarding buprenorphine, endocrinopathy, hypogonadism, bone density, opioids. Case reports were also reviewed, although prospective studies and randomized controlled trials received more weight. Results Opioid induced hypogonadism is well established. Most studies report that buprenorphine being a partial agonist/antagonist may not be impacting the pituitary trophic hormones as much. There are reports of sexual dysfunction in subjects maintained on buprenorphine, some without hormonal correlation. Thus with the understanding that pertinent clinical studies are limited in number, varied in methodology, mostly cross sectional, predominantly in men and small number of participants, more research in this area is warranted. Conclusion Based on a comprehensive review of the available literature, we conclude that despite its increasing popularity, buprenorphine has not been adequately studied in respect to its long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis. There is a great need for longitudinal systematic trials to define the potential buprenorphine-induced endocrine consequences.

Chronic Pain, Chronic Opioid Addiction: a Complex Nexus.

Science.gov (United States)

Salsitz, Edwin A

2016-03-01

Over the past two decades, there has been a significant increase in the prescribing of opioids, with associated increases in opioid addiction and overdose deaths. This article reviews the evidence for the effectiveness and risk of developing an opioid use disorder (OUD) in those patients treated with chronic opioid therapy (COT) for chronic non-cancer pain (CNCP). Rates of development of OUD range from 0-50 %, and aberrant drug related behaviors (ADRBs) are reported to be 20 %. Health care providers must properly assess, screen, and carefully monitor patients on COT utilizing evidence-based tools.

Inhibition of GABAergic Neurotransmission by HIV-1 Tat and Opioid Treatment in the Striatum Involves μ-opioid Receptors

Directory of Open Access Journals (Sweden)

Changqing Xu

2016-11-01

Full Text Available Due to combined antiretroviral therapy (cART, human immunodeficiency virus type 1 (HIV-1 is considered a chronic disease with high prevalence of mild forms of neurocognitive impairments, also referred to as HIV-associated neurocognitive disorders (HAND. Although opiate drug use can exacerbate HIV-1 Tat-induced neuronal damage, it remains unknown how and to what extent opioids interact with Tat on the GABAergic system. We conducted whole-cell recordings in mouse striatal slices and examined the effects of HIV-1 Tat in the presence and absence of morphine (1 μM and damgo (1 μM on GABAergic neurotransmission. Results indicated a decrease in the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs and miniature IPSCs (mIPSCs by Tat (5 – 50 nM in a concentration-dependent manner. The significant Tat-induced decrease in IPSCs was abolished when removing extracellular and/or intracellular calcium. Treatment with morphine or damgo alone significantly decreased the frequency, but not amplitude of IPSCs. Interestingly, morphine but not damgo indicated an additional downregulation of the mean frequency of mIPSCs in combination with Tat. Pretreatment with naloxone (1 μM and CTAP (1 μM prevented the Tat-induced decrease in sIPSCs frequency but only naloxone prevented the combined Tat and morphine effect on mIPSCs frequency. Results indicate a Tat- or opioid-induced decrease in GABAergic neurotransmission via µ-opioid receptors with combined Tat and morphine effects involving additional opioid receptor-related mechanisms. Exploring the interactions between Tat and opioids on the GABAergic system may help to guide future research on HAND in the context of opiate drug use.

Unused Opioid Pills After Outpatient Shoulder Surgeries Given Current Perioperative Prescribing Habits.

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Kumar, Kanupriya; Gulotta, Lawrence V; Dines, Joshua S; Allen, Answorth A; Cheng, Jennifer; Fields, Kara G; YaDeau, Jacques T; Wu, Christopher L

2017-03-01

In the past 16 years, the number of prescription opioids sold in the United States, as well as deaths from prescription opioids, has nearly quadrupled. However, the overall amount of pain reported by patients has not changed significantly. Specific information about opioid prescriptions in the perioperative period is lacking. Of the studies that have been published, investigators have shown that the majority of patients have unused postoperative opioid pills. Moreover, patients appear to lack information about disposal of unused opioid pills. To compare the number of pills prescribed versus the numbers left unused after outpatient shoulder surgeries at an orthopaedic surgery institution. Case series; Level of evidence, 4. In this prospective, observational study, 100 patients (age >18 years) undergoing outpatient shoulder surgery (rotator cuff repair, labral repair, stabilization/Bankart repair, debridement) were enrolled. Follow-ups were conducted via surveys on postoperative days (PODs) 7, 14, 28, and 90. The primary outcome was the number of unused pills from the originally prescribed medication. For all procedure types, the median (Q1, Q3) number of prescribed pills was 60 (40, 80). On POD 90, patients reported a median (Q1, Q3) of 13 (0, 32) unused pills; patients who underwent rotator cuff repairs had the lowest number of pills remaining (median [Q1, Q3], 0 [0, 16]), whereas patients who had stabilization/Bankart repairs had the highest number of unused pills (median [Q1, Q3], 37 [29, 50]). Patient satisfaction with pain management ranged from an average of 70% to 90%. Only 25 patients received instructions or education about opioid disposal. Most outpatient shoulder surgery patients who underwent certain operations were prescribed more opioid analgesics than they consumed. Patient education regarding the disposal of opioids was lacking.

The impact of cannabis use on patients enrolled in opioid agonist therapy in Ontario, Canada.

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Franklyn, Alexandra M; Eibl, Joseph K; Gauthier, Graham J; Marsh, David C

2017-01-01

With the Canadian government legalizing cannabis in the year 2018, the potential harms to certain populations-including those with opioid use disorder-must be investigated. Cannabis is one of the most commonly used substances by patients who are engaged in medication-assisted treatment for opioid use disorder, the effects of which are largely unknown. In this study, we examine the impact of baseline and ongoing cannabis use, and whether these are impacted differentially by gender. We conducted a retrospective cohort study using anonymized electronic medical records from 58 clinics offering opioid agonist therapy in Ontario, Canada. One-year treatment retention was the primary outcome of interest and was measured for patients who did and did not have a cannabis positive urine sample in their first month of treatment, and as a function of the proportion of cannabis-positive urine samples throughout treatment. Our cohort consisted of 644 patients, 328 of which were considered baseline cannabis users and 256 considered heavy users. Patients with baseline cannabis use and heavy cannabis use were at increased risk of dropout (38.9% and 48.1%, respectively). When evaluating these trends by gender, only female baseline users and male heavy users are at increased risk of premature dropout. Both baseline and heavy cannabis use are predictive of decreased treatment retention, and differences do exist between genders. With cannabis being legalized in the near future, physicians should closely monitor cannabis-using patients and provide education surrounding the potential harms of using cannabis while receiving treatment for opioid use disorder.

Neuraxial opioid-induced pruritus: a review.

LENUS (Irish Health Repository)

Szarvas, Szilvia

2012-02-03

When intrathecal and epidural opioids are administered, pruritus occurs as an unwanted and troublesome side effect. The reported incidence varies between 30% and 100%. The exact mechanisms of neuraxial opioid-induced pruritus remain unclear. Postulated mechanisms include the presence of an "itch center" in the central nervous system, medullary dorsal horn activation, and antagonism of inhibitory transmitters. The treatment of intrathecal opioid-induced pruritus remains a challenge. Many pharmacological therapies, including antihistamines, 5-HT(3)-receptor antagonists, opiate-antagonists, propofol, nonsteroid antiinflammatory drugs, and droperidol, have been studied. In this review, we will summarize pathophysiological and pharmacological advances that will improve understanding and ultimately the management of this troublesome problem.

Managing Opioid Addiction Risk in Plastic Surgery during the Perioperative Period.

Science.gov (United States)

Demsey, Daniel; Carr, Nicholas J; Clarke, Hance; Vipler, Sharon

2017-10-01

Opioid addiction is a public health crisis that affects all areas of medicine. Large numbers of the population across all racial and economic demographics misuse prescription opioids and use illicit opioids. The current understanding is that opioid misuse is a disease that requires treatment, and is not an issue of choice or character. Use of opioid medication is a necessary part of postoperative analgesia, but many physicians are unsure of how to do this safely given the risk of patients developing an opioid misuse disorder. This review gives an update of the current state of the opioid crisis, explains how current surgeons' prescribing practices are contributing to it, and gives recommendations on how to use opioid medication safely in the perioperative period.

Opioids Switching with Transdermal Systems in Chronic Cancer Pain

Directory of Open Access Journals (Sweden)

Barbarisi M

2009-05-01

Full Text Available Abstract Background Due to tolerance development and adverse side effects, chronic pain patients frequently need to be switched to alternative opioid therapy Objective To assess the efficacy and tolerability of an alternative transdermally applied (TDS opioid in patients with chronic cancer pain receiving insufficient analgesia using their present treatment. Methods A total of 32 patients received alternative opioid therapy, 16 were switched from buprenorphine to fentanyl and 16 were switched from fentanyl to buprenorphine. The dosage used was 50% of that indicated in equipotency conversion tables. Pain relief was assessed at weekly intervals for the next 3 weeks Results Pain relief as assessed by VAS, PPI, and PRI significantly improved (p Conclusion Opioid switching at 50% of the calculated equianalgesic dose produced a significant reduction in pain levels and rescue medication. The incidence of side effects decreased and no new side effects were noted. Further studies are required to provide individualized treatment for patients according to their different types of cancer.

Multidimensional Family Therapy (MDFT) for Young People in Treatment for Non-opioid Drug Abuse:

DEFF Research Database (Denmark)

Filges, Trine; Rasmussen, Pernille; Andersen, Ditte

2015-01-01

The main objectives of this review are to evaluate the current evidence on the effects of MDFT on drug abuse reduction for young people (aged 11-21 years) in treatment for non-opioid drug abuse, and if possible to examine moderators of drug abuse reduction effects, specifically analysing whether...

Detecting aberrant opioid behavior in the emergency department: a prospective study using the screener and Opioid Assessment for Patients with Pain-Revised (SOAPP®-R), Current Opioid Misuse Measure (COMM)™, and provider gestalt.

Science.gov (United States)

Varney, Shawn M; Perez, Crystal A; Araña, Allyson A; Carey, Katherine R; Ganem, Victoria J; Zarzabal, Lee A; Ramos, Rosemarie G; Bebarta, Vikhyat S

2018-03-03

Emergency department (ED) providers have limited time to evaluate patients at risk for opioid misuse. A validated tool to assess the risk for aberrant opioid behavior may mitigate adverse sequelae associated with prescription opioid misuse. We sought to determine if SOAPP-R, COMM, and provider gestalt were able to identify patients at risk for prescription opioid misuse as determined by pharmacy records at 12 months. We conducted a prospective observational study of adult patients in a high volume US ED. Patients completed the SOAPP-R and COMM, and treating EM providers evaluated patients' opioid misuse risk. We performed variable-centered, person-centered, and hierarchical cluster analyses to determine whether provider gestalt, SOAPP-R, or COMM, or a combination, predicted higher misuse risk. The primary outcome was the number of opioid prescriptions at 12 months according to pharmacy records. For 169 patients (mean age 43 years, 51% female, 73% white), correlation analysis showed a strong relationship between SOAPP-R and COMM with predicting the number of opioid prescriptions dispensed at 12 months. Provider scores estimating opioid misuse were not related to SOAPP-R and only weakly associated with COMM. In our adjusted regression models, provider gestalt and SOAPP-R uniquely predicted opioid prescriptions at 6 and 12 months. Using designated cutoff scores, only SOAPP-R detected a difference in the number of opioid prescriptions. Cluster analysis revealed that provider gestalt, SOAPP-R, and COMM scores jointly predicted opioid prescriptions. Provider gestalt and self-report instruments uniquely predicted the number of opioid prescriptions in ED patients. A combination of gestalt and self-assessment scores can be used to identify at-risk patients who otherwise miss the cutoff scores for SOAPP-R and COMM.

Tolerance and withdrawal from prolonged opioid use in critically ill children.

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Anand, Kanwaljeet J S; Willson, Douglas F; Berger, John; Harrison, Rick; Meert, Kathleen L; Zimmerman, Jerry; Carcillo, Joseph; Newth, Christopher J L; Prodhan, Parthak; Dean, J Michael; Nicholson, Carol

2010-05-01

After prolonged opioid exposure, children develop opioid-induced hyperalgesia, tolerance, and withdrawal. Strategies for prevention and management should be based on the mechanisms of opioid tolerance and withdrawal. Relevant manuscripts published in the English language were searched in Medline by using search terms "opioid," "opiate," "sedation," "analgesia," "child," "infant-newborn," "tolerance," "dependency," "withdrawal," "analgesic," "receptor," and "individual opioid drugs." Clinical and preclinical studies were reviewed for data synthesis. Mechanisms of opioid-induced hyperalgesia and tolerance suggest important drug- and patient-related risk factors that lead to tolerance and withdrawal. Opioid tolerance occurs earlier in the younger age groups, develops commonly during critical illness, and results more frequently from prolonged intravenous infusions of short-acting opioids. Treatment options include slowly tapering opioid doses, switching to longer-acting opioids, or specifically treating the symptoms of opioid withdrawal. Novel therapies may also include blocking the mechanisms of opioid tolerance, which would enhance the safety and effectiveness of opioid analgesia. Opioid tolerance and withdrawal occur frequently in critically ill children. Novel insights into opioid receptor physiology and cellular biochemical changes will inform scientific approaches for the use of opioid analgesia and the prevention of opioid tolerance and withdrawal.

Analgesic synergy between opioid and α2 -adrenoceptors.

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Chabot-Doré, A-J; Schuster, D J; Stone, L S; Wilcox, G L

2015-01-01

Opioid and α2 -adrenoceptor agonists are potent analgesic drugs and their analgesic effects can synergize when co-administered. These supra-additive interactions are potentially beneficial clinically; by increasing efficacy and/or reducing the total drug required to produce sufficient pain relief, undesired side effects can be minimized. However, combination therapies of opioids and α2 -adrenoceptor agonists remain underutilized clinically, in spite of a large body of preclinical evidence describing their synergistic interaction. One possible obstacle to the translation of preclinical findings to clinical applications is a lack of understanding of the mechanisms underlying the synergistic interactions between these two drug classes. In this review, we provide a detailed overview of the interactions between different opioid and α2 -adrenoceptor agonist combinations in preclinical studies. These studies have identified the spinal cord as an important site of action of synergistic interactions, provided insights into which receptors mediate these interactions and explored downstream signalling events enabling synergy. It is now well documented that the activation of both μ and δ opioid receptors can produce synergy with α2 -adrenoceptor agonists and that α2 -adrenoceptor agonists can mediate synergy through either the α2A or the α2C adrenoceptor subtypes. Current hypotheses surrounding the cellular mechanisms mediating opioid-adrenoceptor synergy, including PKC signalling and receptor oligomerization, and the evidence supporting them are presented. Finally, the implications of these findings for clinical applications and drug discovery are discussed. This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2. © 2014 The British Pharmacological Society.

South African guideline for the use of chronic opioid therapy for ...

African Journals Online (AJOL)

pain and chronic pain associated with cancer and at the end of life. Although .... Opioid drugs are agonists that bind to endogenous opioid receptors and mimic ..... interstitial cystitis/painful bladder syndrome, chronic prostate pain, and irritable ...

Association Between Facility-Level Utilization of Non-pharmacologic Chronic Pain Treatment and Subsequent Initiation of Long-Term Opioid Therapy.

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Carey, Evan P; Nolan, Charlotte; Kerns, Robert D; Ho, P Michael; Frank, Joseph W

2018-05-01

Expert guidelines recommend non-pharmacologic treatments and non-opioid medications for chronic pain and recommend against initiating long-term opioid therapy (LTOT). We examined whether veterans with incident chronic pain receiving care at facilities with greater utilization of non-pharmacologic treatments and non-opioid medications are less likely to initiate LTOT. Retrospective cohort study PARTICIPANTS: Veterans receiving primary care from a Veterans Health Administration facility with incident chronic pain between 1/1/2010 and 12/31/2015 based on either of 2 criteria: (1) persistent moderate-to-severe patient-reported pain and (2) diagnoses "likely to represent" chronic pain. The independent variable was facility-level utilization of pain-related treatment modalities (non-pharmacologic, non-opioid medications, LTOT) in the prior calendar year. The dependent variable was patient-level initiation of LTOT (≥ 90 days within 365 days) in the subsequent year, adjusting for patient characteristics. Among 1,094,569 veterans with incident chronic pain from 2010 to 2015, there was wide facility-level variation in utilization of 10 pain-related treatment modalities, including initiation of LTOT (median, 16%; range, 5-32%). Veterans receiving care at facilities with greater utilization of non-pharmacologic treatments were less likely to initiate LTOT in the year following incident chronic pain. Conversely, veterans receiving care at facilities with greater non-opioid and opioid medication utilization were more likely to initiate LTOT; this association was strongest for past year facility-level LTOT initiation (adjusted rate ratio, 2.10; 95% confidence interval, 2.06-2.15, top vs. bottom quartile of facility-level LTOT initiation in prior calendar year). Facility-level utilization patterns of non-pharmacologic, non-opioid, and opioid treatments for chronic pain are associated with subsequent patient-level initiation of LTOT among veterans with incident chronic pain

Neurophysiological mechanisms in acceptance and commitment therapy in opioid-addicted patients with chronic pain.

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Smallwood, Rachel F; Potter, Jennifer S; Robin, Donald A

2016-04-30

Acceptance and Commitment Therapy (ACT) has been effectively utilized to treat both chronic pain and substance use disorder independently. Given these results and the vital need to treat the comorbidity of the two disorders, a pilot ACT treatment was implemented in individuals with comorbid chronic pain and opioid addiction. This pilot study supported using neurophysiology to characterize treatment effects and revealed that, following ACT, participants with this comorbidity exhibited reductions in brain activation due to painful stimulus and in connectivity at rest. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Opioid antagonists with minimal sedation for opioid withdrawal.

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Gowing, Linda; Ali, Robert; White, Jason M

2017-05-29

hours following administration of opioid antagonists because of the possibility of vomiting, diarrhoea and delirium.Using opioid antagonists to induce and accelerate opioid withdrawal is not currently an active area of research or clinical practice, and the research community should give greater priority to investigating approaches, such as those based on buprenorphine, that facilitate the transition to sustained-release preparations of naltrexone.

Opioid Use Disorder Induces Oxidative Stress and Inflammation: The Attenuating Effect of Methadone Maintenance Treatment

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Ali Salarian

2018-02-01

Full Text Available Objective: Frequent use of opioids produces reactive oxygen species, upregulates inflammatory factors, and contributes to opiate dependence. In this study, we examined perturbations of plasma oxidative and inflammatory markers in patients with opioid use disorder in two phases. In the first phase, we compared the oxidative status in patients with opioid use disorders and in healthy controls; and in the second phase, we examined oxidative changes before and after methadone maintenance treatment.Method: To explore whether oxidative changes were associated with opioid use disorder, we compared plasma oxidative and inflammatory markers in patients with opioid use disorder and in smoking and non-smoking healthy participants. All participants completed measures of catalase (CAT, glutathione (GSH, malondialdehyde (MDA, superoxide dismutase (SOD, matrix metalloproteinase (MMP-9, and TNF-α at baseline. Baseline measures were compared using Kruskal-Wallis test. In the second phase, to explore oxidative changes during transition from opium use to methadone, blood and urine samples of patients with opioid use disorder were re-evaluated on Days 3, 7, and 14 after methadone therapy. Repeated measures analysis was used to determine the relative contribution of intervention to changes in CAT, GSH, MDA, SOD, MMP-9, and TNF-α level over time.Results: We observed lower SOD and catalase activities, and higher TNF-α and MMP-9 level in patients compared to the two comparison groups. Opioids exacerbated the oxidative imbalance and superimposed the underlying oxidative injury in smoker comparison group. Methadone therapy was associated with lower MMP-9 and TNF-α level, and higher SOD and catalase activities two weeks after therapy; showing an improvement in oxidative profile.Conclusion: This was an investigation indicating an oxidative imbalance before methadone therapy and during early days of transition from opium use to methadone. Being aware of redox status is

Patient Outcomes in Dose Reduction or Discontinuation of Long-Term Opioid Therapy: A Systematic Review.

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Frank, Joseph W; Lovejoy, Travis I; Becker, William C; Morasco, Benjamin J; Koenig, Christopher J; Hoffecker, Lilian; Dischinger, Hannah R; Dobscha, Steven K; Krebs, Erin E

2017-08-01

Expert guidelines recommend reducing or discontinuing long-term opioid therapy (LTOT) when risks outweigh benefits, but evidence on the effect of dose reduction on patient outcomes has not been systematically reviewed. To synthesize studies of the effectiveness of strategies to reduce or discontinue LTOT and patient outcomes after dose reduction among adults prescribed LTOT for chronic pain. MEDLINE, EMBASE, PsycINFO, CINAHL, and the Cochrane Library from inception through April 2017; reference lists; and expert contacts. Original research published in English that addressed dose reduction or discontinuation of LTOT for chronic pain. Two independent reviewers extracted data and assessed study quality using the U.S. Preventive Services Task Force quality rating criteria. All authors assessed evidence quality using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Prespecified patient outcomes were pain severity, function, quality of life, opioid withdrawal symptoms, substance use, and adverse events. Sixty-seven studies (11 randomized trials and 56 observational studies) examining 8 intervention categories, including interdisciplinary pain programs, buprenorphine-assisted dose reduction, and behavioral interventions, were found. Study quality was good for 3 studies, fair for 13 studies, and poor for 51 studies. Many studies reported dose reduction, but rates of opioid discontinuation ranged widely across interventions and the overall quality of evidence was very low. Among 40 studies examining patient outcomes after dose reduction (very low overall quality of evidence), improvement was reported in pain severity (8 of 8 fair-quality studies), function (5 of 5 fair-quality studies), and quality of life (3 of 3 fair-quality studies). Heterogeneous interventions and outcome measures; poor-quality studies with uncontrolled designs. Very low quality evidence suggests that several types of interventions may be effective to reduce or

National Institute on Drug Abuse International Program: improving opioid use disorder treatment through international research training.

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Gust, Steven W; McCormally, Judy

2018-07-01

For more than 25 years, the National Institute on Drug Abuse (NIDA) has supported research-training programs, establishing a global research network and expanding the knowledge base on substance use disorders. International research to inform approaches to opioid addiction is particularly important and relevant to the United States, where opioid misuse, addiction, and overdose constitute an emerging public health crisis. This article summarizes the NIDA International Program and illustrates its impact by reviewing recent articles about treatment approaches for opioid use disorders (OUD). Studies in several countries have demonstrated the effectiveness of physician office-based opioid substitution therapies. Other research has demonstrated the effectiveness of different formulations and doses of the opioid antagonist naltrexone, as well as different approaches to providing naloxone to treat opioid overdose. Continuing research into implementation of evidence-based treatment in international settings with limited resources is applicable to US regions that face similar structural, legal, and fiscal constraints. The current review describes international research on OUD treatment and opioid overdose, most coauthored by former NIDA fellows. The findings from outside the United States have important implications for best practices domestically and in other countries that are experiencing increases in OUD prevalence and related overdose deaths.

Opioid maintenance therapy in Switzerland: an overview of the Swiss IMPROVE study.

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Besson, J; Beck, T; Wiesbeck, G; Hämmig, R; Kuntz, A; Abid, S; Stohler, R

2014-01-01

Switzerland's drug policy model has always been unique and progressive, but there is a need to reassess this system in a rapidly changing world. The IMPROVE study was conducted to gain understanding of the attitudes and beliefs towards opioid maintenance therapy (OMT) in Switzerland with regards to quality and access to treatment. To obtain a "real-world" view on OMT, the study approached its goals from two different angles: from the perspectives of the OMT patients and of the physicians who treat patients with maintenance therapy. The IMPROVE study collected a large body of data on OMT in Switzerland. This paper presents a small subset of the dataset, focusing on the research design and methodology, the profile of the participants and the responses to several key questions addressed by the questionnaires. IMPROVE was an observational, questionnaire-based cross-sectional study on OMT conducted in Switzerland. Respondents consisted of OMT patients and treating physicians from various regions of the country. Data were collected using questionnaires in German and French. Physicians were interviewed by phone with a computer-based questionnaire. Patients self-completed a paper-based questionnaire at the physicians' offices or OMT treatment centres. A total of 200 physicians and 207 patients participated in the study. Liquid methadone and methadone tablets or capsules were the medications most commonly prescribed by physicians (60% and 20% of patient load, respectively) whereas buprenorphine use was less frequent. Patients (88%) and physicians (83%) were generally satisfied with the OMT currently offered. The current political framework and lack of training or information were cited as determining factors that deter physicians from engaging in OMT. About 31% of OMT physicians interviewed were ≥60 years old, indicating an ageing population. Diversion and misuse were considered a significant problem in Switzerland by 45% of the physicians. The subset of IMPROVE data

The introduction of buprenorphine-naloxone film in opioid substitution therapy in Australia: Uptake and issues arising from changing buprenorphine formulations.

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Larance, Briony; Dietze, Paul; Ali, Robert; Lintzeris, Nicholas; White, Nancy; Jenkinson, Rebecca; Degenhardt, Louisa

2015-11-01

Buprenorphine-naloxone (BNX) film for opioid dependence treatment was introduced in Australia in 2011. A key difference in State policy approaches saw transfer from BNX tablets to BNX film mandated in South Australia (SA) with New South Wales (NSW) and Victoria (VIC) having less stringent policies. This study examined (i) how initiations and transfers were implemented, (ii) the profile and predictors of adverse effects as self-reported by BNX film clients, and (iii) dosing issues. Survey of 334 buprenorphine (BPN), BNX tablet and BNX film clients and semi-structured interviews with 39 key experts (KEs) in 2012. Comparisons are made between clients interviewed in SA versus NSW and VIC combined. Among the 180 current BNX film clients, 23% started treatment on BNX film, 18% requested a transfer to BNX film and 59% (n = 106) reported their clinic/prescriber recommended transfer to BNX film. Among clients who were offered but refused a transfer to BNX film (n = 66), the most common reason was 'I am happy with my current treatment and do not see a reason to change' (53%). Some opioid substitution therapy clients and KE viewed transfers as 'forced' (i.e. no choice of buprenorphine formulation). Multivariable regression showed residing in SA (vs. NSW/VIC) and a shorter length of current treatment episode were associated with more BNX film-attributed adverse effects but clinic/prescriber-recommended transfer was not. The introduction of BNX film in Australia varied across States. A perception of restricted choice in medication may have undermined initial acceptance in SA. © 2015 Australasian Professional Society on Alcohol and other Drugs.

Opioid withdrawal syndrome: emerging concepts and novel therapeutic targets.

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Rehni, Ashish K; Jaggi, Amteshwar S; Singh, Nirmal

2013-02-01

Opioid withdrawal syndrome is a debilitating manifestation of opioid dependence and responds poorly to the available clinical therapies. Studies from various in vivo and in vitro animal models of opioid withdrawal syndrome have led to understanding of its pathobiology which includes complex interrelated pathways leading to adenylyl cyclase superactivation based central excitation. Advancements in the elucidation of opioid withdrawal syndrome mechanisms have revealed a number of key targets that have been hypothesized to modulate clinical status. The present review discusses the neurobiology of opioid withdrawal syndrome and its therapeutic target recptors like calcitonin gene related peptide receptors (CGRP), N-methyl-D-aspartate (NMDA) receptors, gamma aminobutyric acid receptors (GABA), G-proteingated inwardly rectifying potassium (GIRK) channels and calcium channels. The present review further details the potential role of second messengers like calcium (Ca2+) / calmodulin-dependent protein kinase (CaMKII), nitric oxide synthase, cytokines, arachidonic acid metabolites, corticotropin releasing factor, fos and src kinases in causing opioid withdrawal syndrome. The exploitation of these targets may provide effective therapeutic agents for the management of opioid dependence-induced abstinence syndrome.

Risk factors for opioid overdose and awareness of overdose risk among veterans prescribed chronic opioids for addiction or pain.

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Wilder, Christine M; Miller, Shannon C; Tiffany, Elizabeth; Winhusen, Theresa; Winstanley, Erin L; Stein, Michael D

2016-01-01

Rising overdose fatalities among U.S. veterans suggest veterans taking prescription opioids may be at risk for overdose. However, it is unclear whether veterans prescribed chronic opioids are aware of this risk. The objective of this study was to identify risk factors and determine awareness of risk for opioid overdose in veterans treated with opioids for chronic pain, using veterans treated with methadone or buprenorphine for opioid use disorder as a high-risk comparator group. In the current study, 90 veterans on chronic opioid medication, for either opioid use disorder or pain management, completed a questionnaire assessing risk factors, knowledge, and self-estimate of risk for overdose. Nearly all veterans in both groups had multiple overdose risk factors, although individuals in the pain management group had on average a significantly lower total number of risk factors than did individuals in the opioid use disorder group (5.9 versus 8.5, p opioid overdose risk factors (12.1 versus 13.5, p opioid overdose risk factors. Our results suggest that veterans in both groups underestimated their risk for opioid overdose. Expansion of overdose education to include individuals on chronic opioids for pain management and a shift in educational approaches to overdose prevention may be indicated.

A Prospective Study to Investigate Predictors of Relapse among Patients with Opioid Use Disorder Treated with Methadone

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Leen Naji

2016-01-01

Full Text Available Introduction Concomitant opioid abuse is a serious problem among patients receiving methadone maintenance treatment (MMT for opioid use disorder. This is an exploratory study that aims to identify predictors of the length of time a patient receiving MMT for opioid use disorder remains abstinent (relapse-free. Methods Data were collected from 250 MMT patients enrolled in addiction treatment clinics across Southern Ontario. The impact of certain clinical and socio-demographic factors on the outcome (time until opioid relapse was determined using a Cox proportional hazard model. Results History of injecting drug use behavior (hazard ratio (HR: 2.26, P = 0.042, illicit benzodiazepine consumption (HR: 1.07, P = 0.002, and the age of onset of opioid abuse (HR: 1.10, P < 0.0001 are important indicators of accelerated relapse among MMT patients. Conversely, current age is positively associated with duration of abstinence from illicit opioid use, serving as a protective factor against relapse (HR: 0.93, P = 0.003. Conclusion This study helps to identify patients at increased risk of relapse during MMT, allowing health care providers to target more aggressive adjunct therapies toward high-risk patients.

Health-Related Quality of Life among Chronic Opioid Users, Nonchronic Opioid Users, and Nonopioid Users with Chronic Noncancer Pain.

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Hayes, Corey J; Li, Xiaocong; Li, Chenghui; Shah, Anuj; Kathe, Niranjan; Bhandari, Naleen Raj; Payakachat, Nalin

2018-02-25

Evaluate the association between opioid therapy and health-related quality of life (HRQoL) in participants with chronic, noncancer pain (CNCP). Medical Expenditure Panel Survey Longitudinal, Medical Conditions, and Prescription Files. Using a retrospective cohort study design, the Mental Health Component (MCS12) and Physical Health Component (PCS12) scores of the Short Form-12 Version 2 were assessed to measure mental and physical HRQoL. Chronic, noncancer pain participants were classified as chronic, nonchronic, and nonopioid users. One-to-one propensity score matching was employed to match chronic opioid users to nonchronic opioid users plus nonchronic opioid users and chronic opioid users to nonopioid users. A total of 5,876 participants were identified. After matching, PCS12 was not significantly different between nonchronic versus nonopioid users (LSM Diff = -0.98, 95% CI: -2.07, 0.10), chronic versus nonopioid users (LSM Diff = -2.24, 95% CI: -4.58, 0.10), or chronic versus nonchronic opioid users (LSM Diff = -2.23, 95% CI: -4.53, 0.05). Similarly, MCS12 was not significantly different between nonchronic versus nonopioid users (LSM Diff = 0.76, 95% CI: -0.46, 1.98), chronic versus nonopioid users (LSM Diff = 1.08, 95% CI: -1.26, 3.42), or chronic versus nonchronic opioid users (LSM Diff = -0.57, 95% CI: -2.90, 1.77). Clinicians should evaluate opioid use in participants with CNCP as opioid use is not correlated with better HRQoL. © Health Research and Educational Trust.

Medication-Assisted Treatment For Opioid Addiction in Opioid Treatment Programs. Treatment Improvement Protocol (TIP) Series 43

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Tinkler, Emily; Vallejos Bartlett, Catalina; Brooks, Margaret; Gilbert, Johnatnan Max; Henderson, Randi; Shuman, Deborah, J.

2005-01-01

TIP 43 provides best-practice guidelines for medication-assisted treatment of opioid addiction in opioid treatment programs (OTPs). The primary intended audience for this volume is substance abuse treatment providers and administrators who work in OTPs. Recommendations in the TIP are based on both an analysis of current research and determinations…

Low efficacy of non-opioid drugs in opioid withdrawal symptoms.

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Hermann, Derik; Klages, Eckard; Welzel, Helga; Mann, Karl; Croissant, Bernhard

2005-06-01

Opioid withdrawal, stress or cues associated with opioid consumption can induce opioid craving. If opioids are not available, opioid-dependent patients usually search for alternative drugs. Because several non-opioid drugs stimulate the endogenous opioidergic system, this concept may explain their frequent use by opioid-dependent patients. We hypothesized that non-opioid drugs alleviate opioid withdrawal symptoms and are therefore consumed by opioid addicts. We asked 89 opioid-dependent patients participating in an out-patient opioid maintenance program to estimate the potential of several non-opioid drugs in being able to alleviate opioid withdrawal. We applied a five-point Lickert scale (1 = very good reduction of opioid withdrawal; 5 = no reduction of opioid withdrawal). Patients could also indicate a worsening of opioid withdrawal. Values (mean +/- SD) were: for benzodiazepines, 3.2 +/- 1.1; tricyclic antidepressants, 3.6 +/- 1.1; cannabis, 3.6 +/- 1.0; alcohol, 4.1 +/- 1.1; cocaine, 4.2 +/- 1.1; amphetamine, 4.4 +/- 0.9; nicotine, 4.7 +/- 0.7; and caffeine, 4.9 +/- 0.5. A worsening of opioid withdrawal was reported by 62% of the patients for cocaine, 62% for amphetamine, 50% for caffeine, 37.5% for cannabis, 27% for nicotine, 26% for alcohol, 8% for tricyclic antidepressants and 3% for benzodiazepines. Our study shows a low efficacy of non-opioid drugs in alleviating opioid withdrawal symptoms. The data basis of this study was good and the sample was suitable to be asked for estimations of drug-drug interactions. Of the patients, 26 - 62% even reported a worsening of opioid withdrawal for cannabis, alcohol, cocaine and amphetamine. Only benzodiazepines and tricyclic antidepressants were reported to have a moderate positive effect on opioid withdrawal.

What do providers want to know about opioid prescribing? A qualitative analysis of their questions.

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Cushman, Phoebe A; Liebschutz, Jane M; Hodgkin, Joseph G; Shanahan, Christopher W; White, Julie L; Hardesty, Ilana; Alford, Daniel P

2017-01-01

In 2012, the US Food and Drug Administration (FDA) responded to the opioid crisis with a Risk Evaluation and Mitigation Strategy, requiring manufacturers of extended-release/long-acting opioids to fund continuing medical education based on the "FDA Blueprint for Prescriber Education." Topics in the Blueprint are "Assessing Patients for Treatment," "Initiating Therapy, Modifying Dosing, and Discontinuing Use," "Managing Therapy," "Counseling Patients and Caregivers about Safe Use," "General Drug Information," and "Specific Drug Information." Based on the FDA Blueprint, Boston University School of Medicine's "Safe and Competent Opioid Prescribing Education" (SCOPE of Pain) offers live trainings for physicians and other prescribers. During trainings, participants submit written questions about the curriculum and/or their clinical experiences. The objective was to compare themes that arose from questions asked by SCOPE of Pain participants with content of the FDA Blueprint in order to evaluate how well the Blueprint answers prescribers' concerns. The authors conducted qualitative analyses of all 1309 questions submitted by participants in 29 trainings across 16 states from May 2013 to May 2015, using conventional content analysis to code the questions. Themes that emerged from participants' questions were then compared with the Blueprint. Most themes fell into the topic categories of the Blueprint. Five main themes diverged: Participants sought information on (1) safe alternatives to opioids, (2) overcoming barriers to safe opioid prescribing, (3) government regulations of opioid prescribing, (4) the role of marijuana in opioid prescribing, and (5) maintaining a positive provider-patient relationship while prescribing opioids. In addition to learning the mechanics of safe opioid prescribing, providers want to understand government regulations and effective patient communication skills. Aware of the limitations of opioids in managing chronic pain, providers seek advice

The current status of opioid maintenance treatment in France: a survey of physicians, patients, and out-of-treatment opioid users

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Benyamina A

2014-09-01

Full Text Available Amine Benyamina National Institute for Medical Research (INSERM U-669, Hôpital Universitaire Paul Brousse, 94804 Villejuif, France Aim: Project Access France was a national survey designed to provide real-world observations on the status of opioid dependence treatment in France. Methods: The views of physicians (n=100, patients (n=130, and out-of-treatment opioid users (n=33 were collected via interviews and questionnaires. Results: Physicians reported being moderately satisfied with treatment programs in their area (rating 6.9 out of 10. Most physicians (82% reported being concerned about misuse and diversion of medication-assisted treatment (MAT medications and 50% identified psychosocial/behavioral counseling as the key change that would most improve patient care. Among patients, the mean number of previous MAT episodes was low (1.5; 78% reported that it was easy to access a doctor to undergo MAT; 14% reported regularly or sometimes using heroin; misuse and diversion were reported in 15% and 39% of patients, respectively; and 57% of patients were not receiving psychosocial help. Out-of-treatment opioid users reported using drugs on a regular basis (42% regularly used heroin and cited 'not wanting to give up drugs completely' as the most frequent reason for staying out of MAT. Conclusion: This survey highlights a number of positive features of the open-access, GP-based treatment model for opioid dependence in France. Challenges remain with regard to continued misuse/diversion of MAT medications and limited patient access to psychosocial support. Keywords: opioid maintenance treatment, medication-assisted treatment, buprenorphine, methadone, buprenorphine–naloxone, France

Health service utilisation by people living with chronic non-cancer pain: findings from the Pain and Opioids IN Treatment (POINT) study.

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Nielsen, Suzanne; Campbell, Gabrielle; Peacock, Amy; Smith, Kimberly; Bruno, Raimondo; Hall, Wayne; Cohen, Milton; Degenhardt, Louisa

2016-11-01

Objective The aims of the present study were to describe the use, and barriers to the use, of non-medication pain therapies and to identify the demographic and clinical correlates of different non-opioid pain treatments. Methods The study was performed on a cohort (n=1514) of people prescribed pharmaceutical opioids for chronic non-cancer pain (CNCP). Participants reported lifetime and past month use of healthcare services, mental and physical health, pain characteristics, current oral morphine equivalent daily doses and financial and access barriers to healthcare services. Results Participants reported the use of non-opioid pain treatments, both before and after commencing opioid therapy. Services accessed most in the past month were complementary and alternative medicines (CAMs; 41%), physiotherapy (16%) and medical and/or pain specialists (15%). Higher opioid dose was associated with increased financial and access barriers to non-opioid treatment. Multivariate analyses indicated being younger, female and having private health insurance were the factors most commonly associated with accessing non-opioid treatments. Conclusions Patients on long-term opioid therapy report using multiple types of pain treatments. High rates of CAM use are concerning given limited evidence of efficacy for some therapies and the low-income status of most people with CNCP. Financial and insurance barriers highlight the importance of considering how different types of treatments are paid for and subsidised. What is known about the topic? Given concerns regarding long-term efficacy, adverse side-effects and risk of misuse and dependence, prescribing guidelines recommend caution in prescribing pharmaceutical opioids in cases of CNCP, typically advising a multidisciplinary approach to treatment. There is a range of evidence supporting different (non-drug) treatment approaches for CNCP to reduce pain severity and increase functioning. However, little is known about the non-opioid treatments

Endogenous Opioid Function and Responses to Morphine: The Moderating Effects of Anger Expressiveness.

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Burns, John W; Bruehl, Stephen; France, Christopher R; Schuster, Erik; Orlowska, Daria; Chont, Melissa; Gupta, Rajnish K; Buvanendran, Asokumar

2017-08-01

Long-term use of opioid analgesics may be ineffective or associated with significant negative side effects for some people. At present, there is no sound method of identifying optimal opioid candidates. Individuals with chronic low back pain (n = 89) and healthy control individuals (n = 102) underwent ischemic pain induction with placebo, opioid blockade (naloxone), and morphine in counterbalanced order. They completed the Spielberger Anger-Out subscale. Endogenous opioid function × Anger-out × Pain status (chronic pain, healthy control) interactions were tested for morphine responses to ischemic threshold, tolerance, and pain intensity (McGill Sensory and Affective subscales) and side effects. For individuals with chronic pain and healthy control participants, those with low endogenous opioid function and low anger-out scores exhibited the largest morphine analgesic responses, whereas those with high anger-out and low endogenous opioid function showed relatively weaker morphine analgesic responses. Further, individuals with chronic pain with low endogenous opioid function and low anger-out scores also reported the fewest negative effects to morphine, whereas those with low endogenous opioid function and high anger-out reported the most. Findings point toward individuals with chronic pain who may strike a favorable balance of good analgesia with few side effects, as well as those who have an unfavorable balance of poor analgesia and many side effects. We sought to identify optimal candidates for opioid pain management. Low back pain patients who express anger and also have deficient endogenous opioid function may be poor candidates for opioid therapy. In contrast, low back patients who tend not to express anger and who also have deficient endogenous opioid function may make optimal candidates for opioid therapy. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

Predicting opioid use disorder in patients with chronic pain who present to the emergency department.

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Gardner, Robert Andrew; Brewer, Kori L; Langston, Dennis B

2018-04-06

Emergency department (ED) patients with chronic pain challenge providers to make quick and accurate assessments without an in-depth pain management consultation. Emergency physicians need reliable means to determine which patients may receive opioid therapy without exacerbating opioid use disorder (OUD). Eighty-nine ED patients with a chief complaint of chronic pain were enrolled. Researchers administered questionnaires and reviewed medical and state prescription monitoring database information. Participants were classified as either OUD or non-OUD. Statistical analysis included a bivariate analysis comparing differences between groups and multivariate logistic regression evaluating ORs. The 45 participants categorised as OUD had a higher proportion of documented or reported psychiatric diagnoses (p=0.049), preference of opioid treatment (p = 0.005), current oxycodone prescription (p = 0.043), borrowed pain medicine (p=0.004) and non-authorised dose increase (pOUD group to have an increased number of opioid prescriptions (p=0.005) and pills (p=0.010). Participants who borrowed pain medicine and engaged in non-authorised dose increase were 5.2 (p=0.025, 95% CI 1.24 to 21.9) and 6.1 times (p=0.001, 95% CI 1.55 to 24.1) more likely to have OUD, respectively. Major limitations of our study include a small sample size, self-reported measures and convenience sample which may introduce selection bias. Patients with chronic pain with OUD have distinguishable characteristics. Emergency physicians should consider such evidence-based variables prior to opioid therapy to ameliorate the opioid crisis and limit implicit bias. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Prescription opioid abuse, pain and addiction: clinical issues and implications.

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Ling, Walter; Mooney, Larissa; Hillhouse, Maureen

2011-05-01

Prescription opioid misuse in the USA has increased over threefold since 1990 to epidemic proportions, with substantial increases in prescription opioid use also reported in other countries, such as Australia and New Zealand. The broad availability of prescription pain medications, coupled with public misconceptions about their safety and addictive potential, have contributed to the recent surge in non-medical use of prescription opioids and corresponding increases in treatment admissions for problems related to opioid misuse. Given competing pressures faced by physicians to both diagnose and treat pain syndromes and identify individuals at risk for addictive disorders, the use of opioids in the treatment of pain poses a significant clinical challenge. This paper reviews the interaction between pain and opioid addiction with a focus on clinical management issues, including risk factors for opioid dependence in patients with chronic pain and the use of assessment tools to identify and monitor at-risk individuals. Treatment options for opioid dependence and pain are reviewed, including the use of the partial µ agonist buprenorphine in the management of concurrent pain and opioid addiction. Physicians should strive to find a reasonable balance between minimising potential adverse effects of opioid medications without diminishing legitimate access to opioids for analgesia. The article discusses the need to identify methods for minimising risks and negative consequences associated with opioid analgesics and poses research directions, including the development of abuse-deterrent opioid formulations, genetic risk factors for opioid dependence and opioid-induced hyperalgesia as a potential target for medication therapy. © 2011 Australasian Professional Society on Alcohol and other Drugs.

The gut-brain interaction in opioid tolerance.

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Akbarali, Hamid I; Dewey, William L

2017-12-01

The prevailing opioid crisis has necessitated the need to understand mechanisms leading to addiction and tolerance, the major contributors to overdose and death and to develop strategies for developing drugs for pain treatment that lack abuse liability and side-effects. Opioids are commonly used for treatment of pain and symptoms of inflammatory bowel disease. The significant effect of opioids in the gut, both acute and chronic, includes persistent constipation and paradoxically may also worsen pain symptoms. Recent work has suggested a significant role of the gastrointestinal microbiome in behavioral responses to opioids, including the development of tolerance to its pain-relieving effects. In this review, we present current concepts of gut-brain interaction in analgesic tolerance to opioids and suggest that peripheral mechanisms emanating from the gut can profoundly affect central control of opioid function. Copyright © 2017 Elsevier Ltd. All rights reserved.

Definition, diagnosis and treatment strategies for opioid-induced bowel dysfunction-Recommendations of the Nordic Working Group.

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Drewes, Asbjørn M; Munkholm, Pia; Simrén, Magnus; Breivik, Harald; Kongsgaard, Ulf E; Hatlebakk, Jan G; Agreus, Lars; Friedrichsen, Maria; Christrup, Lona L

2016-04-01

Opioid-induced bowel dysfunction (OIBD) is an increasing problem due to the common use of opioids for pain worldwide. It manifests with different symptoms, such as dry mouth, gastro-oesophageal reflux, vomiting, bloating, abdominal pain, anorexia, hard stools, constipation and incomplete evacuation. Opioid-induced constipation (OIC) is one of its many symptoms and probably the most prevalent. The current review describes the pathophysiology, clinical implications and treatment of OIBD. The Nordic Working Group was formed to provide input for Scandinavian specialists in multiple, relevant areas. Seven main topics with associated statements were defined. The working plan provided a structured format for systematic reviews and included instructions on how to evaluate the level of evidence according to the GRADE guidelines. The quality of evidence supporting the different statements was rated as high, moderate or low. At a second meeting, the group discussed and voted on each section with recommendations (weak and strong) for the statements. The literature review supported the fact that opioid receptors are expressed throughout the gastrointestinal tract. When blocked by exogenous opioids, there are changes in motility, secretion and absorption of fluids, and sphincter function that are reflected in clinical symptoms. The group supported a recent consensus statement for OIC, which takes into account the change in bowel habits for at least one week rather than focusing on the frequency of bowel movements. Many patients with pain receive opioid therapy and concomitant constipation is associated with increased morbidity and utilization of healthcare resources. Opioid treatment for acute postoperative pain will prolong the postoperative ileus and should also be considered in this context. There are no available tools to assess OIBD, but many rating scales have been developed to assess constipation, and a few specifically address OIC. A clinical treatment strategy for OIBD

Opioid withdrawal signs and symptoms in children: frequency and determinants.

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Fisher, Deborah; Grap, Mary Jo; Younger, Janet B; Ameringer, Suzanne; Elswick, R K

2013-01-01

The purpose of this study was to, in a pediatric population, describe the frequency of opioid withdrawal signs and symptoms and to identify factors associated with these opioid withdrawal signs and symptoms. Opioids are used routinely in the pediatric intensive care population for analgesia, sedation, blunting of physiologic responses to stress, and safety. In children, physical dependence may occur in as little as 2-3 days of continuous opioid therapy. Once the child no longer needs the opioid, the medications are reduced over time. A prospective, descriptive study was conducted. The sample of 26 was drawn from all patients, ages 2 weeks to 21 years admitted to the Children's Hospital of Richmond pediatric intensive care unit (PICU) and who have received continuous infusion or scheduled opioids for at least 5 days. Data collected included: opioid withdrawal score (WAT-1), opioid taper rate (total dose of opioid per day in morphine equivalents per kilogram [MEK]), pretaper peak MEK, pretaper cumulative MEK, number of days of opioid exposure prior to taper, and age. Out of 26 enrolled participants, only 9 (45%) had opioid withdrawal on any given day. In addition, there was limited variability in WAT-1 scores. The most common symptoms notes were diarrhea, vomit, sweat, and fever. For optimal opioid withdrawal assessments, clinicians should use a validated instrument such as the WAT-1 to measure for signs and symptoms of opioid withdrawal. Further research is indicated to examine risk factors for opioid withdrawal in children. Copyright © 2013 Elsevier Inc. All rights reserved.

Gabapentin, opioids, and the risk of opioid-related death: A population-based nested case-control study.

Directory of Open Access Journals (Sweden)

Tara Gomes

2017-10-01

Full Text Available Prescription opioid use is highly associated with risk of opioid-related death, with 1 of every 550 chronic opioid users dying within approximately 2.5 years of their first opioid prescription. Although gabapentin is widely perceived as safe, drug-induced respiratory depression has been described when gabapentin is used alone or in combination with other medications. Because gabapentin and opioids are both commonly prescribed for pain, the likelihood of co-prescription is high. However, no published studies have examined whether concomitant gabapentin therapy is associated with an increased risk of accidental opioid-related death in patients receiving opioids. The objective of this study was to investigate whether co-prescription of opioids and gabapentin is associated with an increased risk of accidental opioid-related mortality.We conducted a population-based nested case-control study among opioid users who were residents of Ontario, Canada, between August 1, 1997, and December 31, 2013, using administrative databases. Cases, defined as opioid users who died of an opioid-related cause, were matched with up to 4 controls who also used opioids on age, sex, year of index date, history of chronic kidney disease, and a disease risk index. After matching, we included 1,256 cases and 4,619 controls. The primary exposure was concomitant gabapentin use in the 120 days preceding the index date. A secondary analysis characterized gabapentin dose as low (<900 mg daily, moderate (900 to 1,799 mg daily, or high (≥1,800 mg daily. A sensitivity analysis examined the effect of concomitant nonsteroidal anti-inflammatory drug (NSAID use in the preceding 120 days. Overall, 12.3% of cases (155 of 1,256 and 6.8% of controls (313 of 4,619 were prescribed gabapentin in the prior 120 days. After multivariable adjustment, co-prescription of opioids and gabapentin was associated with a significantly increased odds of opioid-related death (odds ratio [OR] 1.99, 95% CI

Gut Homeostasis, Microbial Dysbiosis, and Opioids.

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Wang, Fuyuan; Roy, Sabita

2017-01-01

Gut homeostasis plays an important role in maintaining animal and human health. The disruption of gut homeostasis has been shown to be associated with multiple diseases. The mutually beneficial relationship between the gut microbiota and the host has been demonstrated to maintain homeostasis of the mucosal immunity and preserve the integrity of the gut epithelial barrier. Currently, rapid progress in the understanding of the host-microbial interaction has redefined toxicological pathology of opioids and their pharmacokinetics. However, it is unclear how opioids modulate the gut microbiome and metabolome. Our study, showing opioid modulation of gut homeostasis in mice, suggests that medical interventions to ameliorate the consequences of drug use/abuse will provide potential therapeutic and diagnostic strategies for opioid-modulated intestinal infections. The study of morphine's modulation of the gut microbiome and metabolome will shed light on the toxicological pathology of opioids and its role in the susceptibility to infectious diseases.

Methylnaltrexone in the treatment of opioid-induced constipation

Directory of Open Access Journals (Sweden)

Beverley Greenwood-Van Meerveld

2008-12-01

Full Text Available Beverley Greenwood-Van Meerveld1, Kelly M Standifer21Veterans Affairs Medical Center, Oklahoma Center for Neuroscience, Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; 2Department of Pharmaceutical Sciences, Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USAAbstract: Constipation is a significant problem related to opioid medications used to manage pain. This review attempts to outline the latest findings related to the therapeutic usefulness of a μ opioid receptor antagonist, methylnaltrexone in the treatment of opioid-induced constipation. The review highlights methylnaltrexone bromide (RelistorTM; Progenics/Wyeth a quaternary derivative of naltrexone, which was recently approved in the United States, Europe and Canada. The Food and Drug Administration in the United States approved a subcutaneous injection for the treatment of opioid bowel dysfunction in patients with advanced illness who are receiving palliative care and when laxative therapy has been insufficient. Methylnaltrexone is a peripherally restricted, μ opioid receptor antagonist that accelerates oral–cecal transit in patients with opioidinduced constipation without reversing the analgesic effects of morphine or inducing symptoms of opioid withdrawal. An analysis of the mechanism of action and the potential benefits of using methylnaltrexone is based on data from published basic research and recent clinical studies.Keywords: methylnaltrexone, constipation, opioid

Opioid Use in Fibromyalgia Is Associated with Negative Health Related Measures in a Prospective Cohort Study

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Mary-Ann Fitzcharles

2013-01-01

Full Text Available As pain is the cardinal symptom of fibromyalgia (FM, strategies directed towards pain relief are an integral component of treatment. Opioid medications comprise a category of pharmacologic treatments which have impact on pain in various conditions with best evidence for acute pain relief. Although opioid therapy other than tramadol has never been formally tested for treatment of pain in FM, these agents are commonly used by patients. We have examined the effect of opioid treatments in patients diagnosed with FM and followed longitudinally in a multidisciplinary pain center over a period of 2 years. In this first study reporting on health related measures and opioid use in FM, opioid users had poorer symptoms and functional and occupational status compared to nonusers. Although opioid users may originally have had more severe symptoms at the onset of disease, we have no evidence that these agents improved status beyond standard care and may even have contributed to a less favourable outcome. Only a formal study of opioid use in FM will clarify this issue, but until then physicians must be vigilant regarding the multiple adverse consequences of opioid therapy.

Yiguanjian cataplasm attenuates opioid dependence in a mouse

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Gao, Shuai; Gao, Hong; Fan, Yuchen; Zhang, Guanghua; Sun, Fengkai; Zhao, Jing; Li, Feng; Yang, Yang; Wang, Kai

2016-08-01

To investigate the effect of Yiguanjian (YGJ) cataplasm on the development of opioid dependence in a mouse model of naloxone-induced opioid withdrawal syndrome. One hundred Swiss albino mice, of equal male to female ratio, were randomly and equally divided into 10 groups. A portion (3 cm2) of the backside hair of the mice was removed 1 day prior to the experiment. Morphine (5 mg/kg) was intraperitoneally administered twice daily for 5 days. YGJ cataplasm was prepared and pasted on the bare region of the mice immediately before morphine administration on day 3 and subsequently removed at the end day 5. On day 6, naloxone (8 mg/kg) was intraperitoneally injected to precipitate opioid withdrawal syndrome. Behavioral observation was performed in two 30-min phases immediately after naloxone injection. The YGJ cataplasm significantly and dose-dependently attenuated morphine-naloxone- induced experimental opioid withdrawal, in terms of withdrawal severity score and the frequencies of jumping, rearing, forepaw licking, and circling behaviors. However, YGJ cataplasm treatment did not alter the acute analgesic effect of morphine. YGJ cataplasm could attenuate opioid dependence and its associated withdrawal symptoms. Therefore, YGJ cataplasm could serve as a potential therapy for opioid addiction in the future.

Side effects and opioid addiction in radiation-induced mucositis pain control in head and neck cancer

International Nuclear Information System (INIS)

Takahashi, Atsuhito; Shoji, Kazuhiko; Mizuta, Masanobu; Morita, Mami; Iki, Takehiro; Kojima, Tsuyoshi

2011-01-01

Radiation therapy in head and neck malignancy may trigger mucositis poorly controlled by nonsteroidal antiinflammatory drugs (NSAIDs). Having already reported early opioid efficacy in radiation-induced mucositis pain in head and neck cancer, we discuss whether this resulted in severe side effects and opioid addiction. Of 11 persons (26.2%) with nausea, 3 could not tolerate opioid. Of 33 (78.6%) with constipation, all were controlled by purgatives. Seven had mild sleepiness. None had severe opioid side effects in radiation-induced mucositis pain treatment, but I showed opioid dependence after 128-days opioid administration. While opioid administration in radiation-induced mucositis pain may not cause addiction, lomg-term opioid use should be carefully monitored. (author)

Atypical Opioid Mechanisms of Control of Injury-Induced Cutaneous Pain by Delta Receptors

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2016-07-01

treat, and current opioids (i.e. mu opioid receptor agonists such as morphine) cause unacceptable side effects including addiction . Injuries suffered...treat, and current opioids that act on mu opioid receptors such as morphine generate significant side effects including addiction . War-related...al., J Neurosci Methods, 1994), starting with 0.1 g and ending with 2.0 g filament as cutoff value. As shown in Figure 2, our preliminary experiments

Newer approaches to opioid detoxification

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Siddharth Sarkar

2012-01-01

Full Text Available Opioid use disorders present with distressing withdrawal symptoms at the time of detoxification. The pharmacological agents and methods currently in use for detoxification mainly include buprenorphine, methadone, and clonidine. Many other pharmacological agents have been tried for opioid detoxification. This review takes a look at the newer pharmacological options, both opioid agonists and non-agonist medications that have been utilized for detoxification. Peer reviewed articles were identified using PubMed and PsychInfo databases. The keywords included for the search were a combination of ′opioid′ and ′detoxification′ and their synonyms. All the articles published in the last 10 years were screened for. Relevant data was extracted from identified studies. Many newer pharmacological agents have been tried in detoxification of opioids. However, the quest for a safe, efficacious, cost-effective pharmacological option which requires minimal monitoring still continues. The role of non-pharmacological measures and alternative medicine needs further evaluation.

Recent advances in acute pain management: understanding the mechanisms of acute pain, the prescription of opioids, and the role of multimodal pain therapy [version 1; referees: 3 approved

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Richa Wardhan

2017-11-01

Full Text Available In this review, we discuss advances in acute pain management, including the recent report of the joint American Pain Society and American Academy of Pain Medicine task force on the classification of acute pain, the role of psychosocial factors, multimodal pain management, new non-opioid therapy, and the effect of the “opioid epidemic”. In this regard, we propose that a fundamental principle in acute pain management is identifying patients who are most at risk and providing an “opioid free anesthesia and postoperative analgesia”. This can be achieved by using a multimodal approach that includes regional anesthesia and minimizing the dose and the duration of opioid prescription. This allows prescribing medications that work through different mechanisms. We shall also look at the recent pharmacologic and treatment advances made in acute pain and regional anesthesia.

The changing landscape of opioid prescribing: long-acting and extended-release opioid class-wide Risk Evaluation and Mitigation Strategy

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Gudin JA

2012-05-01

Full Text Available Jeffrey A GudinEnglewood Hospital and Medical Center, Englewood, NJ, USAAbstract: Prescriptions for opioid analgesics to manage moderate-to-severe chronic noncancer pain have increased markedly over the last decade, as have postmarketing reports of adverse events associated with opioids. As an unintentional consequence of greater prescription opioid utilization, there has been the parallel increase in misuse, abuse, and overdose, which are serious risks associated with all opioid analgesics. In response to these concerns, the Food and Drug Administration announced the requirement for a class-wide Risk Evaluation and Mitigation Strategy (REMS for long-acting and extended-release (ER opioid analgesics in April 2011. An understanding of the details of this REMS will be of particular importance to primary care providers. The class-wide REMS is focused on educating health care providers and patients on appropriate prescribing and safe use of ER opioids. Support from primary care will be necessary for the success of this REMS, as these clinicians are the predominant providers of care and the main prescribers of opioid analgesics for patients with chronic pain. Although currently voluntary, future policy will likely dictate that providers undergo mandatory training to continue prescribing medications within this class. This article outlines the elements of the class-wide REMS for ER opioids and clarifies the impact on primary care providers with regard to training, patient education, and clinical practice.Keywords: long-acting opioid, extended-release opioid, risk, REMS, FDA, primary care

Usefulness of the Brief Pain Inventory in Patients with Opioid Addiction Receiving Methadone Maintenance Treatment.

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Dennis, Brittany B; Roshanov, Pavel S; Bawor, Monica; Paul, James; Varenbut, Michael; Daiter, Jeff; Plater, Carolyn; Pare, Guillame; Marsh, David C; Worster, Andrew; Desai, Dipika; Thabane, Lehana; Samaan, Zainab

2016-01-01

opioid urine screens (estimated coefficient: 7.79; 95% CI 0.74, 14.85: P = 0.031) and a 4 times greater odds (odds ratio [OR]: 4.10 P = 0.008; 95% CI: 1.44, 11.63) of engaging in a "high risk" level of illicit opioids use. The prognostic relevance of pain classification was not maintained for the additional participants classified by the BPI (n = 143 discordant). These results suggest that while the BPI may be more sensitive in capturing pain among patients with opioid addiction, this tool is of less value for predicting the impact of pain on illicit opioid use for opioid addiction patients on methadone maintenance treatment. The GENOA CRF showed high predictive ability, whereby patients classified according to the GENOA CRF are at serious risk for opioid relapse. Using the appropriate tool to assess pain in opioid addiction may serve to improve the current detection and management of comorbid pain. We caution the interpretation of these result since they are still reflective of participants already maintained on an opioid substitution therapy (OST), which can largely differ from patients who drop out of methadone maintenance treatment (MMT) or never seek treatment altogether.

The Future of Opioid Agonist Therapies in Ukraine: A Qualitative Assessment of Multilevel Barriers and Ways Forward to Promote Retention in Treatment.

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Bojko, Martha J; Mazhnaya, Alyona; Marcus, Ruthanne; Makarenko, Iuliia; Islam, Zahedul; Filippovych, Sergey; Dvoriak, Sergii; Altice, Frederick L

2016-07-01

Opioid agonist therapies (OAT) to treat opioid addiction in people who inject drugs (PWID) began in Ukraine in 2004. Scale-up of OAT, however, has been hampered by both low enrollment and high attrition. To better understand the factors influencing OAT retention among PWID in Ukraine, qualitative data from 199 PWIDs were collected during 25 focus groups conducted in five Ukrainian cities from February to April 2013. The experiences of PWID who were currently or previously on OAT or currently trying to access OAT were analyzed to identify entry and retention barriers encountered. Transcribed data were analyzed using a grounded theory approach. Individual beliefs about OAT, particularly misaligned treatment goals between clients and providers, influenced PWID's treatment seeking behaviors. Multiple programmatic and structural issues, including inconvenient hours and treatment site locations, complicated dosing regimens, inflexible medication dispensing guidelines, and mistreatment by clinic and medical staff also strongly influenced OAT retention. Findings suggest the need for both programmatic and policy-level structural changes such as revising legal regulations covering OAT dispensing, formalizing prescription dosing policies and making OAT more available through other sites, including primary care settings as a way to improve treatment retention. Quality improvement interventions that target treatment settings could also be deployed to overcome healthcare delivery barriers. Additional patient education and medical professional development around establishing realistic treatment goals as well as community awareness campaigns that address the myths and fears associated with OAT can be leveraged to overcome individual, family and community-level barriers. Copyright © 2016 Elsevier Inc. All rights reserved.

Cost of provision of opioid substitution therapy provision in Tijuana, Mexico.

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Burgos, Jose Luis; Cepeda, Javier A; Kahn, James G; Mittal, Maria Luisa; Meza, Emilio; Lazos, Raúl Rafael Palacios; Vargas, Psyché Calderón; Vickerman, Peter; Strathdee, Steffanie A; Martin, Natasha K

2018-05-23

Mexico recently enacted drug policy reform to decriminalize possession of small amounts of illicit drugs and mandated that police refer identified substance users to drug treatment. However, the economic implications of drug treatment expansion are uncertain. We estimated the costs of opioid substitution therapy (OST) provision in Tijuana, Mexico, where opioid use and HIV are major public health concerns. We adopted an economic health care provider perspective and applied an ingredients-based micro-costing approach to quantify the average monthly cost of OST (methadone maintenance) provision at two providers (one private and one public) in Tijuana, Mexico. Costs were divided by type of input (capital, recurrent personnel and non-personnel). We defined "delivery cost" as all costs except for the methadone and compared total cost by type of methadone (powdered form or capsule). Cost data were obtained from interviews with senior staff and review of expenditure reports. Service provision data were obtained from activity logs and senior staff interviews. Outcomes were cost per OST contact and cost per person month of OST. We additionally collected information on patient charges for OST provision from published rates. The total cost per OST contact at the private and public sites was $3.12 and $5.90, respectively, corresponding to $95 and $179 per person month of OST. The costs of methadone delivery per OST contact were similar at both sites ($2.78 private and $3.46 public). However, cost of the methadone itself varied substantially ($0.34 per 80 mg dose [powder] at the private site and $2.44 per dose [capsule] at the public site). Patients were charged $1.93-$2.66 per methadone dose. The cost of OST provision in Mexico is consistent with other upper-middle income settings. However, evidenced-based (OST) drug treatment facilities in Mexico are still unaffordable to most people who inject drugs.

New developments in managing opioid addiction: impact of a subdermal buprenorphine implant

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Itzoe M

2017-05-01

Full Text Available MariaLisa Itzoe, Michael Guarnieri Department of Neurological Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA Abstract: Opioid addiction to prescription and illicit drugs is a serious and growing problem. In the US alone, >2.4 million people suffer from opioid use disorder. Government and pharmaceutical agencies have begun to address this crisis with recently released and revised task forces and medication-assisted therapies (MAT. For decades, oral or intravenous (IV MATs have helped patients in their recovery by administration of opioid agonists (methadone, buprenorphine, oxycodone, antagonists (naltrexone, naloxone, and combinations of the two (buprenorphine/naloxone. While shown to be successful, particularly when combined with psychological counseling, oral and IV forms of treatment come with constraints and challenges. Patients can become addicted to the agonists themselves, and there is increased risk for diversion, abuse, or missed dosages. Consequently, long-acting implants have begun to be developed as a potentially preferable method of agonist delivery. To date, the newest implant approved by the US Food and Drug Administration (May 2016 is Probuphine®, which delivers steady-state levels of buprenorphine over the course of 6 months. Numerous studies have demonstrated its efficacy and safety. Yet, implants come with their own risks such as surgical site irritation, possible movement, and protrusion of implant out of skin. This review introduces the opioid abuse epidemic, examines existing medications used for therapy, and highlights Probuphine as a new treatment option. Costs associated with MATs are also discussed. Keywords: addiction, opioids, medication-assisted therapy, long-acting implant, buprenorphine, Probuphine®

A Systematic Review on the Use of Psychosocial Interventions in Conjunction With Medications for the Treatment of Opioid Addiction.

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Dugosh, Karen; Abraham, Amanda; Seymour, Brittany; McLoyd, Keli; Chalk, Mady; Festinger, David

2016-01-01

Opioid use and overdose rates have risen to epidemic levels in the United States during the past decade. Fortunately, there are effective medications (ie, methadone, buprenorphine, and oral and injectable naltrexone) available for the treatment of opioid addiction. Each of these medications is approved for use in conjunction with psychosocial treatment; however, there is a dearth of empirical research on the optimal psychosocial interventions to use with these medications. In this systematic review, we outline and discuss the findings of 3 prominent prior reviews and 27 recent publications of empirical studies on this topic. The most widely studied psychosocial interventions examined in conjunction with medications for opioid addiction were contingency management and cognitive behavioral therapy, with the majority focusing on methadone treatment. The results generally support the efficacy of providing psychosocial interventions in combination with medications to treat opioid addictions, although the incremental utility varied across studies, outcomes, medications, and interventions. The review highlights significant gaps in the literature and provides areas for future research. Given the enormity of the current opioid problem in the United States, it is critical to gain a better understanding of the most effective ways to deliver psychosocial treatments in conjunction with these medications to improve the health and well-being of individuals suffering from opioid addiction.

Influence of intravenous opioid dose on postoperative ileus.

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Barletta, Jeffrey F; Asgeirsson, Theodor; Senagore, Anthony J

2011-07-01

Intravenous opioids represent a major component in the pathophysiology of postoperative ileus (POI). However, the most appropriate measure and threshold to quantify the association between opioid dose (eg, average daily, cumulative, maximum daily) and POI remains unknown. To evaluate the relationship between opioid dose, POI, and length of stay (LOS) and identify the opioid measure that was most strongly associated with POI. Consecutive patients admitted to a community teaching hospital who underwent elective colorectal surgery by any technique with an enhanced-recovery protocol postoperatively were retrospectively identified. Patients were excluded if they received epidural analgesia, developed a major intraabdominal complication or medical complication, or had a prolonged workup prior to surgery. Intravenous opioid doses were quantified and converted to hydromorphone equivalents. Classification and regression tree (CART) analysis was used to determine the dosing threshold for the opioid measure most associated with POI and define high versus low use of opioids. Risk factors for POI and prolonged LOS were determined through multivariate analysis. The incidence of POI in 279 patients was 8.6%. CART analysis identified a maximum daily intravenous hydromorphone dose of 2 mg or more as the opioid measure most associated with POI. Multivariate analysis revealed maximum daily hydromorphone dose of 2 mg or more (p = 0.034), open surgical technique (p = 0.045), and days of intravenous narcotic therapy (p = 0.003) as significant risk factors for POI. Variables associated with increased LOS were POI (p POI and prolonged LOS, particularly when the maximum hydromorphone dose per day exceeds 2 mg. Clinicians should consider alternative, nonopioid-based pain management options when this occurs.

Evolving paradigms in the treatment of opioid-induced bowel dysfunction.

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Poulsen, Jakob Lykke; Brock, Christina; Olesen, Anne Estrup; Nilsson, Matias; Drewes, Asbjørn Mohr

2015-11-01

In recent years prescription of opioids has increased significantly. Although effective in pain management, bothersome gastrointestinal adverse effects are experienced by a substantial proportion of opioid-treated patients. This can lead to difficulties with therapy and subsequently inadequate pain relief. Collectively referred to as opioid-induced bowel dysfunction, these adverse effects are the result of binding of exogenous opioids to opioid receptors in the gastrointestinal tract. This leads to disturbance of three important gastrointestinal functions: motility, coordination of sphincter function and secretion. In the clinic this manifests in a wide range of symptoms such as reflux, bloating, abdominal cramping, hard, dry stools, and incomplete evacuation, although the most known adverse effect is opioid-induced constipation. Traditional treatment with laxatives is often insufficient, but in recent years a number of novel pharmacological approaches have been introduced. In this review the pathophysiology, symptomatology and prevalence of opioid-induced bowel dysfunction is presented along with the benefits and caveats of a suggested consensus definition for opioid-induced constipation. Finally, traditional treatment is appraised and compared with the latest pharmacological developments. In conclusion, opioid antagonists restricted to the periphery show promising results, but use of different definitions and outcome measures complicate comparison. However, an international working group has recently suggested a consensus definition for opioid-induced constipation and relevant outcome measures have also been proposed. If investigators within this field adapt the suggested consensus and include symptoms related to dysfunction of the upper gut, it will ease comparison and be a step forward in future research.

Opioid intoxication

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... easily result in intoxication. The provider prescribes a sleep medicine (sedative) in addition to the opioid. The provider ... an opioid with certain other drugs, such as sleep medicines or alcohol Taking the opioid in ways not ...

[Opioid therapy for chronic noncancer pain: retrospective analysis of patients hospitalized for withdrawal].

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Faure, Delinger; Giniès, Patrick; Eiden, Céline; Portet, Laure; Peyrière, Hélène

2013-01-01

The prescription of opioids for the treatment of chronic non-cancer pain (CNCP) is not recommended for all of them, and can expose the patients to a benefit/risk ratio unfavorable. The objective of this study was to evaluate the management of patients hospitalized at the centre for evaluation and treatment of pain for opioid withdrawal, their outcome during hospitalization. This is a retrospective descriptive study. The medical record of each patient was consulted to identify relevant data (demographics, treatments at the entrance and discharge of hospitalization, comorbidities, rating scale of pain). During the study period (3 years), 53 patients (64% of women), with a median age of 52 years, were included. Pain was mainly back pain and neck pain (52%). Morphine (43%) and fentanyl (42%) were the most frequently used opioids. At admission, 62% of patients had a depressive state. At hospital discharge, withdrawal was total in 18 patients (34%) and a total improvement of pain was observed for 19% of them. In this study, 57% of patients received, at admission to hospital, an opioid other than morphine in the treatment of CNCP. The management of pain offered by the pain clinic led to a total or partial opioid withdrawal in 94% of patients. © 2013 Société Française de Pharmacologie et de Thérapeutique.

Designing an automated clinical decision support system to match clinical practice guidelines for opioid therapy for chronic pain

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Clark Michael E

2010-04-01

Full Text Available Abstract Background Opioid prescribing for chronic pain is common and controversial, but recommended clinical practices are followed inconsistently in many clinical settings. Strategies for increasing adherence to clinical practice guideline recommendations are needed to increase effectiveness and reduce negative consequences of opioid prescribing in chronic pain patients. Methods Here we describe the process and outcomes of a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS to encourage good opioid prescribing practices during primary care visits. We based the DSS on the existing ATHENA-DSS. We used an iterative process of design, testing, and revision of the DSS by a diverse team including guideline authors, medical informatics experts, clinical content experts, and end-users to convert the written clinical practice guideline into a computable algorithm to generate patient-specific recommendations for care based upon existing information in the electronic medical record (EMR, and a set of clinical tools. Results The iterative revision process identified numerous and varied problems with the initially designed system despite diverse expert participation in the design process. The process of operationalizing the guideline identified areas in which the guideline was vague, left decisions to clinical judgment, or required clarification of detail to insure safe clinical implementation. The revisions led to workable solutions to problems, defined the limits of the DSS and its utility in clinical practice, improved integration into clinical workflow, and improved the clarity and accuracy of system recommendations and tools. Conclusions Use of this iterative process led to development of a multifunctional DSS that met the approval of the clinical practice guideline authors, content experts, and clinicians involved in testing. The

The role of opioid antagonist efficacy and constitutive opioid receptor activity in the opioid withdrawal syndrome in mice

OpenAIRE

Navani, Dipesh M.; Sirohi, Sunil; Madia, Priyanka A.; Yoburn, Byron C.

2011-01-01

On the basis of efficacy, opioid antagonists are classified as inverse opioid agonists (e.g. naltrexone) or neutral opioid antagonists (e.g. 6β-naltrexol). This study examined the interaction between naltrexone and 6β-naltrexol in the precipitated opioid withdrawal syndrome in morphine dependent mice. Furthermore, the possible contribution of constitutive opioid receptor activity to precipitated withdrawal was evaluated using increasing levels of morphine dependence. In the first experiment, ...

Radioreceptor opioid assay

International Nuclear Information System (INIS)

Miller, R.J.; Chang, K.-J.

1981-01-01

A radioreceptor assay is described for assaying opioid drugs in biological fluids. The method enables the assay of total opioid activity, being specific for opioids as a class but lacking specificity within the class. A radio-iodinated opioid and the liquid test sample are incubated with an opiate receptor material. The percentage inhibition of the binding of the radio-iodinated compound to the opiate receptor is calculated and the opioid activity of the test liquid determined from a standard curve. Examples of preparing radio-iodinated opioids and assaying opioid activity are given. A test kit for the assay is described. Compared to other methods, this assay is cheap, easy and rapid. (U.K.)

Validation and usefulness of the Danish version of the Pain Medication Questionnaire in opioid-treated chronic pain patients

DEFF Research Database (Denmark)

Højsted, J; Nielsen, P R; Kendall, S

2011-01-01

Addiction is a feared complication of long-term opioid therapy for chronic pain patients. A screening tool to assess the potential risk of addiction may be helpful.......Addiction is a feared complication of long-term opioid therapy for chronic pain patients. A screening tool to assess the potential risk of addiction may be helpful....

The effect of benfotiamine on mu-opioid receptor mediated antinociception in experimental diabetes.

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Nacitarhan, C; Minareci, E; Sadan, G

2014-03-01

Diabetic neuropathy is a prevalent, disabling disorder. Currently, the only treatments available to patients with diabetic neuropathy are glucose control and pain management. B vitamin present neuroprotective effects, which are suggested to be related to their analgesic action in various models of neuropathic pain. According to our literature knowledge there is no report about antinociceptive effects of thiamine as benfotiamine and opioids together in diabetic mice. The purpose of this study was to determine the effects of benfotiamine on the antinociception produced by mu-opioid receptor agonist fentanyl in diabetic mice. The effects of benfotiamine on antinociception produced by fentanyl in diabetic mice were studied in 4 groups. Antinociceptive effect was determined with tail flick, hot plate and formalin test. Our results showed that, mu-opioid agonist fentanyl in benfotiamine applied diabetic group caused more potent antinociceptive effect than in diabetic group without benfotiamine treatment. In brief benfotiamine supplement in diet did not bring out antinociceptive effect itself, but during development of STZ diabetes, benfotiamine replacement increased the antinociceptive effect of fentanyl in mice tail-flick test. This effect is probably due to the replacement of benfotiamine efficiency occurring in diabetes mellitus. Finally, we suppose that oral benfotiamine replacement therapy may be useful to ameliorate analgesic effect of mu-opioid agonists on neuropathic pain in diabetic case. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

Opioids in Cancer Pain: Right or Privilege?

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Jackson, Leanne K; Imam, Syed N; Braun, Ursula K

2017-09-01

Opioid analgesia is a mainstay of the treatment of cancer pain. Treatment of pain in patients with cancer with an ongoing substance abuse disorder can be difficult. We report the ethical challenges of treating a patient with cancer with a concomitant substance abuse disorder in an outpatient palliative care setting. We present an analysis of ethical considerations for the palliative care physician and strategies to aid in the successful treatment of such patients. We argue that there are select patients with cancer for whom exclusion from treatment with opioid therapy is warranted if their health is endangered by prescription of these medications.

Constipation Prophylaxis Is Rare for Adults Prescribed Outpatient Opioid Therapy From U.S. Emergency Departments.

Science.gov (United States)

Hunold, Katherine M; Smith, Samantha A; Platts-Mills, Timothy F

2015-09-01

Constipation is a common and potentially serious side effect of oral opioids. Accordingly, most clinical guidelines suggest routine use of laxatives to prevent opioid-induced constipation. The objective was to characterize emergency provider prescribing of laxatives to prevent constipation among adults initiating outpatient opioid treatment. National Hospital Ambulatory Medical Care Survey (NHAMCS) data from 2010 were analyzed. Among visits by individuals aged 18 years and older discharged from the emergency department (ED) with opioid prescriptions, the authors estimated the survey-weighted proportion of visits in which laxatives were also prescribed. A subgroup analysis was conducted for individuals aged 65 years and older, as the potential risks associated with opioid-induced constipation are greater among older individuals. To examine a group expected to be prescribed laxative medication and confirm that NHAMCS captures prescriptions for these medications, the authors estimated the proportion of visits by individuals discharged with prescriptions for laxatives among those who presented with constipation. Among visits in 2010 by adults aged 18 years and older discharged from the ED with opioid prescriptions, 0.9% (95% confidence interval [CI] = 0.7% to 1.3%, estimated total n = 191,203 out of 21,075,050) received prescriptions for laxatives. Among the subset of visits by adults aged 65 years and older, 1.0% (95% CI = 0.5% to 2.0%, estimated total n = 18,681 out of 1,904,411) received prescriptions for laxatives. In comparison, among visits by individuals aged 18 years and older with constipation as a reason for visit, 42% received prescriptions for laxatives. In this nationally representative sample, laxatives were not routinely prescribed to adults discharged from the ED with prescriptions for opioid pain medications. Routine prescribing of laxatives for ED visits may improve the safety and effectiveness of outpatient opioid pain management. © 2015 by the

β-Arrestin-2 knockout prevents development of cellular μ-opioid receptor tolerance but does not affect opioid-withdrawal-related adaptations in single PAG neurons.

Science.gov (United States)

Connor, M; Bagley, E E; Chieng, B C; Christie, M J

2015-01-01

Tolerance to the behavioural effects of morphine is blunted in β-arrestin-2 knockout mice, but opioid withdrawal is largely unaffected. The cellular mechanisms of tolerance have been studied in some neurons from β-arrestin-2 knockouts, but tolerance and withdrawal mechanisms have not been examined at the cellular level in periaqueductal grey (PAG) neurons, which are crucial for central tolerance and withdrawal phenomena. μ-Opioid receptor (MOPr) inhibition of voltage-gated calcium channel currents (ICa ) was examined by patch-clamp recordings from acutely dissociated PAG neurons from wild-type and β-arrestin-2 knockout mice treated chronically with morphine (CMT) or vehicle. Opioid withdrawal-induced activation of GABA transporter type 1 (GAT-1) currents was determined using perforated patch recordings from PAG neurons in brain slices. MOPr inhibition of ICa in PAG neurons was unaffected by β-arrestin-2 deletion. CMT impaired coupling of MOPrs to ICa in PAG neurons from wild-type mice, but this cellular tolerance was not observed in neurons from CMT β-arrestin-2 knockouts. However, β-arrestin-2 knockouts displayed similar opioid-withdrawal-induced activation of GAT-1 currents as wild-type PAG neurons. In β-arrestin-2 knockout mice, the central neurons involved in the anti-nociceptive actions of opioids also fail to develop cellular tolerance to opioids following chronic morphine. The results also provide the first cellular physiological evidence that opioid withdrawal is not disrupted by β-arrestin-2 deletion. However, the unaffected basal sensitivity to opioids in PAG neurons provides further evidence that changes in basal MOPr sensitivity cannot account for the enhanced acute nociceptive response to morphine reported in β-arrestin-2 knockouts. This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2. © 2014 The British

Opioid-induced hyponatremia in a patient with central diabetes insipidus: independence from ADH.

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Bhat, Nandini; Balliu, Erjola; Osipoff, Jennifer; Lane, Andrew; Wilson, Thomas

2017-05-24

Hyponatremia can be a complication of opioid therapy, which has been postulated to occur secondary to inappropriate antidiuretic hormone secretion (syndrome of inappropriate antidiuretic hormone secretion [SIADH]). We report severe hyponatremia following wisdom teeth extraction with opioid analgesia in a 19-year-old female with diabetes insipidus (DI) and acquired panhypopituitarism that challenges this theory. As this patient has DI, we believe opioid treatment caused severe hyponatremia by the following mechanisms: (1) Opioids have a direct antidiuretic effect independent of changes in ADH, as demonstrated in Brattleboro rats with central DI. (2) Hydrocodone may have stimulated this patient's thirst center contributing to hyponatremia, as demonstrated in animal studies. Opioid use can cause hyponatremia in patients independent of ADH. It is important for clinicians to be aware of this so that patients can be appropriately counseled.

Opioid Addiction: Social Problems Associated and Implications of Both Current and Possible Future Treatments, including Polymeric Therapeutics for Giving Up the Habit of Opioid Consumption.

Science.gov (United States)

Benéitez, M Cristina; Gil-Alegre, M Esther

2017-01-01

Detoxification programmes seek to implement the most secure and compassionate ways of withdrawing from opiates so that the inevitable withdrawal symptoms and other complications are minimized. Once detoxification has been achieved, the next stage is to enable the patient to overcome his or her drug addiction by ensuring consumption is permanently and completely abandoned, only after which can the subject be regarded as fully recovered. A systematic search on the common databases of relevant papers published until 2016 inclusive. Our study of the available oral treatments for opioid dependence has revealed that no current treatment can actually claim to be fully effective. These treatments require daily oral administration and, consequently, regular visits to dispensaries, which in most cases results in a lack of patient compliance, which causes fluctuations in drug plasma levels. We then reviewed alternative treatments in the available scientific literature on polymeric sustained release formulations. Research has been done not only on release systems for detoxification but also on release systems for giving up the habit of taking opioids. These efforts have obtained the recent authorization of polymeric systems for use in patients that could help them to reduce their craving for drugs.

Reviewing opioid use, monitoring, and legislature: Nursing perspectives

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Deniece A. Jukiewicz

2017-10-01

Full Text Available The phenomena of prescription opioid misuse and abuse have a complicated history of contributing factors including policies, practices, and prescribing leading to contemporary phenomena. Some factors implicated in the opioid drug abuse problem include inefficient prescribing and improper use, lack of knowledge related to interpretation and assessment of pain levels, and decreased oversight and regulation from government and policy agents. Nurses, often frontline providers, need to be knowledgeable and embrace the guidelines, and necessary implications associated with both prescribing and administration of opioids. Additionally, all providers including physicians, physician assistants, nurse practitioners, and bedside nurses must have a firm understanding of the improper use and abuse of opioids. The examination and review of opioid policies at the state and federal level has revealed inconsistency with regulations, policies, and guidelines that have lead to the current situation. The use of an interdisciplinary team with nurses and various other practitioners is a good strategy to help reduce this problem. Keywords: Abuse, Administration, Legislature, Nursing, Opioid, Overdose, Policy, Prescribing

Increased Burden of Healthcare Utilization and Cost Associated with Opioid-Related Constipation Among Patients with Noncancer Pain

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Fernandes, Ancilla W.; Kern, David M.; Datto, Catherine; Chen, Yen-Wen; McLeskey, Charles; Tunceli, Ozgur

2016-01-01

Background Opioids are widely accepted as treatment for moderate to severe pain, and opioid-induced constipation is one of the most common side effects of opioids. This side effect negatively affects pain management and patients’ quality of life, which could result in increased healthcare utilization and costs. Objective To assess healthcare utilization and costs (all-cause, constipation-related, and pain-related) for individuals with and without opioid-induced constipation during the 12 months after initiation of opioid therapy for noncancer pain. Methods This retrospective cohort study was conducted using administrative claims data from HealthCore Integrated Research Environment between January 1, 2006, and June 30, 2014. The analysis was limited to patients aged ≥18 years who filled a prescription for continuous opioid treatment (≥28 days) for noncancer pain. Propensity scores were used to match opioid users with constipation (cohort 1) and opioid users without constipation (cohort 2), using a 1:1 ratio. Generalized linear models were used to estimate all-cause, constipation-related, and pain-related healthcare utilization and costs during the 12 months after the initiation of opioid therapy. Results After matching and balancing for all prespecified variables, 17,384 patients were retained in each cohort (mean age, 56 years; 63% female). Opioid users with constipation were twice as likely as those without constipation to have ≥1 inpatient hospitalizations (odds ratio, 2.28; 95% confidence interval [CI], 2.17–2.39) during the 12 months. The total mean adjusted overall costs per patient during the study period were $12,413 higher for patients with constipation versus those without it (95% CI, $11,726–$13,116). The total mean adjusted overall pain-related costs per patient were $6778 (95% CI, $6293–$7279) higher for the patients with constipation than those without. Among patients using opioids for noncancer pain, the annual mean constipation

Comparison of the risks of shopping behavior and opioid abuse between tapentadol and oxycodone and association of shopping behavior and opioid abuse.

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Cepeda, M Soledad; Fife, Daniel; Kihm, Mary A; Mastrogiovanni, Greg; Yuan, Yingli

2014-12-01

This study compared the risks of opioid shopping behavior and opioid abuse between tapentadol immediate release and oxycodone immediate release and, to validate the definition of shopping, examined the association between opioid shopping and opioid abuse further. This retrospective cohort study using linked dispensing and diagnosis databases followed opioid-naive patients for development of shopping behavior and/or opioid abuse during 1 year after initial exposure to tapentadol or oxycodone. Shopping was defined by having overlapping opioid prescriptions from >1 prescriber filled at ≥3 pharmacies; abuse by having International Classification of Diseases, 9th revision diagnoses reflecting opioid abuse, addiction, or dependence. To determine their association, we cross-tabulated shopping and opioid abuse and calculated odds ratios. Risks of developing each outcome were estimated using logistic regression. Among 277,401 participants initiating opioid use with tapentadol (39,524) or oxycodone (237,877), 0.6% developed shopping behavior, 0.75% developed abuse. Higher proportions of patients in the oxycodone group developed shopping behavior and abuse than in the tapentadol group (shopping: adjusted odds ratio [95% confidence interval], 0.45 [0.36-0.55]; abuse: 0.44 [0.37-0.54]). Shopping behavior and abuse were associated; of those with shopping behavior, 6.5% had abuse. Age (18 to 64 y), sex (male), prior benzodiazepine use, paying cash, and history (mood disorders, abuse of nonopioid medications, and back pain) were risk factors for developing either outcome. Shopping behavior and abuse measure complementary, but associated, constructs, which further validates the current definition of shopping. The risk of developing either is lower among patients who initiate opioid use with tapentadol than those who initiate opioid use with oxycodone.

Mu Opioid Receptor Gene: New Point Mutations in Opioid Addicts

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Amin Dinarvand

2014-02-01

Full Text Available Introduction: Association between single-nucleotide polymorphisms (SNPs in mu opioid receptor gene and drug addiction has been shown in various studies. Here, we have evaluated the existence of polymorphisms in exon 3 of this gene in Iranian population and investigated the possible association between these mutations and opioid addiction.  Methods: 79 opioid-dependent subjects (55 males, 24 females and 134 non-addict or control individuals (74 males, 60 females participated in the study. Genomic DNA was extracted from volunteers’ peripheral blood and exon 3 of the mu opioid receptor gene was amplified by polymerase chain reaction (PCR whose products were then sequenced.  Results: Three different heterozygote polymorphisms were observed in 3 male individuals: 759T>C and 877G>A mutations were found in 2 control volunteers and 1043G>C substitution was observed in an opioid-addicted subject. Association between genotype and opioid addiction for each mutation was not statistically significant.  Discussion: It seems that the sample size used in our study is not enough to confirm or reject any association between 759T>C, 877G>A and 1043G>C substitutions in exon 3 of the mu opioid receptor gene and opioid addiction susceptibility in Iranian population.

Studies on the optimization of leukemia and non-Hodgkin lymphoma therapies using opioids, chemotherapy and radioimmunotherapy

International Nuclear Information System (INIS)

Roscher, Mareike

2013-01-01

Despite complex treatment schedules for cancer, the occurrence of resistances and relapses is a major concern in oncology. Hence, novel treatment options are needed. In this thesis, different approaches using radioimmunotherapy and the opioid D,L-methadone alone or in combination with doxorubicin were analyzed regarding their cytotoxic potential and the triggered signalling pathways in sensitive and resistant leukaemia and non-Hodgkin lymphoma (NHL). The radioimmunoconjugates [Bi-213]anti-CD33 and [Bi-213]anti-CD20 for treatment of acute myeloid leukaemia (AML) or NHL, respectively, were applied exemplary for the use of targeted alpha-therapies (TAT). Depending on the analyzed cell lines, the used activity concentrations and specific activities (MBq/μg antibody) apoptosis was induced abrogating radio- and chemo-cross-resistances specifically. The cell death was caspase-dependent activating the mitochondrial pathway and was executed by downregulation of the anti-apoptotic proteins XIAP and Bcl-xL. D,L-Methadone induces apoptosis in vitro and in vivo in opioid-receptor (OR) expressing cells depending on the OR density and the used concentrations. Resistances could be overcome and proliferation was inhibited. In combination with doxorubicin, a synergistic effect regarding cytotoxicity in ex vivo patient cells and cell lines was observed. This effect depends on the increase of doxorubicin uptake co-administering D,L-methadone whereas doxorubicin enhances OR expression. The activation of OR leads to the downregulation of cAMP playing a pivotal role in apoptosis induction. In vivo, the therapeutic potential of D,L-methadone alone or in combination with doxorubicin could be proven as mice transplanted with human T-ALL-cells could be identified as tumour free. In summary, these studies show that TAT using [Bi-213]anti-CD33 and [Bi-213]anti-CD20 as well as the opioid D,L-methadone harbour the potential to optimize conventional treatment modalities for leukaemia and NHL.

Chimeric opioid peptides: Tools for identifying opioid receptor types

International Nuclear Information System (INIS)

Xie, G.; Miyajima, A.; Yokota, T.; Arai, K.; Goldstein, A.

1990-01-01

The authors synthesized several chimeric [125J-labelled] peptides in which the N-terminal nine residues of dynorphin-32, a peptide selective for the κ opioid receptor, were replaced by opioid peptides selective for other opioid receptor types. Each chimeric peptide retained the high affinity and type selectivity characteristic of its N-terminal sequence. The common C-terminal two-thirds of the chimeric peptides served as an epitope recognized by the same monoclonal antibody. When bound to receptors on a cell surface or membrane preparation, these peptides could still bind specifically to the monoclonal antibody. These chimeric peptides should be useful for isolating μ, δ, and κ opioid receptors and for identifying opioid receptors on transfected cells in expression cloning procedures. The general approach using chimeric peptides should be applicable to other peptide receptors

Good clinical practice guide for opioids in pain management: the three Ts - titration (trial, tweaking (tailoring, transition (tapering

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Flaminia Coluzzi

2016-06-01

Full Text Available ABSTRACT BACKGROUND AND OBJECTIVES: Achieving good clinical practice in the use of opioids as part of a comprehensive pain management regimen can face significant challenges. Despite guidelines from governmental and pain society/organization sources, there are still significant hurdles. A review of some basic tenets of opioid analgesia based on current published knowledge and experiences about this important healthcare imperative is warranted. CONTENT: Consistent with guidelines, the literature supports using the lowest total opioid dose that provides adequate pain control with the fewest adverse effects. Titration (or trial during opioid initiation is a way of starting low and going slow (and assessing the appropriateness of a specific opioid and formulation. Recognizing that multiple factors contribute to an individual's personal experience of pain, the physical, psychological, social, cultural, spiritual, pharmacogenomic, and behavioral factors of the individual patient should be taken into account (tweaking, or tailoring. Finally, for those patients for whom transition (tapering from opioid is desired, doing so too rapidly can have negative consequences and minimization of problems during this step can be achieved by proper tapering. CONCLUSION: We conclude that a simultaneously aggressive, yet conservative, approach is advocated in the literature in which opioid therapy is divided into three key steps (the 3 T's: titration (or trial, tweaking (or tailoring, and transition (or tapering. Establishment of the 3 T's along with the application of other appropriate good medical practice and clinical experience/judgment, including non-pharmacologic approaches, can assist healthcare providers in the effort to achieve optimal management of pain.

High-Dose Opioid Prescribing and Opioid-Related Hospitalization: A Population-Based Study.

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Kimberly Fernandes

Full Text Available To examine the impact of national clinical practice guidelines and provincial drug policy interventions on prevalence of high-dose opioid prescribing and rates of hospitalization for opioid toxicity.Interventional time-series analysis.Ontario, Canada, from 2003 to 2014.Ontario Drug Benefit (ODB beneficiaries aged 15 to 64 years from 2003 to 2014.Publication of Canadian clinical practice guidelines for use of opioids in chronic non-cancer pain (May 2010 and implementation of Ontario's Narcotics Safety and Awareness Act (NSAA; November 2011.Three outcomes were explored: the rate of opioid use among ODB beneficiaries, the prevalence of opioid prescriptions exceeding 200 mg and 400 mg morphine equivalents per day, and rates of opioid-related emergency department visits and hospital admissions.Over the 12 year study period, the rate of opioid use declined 15.2%, from 2764 to 2342 users per 10,000 ODB eligible persons. The rate of opioid use was significantly impacted by the Canadian clinical practice guidelines (p-value = .03 which led to a decline in use, but no impact was observed by the enactment of the NSAA (p-value = .43. Among opioid users, the prevalence of high-dose prescribing doubled (from 4.2% to 8.7% over the study period. By 2014, 40.9% of recipients of long-acting opioids exceeded daily doses of 200 mg morphine or equivalent, including 55.8% of long-acting oxycodone users and 76.3% of transdermal fentanyl users. Moreover, in the last period, 18.7% of long-acting opioid users exceeded daily doses of 400 mg morphine or equivalent. Rates of opioid-related emergency department visits and hospital admissions increased 55.0% over the study period from 9.0 to 14.0 per 10,000 ODB beneficiaries from 2003 to 2013. This rate was not significantly impacted by the Canadian clinical practice guidelines (p-value = .68 or enactment of the NSAA (p-value = .59.Although the Canadian clinical practice guidelines for use of opioids in chronic non

Opioid Prescriptions by Specialty in Ohio, 2010-2014.

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Weiner, Scott G; Baker, Olesya; Rodgers, Ann F; Garner, Chad; Nelson, Lewis S; Kreiner, Peter W; Schuur, Jeremiah D

2018-05-01

The current US opioid epidemic is attributed to the large volume of prescribed opioids. This study analyzed the contribution of different medical specialties to overall opioids by evaluating the pill counts and morphine milligram equivalents (MMEs) of opioid prescriptions, stratified by provider specialty, and determined temporal trends. This was an analysis of the Ohio prescription drug monitoring program database, which captures scheduled medication prescriptions filled in the state as well as prescriber specialty. We extracted prescriptions for pill versions of opioids written in the calendar years 2010 to 2014. The main outcomes were the number of filled prescriptions, pill counts, MMEs, and extended-released opioids written by physicians in each specialty, and annual prescribing trends. There were 56,873,719 prescriptions for the studied opioids dispensed, for which 41,959,581 (73.8%) had prescriber specialty type available. Mean number of pills per prescription and MMEs were highest for physical medicine/rehabilitation (PM&R; 91.2 pills, 1,532 mg, N = 1,680,579), anesthesiology/pain (89.3 pills, 1,484 mg, N = 3,261,449), hematology/oncology (88.2 pills, 1,534 mg, N = 516,596), and neurology (84.4 pills, 1,230 mg, N = 573,389). Family medicine (21.8%) and internal medicine (17.6%) wrote the most opioid prescriptions overall. Time trends in the average number of pills and MMEs per prescription also varied depending on specialty. The numbers of pills and MMEs per opioid prescription vary markedly by prescriber specialty, as do trends in prescribing characteristics. Pill count and MME values define each specialty's contribution to overall opioid prescribing more accurately than the number of prescriptions alone.

Opioid tapering in patients with prescription opioid use disorder : A retrospective study

NARCIS (Netherlands)

Zhou, Kehua; Jia, Peng; Bhargava, Swati; Zhang, Yong; Reza, Taslima; Peng, Yuan Bo; Wang, Gary G.

2017-01-01

Background and aims: Opioid use disorder (OUD) refers to a maladaptive pattern of opioid use leading to clinically significant impairment or distress. OUD causes, and vice versa, misuses and abuse of opioid medications. Clinicians face daily challenges to treat patients with prescription opioid use

Past-year Prescription Drug Monitoring Program Opioid Prescriptions and Self-reported Opioid Use in an Emergency Department Population With Opioid Use Disorder.

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Hawk, Kathryn; D'Onofrio, Gail; Fiellin, David A; Chawarski, Marek C; O'Connor, Patrick G; Owens, Patricia H; Pantalon, Michael V; Bernstein, Steven L

2017-11-22

Despite increasing reliance on prescription drug monitoring programs (PDMPs) as a response to the opioid epidemic, the relationship between aberrant drug-related behaviors captured by the PDMP and opioid use disorder is incompletely understood. How PDMP data should guide emergency department (ED) assessment has not been studied. The objective was to evaluate a relationship between PDMP opioid prescription records and self-reported nonmedical opioid use of prescription opioids in a cohort of opioid-dependent ED patients enrolled in a treatment trial. PDMP opioid prescription records during 1 year prior to study enrollment on 329 adults meeting Diagnostic and Statistical Manual IV criteria for opioid dependence entering a randomized clinical trial in a large, urban ED were cross-tabulated with data on 30-day nonmedical prescription opioid use self-report. The association among these two types of data was assessed by the Goodman and Kruskal's gamma; a logistic regression was used to explore characteristics of participants who had PDMP record of opioid prescriptions. During 1 year prior to study enrollment, 118 of 329 (36%) patients had at least one opioid prescription (range = 1-51) in our states' PDMP. Patients who reported ≥15 of 30 days of nonmedical prescription opioid use were more likely to have at least four PDMP opioid prescriptions (20/38; 53%) than patients reporting 1 to 14 days (14/38, 37%) or zero days of nonmedical prescription opioid use (4/38, 11%; p = 0.002). Female sex and having health insurance were significantly more represented in the PDMP (p Medicine.

Improving opioid safety practices in primary care: protocol for the development and evaluation of a multifaceted, theory-informed pilot intervention for healthcare providers

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Leece, Pamela; Buchman, Daniel Z; Hamilton, Michael; Timmings, Caitlyn; Shantharam, Yalnee; Moore, Julia; Furlan, Andrea D

2017-01-01

Introduction In North America, drug overdose deaths are reaching unprecedented levels, largely driven by increasing prescription opioid-related deaths. Despite the development of several opioid guidelines, prescribing behaviours still contribute to poor patient outcomes and societal harm. Factors at the provider and system level may hinder or facilitate the application of evidence-based guidelines; interventions designed to address such factors are needed. Methods and analysis Using implementation science and behaviour change theory, we have planned the development and evaluation of a comprehensive Opioid Self-Assessment Package, designed to increase adherence to the Canadian Opioid Guideline among family physicians. The intervention uses practical educational and self-assessment tools to provide prescribers with feedback on their current knowledge and practices, and resources to improve their practice. The evaluation approach uses a pretest and post-test design and includes both quantitative and qualitative methods at baseline and 6 months. We will recruit a purposive sample of approximately 10 family physicians in Ontario from diverse practice settings, who currently treat patients with long-term opioid therapy for chronic pain. Quantitative data will be analysed using basic descriptive statistics, and qualitative data will be analysed using the Framework Method. Ethics and dissemination The University Health Network Research Ethics Board approved this study. Dissemination plan includes publications, conference presentations and brief stakeholder reports. This evidence-informed, theory-driven intervention has implications for national application of opioid quality improvement tools in primary care settings. We are engaging experts and end users in advisory and stakeholder roles throughout our project to increase its national relevance, application and sustainability. The performance measures could be used as the basis for health system quality improvement

Neurogenetics of acute and chronic opiate/opioid abstinence: treating symptoms and the cause.

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Blum, Kenneth; Gold, Mark S; Jacobs, William; McCall, William Vaughn; Febo, Marcelo; Baron, David; Dushaj, Kristina; Demetrovics, Zsolt; Badgaiyan, Rajendra D

2017-03-01

This review begins with a comprehensive history of opioid dependence and treatment in the United States. The focus is an evidence-based treatment model for opioid/opiate dependent individuals. The role of reward genetic polymorphisms and the epigenetic modifications that lead to vulnerability to use and misuse of opiates/opioid to treat pain are reviewed. The neurochemical mechanisms of acute opiate withdrawal and opiate/opioid reward mechanisms are explored with a goal of identifying specific treatment targets. Alterations in functional brain connectivity based on neurobiological mechanisms in heroin dependence and abstinence are also reviewed. A new clinical model an alternative to merely blocking acute withdrawal symptoms as identified in the DSM -5 is proposed. Genetic diagnosis at the onset of detoxification, to determine risk stratification, and identify polymorphic gene targets for pharmaceutical and nutraceutical interventions, followed by the simultaneous initiation of Medication Assisted Therapy (MAT), to enable psychological extinction, and steady pro-dopaminergic therapy with the goal of developing "dopamine homeostasis" is recommended. The objective of these interventions is to prevent future relapse by treating all "Reward Deficiency Syndrome" (RDS) behaviors and eventually make an addiction-free life possible .

Role and psychological dependenci arrangement of opioid by type of reseptor opioid

OpenAIRE

Arif Nurrochmad, Arif Nurrochmad

2015-01-01

Opioid receptor can be classified as p., 8, and K-opioid receptor that widely expressed in the CNS. The development of selective receptor agonist and cloning of each receptor have contributed greatly to our increasing knowledge of the neuropharmacological profile of each opioid receptor type. This review focuses on the functional interaction among these opioid receptor types that contribute to opioid dependence especially in psychological dependence. Several lines of evidence provide argument...

Healthcare utilization in adults with opioid dependence receiving extended release naltrexone compared to treatment as usual.

Science.gov (United States)

Soares, William E; Wilson, Donna; Rathlev, Niels; Lee, Joshua D; Gordon, Michael; Nunes, Edward V; O'Brien, Charles P; Friedmann, Peter D

2018-02-01

Opioid use disorders have reached epidemic proportions, with overdose now the leading cause of accidental death in the United States. Extended release naltrexone (XR-NTX) has emerged as a medication treatment that reduces opioid use and craving. However, the effect of XR-NTX therapy on acute healthcare utilization, including emergency department visits and inpatient hospitalizations, remains uncertain. The objective of the current study is to evaluate hospital-based healthcare resource utilization in adults involved in the criminal justice system with a history of opioid use disorder randomized to XR-NTX therapy compared with treatment as usual (TAU) during a 6-month treatment phase and 12months post-treatment follow up. This retrospective exploratory analysis uses data collected in a published randomized trial. Comparisons of the number of emergency department visits and hospital admissions (for drug detox, psychiatric care and other medical reasons) were performed using chi square tests for any admission and negative binomial models for number of admissions. Of the 308 participants randomized, 96% had utilization data (76% complete 6months, 67% complete follow up). No significant differences were seen in overall healthcare utilization (IRR=0.88, 95%CI 0.63-1.23, p=0.45), or substance use-related drug detox hospitalizations (IRR=0.83, 95%CI 0.32-2.16, p=0.71). Despite having more participants report chronic medical problems at baseline (43% vs. 32%, p=0.05), those receiving XR-NTX generally experienced equivalent or lower rates of healthcare utilization compared to TAU. The XR-NTX group had significantly lower medical/surgical related hospital admissions (IRR=0.55, 95%CI 0.30-1.00, p=0.05) during the course of the entire study. XR-NTX did not significantly increase rates of healthcare utilization compared to TAU. Provider concerns regarding healthcare utilization should not preclude the consideration of XR-NTX as therapy for opioid use disorders. Copyright © 2018

Pharmacogenomics and Patient Treatment Parameters to Opioid Treatment in Chronic Pain: A Focus on Morphine, Oxycodone, Tramadol, and Fentanyl.

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Lloyd, Renae A; Hotham, Elizabeth; Hall, Catherine; Williams, Marie; Suppiah, Vijayaprakash

2017-12-01

Opioids are one of the most commonly prescribed medicines for chronic pain. However, their use for chronic pain has been controversial. The objective of this literature review was to identify the role of genetic polymorphisms on patient treatment parameters (opioid dose requirements, response, and adverse effects) for opioids used in malignant and nonmalignant chronic pain. The opioids that this review focuses on are codeine, morphine, oxycodone, tramadol, and fentanyl. A literature search of databases Medline and Embase was carried out, and studies up to April 2016 were included in this review. Studies were included based on a combination of key words: chronic pain and related terms, pharmacogenetics and related terms, and opioids and related terms. Among the 1,408 individual papers retrieved from the search in Medline and Embase, 32 original articles were included in this review, with none related to codeine. The 32 papers reported various study designs, opioids, and polymorphisms being studied for associations with treatment outcomes. This literature review reveals that variants in ABCB1, OPRM1, and COMT have been replicated for opioid dosing and variants in ABCB1 have been replicated for both treatment response and adverse effects. Currently, there are few validated studies to form a strong evidence base to support pharmacogenomics testing when initiating opioid therapy. However, the field of pharmacogenomics in chronic pain is likely to expand over the coming years, with the increasing number of treatment options available and larger cohorts being assembled in order to identify true associations. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Nurses and opioids: results of a bi-national survey on mental models regarding opioid administration in hospitals

Directory of Open Access Journals (Sweden)

Guest C

2017-03-01

Full Text Available Charlotte Guest,1 Fabian Sobotka,2 Athina Karavasopoulou,3 Stephen Ward,3 Carsten Bantel4,5 1Pain Medicine, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK; 2Division of Epidemiology and Biometry, Department of Health Services Research, Faculty 6, Medicine and Health Sciences, Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany; 3Pain Service, Barts Health, St Bartholomew’s Hospital, London, UK; 4Department of Anaesthesiology, Intensive Care, Emergency Medicine and Pain Therapy, Oldenburg University, Klinikum Oldenburg Campus, Oldenburg, Germany; 5Department of Surgery and Cancer, Anaesthetics Section, Imperial College London, Chelsea and Westminster Hospital Campus, London, UK Objective: Pain remains insufficiently treated in hospitals. Increasing evidence suggests human factors contribute to this, due to nurses failing to administer opioids. This behavior might be the consequence of nurses’ mental models about opioids. As personal experience and conceptions shape these models, the aim of this prospective survey was to identify model-influencing factors. Material and methods: A questionnaire was developed comprising of 14 statements concerning ideations about opioids and seven questions concerning demographics, indicators of adult learning, and strength of religious beliefs. Latent variables that may underlie nurses’ mental models were identified using undirected graphical dependence models. Representative items of latent variables were employed for ordinal regression analysis. Questionnaires were distributed to 1,379 nurses in two London, UK, hospitals (n=580 and one German (n=799 hospital between September 2014 and February 2015. Results: A total of 511 (37.1% questionnaires were returned. Mean (standard deviation age of participants were 37 (11 years; 83.5% participants were female; 45.2% worked in critical care; and 51.5% had more than 10 years experience. Of the nurses, 84% were not scared of opioids, 87

E-cigarette knowledge, attitudes, and use in opioid dependent smokers

OpenAIRE

Stein, Michael D.; Caviness, Celeste M.; Grimone, Kristin; Audet, Daniel; Borges, Allison; Anderson, Bradley J.

2014-01-01

Individuals in treatment for opioid dependence have smoking rates 3-5 times greater than U.S. prevalence rate. Traditional smoking cessation strategies have been ineffective in this population. Novel approaches are needed as well as harm reduction avenues. E-cigarettes (ecigs) may provide such a novel harm reduction and cessation opportunity but little is known about the knowledge of, attitudes about, and usage of e-cigs in opioid dependent smokers. The current study enrolled 315 opioid depen...

Opioid Addiction in Pregnancy: Does Depression Negatively Impact Adherence With Prenatal Care?

Science.gov (United States)

Hensley, Lauren; Sulo, Suela; Kozmic, Sarah; Parilla, Barbara V

We aimed to evaluate whether depression in pregnancy in women with opioid dependency negatively impacts adherence with prenatal care. This was a retrospective chart analysis of opioid-dependent pregnant women over a 6-year period at 2 large referral and tertiary care centers. The primary outcome was adherence with prenatal care based on the concurrent diagnosis of depression. Adherence was assessed by looking at the number of observed versus expected prenatal visits. Secondary outcomes included neonatal intensive care unit (NICU) stay, and incidence and severity of neonatal abstinence syndrome (NAS). A total of 74 patient charts were reviewed. 45/74 (60.8%) of the opioid-dependent pregnant patients were either diagnosed with depression (n = 41), anxiety (n = 2), or scored >10 on the Edinburgh Prenatal Depression Scale (n = 1). Patients with a diagnosis of depression were significantly less adherent with prenatal care; 80% adherent (73% vs 93%; P = 0.03), 90% adherent (62% vs 93%; P = 0.003). A higher number of patients in the depression group had an infant treated for withdrawal (62% vs 38%; P = 0.041), and had longer NICU stays (27% vs 21%; P = 0.018). Analysis of the whole cohort of opioid dependent gravidas revealed Buprenorphine maintenance therapy had the lowest mean NAS score 6.5 ± 4.4, compared with methadone maintenance 10.6 ± 3.6, and no maintenance therapy 9.4 ± 4.0 (P = 0.008). Depression negatively impacts adherence with prenatal care and was significantly associated with a higher incidence of neonatal withdrawal and longer NICU stays. Buprenorphine therapy had the lowest incidence and severity of NAS when compared with methadone and no maintenance therapy.

Opioid Addiction: Social Problems Associated and Implications of Both Current and Possible Future Treatments, including Polymeric Therapeutics for Giving Up the Habit of Opioid Consumption

Directory of Open Access Journals (Sweden)

M. Cristina Benéitez

2017-01-01

Full Text Available Background. Detoxification programmes seek to implement the most secure and compassionate ways of withdrawing from opiates so that the inevitable withdrawal symptoms and other complications are minimized. Once detoxification has been achieved, the next stage is to enable the patient to overcome his or her drug addiction by ensuring consumption is permanently and completely abandoned, only after which can the subject be regarded as fully recovered. Methods. A systematic search on the common databases of relevant papers published until 2016 inclusive. Results and Conclusion. Our study of the available oral treatments for opioid dependence has revealed that no current treatment can actually claim to be fully effective. These treatments require daily oral administration and, consequently, regular visits to dispensaries, which in most cases results in a lack of patient compliance, which causes fluctuations in drug plasma levels. We then reviewed alternative treatments in the available scientific literature on polymeric sustained release formulations. Research has been done not only on release systems for detoxification but also on release systems for giving up the habit of taking opioids. These efforts have obtained the recent authorization of polymeric systems for use in patients that could help them to reduce their craving for drugs.

Use of opioid substitution therapies in the treatment of opioid use disorder: results of a UK cost-effectiveness modelling study.

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Kenworthy, James; Yi, Yunni; Wright, Antony; Brown, Jim; Maria Madrigal, Ana; Dunlop, William C N

2017-07-01

This study investigated the cost-effectiveness of buprenorphine maintenance treatment (BMT) and methadone maintenance treatment (MMT) vs no opioid substitution therapy (OST) for the treatment of opioid use disorder, from the UK National Health Service (NHS)/personal social services (PSS) and societal perspectives over 1 year. Cost-effectiveness of OST vs no OST was evaluated by first replicating and then expanding an existing UK health technology assessment model. The expanded model included the impact of OST on infection rates of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. Versus no OST, incremental cost-effectiveness ratios (ICERs) for BMT and MMT were £13,923 and £14,206 per quality-adjusted life year (QALY), respectively, from a NHS/PSS perspective. When total costs (NHS/PSS and societal) are considered, there are substantial savings associated with adopting OST; these savings are in excess of £14,032 for BMT vs no OST and £17,174 for MMT vs no OST over 1 year. This is primarily driven by a reduction in victim costs. OST treatment also impacted other aspects of criminality and healthcare resource use. The model's 1-year timeframe means long-term costs and benefits, and the influence of changes over time are not captured. OST can be considered cost-effective vs no OST from the UK NHS/PSS perspective, with a cost per QALY well below the UK's willingness-to-pay threshold. There were only small differences between BMT and MMT. The availability of two or more cost-effective options is beneficial to retaining patients in OST programs. From a societal perspective, OST is estimated to save over £14,032 and £17,174 per year for BMT and MMT vs no OST, respectively, due to savings in victim costs. Further work is required to fully quantify the clinical and health economic impacts of different OST formulations and their societal impact over the long-term.

Co-morbid pain and opioid addiction: long term effect of opioid maintenance on acute pain.

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Wachholtz, Amy; Gonzalez, Gerardo

2014-12-01

Medication assisted treatment for opioid dependence alters the pain experience. This study will evaluate changes pain sensitivity and tolerance with opioid treatments; and duration of this effect after treatment cessation. 120 Individuals with chronic pain were recruited in 4 groups (N = 30): 1-methadone for opioid addiction; 2-buprenorphine for opioid addiction; 3-history of opioid maintenance treatment for opioid addiction but with prolonged abstinence (M = 121 weeks; SD = 23.3); and 4-opioid naïve controls. Participants completed a psychological assessment and a cold water task including, time to first pain (sensitivity) and time to stopping the pain task (tolerance). Data analysis used survival analyses. A Kaplan-Meier-Cox survival analysis showed group differences for both pain sensitivity (log rank = 15.50; p opioid maintenance resulted in differing pain sensitivity compared to opioid naïve (p's opioid maintenance compared to active methadone patients (p opioid naïve control group participants (p's opioid abstinence increased (R = .37; p opioid maintenance, there appears to be long-term differences in pain sensitivity that do not resolve with discontinuation of opioid maintenance. Although pain sensitivity does not change, pain tolerance does improve after opioid maintenance cessation. Implications for treating co-morbid opioid addiction and pain (acute and chronic) are discussed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Design and implementation of a factorial randomized controlled trial of methadone maintenance therapy and an evidence-based behavioral intervention for incarcerated people living with HIV and opioid dependence in Malaysia.

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Bazazi, Alexander R; Wickersham, Jeffrey A; Wegman, Martin P; Culbert, Gabriel J; Pillai, Veena; Shrestha, Roman; Al-Darraji, Haider; Copenhaver, Michael M; Kamarulzaman, Adeeba; Altice, Frederick L

2017-08-01

Incarcerated people living with HIV and opioid dependence face enormous challenges to accessing evidence-based treatment during incarceration and after release into the community, placing them at risk of poor HIV treatment outcomes, relapse to opioid use and accompanying HIV transmission risk behaviors. Here we describe in detail the design and implementation of Project Harapan, a prospective clinical trial conducted among people living with HIV and opioid dependence who transitioned from prison to the community in Malaysia from 2010 to 2014. This trial involved 2 interventions: within-prison initiation of methadone maintenance therapy and an evidence-based behavioral intervention adapted to the Malaysian context (the Holistic Health Recovery Program for Malaysia, HHRP-M). Individuals were recruited and received the interventions while incarcerated and were followed for 12months after release to assess post-release HIV transmission risk behaviors and a range of other health-related outcomes. Project Harapan was designed as a fully randomized 2×2 factorial trial where individuals would be allocated in equal proportions to methadone maintenance therapy and HHRP-M, methadone maintenance therapy alone, HHRP-M alone, or control. Partway through study implementation, allocation to methadone maintenance therapy was changed from randomization to participant choice; randomization to HHRP-M continued throughout. We describe the justification for this study; the development and implementation of these interventions; changes to the protocol; and screening, enrollment, treatment receipt, and retention of study participants. Logistical, ethical, and analytic issues associated with the implementation of this study are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

Advances in the delivery of buprenorphine for opioid dependence

Directory of Open Access Journals (Sweden)

Rosenthal RN

2017-08-01

Full Text Available Richard N Rosenthal,1 Viral V Goradia2 1Department of Psychiatry, Addiction Institute at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, 2Department of Psychiatry, Upstate Medical University, Syracuse, NY, USA Abstract: Opioid use disorders (OUDs have long been a global problem, but the prevalence rates have increased over 20 years to epidemic proportions in the US, with concomitant increases in morbidity and all-cause mortality, but especially opioid overdose. These increases are in part attributable to a several-fold expansion in the prescription of opioid pain medications over the same time period. Opioid detoxification and psychosocial treatments alone have each not yielded sufficient efficacy for OUD, but μ-opioid receptor agonist, partial agonist, and antagonist medications have demonstrated the greatest overall benefit in OUD treatment. Buprenorphine, a μ-opioid receptor partial agonist, has been used successfully on an international basis for several decades in sublingual tablet and film preparations for the treatment of OUD, but the nature of formulation, which is typically self-administered, renders it susceptible to nonadherence, diversion, and accidental exposure. This article reviews the clinical trial data for novel buprenorphine delivery systems in the form of subcutaneous depot injections, transdermal patches, and subdermal implants for the treatment of OUD and discusses both the clinical efficacy of longer-acting formulations through increasing consistent medication exposure and their potential utility in reducing diversion. These new delivery systems also offer new dosing opportunities for buprenorphine and strategies for dosing intervals in the treatment of OUD. Keywords: opioid use disorder, buprenorphine, drug diversion, drug implants, depot medications, maintenance therapy, treatment adherence

Opioid addiction and misuse in adult and adolescent patients with cancer.

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Pinkerton, Ross; Hardy, Janet R

2017-06-01

In the context of a therapeutic opioid epidemic, particularly in the USA, where increasingly stringent screening for 'at risk' individuals and close monitoring of opioid prescription and use is strongly recommended, the issue of misuse within the cancer population must be addressed. Most patients with advanced cancer will have pain requiring opioid therapy at some stage during their disease course. In the majority, this will provide good pain relief with no short- or longer-term adverse sequelae. A subset will present with substance misuse issues that will influence management and prescribing practice. The potential ethical issues of limiting effective analgesia on the basis of addiction risk or history must be acknowledged. Both a judgemental or 'relaxed' approach to such patients is problematic. Ignoring the situation will not be in the patient's best interest, but an undue focus on this aspect may damage therapeutic relationships with clinicians and adversely affect a holistic approach to care. Clinical practitioners must be aware of the risk factors for opioid misuse and in patients who are not under palliative care consider screening prior to commencing opioids. Clinicians must be able to manage and monitor those identified as having an opioid misuse problem. © 2017 Royal Australasian College of Physicians.

Assessing Differences in the Availability of Opioid Addiction Therapy Options: Rural Versus Urban and American Indian Reservation Versus Nonreservation.

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Hirchak, Katherine A; Murphy, Sean M

2017-01-01

Opioid misuse is a large public health problem in the United States. Residents of rural areas and American Indian (AI) reservation/trust lands represent traditionally underserved populations with regard to substance-use disorder therapy. Assess differences in the number of opioid agonist therapy (OAT) facilities and physicians with Drug Addiction Treatment Act (DATA) waivers for rural versus urban, and AI reservation/trust land versus non-AI reservation/trust land areas in Washington State. The unit of analysis was the ZIP code. The dependent variables were the number of OAT facilities and DATA-waivered physicians in a region per 10,000 residents aged 18-64 in a ZIP code. A region was defined as a ZIP code and its contiguous ZIP codes. The independent variables were binary measures of whether a ZIP code was classified as rural versus urban, or AI reservation/trust land versus non-AI reservation/trust land. Zero-inflated negative binomial regressions with robust standard errors were estimated. The number of OAT clinics in a region per 10,000 ZIP-code residents was significantly lower in rural versus urban areas (P = .002). This did not differ significantly between AI reservation/trust land and non-AI reservation/trust land areas (P = .79). DATA-waivered physicians in a region per 10,000 ZIP-code residents was not significantly different between rural and urban (P = .08), or AI reservation/trust land versus non-AI reservation/trust land areas (P = .21). It appears that the potential for Washington State residents of rural and AI reservation areas to receive OAT is similar to that of residents outside of those areas; however, difficulties in accessing therapy may remain, highlighting the importance of expanding health care insurance and providing support for DATA-waivered physicians. © 2016 National Rural Health Association.

Distance traveled and frequency of interstate opioid dispensing in opioid shoppers and nonshoppers.

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Cepeda, M Soledad; Fife, Daniel; Yuan, Yingli; Mastrogiovanni, Greg

2013-10-01

Little is known about how far opioid shoppers travel or how often they cross state lines to fill their opioid prescriptions. This retrospective cohort study evaluated these measures for opioid shoppers and nonshoppers using a large U.S. prescription database. Patients with ≥3 opioid dispensings were followed for 18 months. A subject was considered a shopper when he or she filled overlapping opioid prescriptions written by >1 prescriber at ≥3 pharmacies. A heavy shopper had ≥5 shopping episodes. Outcomes assessed were distance traveled among pharmacies and number of states visited to fill opioid prescriptions. A total of 10,910,451 subjects were included; .7% developed any shopping behavior and their prescriptions accounted for 8.6% of all opioid dispensings. Shoppers and heavy shoppers were younger than the nonshoppers. Shoppers traveled a median of 83.8 miles, heavy shoppers 199.5 miles, and nonshoppers 0 miles. Almost 20% of shoppers or heavy shoppers, but only 4% of nonshoppers, visited >1 state. Shoppers traveled greater distances and more often crossed state borders to fill opioid prescriptions than nonshoppers, and their dispensings accounted for a disproportionate number of opioid dispensings. Sharing of data among prescription-monitoring programs will likely strengthen those programs and may decrease shopping behavior. This study shows that opioid shoppers travel greater distances and more often cross state borders to fill opioid prescriptions than nonshoppers, and their dispensings accounted for a disproportionate number of opioid dispensings. The findings support the need for data sharing among prescription-monitoring programs to deter opioid shopping behavior. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

The impact of chronic pain on opioid addiction treatment: a systematic review protocol.

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Dennis, Brittany B; Bawor, Monica; Paul, James; Varenbut, Michael; Daiter, Jeff; Plater, Carolyn; Pare, Guillaume; Marsh, David C; Worster, Andrew; Desai, Dipika; Thabane, Lehana; Samaan, Zainab

2015-04-16

The consequences of opioid relapse among patients being treated with opioid substitution treatment (OST) are serious and can result in abnormal cardiovascular function, overdose, and mortality. Chronic pain is a major risk factor for opioid relapse within the addiction treatment setting. There exist a number of opioid maintenance therapies including methadone, buprenorphine, naltrexone, and levomethadyl acetate (LAAM), of which the mediating effects of pain on treatment attrition, substance use behavior, and social functioning may differ across therapies. We aim to 1) evaluate the impact of pain on the treatment outcomes of addiction patients being managed with OST and 2) identify the most recently published opioid maintenance treatment guidelines from the United States, Canada, and the UK to determine how the evidence is being translated into clinical practice. The authors will search Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Database of Systematic Reviews, ProQuest Dissertations and theses Database, Cochrane Central Register of Controlled Trials (CENTRAL), World Health Organization International Clinical Trials Registry Platform Search Portal, and the National Institutes for Health Clinical Trials Registry. We will search www. gov and the National Institute for Care and Excellence (NICE) databases to identify the most recently published OST guidelines. All screening and data extraction will be completed in duplicate. Provided the data are suitable, we will perform a multiple treatment comparison using Bayesian meta-analytic methods to produce summary statistics estimating the effect of chronic pain on all OSTs. Our primary outcome is substance use behavior, which includes opioid and non-opioid substance use. We will also evaluate secondary endpoints such as treatment retention, general physical health, intervention adherence, personal and social functioning, as well as psychiatric symptoms. This review will capture the experience of treatment

Pharmacotherapy of Opioid Addiction: "Putting a Real Face on a False Demon".

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Salsitz, E; Wiegand, T

2016-03-01

Methadone maintenance therapy (MMT), a pharmacological treatment for opioid use disorder for the past 50 years, continues to remain controversial. Despite consistent and overwhelming evidence confirming the effectiveness and safety of MMT, misconceptions and myths persist regarding its legitimacy as a treatment for opioid addiction. This often results in the underutilization and limited availability of this treatment modality. Despite successful outcomes, the controversial nature of MMT, and the stigma experienced by the patients on methadone, has been a particularly difficult obstacle to overcome. We present the history of MMT, review the evidence for its efficacy in the treatment of opioid dependence, and explore the origins of the stigma and misconceptions related to MMT.

Medications Development for Opioid Abuse

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Negus, S. Stevens; Banks, Matthew L.

2013-01-01

Here we describe methods for preclinical evaluation of candidate medications to treat opioid abuse and dependence. Our perspective is founded on the propositions that (1) drug self-administration procedures provide the most direct method for assessment of medication effects, (2) procedures that assess choice between opioid and nondrug reinforcers are especially useful, and (3) the states of opioid dependence and withdrawal profoundly influence both opioid reinforcement and the effects of candidate medications. Effects of opioid medications on opioid choice in nondependent and opioid-dependent subjects are reviewed. Various nonopioid medications have also been examined, but none yet have been identified that safely and reliably reduce opioid choice. Future research will focus on (1) strategies for increasing safety and/or effectiveness of opioid medications, and (2) continued development of nonopioids such as inhibitors of endocannabinoid catabolic enzymes or inhibitors of opioid-induced glial activation. PMID:23125072

Cancer pain in the opioid-addicted patient: can we treat it right?

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Modesto-Lowe, Vania; Girard, Lisa; Chaplin, Margaret

2012-01-01

Although cancer elicits an array of physical and emotional symptoms, pain is often identified as the most distressing. Cancer pain may result from the primary tumor, metastasis, surgery, radiation, chemotherapy, or medical comorbidities. Although treatment with opioid analgesics is accepted as appropriate therapy for cancer-related pain, under treatment may persist among certain patients. Opioid-addicted individuals represent a challenging and heterogeneous population to treat. Addiction is linked to psychopathology and antisocial behaviors (eg, lying) which often complicate evaluation. Chronic exposure to opioids may lead to physiologic dependence and its correlates, tolerance and hyperalgesia. Given the variability and subjectivity of the cancer pain experience, there are no objective measures which capture the adequacy of pain control. Thus, when faced with complaints of uncontrolled pain, clinicians must consider a differential diagnosis of tolerance, disease progression, addiction, pseudoaddiction, chemical coping, or even criminal behavior. This article explores the cognitive, behavioral, and physiological correlates of opioid addiction that may impact cancer pain management. It also discusses risk reduction strategies for opioid misuse and research directions that may lead to improved clinical outcomes in these patients.

Opioid tapering in patients with prescription opioid use disorder: A retrospective study.

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Zhou, Kehua; Jia, Peng; Bhargava, Swati; Zhang, Yong; Reza, Taslima; Peng, Yuan Bo; Wang, Gary G

2017-10-01

Opioid use disorder (OUD) refers to a maladaptive pattern of opioid use leading to clinically significant impairment or distress. OUD causes, and vice versa, misuses and abuse of opioid medications. Clinicians face daily challenges to treat patients with prescription opioid use disorder. An evidence-based management for people who are already addicted to opioids has been identified as the national priority in the US; however, options are limited in clinical practices. In this study, we aimed to explore the success rate and important adjuvant medications in the medication assisted treatment with temporary use of methadone for opioid discontinuation in patients with prescription OUD. This is a retrospective chart review performed at a private physician office for physical medicine and rehabilitation. We reviewed all medical records dated between December 1st, 2011 and August 30th, 2016. The initial evaluation of the included patients (N=140) was completed between December 1st, 2011 and December 31st, 2014. They all have concumittant prescription OUD and chronic non-cancer pain. The patients (87 female and 53 male) were 46.7±12.7 years old, and had a history of opioid use of 7.7±6.1 years. All patients received the comprehensive opioid taper treatments (including interventional pain management techniques, psychotherapy, acupuncture, physical modalities and exercises, and adjuvant medications) on top of the medication assisted treatment using methadone (transient use). Opioid tapering was considered successful when no opioid medication was used in the last patient visit. The 140 patients had pain of 9.6±8.4 years with 8/10 intensity before treatment which decreased after treatment in all comparisons (pOUD. For patients with OUD, indefinite opioid maintenance treatment may not be necessary. Considering the ethical values of autonomy, nonmaleficence, and beneficence, clinicians should provide patients with OUD the option of opioid tapering. Copyright © 2017

Update on prescription extended-release opioids and appropriate patient selection

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Brennan MJ

2013-07-01

Full Text Available Michael J Brennan The Pain Center of Fairfield, Fairfield, CT, USA Abstract: Chronic pain is largely underdiagnosed, often undertreated, and expected to increase as the American population ages. Many patients with chronic pain require long-term treatment with analgesic medications, and pain management may involve use of prescription opioids for patients whose pain is inadequately controlled through other therapies. Yet because of the potential for abuse and addiction, many clinicians hesitate to treat their patients with pain with potentially beneficial agents. Finding the right opioid for the right patient is the first – often complicated – step. Ensuring that patients continue to properly use the medication while achieving therapeutic analgesic effects is the long-term goal. Combined with careful patient selection and ongoing monitoring, new formulations using extended-release technologies incorporating tamper-resistant features may help combat the growing risk of abuse or misuse, which will hopefully reduce individual suffering and the societal burden of chronic pain. The objective of this manuscript is to provide an update on extended-release opioids and to provide clinicians with a greater understanding of which patients might benefit from these new opioid formulations and how to integrate the recommended monitoring for abuse potential into clinical practice. Keywords: chronic pain, opioid analgesics, extended release, abuse prevention

Chimeric opioid peptides: tools for identifying opioid receptor types.

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Xie, G X; Miyajima, A; Yokota, T; Arai, K; Goldstein, A

1990-01-01

We synthesized several chimeric peptides in which the N-terminal nine residues of dynorphin-32, a peptide selective for the kappa opioid receptor, were replaced by opioid peptides selective for other opioid receptor types. Each chimeric peptide retained the high affinity and type selectivity characteristic of its N-terminal sequence. The common C-terminal two-thirds of the chimeric peptides served as an epitope recognized by the same monoclonal antibody. When bound to receptors on a cell surf...

Co-relationship between sexual dysfunction and high-risk sexual behavior in patients receiving buprenorphine and naltrexone maintenance therapy for opioid dependence.

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Ramdurg, Santosh; Ambekar, Atul; Lal, Rakesh

2015-01-01

People suffering from substance dependence suffer from various sexual dysfunctions and are at risk for indulging in various high-risk sexual behaviors and thus are vulnerable to acquire various infections such as HIV/AIDS and other sexually transmitted infections. The aim of the study was to evaluate the correlation between sexual dysfunction and high-risk sexual behavior in opioid-dependent men receiving buprenorphine and naltrexone maintenance therapy. Semi-structured questionnaire, brief male sexual functioning inventory and HIV-risk taking behavior scale was administered to a sample of 60 sexually active men, receiving buprenorphine (n = 30) and naltrexone (n = 30) maintenance therapy for opioid dependence. The main outcomes are correlation between severity of sexual dysfunction and HIV-risk taking behavior. The study results showed 83% of the men on buprenorphine and 90% on naltrexone reported at least one of the sexual dysfunction symptoms. There was a negative correlation between sexual dysfunction and HIV-risk taking behavior that suggest severe the dysfunction, higher the risk taking behavior. Significant correlation was present with overall sexual dysfunction and HIV-risk taking behavior (P = 0.028 and in naltrexone receiving group premature ejaculation versus HIV-risk taking behavior however, (P = 0.022, P sexual dysfunctions and HIV-risk taking behavior, which has clinical implication. Future research should explore this further using biochemical analyses.

Analgesia and Opioids: A Pharmacogenetics Shortlist for Implementation in Clinical Practice.

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Matic, Maja; de Wildt, Saskia N; Tibboel, Dick; van Schaik, Ron H N

2017-07-01

The use of opioids to alleviate pain is complicated by the risk of severe adverse events and the large variability in dose requirements. Pharmacogenetics (PGx) could possibly be used to tailor pain medication based on an individual's genetic background. Many potential genetic markers have been described, and the importance of genetic predisposition in opioid efficacy and toxicity has been demonstrated in knockout mouse models and human twin studies. Such predictors are especially of value for neonates and young children, in whom the assessment of efficacy or side effects is complicated by the inability of the patient to communicate this properly. The current problem is determining which of the many potential candidates to focus on for clinical implementation. We systematically searched publications on PGx for opioids in 5 databases, aiming to identify PGx markers with sufficient robust data and high enough occurrence for potential clinical application. The initial search yielded 4257 unique citations, eventually resulting in 852 relevant articles covering 24 genes. From these genes, we evaluated the evidence and selected the most promising 10 markers: cytochrome P450 family 2 subfamily D member 6 ( CYP2D6 ), cytochrome P450 family 3 subfamily A member 4 ( CYP3A4 ), cytochrome P450 family 3 subfamily A member 5 ( CYP3A5 ), UDP glucuronosyltransferase family 2 member B7 ( UGT2B7 ), ATP binding cassette subfamily B member 1 ( ABCB1 ), ATP binding cassette subfamily C member 3 ( ABCC3 ), solute carrier family 22 member 1 ( SLC22A1 ), opioid receptor kappa 1 ( OPRM1 ), catechol- O -methyltransferase ( COMT ), and potassium voltage-gated channel subfamily J member 6 ( KCNJ6 ). Treatment guidelines based on genotype are already available only for CYP2D6 . The application of PGx in the management of pain with opioids has the potential to improve therapy. We provide a shortlist of 10 genes that are the most promising markers for clinical use in this context. © 2016

μ opioid receptor activation hyperpolarizes respiratory-controlling Kölliker-Fuse neurons and suppresses post-inspiratory drive.

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Levitt, Erica S; Abdala, Ana P; Paton, Julian F R; Bissonnette, John M; Williams, John T

2015-10-01

the neuron in response to either current injection or local application of glutamate. In voltage-clamp recordings the outward current produced by the opioid agonist ME was concentration dependent, reversed at the potassium equilibrium potential and was blocked by BaCl2 , characteristics of a G protein-coupled inwardly rectifying potassium (GIRK) conductance. The clinically used drug morphine produced an outward current in KF neurons with similar potency to morphine-mediated currents in locus coeruleus brain slice preparations. Thus, the population of KF neurons that are hyperpolarized by μ opioid agonists are likely mediators of the opioid-induced loss of post-inspiration and induction of apneusis. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans.

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Lofwall, Michelle R; Babalonis, Shanna; Nuzzo, Paul A; Elayi, Samy Claude; Walsh, Sharon L

2016-07-01

The cannabinoid (CB) system is a rational novel target for treating opioid dependence, a significant public health problem around the world. This proof-of-concept study examined the potential efficacy of a CB1 receptor partial agonist, dronabinol, in relieving signs and symptoms of opioid withdrawal. Twelve opioid dependent adults participated in this 5-week, inpatient, double-blind, randomized, placebo-controlled study. Volunteers were maintained on double-blind oxycodone (30mg oral, four times/day) and participated in a training session followed by 7 experimental sessions, each testing a single oral test dose (placebo, oxycodone 30 and 60mg, dronabinol 5, 10, 20, and 30mg [decreased from 40mg]). Placebo was substituted for oxycodone maintenance doses for 21h before each session in order to produce measurable opioid withdrawal. Outcomes included observer- and participant-ratings of opioid agonist, opioid withdrawal and psychomotor/cognitive performance. Oxycodone produced prototypic opioid agonist effects (i.e. suppressing withdrawal and increasing subjective effects indicative of abuse liability). Dronabinol 5 and 10mg produced effects most similar to placebo, while the 20 and 30mg doses produced modest signals of withdrawal suppression that were accompanied by dose-related increases in high, sedation, bad effects, feelings of heart racing, and tachycardia. Dronabinol was not liked more than placebo, showed some impairment in cognitive performance, and was identified as marijuana with increasing dose. CB1 receptor activation is a reasonable strategy to pursue for the treatment of opioid withdrawal; however, dronabinol is not a likely candidate given its modest withdrawal suppression effects of limited duration and previously reported tachycardia during opioid withdrawal. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

New developments in managing opioid addiction: impact of a subdermal buprenorphine implant.

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Itzoe, MariaLisa; Guarnieri, Michael

2017-01-01

Opioid addiction to prescription and illicit drugs is a serious and growing problem. In the US alone, >2.4 million people suffer from opioid use disorder. Government and pharmaceutical agencies have begun to address this crisis with recently released and revised task forces and medication-assisted therapies (MAT). For decades, oral or intravenous (IV) MATs have helped patients in their recovery by administration of opioid agonists (methadone, buprenorphine, oxycodone), antagonists (naltrexone, naloxone), and combinations of the two (buprenorphine/naloxone). While shown to be successful, particularly when combined with psychological counseling, oral and IV forms of treatment come with constraints and challenges. Patients can become addicted to the agonists themselves, and there is increased risk for diversion, abuse, or missed dosages. Consequently, long-acting implants have begun to be developed as a potentially preferable method of agonist delivery. To date, the newest implant approved by the US Food and Drug Administration (May 2016) is Probuphine ® , which delivers steady-state levels of buprenorphine over the course of 6 months. Numerous studies have demonstrated its efficacy and safety. Yet, implants come with their own risks such as surgical site irritation, possible movement, and protrusion of implant out of skin. This review introduces the opioid abuse epidemic, examines existing medications used for therapy, and highlights Probuphine as a new treatment option. Costs associated with MATs are also discussed.

Sex differences in opioid analgesia and addiction: interactions among opioid receptors and estrogen receptors

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2013-01-01

Opioids are widely used as the pain reliever and also notorious for being addictive drugs. Sex differences in the opioid analgesia and addiction have been reported and investigated in human subjects and animal models. Yet, the molecular mechanism underlying the differences between males and females is still unclear. Here, we reviewed the literature describing the sex differences in analgesic responses and addiction liabilities to clinically relevant opioids. The reported interactions among opioids, estrogens, opioid receptors, and estrogen receptors are also evaluated. We postulate that the sex differences partly originated from the crosstalk among the estrogen and opioid receptors when stimulated by the exogenous opioids, possibly through common secondary messengers and the downstream gene transcriptional regulators. PMID:24010861

An update on the role of opioids in the management of chronic pain of nonmalignant origin.

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Højsted, Jette; Sjøgren, Per

2007-10-01

To summarize and reflect over primarily recent epidemiological and randomized controlled trials in opioid-treated chronic nonmalignant pain patients, focusing on effects, side effects, risks and long-term consequences of the treatment. In the western world opioids are increasingly being used for long-term treatment of chronic nonmalignant pain. While the long-term benefits of opioids regarding pain relief, functional capacity and health-related quality of life still remain to be proven, studies are emerging that describe serious long-term consequences such as addiction, opioid-induced hyperalgesia, cognitive disorders, and suppression of the immune and reproductive systems. Much more research is needed concerning long-time effects and consequences of opioid therapy in chronic nonmalignant pain patients; however, some clear warning signals have been sent out within recent years.

Intolerance of uncertainty in opioid dependency - Relationship with trait anxiety and impulsivity.

Directory of Open Access Journals (Sweden)

Julia Garami

Full Text Available Intolerance of uncertainty (IU is the tendency to interpret ambiguous situations as threatening and having negative consequences, resulting in feelings of distress and anxiety. IU has been linked to a number of anxiety disorders, and anxiety felt in the face of uncertainty may result in maladaptive behaviors such as impulsive decision making. Although there is strong evidence that anxiety and impulsivity are risk factors for addiction, there is a paucity of research examining the role of IU in this disorder. The rate of opioid addiction, in particular, has been rising steadily in recent years, which necessitates deeper understanding of risk factors in order to develop effective prevention and treatment methods. The current study tested for the first time whether opioid-dependent adults are less tolerant of uncertainty compared to a healthy comparison group. Opioid dependent patients undergoing methadone maintenance therapy (n = 114 and healthy comparisons (n = 69 completed the following scales: Intolerance of Uncertainty Scale, the Barrett Impulsivity Scale, and the State Trait Anxiety Inventory. Analysis revealed that these measures were positively correlated with each other and that opioid-dependent patients had significantly higher IU scores. Regression analysis revealed that anxiety mediated the relationship between IU and impulsivity. Hierarchical moderation regression found an interaction between addiction status and impulsivity on IU scores in that the relationship between these variables was only observed in the patient group. Findings suggest that IU is a feature of addiction but does not necessarily play a unique role. Further research is needed to explore the complex relationship between traits and how they may contribute to the development and maintenance of addiction.

Craving and subsequent opioid use among opioid dependent patients who initiate treatment with buprenorphine

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Tsui, Judith I.; Anderson, Bradley J.; Strong, David R.; Stein, Michael D.

2016-01-01

Background Few studies have directly assessed associations between craving and subsequent opioid use among treated patients. Our objective was to prospectively evaluate the relative utility of two craving questionnaires to predict opioid use among opioid dependent patients in treatment. Method Opioid dependent patients (n=147) initiating buprenorphine treatment were assessed for three months. Craving was measured using: 1) the Desires for Drug Questionnaire (DDQ) and 2) the Penn Alcohol-Craving Scale adapted for opioid craving (PCS) for this study. Multi-level logistic regression models estimated the effects of craving on the likelihood of opioid use after adjusting for gender, age, ethnicity, education, opioid of choice, frequency of use, pain and depression. In these analyses craving assessed at time t was entered as a time-varying predictor of opioid use at time t+1. Results In adjusted regression models, a 1-point increase in PCS scores (on a 7-point scale) was associated with a significant increase in the odds of opioid use at the subsequent assessment (OR = 1.27, 95% CI 1.08; 1.49, p .05) or DDQ control (OR = 0.97, 95%CI 0.85; 1.11, p > .05) scores. Conclusion Self-reported craving for opioids was associated with subsequent lapse to opioid use among a cohort of patients treated with buprenorphine. PMID:24521036

A text-mining analysis of the public's reactions to the opioid crisis.

Science.gov (United States)

Glowacki, Elizabeth M; Glowacki, Joseph B; Wilcox, Gary B

2017-07-19

Opioid abuse has become an epidemic in the United States. On August 25, 2016, the former Surgeon General of the United States sent an open letter to care providers asking for their help with combatting this growing health crisis. Social media forums such as Twitter allow for open discussions among the public and up-to-date exchanges of information about timely topics such as opioids. Therefore, the goal of the current study is to identify the public's reactions to the opioid epidemic by identifying the most popular topics tweeted by users. A text miner, algorithmic-driven statistical program was used to capture 73,235 original tweets and retweets posted within a 2-month time span 15 (August 15, 2016, through October 15, 2016). All tweets contained references to "opioids," "turnthetide," or similar keywords. The sets of tweets were then analyzed to identify the most prevalent topics. The most discussed topics had to do with public figures addressing opioid abuse, creating better treatment options for teen addicts, using marijuana as an alternative for managing pain, holding foreign and domestic drug makers accountable for the epidemic, promoting the "Rx for Change" campaign, addressing double standards in the perceptions and treatment of black and white opioid users, and advertising opioid recovery programs. Twitter allows users to find current information, voice their concerns, and share calls for action in response to the opioid epidemic. Monitoring the conversations about opioids that are taking place on social media forums such as Twitter can help public health officials and care providers better understand how the public is responding to this health crisis.

Differences between opioids

DEFF Research Database (Denmark)

Drewes, Asbjørn; Jensen, Rasmus D.; Nielsen, Lecia M.

2013-01-01

to morphine. Although this approach is recognized as cost-effective in most cases there is solid evidence that, on an individual patient basis, opioids are not all equal. Therefore it is important to have an armamentarium of strong analgesics in clinical practice to ensure a personalized approach in patients...... who do not respond to standard treatment. In this review we highlight differences between opioids in human studies from a pharmacological, experimental, clinical and health economics point of view. We provide evidence that individuals respond differently to opioids, and that general differences......Clinical studies comparing the response and side effects of various opioids have not been able to show robust differences between drugs. Hence, recommendations of the regulatory authorities have been driven by costs with a general tendency in many countries to restrict physician's use of opioids...

Assessing Differences in the Availability of Opioid Addiction Therapy Options: Rural Versus Urban and American Indian Reservation Versus Non-Reservation

Science.gov (United States)

Hirchak, Katherine A.; Murphy, Sean M.

2017-01-01

Background Opioid misuse is a large public health problem in the United States. Residents of rural areas and American Indian (AI) reservation/trust lands represent traditionally underserved populations with regard to substance-use-disorder therapy. Purpose Assess differences in the number of opioid agonist therapy (OAT) facilities and physicians with Drug Addiction Treatment Act (DATA) waivers for rural versus urban, and AI reservation/trust land versus non-AI reservation/trust land areas in Washington State. Methods The unit of analysis was the zip code. The dependent variables were the number of OAT facilities and DATA-waivered physicians in a region per 10,000 residents aged 18–64 in a zip code. A region was defined as a zip code and its contiguous zip codes. The independent variables were binary measures of whether a zip code was classified as rural versus urban, or AI reservation/trust land versus non-AI reservation/trust land. Zero-inflated negative binomial regressions with robust standard errors were estimated. Results The number of OAT clinics in a region per 10,000 zip-code residents was significantly lower in rural versus urban areas (P = .002). This did not differ significantly between AI reservation/trust land and non-AI reservation/trust land areas (P = .79). DATA-waivered physicians in a region per 10,000 zip-code residents was not significantly different between rural and urban (P = .08), or AI reservation/trust land versus non-AI reservation/trust land areas (P = .21). Conclusions It appears that the potential for Washington State residents of rural and AI reservation areas to receive OAT is similar to that of residents outside of those areas; however, difficulties in accessing therapy may remain, highlighting the importance of expanding health care insurance and providing support for DATA-waivered physicians. PMID:26987797

Opioid-induced constipation negatively impacts pain management, productivity, and health-related quality of life: findings from the National Health and Wellness Survey.

Science.gov (United States)

Bell, Timothy; Annunziata, Kathy; Leslie, John B

2009-01-01

To characterize the impact of opioid-induced constipation (OIC) on healthcare resource use, work productivity, and health-related quality of life (HRQOL) in patients receiving chronic opioid therapy. Data were collected via Internet questionnaires during the international National Health and Wellness Survey (NHWS) 2004 from individuals aged > or = 18 years who reported taking opioids for > or = 6 months. Healthcare resource utilization, Work Productivity, and Activity Impairment, and Short-Form 8 (SF-8) questionnaire responses were compared between those who did or did not report OIC. Data were available from 2,430 individuals receiving opioids, of whom 359 reported OIC. Participants with OIC reported significantly more physician visits (mean difference 3.84 visits; p hospitalization were observed. Respondents with OIC also reported significantly greater time missed from work, impairment while working, overall work impairment, and activity impairment (p constipation in patients receiving chronic opioid therapy.

Ibogaine Detoxification Transitions Opioid and Cocaine Abusers Between Dependence and Abstinence: Clinical Observations and Treatment Outcomes

Directory of Open Access Journals (Sweden)

Deborah C. Mash

2018-06-01

Full Text Available Ibogaine may be effective for transitioning opioid and cocaine dependent individuals to sobriety. American and European self-help groups provided public testimonials that ibogaine alleviated drug craving and opioid withdrawal symptoms after only a single dose administration. Preclinical studies in animal models of addiction have provided proof-of-concept evidence in support of these claims. However, the purported therapeutic benefits of ibogaine are based on anecdotal reports from a small series of case reports that used retrospective recruitment procedures. We reviewed clinical results from an open label case series (N = 191 of human volunteers seeking to detoxify from opioids or cocaine with medical monitoring during inpatient treatment. Whole blood was assayed to obtain pharmacokinetic measures to determine the metabolism and clearance of ibogaine. Clinical safety data and adverse events (AEs were studied in male and female subjects. There were no significant adverse events following administration of ibogaine in a dose range that was shown to be effective for blocking opioid withdrawal symptoms in this study. We used multi-dimensional craving questionnaires during inpatient detoxification to test if ibogaine was effective in diminishing heroin and cocaine cravings. Participants also completed standardized questionnaires about their health and mood before and after ibogaine treatment, and at program discharge. One-month follow-up data were reviewed where available to determine if ibogaine’s effects on drug craving would persist outside of an inpatient setting. We report here that ibogaine therapy administered in a safe dose range diminishes opioid withdrawal symptoms and reduces drug cravings. Pharmacological treatments for opioid dependence include detoxification, narcotic antagonists and long-term opioid maintenance therapy. Our results support product development of single oral dose administration of ibogaine for the treatment of opioid

Latin-American guidelines for opioid use in chronic nononcologic pain.

Science.gov (United States)

Lara-Solares, Argelia; Aguayo Zamora, Carlos; Amescua García, César; Garcia, João Batista Santos; Berenguel Cook, María Del Rosario; Bonilla Sierra, Patricia; Campos Kraychete, Durval; Flores Cantisani, José Alberto; Guerrero, Carlos; Guillén Núñez, María Del Rocío; Hernández Castro, John Jairo; Hernández Ortíz, Andrés; Jreige Iskandar, Aziza; Lech, Osvandré; Macías Guerra, Jacqueline; Ramírez Samayoa, Gerardo; Rangel Morillo, Edwin; Rico Pazos, María Antonieta; Sempértegui Gallegos, Manuel

2017-05-01

Latin-American experts in the use of opioids in patients with chronic nononcologic pain (CNOP) have updated existing recommendations to current Latin-American reality. Several key opinion leaders from Latin America participated in a face-to-face meeting in Guatemala (April 2015) to discuss the use of opioids in CNOP. Subgroups of experts worked on specific topics, reviewed the literature and shaped the final manuscript. The expert panel developed guidelines taking into consideration the utility of both opioid and nonopioid analgesics and factors pertaining to their efficacy, safety, adherence, administration and risks for abuse/addiction. Latin-American guidelines for the use of opioids in CNOP should improve pain relief and patients' quality of life by increasing access to these effective agents.

Current perspectives of radiation therapy. History of radiation therapy

International Nuclear Information System (INIS)

Itami, Jun

2011-01-01

More than 100 years have passed since the discovery of X-Strahlen by Roentgen. The history of radiation therapy has evolved under mutual stimulating relationships of the external beam radiation therapy by X-ray tubes and accelerators, and the internal radiation therapy employing radium and other radionuclides. The currently employed technologies in radiation therapy have its origin already till nineteen sixties and the development of physics and engineering have realized the original concept. (author)

Opioid Concentrations in Oral Fluid and Plasma in Cancer Patients With Pain.

Science.gov (United States)

Heiskanen, Tarja; Langel, Kaarina; Gunnar, Teemu; Lillsunde, Pirjo; Kalso, Eija A

2015-10-01

Measuring opioid concentrations in pain treatment is warranted in situations where optimal opioid analgesia is difficult to reach. To assess the usefulness of oral fluid (OFL) as an alternative to plasma in opioid concentration monitoring in cancer patients on chronic opioid therapy. We collected OFL and plasma samples from 64 cancer patients on controlled-release (CR) oral morphine, CR oral oxycodone, or transdermal (TD) fentanyl for pain. Samples were obtained on up to five separate days. A total of 213 OFL and plasma samples were evaluable. All patients had detectable amounts of the CR or TD opioid in both plasma and OFL samples. The plasma concentrations of oxycodone and fentanyl (determination coefficient R(2) = 0.628 and 0.700, respectively), but not morphine (R(2) = 0.292), were moderately well correlated to the daily opioid doses. In contrast to morphine and fentanyl (mean OFL/plasma ratio 2.0 and 3.0, respectively), the OFL oxycodone concentrations were significantly higher than the respective plasma concentrations (mean OFL/plasma ratio 14.9). An active transporter could explain the much higher OFL vs. plasma concentrations of oxycodone compared with morphine and fentanyl. OFL analysis is well suited for detecting the studied opioids. For morphine and fentanyl, an approximation of the plasma opioid concentrations is obtainable, whereas for oxycodone, the OFL/plasma concentration relationship is too variable for reliable approximation results. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Improving opioid safety practices in primary care: protocol for the development and evaluation of a multifaceted, theory-informed pilot intervention for healthcare providers.

Science.gov (United States)

Leece, Pamela; Buchman, Daniel Z; Hamilton, Michael; Timmings, Caitlyn; Shantharam, Yalnee; Moore, Julia; Furlan, Andrea D

2017-04-26

In North America, drug overdose deaths are reaching unprecedented levels, largely driven by increasing prescription opioid-related deaths. Despite the development of several opioid guidelines, prescribing behaviours still contribute to poor patient outcomes and societal harm. Factors at the provider and system level may hinder or facilitate the application of evidence-based guidelines; interventions designed to address such factors are needed. Using implementation science and behaviour change theory, we have planned the development and evaluation of a comprehensive Opioid Self-Assessment Package, designed to increase adherence to the Canadian Opioid Guideline among family physicians. The intervention uses practical educational and self-assessment tools to provide prescribers with feedback on their current knowledge and practices, and resources to improve their practice. The evaluation approach uses a pretest and post-test design and includes both quantitative and qualitative methods at baseline and 6 months. We will recruit a purposive sample of approximately 10 family physicians in Ontario from diverse practice settings, who currently treat patients with long-term opioid therapy for chronic pain. Quantitative data will be analysed using basic descriptive statistics, and qualitative data will be analysed using the Framework Method. The University Health Network Research Ethics Board approved this study. Dissemination plan includes publications, conference presentations and brief stakeholder reports. This evidence-informed, theory-driven intervention has implications for national application of opioid quality improvement tools in primary care settings. We are engaging experts and end users in advisory and stakeholder roles throughout our project to increase its national relevance, application and sustainability. The performance measures could be used as the basis for health system quality improvement indicators to monitor opioid prescribing. Additionally, the

Opioid dependence - management in general practice.

Science.gov (United States)

Frei, Matthew

2010-08-01

Addiction to opioids, or opioid dependence, encompasses the biopsychosocial dysfunction seen in illicit heroin injectors, as well as aberrant behaviours in patients prescribed opioids for chronic nonmalignant pain. To outline the management of opioid dependence using opioid pharmacotherapy as part of a comprehensive chronic illness management strategy. The same principles and skills general practitioners employ in chronic illness management underpin the care of patients with opioid dependence. Opioid pharmacotherapy, with the substitution medications methadone and buprenorphine, is an effective management of opioid dependence. Training and regulatory requirements for prescribing opioid pharmacotherapies vary between jurisdictions, but this treatment should be within the scope of most Australian GPs.

Safety of oral dronabinol during opioid withdrawal in humans.

Science.gov (United States)

Jicha, Crystal J; Lofwall, Michelle R; Nuzzo, Paul A; Babalonis, Shanna; Elayi, Samy Claude; Walsh, Sharon L

2015-12-01

Opioid dependence remains a significant public health problem worldwide with only three FDA-approved treatments, all targeting the mu-opioid receptor. Dronabinol, a cannabinoid (CB) 1 receptor agonist, is currently under investigation as a novel opioid withdrawal treatment. This study reports on safety outcomes of dronabinol among adults in opioid withdrawal. Twelve adults physically dependent on short-acting opioids participated in this 5-week within-subject, randomized, double blind, placebo-controlled inpatient study. Volunteers were maintained on oral oxycodone 30 mg qid. Double-blind placebo substitutions occurred for 21 h before each of 7 experimental sessions in order to produce opioid withdrawal. A single oral test dose was administered each session (placebo, oxycodone 30 and 60 mg, dronabinol 5, 10, 20, and 30 mg [decreased from 40 mg]). Heart rate, blood pressure, respiratory outcomes and pupil diameter were assessed repeatedly. Dronabinol 40 mg produced sustained sinus tachycardia accompanied by anxiety and panic necessitating dose reduction to 30 mg. Sinus tachycardia and anxiety also occurred in one volunteer after dronabinol 20mg. Compared to placebo, dronabinol 20 and 30 mg produced significant increases in heart rate beginning 1h after drug administration that lasted approximately 2h (popioid agonist effects (e.g., miosis). Dronabinol 20mg and higher increased heart rate among healthy adults at rest who were in a state of opioid withdrawal, raising concern about its safety. These results have important implications for future dosing strategies and may limit the utility of dronabinol as a treatment for opioid withdrawal. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Association of childhood abuse and prescription opioid use in early adulthood.

Science.gov (United States)

Austin, Anna E; Shanahan, Meghan E; Zvara, Bharathi J

2018-01-01

Previous research has examined the association of childhood abuse with opioid misuse and dependence in adulthood. However, little research has focused specifically on prescription opioids, and no studies have examined associations with prescription opioid use, a potential pathway to later opioid misuse and dependence. The aim of the present study was to examine the association of childhood emotional, physical, and sexual abuse with prescription opioid use in early adulthood. We used data from Waves I (12-18years) and IV (24-32years) of the National Longitudinal Study of Adolescent to Adult Health. At Wave IV, respondents reported experiences of childhood abuse occurring prior to age 18years and prescription opioid use in the last four weeks. We conducted multivariable logistic regression to examine associations of childhood abuse with recent prescription opioid use. In multivariable models adjusted for respondent sex, race/ethnicity, age, and socioeconomic status, childhood emotional abuse (OR=1.57, 95% CI 1.29, 1.90), physical abuse (OR=1.46, 95% CI 1.14, 1.87), and any childhood abuse (OR=1.51, 95% CI 1.24, 1.82) were significantly associated with recent prescription opioid use. Given continued increases in prescription opioid use and opioid-related morbidity and mortality in the U.S., understanding upstream social and environmental factors associated with prescription opioid use is important to strengthening and expanding current prevention and intervention strategies. Future research is needed to examine factors potentially mediating the association between childhood abuse and prescription opioid use in order to provide additional insights for prevention and intervention efforts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Barriers to access to opioid medicines for patients with opioid dependence: a review of legislation and regulations in eleven central and eastern European countries.

Science.gov (United States)

Vranken, Marjolein J M; Mantel-Teeuwisse, Aukje K; Jünger, Saskia; Radbruch, Lukas; Scholten, Willem; Lisman, John A; Subataite, Marija; Schutjens, Marie-Hélène D B

2017-06-01

Barriers linked to drug control systems are considered to contribute to inequitable access to controlled medicines, leaving millions of people in pain and suffering. Most studies focus on access to opioids for the treatment of severe (cancer) pain. This study aims to identify specific access barriers for patients with opioid dependence in legislation and regulations of 11 central and eastern European countries. This study builds on a previous analysis of legislation and regulations as part of the EU 7th Framework Access To Opioid Medication in Europe (ATOME) project. An in-depth analysis was undertaken to determine specific barriers for patients with opioid dependence in need of opioid analgesics or opioid agonist therapy (OAT). For each country, the number and nature of specific potential barriers for these patients were assessed according to eight categories: prescribing; dispensing; manufacturing; usage; trade and distribution; affordability; penalties; and other. An additional keyword search was conducted to minimize the omission of barriers. Barriers in an additional category, language, were recorded qualitatively. Countries included Bulgaria, Cyprus, Estonia, Greece, Hungary, Latvia, Lithuania, Serbia, Slovakia, Slovenia and Turkey. Ten of the 11 countries (all except Estonia) showed specific potential barriers in their legislation and regulations. The total number of barriers varied from two (Slovenia) to 46 (Lithuania); the number of categories varied from one (Slovenia) to five (Lithuania). Most specific potential barriers were shown in the categories 'prescribing', 'usage' and 'other'. The total number in a single category varied from one to 18 (Lithuania, prescribing). Individual differences between countries in the same specific potential barrier were shown; for example, variation in minimum age criteria for admission to OAT ranging from 15 (Lithuania, in special cases) to 20 years (Greece). All countries had stigmatizing language in their legislation

The Current State of Music Therapy Theory?

DEFF Research Database (Denmark)

Bonde, Lars Ole

2015-01-01

An essay on themes from Ken Aigen (2014): "The Study of Music Therapy. Current Issues and Concepts"......An essay on themes from Ken Aigen (2014): "The Study of Music Therapy. Current Issues and Concepts"...

Diagnostic Performance of Self-Assessment for Constipation in Patients With Long-Term Opioid Treatment.

Science.gov (United States)

Tafelski, Sascha; Bellin, Felicitas; Denke, Claudia; Beutlhauser, Torsten; Fritzsche, Thomas; West, Christina; Schäfer, Michael

2015-12-01

Constipation is a prevalent comorbidity affecting ∼50% of patients with long-term opioid therapy. In clinical routine different diagnostic instruments are in use to identify patients under risk. The aim of this study was to assess the diagnostic performance of an 11-item Likert scale for constipation used as a self-assessment in opioid-treated patients. This trial was conducted as a retrospective cohort study in Berlin, Germany. Patients with long-term opioid therapy treated in 2 university-affiliated outpatient pain facilities at the Charité hospital were included from January 2013 to August 2013. Constipation was rated in a self-assessment using a numeric rating scale from 0 to 10 (Con-NRS) and compared with results from a structured assessment based on ROME-III criteria. Altogether, 171 patients were included. Incidence of constipation was 49% of patients. The receiver-operating characteristic of Con-NRS achieved an area under the curve of 0.814 (AUC 95% confidence interval 0.748-0.880, P < 0.001). Con-NRS ≥ 1 achieved sensitivity and specificity of 79.7% and 77.2%, respectively. The positive predictive value and the negative predictive value were 70.3% and 81.6%, respectively. Overall diagnostic performance of a concise 11-item Likert scale for constipation was moderate. Although patients with long-term opioid therapy are familiar with numeric rating scales, a significant number of patients with constipation were not identified. The instrument may be additionally useful to facilitate individualized therapeutic decision making and to control therapeutic success when measured repetitively.

The Opioid Epidemic: What Does it Mean for Nurses?

Science.gov (United States)

Leahy, Laura G

2017-01-01

The United States is facing a major crisis with the current opioid epidemic. Tens of thousands of individuals are dying each year due to abuse and misuse of heroin and prescription opiate drugs. Nurses play an integral role in these aspects of health care and offer solutions by providing education; preventive measures; treatments, including medication-assisted treatments (MATs); and ongoing recovery options for individuals with opioid use disorders. Nurses provide education, issue prescriptions and dispense medications, and provide overall physical and mental health care to patients struggling with this "disease of the brain," and with the signing of the Comprehensive Addiction and Recovery Act, advanced practice RNs will soon be able to include MATs related to buprenorphine as part of their treatment plan. The current article explores the anatomy, physiology, and genetics of addiction and how they relate to the pharmacological MATs used to treat opioid use disorders. [Journal of Psychosocial Nursing and Mental Health Services, 55(1), 18-23.]. Copyright 2017, SLACK Incorporated.

Effectiveness of Mindfulness-Based Relapse Prevention in opioid Dependence Treatment &Mental Health

Directory of Open Access Journals (Sweden)

2008-11-01

Findings: therapy compliance, retention in treatment, decrease in somatic symptoms, anxiety, social dysfunction and increase in health was significantly in both combination of psychological intervention method than the Naltroxan group. Mindfulness-based on relapse prevention was more effective than CBT relapse prevention in decreasing of, social dysfunction, relapse prevention, increase of therapy compliance, and health. Results: Mindfulness based relapse prevention was superior to CBT and Naltroxan and considerably increased effectiveness of opioid relapse prevention therapy.

Opioid system and human emotions.

Science.gov (United States)

Nummenmaa, Lauri; Tuominen, Lauri

2017-04-10

Emotions are states of vigilant readiness that guide human and animal behaviour during survival-salient situations. Categorical models of emotions posit neurally and physiologically distinct basic human emotions (anger, fear, disgust, happiness, sadness and surprise) that govern different survival functions. Opioid receptors are expressed abundantly in the mammalian emotion circuit, and the opioid system modulates a variety of functions related to arousal and motivation. Yet, its specific contribution to different basic emotions has remained poorly understood. Here, we review how the endogenous opioid system and particularly the μ receptor contribute to emotional processing in humans. Activation of the endogenous opioid system is consistently associated with both pleasant and unpleasant emotions. In general, exogenous opioid agonists facilitate approach-oriented emotions (anger, pleasure) and inhibit avoidance-oriented emotions (fear, sadness). Opioids also modulate social bonding and affiliative behaviour, and prolonged opioid abuse may render both social bonding and emotion recognition circuits dysfunctional. However, there is no clear evidence that the opioid system is able to affect the emotions associated with surprise and disgust. Taken together, the opioid systems contribute to a wide array of positive and negative emotions through their general ability to modulate the approach versus avoidance motivation associated with specific emotions. Because of the protective effects of opioid system-mediated prosociality and positive mood, the opioid system may constitute an important factor contributing to psychological and psychosomatic resilience. © 2017 The British Pharmacological Society.

Cross-Sectional Analysis of Per Capita Supply of Doctors of Chiropractic and Opioid Use in Younger Medicare Beneficiaries.

Science.gov (United States)

Weeks, William B; Goertz, Christine M

2016-05-01

The purpose of this study was to determine whether the per-capita supply of doctors of chiropractic (DCs) or Medicare spending on chiropractic care was associated with opioid use among younger, disabled Medicare beneficiaries. Using 2011 data, at the hospital referral region level, we correlated the per-capita supply of DCs and spending on chiropractic manipulative therapy (CMT) with several measures of per-capita opioid use by younger, disabled Medicare beneficiaries. Per-capita supply of DCs and spending on CMT were strongly inversely correlated with the percentage of younger Medicare beneficiaries who had at least 1, as well as with 6 or more, opioid prescription fills. Neither measure was correlated with mean daily morphine equivalents per opioid user or per chronic opioid user. A higher per-capita supply of DCs and Medicare spending on CMT were inversely associated with younger, disabled Medicare beneficiaries obtaining an opioid prescription. However, neither measure was associated with opioid dosage among patients who obtained opioid prescriptions. Copyright © 2016. Published by Elsevier Inc.

Reconciling Patient Safety and Epistemic Humility: An Ethical Use of Opioid Treatment Plans.

Science.gov (United States)

Ho, Anita

2017-05-01

In this issue of the Hastings Center Report, Joshua Rager and Peter Schwartz suggest using opioid treatment agreements as public health monitoring tools to inform patients about "the requirements entailed by undergoing opioid therapy," rather than as contractual agreements to alter patients' individual behavior or to benefit them directly. Because Rager and Schwartz's argument presents suspected OTA violations as a justification to stop providing opioids yet does not highlight the broader epistemic and systemic context within which clinicians prescribe these medications, their proposal may perpetuate a climate of distrust and stigmatization without correcting systemic factors that may have placed patients and others at risk in the first place. Given the context of epistemic uncertainty regarding opioid safety and efficacy, insufficient training for opioid prescribers, and inadequate patient education, I propose replacing OTAs, which have a narrow focus on patient behaviors, with opioid treatment plans, which would promote mutual, collaborative, and shared decision-making on the most appropriate pain management program. An OTP can be ethically justified as a tool to prevent and treat iatrogenic addiction under a specific paradigm-one that adopts a default position of professional epistemic humility and holds all collaborative parties accountable in chronic pain management. © 2017 The Hastings Center.

Biased Agonism of Endogenous Opioid Peptides at the μ-Opioid Receptor.

Science.gov (United States)

Thompson, Georgina L; Lane, J Robert; Coudrat, Thomas; Sexton, Patrick M; Christopoulos, Arthur; Canals, Meritxell

2015-08-01

Biased agonism is having a major impact on modern drug discovery, and describes the ability of distinct G protein-coupled receptor (GPCR) ligands to activate different cell signaling pathways, and to result in different physiologic outcomes. To date, most studies of biased agonism have focused on synthetic molecules targeting various GPCRs; however, many of these receptors have multiple endogenous ligands, suggesting that "natural" bias may be an unappreciated feature of these GPCRs. The μ-opioid receptor (MOP) is activated by numerous endogenous opioid peptides, remains an attractive therapeutic target for the treatment of pain, and exhibits biased agonism in response to synthetic opiates. The aim of this study was to rigorously assess the potential for biased agonism in the actions of endogenous opioids at the MOP in a common cellular background, and compare these to the effects of the agonist d-Ala2-N-MePhe4-Gly-ol enkephalin (DAMGO). We investigated activation of G proteins, inhibition of cAMP production, extracellular signal-regulated kinase 1 and 2 phosphorylation, β-arrestin 1/2 recruitment, and MOP trafficking, and applied a novel analytical method to quantify biased agonism. Although many endogenous opioids displayed signaling profiles similar to that of DAMGO, α-neoendorphin, Met-enkephalin-Arg-Phe, and the putatively endogenous peptide endomorphin-1 displayed particularly distinct bias profiles. These may represent examples of natural bias if it can be shown that they have different signaling properties and physiologic effects in vivo compared with other endogenous opioids. Understanding how endogenous opioids control physiologic processes through biased agonism can reveal vital information required to enable the design of biased opioids with improved pharmacological profiles and treat diseases involving dysfunction of the endogenous opioid system. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Inhibition of GABAergic Neurotransmission by HIV-1 Tat and Opioid Treatment in the Striatum Involves ?-Opioid Receptors

OpenAIRE

Xu, Changqing; Fitting, Sylvia

2016-01-01

Due to combined antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) is considered a chronic disease with high prevalence of mild forms of neurocognitive impairments, also referred to as HIV-associated neurocognitive disorders (HAND). Although opiate drug use can exacerbate HIV-1 Tat-induced neuronal damage, it remains unknown how and to what extent opioids interact with Tat on the GABAergic system. We conducted whole-cell recordings in mouse striatal slices and examined...

Changing patterns in opioid addiction

Science.gov (United States)

Sproule, Beth; Brands, Bruna; Li, Selina; Catz-Biro, Laura

2009-01-01

ABSTRACT OBJECTIVE To evaluate the clinical observation that the number of individuals seeking opioid detoxification from oxycodone was increasing at the Centre for Addiction and Mental Health (CAMH) in Toronto, Ont; and to identify the characteristics of individuals seeking opioid detoxification at CAMH. DESIGN Retrospective analysis of patient health records. SETTING Medical Withdrawal Management Service at CAMH. PARTICIPANTS All patients admitted for opioid detoxification between January 2000 and December 2004. MAIN OUTCOME MEASURES Number of opioid detoxification admissions each year; type, dose, and source of opioids; comorbid problems and symptoms. RESULTS There were 571 opioid detoxification admissions during the 5-year study period. The number of admissions increased steadily over the 5 years; in particular, the number of admissions related to controlled-release oxycodone increased substantially (3.8%, 8.3%, 20.8%, 30.6%, and 55.4% of the total opioid admissions in 2000 to 2004, respectively; χ42= 105.5, P < .001). The rates of admissions involving heroin remained low and stable. Use of controlled-release oxycodone was associated with considerably higher doses than use of other prescription opioids was. Physician prescriptions were the source of the prescription opioids for a large percentage of patients, particularly for older patients. Prescription opioid users reported considerable comorbid substance use problems, pain, and psychiatric symptoms. CONCLUSION This study has demonstrated a significant rise in the number of individuals seeking treatment at CAMH for controlled-release oxycodone addiction. The substantial comorbid pain, psychiatric symptoms, and other psychoactive substance use problems in these patients, coupled with the finding that prescriptions were an important source of opioids, highlight the clinical complexities encountered in the treatment of these individuals. Further research examining these complexities and the many possible

Misuse of Novel Synthetic Opioids: A Deadly New Trend

Science.gov (United States)

Prekupec, Matthew P.; Mansky, Peter A.; Baumann, Michael H.

2017-01-01

Novel synthetic opioids (NSOs) include various analogs of fentanyl and newly emerging non-fentanyl compounds. Together with illicitly manufactured fentanyl (IMF), these drugs have caused a recent spike in overdose deaths, whereas deaths from prescription opioids have stabilized. NSOs are used as stand-alone products, as adulterants in heroin, or as constituents of counterfeit prescription medications. During 2015 alone, there were 9580 deaths from synthetic opioids other than methadone. Most of these fatalities were associated with IMF rather than diverted pharmaceutical fentanyl. In opioid overdose cases, where the presence of fentanyl analogs was examined, analogs were implicated in 17% of fatalities. Recent data from law enforcement sources show increasing confiscation of acetylfentanyl, butyrylfentanyl, and furanylfentanyl, in addition to non-fentanyl compounds such as U-47700. Since 2013, deaths from NSOs in the United States were 52 for acetylfentanyl, 40 for butyrylfentanyl, 128 for furanylfentanyl, and 46 for U-47700. All of these substances induce a classic opioid toxidrome, which can be reversed with the competitive antagonist naloxone. However, due to the putative high potency of NSOs and their growing prevalence, it is recommended to forgo the 0.4 mg initial dose of naloxone and start with 2 mg. Because NSOs offer enormous profit potential, and there is strong demand for their use, these drugs are being trafficked by organized crime. NSOs present major challenges for medical professionals, law enforcement agencies, and policymakers. Resources must be distributed equitably to enhance harm reduction though public education, medication-assisted therapies, and improved access to naloxone. PMID:28590391

Distinct roles of exogenous opioid agonists and endogenous opioid peptides in the peripheral control of neuropathy-triggered heat pain.

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Labuz, Dominika; Celik, Melih Ö; Zimmer, Andreas; Machelska, Halina

2016-09-08

Neuropathic pain often results from peripheral nerve damage, which can involve immune response. Local leukocyte-derived opioid peptides or exogenous opioid agonists inhibit neuropathy-induced mechanical hypersensitivity in animal models. Since neuropathic pain can also be augmented by heat, in this study we investigated the role of opioids in the modulation of neuropathy-evoked heat hypersensitivity. We used a chronic constriction injury of the sciatic nerve in wild-type and opioid peptide-knockout mice, and tested opioid effects in heat and mechanical hypersensitivity using Hargreaves and von Frey tests, respectively. We found that although perineural exogenous opioid agonists, including peptidergic ligands, were effective, the endogenous opioid peptides β-endorphin, Met-enkephalin and dynorphin A did not alleviate heat hypersensitivity. Specifically, corticotropin-releasing factor, an agent triggering opioid peptide secretion from leukocytes, applied perineurally did not attenuate heat hypersensitivity in wild-type mice. Exogenous opioids, also shown to release opioid peptides via activation of leukocyte opioid receptors, were equally analgesic in wild-type and opioid peptide-knockout mice, indicating that endogenous opioids do not contribute to exogenous opioid analgesia in heat hypersensitivity. Furthermore, exogenously applied opioid peptides were ineffective as well. Conversely, opioid peptides relieved mechanical hypersensitivity. Thus, both opioid type and sensory modality may determine the outcome of neuropathic pain treatment.

Low pain intensity after opioid withdrawal as a first step of a comprehensive pain rehabilitation program predicts long-term nonuse of opioids in chronic noncancer pain.

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Krumova, Elena K; Bennemann, Philipp; Kindler, Doris; Schwarzer, Andreas; Zenz, Michael; Maier, Christoph

2013-09-01

In specialized pain clinics there is an increasing number of patients with severe chronic noncancer pain (CNCP) despite long-term opioid medication. Few clinical studies show short-term pain relief after opioid withdrawal (OW). We have evaluated the relation between pain intensity after OW and long-term opioid nonuse. One hundred two consecutive patients with severe CNCP despite opioid medication (mean treatment duration, 43 mo) reported pain intensity (numerical rating scale, 0 to 10), Pain Disability Index, mood (CES-D), and quality of life (Short Form 36) before, shortly, and 12 to 24 months after inpatient OW. Total opioid withdrawal (n = 78) or significant dose reduction (DR; n = 24, mean reduction, 82%) was performed after individual decision. Opioid intake 12 to 24 months later, respectively dose increase ≥ 100% (DR group), was considered relapse. T tests, multivariable analysis of variance, logistic regression. After OW current pain intensity significantly decreased on an average by 41% (6.4 ± 2.4 vs. 3.8 ± 2.5), maximal and average pain by 18% and 24%, respectively. Twelve to 24 months later 42 patients (41%) relapsed (31 of the total opioid withdrawal group, 6 of the DR group, 5 lost). Patients without later relapse showed significantly lower pain scores than the later relapsed patients already shortly after OW (5.0 ± 2.2 vs. 5.9 ± 2.1) and 12 to 24 months later (5.5 ± 2.4 vs. 6.5 ± 2.0). There was a significant relation between relapse probability and pain intensity immediately after OW. In many patients with severe CNCP, despite opioid medication, sustainable pain relief can be achieved if OW is included in the rehabilitation program. Consequently, we recommend OW for opioid-resistant CNCP before any opioid escalation. Lower pain intensity shortly after OW may predict the long-term opioid nonuse probability.

Opioid Abuse and Addiction - Multiple Languages

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... Spanish) PDF The basics - Opioids, part 1 - English MP3 The basics - Opioids, part 1 - español (Spanish) MP3 The basics - Opioids, part 1 - English MP4 The ... español (Spanish) PDF Pain - Opioids, part 2 - English MP3 Pain - Opioids, part 2 - español (Spanish) MP3 Pain - ...

The endogenous opioid system: a common substrate in drug addiction.

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Trigo, José Manuel; Martin-García, Elena; Berrendero, Fernando; Robledo, Patricia; Maldonado, Rafael

2010-05-01

Drug addiction is a chronic brain disorder leading to complex adaptive changes within the brain reward circuits that involve several neurotransmitters. One of the neurochemical systems that plays a pivotal role in different aspects of addiction is the endogenous opioid system (EOS). Opioid receptors and endogenous opioid peptides are largely distributed in the mesolimbic system and modulate dopaminergic activity within these reward circuits. Chronic exposure to the different prototypical drugs of abuse, including opioids, alcohol, nicotine, psychostimulants and cannabinoids has been reported to produce significant alterations within the EOS, which seem to play an important role in the development of the addictive process. In this review, we will describe the adaptive changes produced by different drugs of abuse on the EOS, and the current knowledge about the contribution of each component of this neurobiological system to their addictive properties.

Ketamine as an adjuvant to opioids for cancer pain.

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Bell, Rae F; Eccleston, Christopher; Kalso, Eija A

2017-06-28

second study with 10 participants examined the addition of intravenous ketamine bolus in two different doses to ongoing morphine therapy, compared with placebo. Both of these studies reported reduction in pain intensity and reduction in morphine requirements when ketamine was added to opioid for refractory cancer pain. The new study identified by the updated search had a parallel group design and 185 participants. This placebo-controlled study examined rapid titration of subcutaneous ketamine to high dose (500 mg) in participants who were using different opioids. There were no differences between groups for patient-reported pain intensity.Pooling of the data from the three included trials was not appropriate because of clinical heterogeneity.The study examining intrathecal drug administration reported no adverse events related to ketamine. In the study using intravenous bolus administration, ketamine caused hallucinations in four of 10 participants. In the rapid dose escalation/high-dose subcutaneous ketamine study, there was almost twice the incidence of adverse events in the ketamine group, compared to the placebo group, with the most common adverse events being needle site irritation and cognitive disturbance. Two serious adverse events (bradyarrhythmia and cardiac arrest) thought to be related to ketamine were also reported in this trial.For all three studies there was an unclear risk of bias overall. Using GRADE, we judged the quality of the evidence to be very low due to study limitations and imprecision due to the small number of participants in all comparisons. Current evidence is insufficient to assess the benefits and harms of ketamine as an adjuvant to opioids for the relief of refractory cancer pain. The evidence was of very low quality, meaning that it does not provide a reliable indication of the likely effect, and the likelihood that the effect will be substantially different is high. Rapid dose escalation of ketamine to high dose (500 mg) does not appear

Carbon Nanotube Membranes for use in the Transdermal Treatment of Nicotine Addiction and Opioid Withdrawal Symptoms

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Caroline L. Strasinger

2009-01-01

Full Text Available Transdermal systems are attractive methods of drug administration specifically when treating patients for drug addiction. Current systems however are deficient in therapies that allow variable flux values of drug, such as nicotine for smoking cessation or complex dosing regimens using clonidine when treating opioid withdrawal symptoms. Through the use of functionalized carbon nanotube (CNT membranes, drug delivery to the skin can be controlled by applying a small electrical bias to create a programmable drug delivery system. Clearly, a transdermal patch system that can be tailored to an individual's needs will increase patient compliance as well as provide much more efficient therapy. The purpose of this paper is to discuss the applicability of using carbon nanotube membranes in transdermal systems for treatment of drug abuse.

Cancer pain management and the opioid crisis in America: How to preserve hard-earned gains in improving the quality of cancer pain management.

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Paice, Judith A

2018-06-15

Cancer pain remains a feared consequence of the disease and its treatment. Although prevalent, cancer pain can usually be managed through the skillful application of pharmacologic and nonpharmacologic interventions. Unfortunately, access to these therapies has been hampered by interventions designed to contain another serious public health problem: the opioid misuse epidemic. This epidemic and the unintended consequences of efforts to control this outbreak are leading to significant barriers to the provision of cancer pain relief. Oncologists and other professionals treating those with cancer pain will require new knowledge and tools to provide safe and effective pain control while preventing additional cases of substance use disorders (SUDs), helping patients in recovery to maintain sobriety, and guiding those not yet in recovery to seek treatment. How do these 2 serious epidemics intersect and affect oncology practice? First, oncology professionals will need to adopt practices to prevent SUDs by assessing risk and providing safe pain care. Second, oncology practices are likely to see an increased number of patients with a current or past SUD, including opioid misuse. Few guidelines exist for the direct management of pain when opioids may be indicated in these individuals. Third, modified prescribing practices along with the education of patients and families are warranted to prevent the exposure of these medications to unintended persons. Finally, advocacy on behalf of those with cancer pain is imperative to avoid losing access to essential therapies, including opioids, for those who might benefit. Cancer 2018;124:2491-7. © 2018 American Cancer Society. © 2018 American Cancer Society.

Is this ?complicated? opioid withdrawal?

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Parkar, S.R.; Seethalakshmi, R; Adarkar, S; Kharawala, S

2006-01-01

Seven patients with opioid dependence admitted in the de-addiction centre for detoxification developed convulsions and delirium during the withdrawal phase. After ruling out all other possible causes of these complications, opioid withdrawal seemed to emerge as the most likely explanation. The unpredictability of the course of opioid dependence and withdrawal needs to be considered when treating patients with opioid dependence.

Opioid analgesics-related pharmacokinetic drug interactions: from the perspectives of evidence based on randomized controlled trials and clinical risk management

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Feng XQ

2017-05-01

Full Text Available Xiu-qin Feng,1 Ling-ling Zhu,2 Quan Zhou3 1Nursing Administration Office, Division of Nursing, 2VIP Care Ward, Division of Nursing, 3Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China Background: Multimorbidity results in complex polypharmacy which may bear a risk of drug interactions. A better understanding of opioid analgesics combination therapy used for pain management could help warrant medication safety, efficacy, and economic relevance. Until now there has been no review summarizing the opioid analgesics-related pharmacokinetic drug interactions from the perspective of evidence based on randomized controlled trials (RCTs. Method: A literature search was performed using PubMed, MEDLINE, and the Cochrane Library, using a PRISMA flowchart. Results: Fifty-two RCTs were included for data interpretation. Forty-two RCTs (80.8% were conducted in healthy volunteers, whereas 10 RCTs (19.2% enrolled true patients. None of the opioid–drug/herb pairs was listed as contraindications of opioids involved in this review. Circumstances in which opioid is comedicated as a precipitant drug include morphine–P2Y12 inhibitors, morphine–gabapentin, and methadone–zidovudine. Circumstances in which opioid is comedicated as an object drug include rifampin–opioids (morphine, tramadol, oxycodone, methadone, quinidine–opioids (morphine, fentanyl, oxycodone, codeine, dihydrocodeine, methadone, antimycotics–opioids (buprenorphine, fentanyl, morphine, oxycodone, methadone, tilidine, tramadol, protease inhibitors–opioids (ritonavir, ritonavir/lopinavir–oxycodone, ritonavir–fentanyl, ritonavir–tilidine, grapefruit juice–opioids (oxycodone, fentanyl, methadone, antidepressants–opioids (paroxetine–tramadol, paroxetine–hydrocodone, paroxetine–oxycodone, escitalopram–tramadol, metoclopramide–morphine, amantadine–morphine, sumatriptan�

The downward spiral of chronic pain, prescription opioid misuse, and addiction: cognitive, affective, and neuropsychopharmacologic pathways.

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Garland, Eric L; Froeliger, Brett; Zeidan, Fadel; Partin, Kaitlyn; Howard, Matthew O

2013-12-01

Prescription opioid misuse and addiction among chronic pain patients are emerging public health concerns of considerable significance. Estimates suggest that more than 10% of chronic pain patients misuse opioid analgesics, and the number of fatalities related to nonmedical or inappropriate use of prescription opioids is climbing. Because the prevalence and adverse consequences of this threat are increasing, there is a pressing need for research that identifies the biobehavioral risk chain linking chronic pain, opioid analgesia, and addictive behaviors. To that end, the current manuscript draws upon current neuropsychopharmacologic research to provide a conceptual framework of the downward spiral leading to prescription opioid misuse and addiction among chronic pain patients receiving opioid analgesic pharmacotherapy. Addictive use of opioids is described as the outcome of a cycle initiated by chronic pain and negative affect and reinforced by opioidergic-dopamingeric interactions, leading to attentional hypervigilance for pain and drug cues, dysfunctional connectivity between self-referential and cognitive control networks in the brain, and allostatic dysregulation of stress and reward circuitry. Implications for clinical practice are discussed; multimodal, mindfulness-oriented treatment is introduced as a potentially effective approach to disrupting the downward spiral and facilitating recovery from chronic pain and opioid addiction. Copyright © 2013 Elsevier Ltd. All rights reserved.

"Bureaucracy & Beliefs": Assessing the Barriers to Accessing Opioid Substitution Therapy by People Who Inject Drugs in Ukraine.

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Bojko, Martha J; Mazhnaya, Alyona; Makarenko, Iuliia; Marcus, Ruthanne; Dvoriak, Sergii; Islam, Zahedul; Altice, Frederick L

Opioid substitution therapy (OST) is an evidence-based HIV prevention strategy for people who inject drugs (PWIDs). Yet, only 2.7% of Ukraine's estimated 310,000 PWIDs receive it despite free treatment since 2004. The multi-level barriers to entering OST among opioid dependent PWIDs have not been examined in Ukraine. A multi-year mixed methods implementation science project included focus group discussions with 199 PWIDs in 5 major Ukrainian cities in 2013 covering drug treatment attitudes and beliefs and knowledge of and experiences with OST. Data were transcribed, translated into English and coded. Coded segments related to OST access, entry, knowledge, beliefs and attitudes were analyzed among 41 PWIDs who were eligible for but had never received OST. A number of programmatic and structural barriers were mentioned by participants as barriers to entry to OST, including compulsory drug user registration, waiting lists, and limited number of treatment slots. Participants also voiced strong negative attitudes and beliefs about OST, especially methadone. Their perceptions about methadone's side effects as well as the stigma of being a methadone client were expressed as obstacles to treatment. Despite expressed interest in treatment, Ukrainian OST-naïve PWIDs evade OST for reasons that can be addressed through changes in program-level and governmental policies and social-marketing campaigns. Voiced OST barriers can effectively inform public health and policy directives related to HIV prevention and treatment in Ukraine to improve evidence-based treatment access and availability.

Relationship between opioid therapy, tissue-damaging procedures, and brain metabolites as measured by proton MRS in asphyxiated term neonates.

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Angeles, Danilyn M; Ashwal, Stephen; Wycliffe, Nathaniel D; Ebner, Charlotte; Fayard, Elba; Sowers, Lawrence; Holshouser, Barbara A

2007-05-01

To examine the effects of opioid and tissue-damaging procedures (TDPs) [i.e. procedures performed in the neonatal intensive care unit (NICU) known to result in pain, stress, and tissue damage] on brain metabolites, we reviewed the medical records of 28 asphyxiated term neonates (eight opioid-treated, 20 non-opioid treated) who had undergone magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) within the first month of life as well as eight newborns with no clinical findings of asphyxial injury. We found that lower creatine (Cr), myoinositol (Ins), and N-acetylaspartate (NAA)/choline (Cho) (p OGM) NAA/Cr was decreased (p = 0.03) and lactate (Lac) was present in a significantly higher amount (40%; p = 0.03) in non-opioid-treated neonates compared with opioid-treated neonates. Compared with controls, untreated neonates showed larger changes in more metabolites in basal ganglia (BG), thalami (TH), and OGM with greater significance than treated neonates. Our data suggest that TDPs affect spectral metabolites and that opioids do not cause harm in asphyxiated term neonates exposed to repetitive TDPs in the first 2-4 DOL and may provide a degree of neuroprotection.

Morphine withdrawal enhances constitutive μ-opioid receptor activity in the ventral tegmental area

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Meye, F.J.; van Zessen, R.; Smidt, M.P.; Adan, R.A.H.; Ramakers, G.M.J.

2012-01-01

μ-opioid receptors (MORs) in the ventral tegmental area (VTA) are pivotally involved in addictive behavior. While MORs are typically activated by opioids, they can also become constitutively active in the absence of any agonist. In the current study, we present evidence that MOR constitutive

Gender issues in the pharmacotherapy of opioid-addicted women: buprenorphine.

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Unger, Annemarie; Jung, Erika; Winklbaur, Bernadette; Fischer, Gabriele

2010-04-01

Gender, a biological determinant of mental health and illness, plays a critical role in determining patients' susceptibility, exposure to mental health risks, and related outcomes. Regarding sex differences in the epidemiology of opioid dependence, one third of the patients are women of childbearing age. Women have an earlier age of initiation of substance use and a more rapid progression to drug involvement and dependence than men. Generally few studies exist which focus on the special needs of women in opioid maintenance therapy. The aim of this paper is to provide an overview of treatment options for opioid-dependent women, with a special focus on buprenorphine, and to look at recent findings related to other factors that should be taken into consideration in optimizing the treatment of opioid-dependent women. Issues addressed include the role of gender in the choice of medication assisted treatment, sex differences in pharmacodynamics and pharmacokinetics of buprenorphine drug interactions, cardiac interactions, induction of buprenorphine in pregnant patients, the neonatal abstinence syndrome and breastfeeding. This paper aims to heighten the awareness for the need to take gender into consideration when making treatment decisions in an effort to optimize services and enhance the quality of life of women suffering from substance abuse.

Genetics Home Reference: opioid addiction

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... Facebook Twitter Home Health Conditions Opioid addiction Opioid addiction Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Opioid addiction is a long-lasting (chronic) disease that can ...

The opioid manager: a point-of-care tool to facilitate the use of the Canadian Opioid Guideline.

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Furlan, Andrea D; Reardon, Rhoda; Salach, Lena

2012-01-01

The Opioid Manager is designed to be used as a point-of-care tool for providers prescribing opioids for chronic noncancer pain. It condenses the key elements from the Canadian Opioid Guideline and can be used as a chart insert. The Opioid Manager has been validated and is available for download from the Guideline's Web site http://nationalpaincentre.mcmaster.ca/opioidmanager/. The Opioid Manager is divided into the following four parts: A) before you write the first script, B) initiation trial, C) maintenance and monitoring, and D) when is it time to decrease the dose or stop the opioid completely? The Opioid Manager has been downloaded by 1,432 users: 47 percent family physicians, 18 percent pharmacists, 13 percent other physicians, and 22 percent miscellaneous. To show how to use the Opioid Manager, the authors created a 10-minute video that is available on the Internet. The Opioid Manager is being translated to French, Spanish, Portuguese, and Farsi.

Implications of prescription drug monitoring and medical cannabis legislation on opioid overdose mortality.

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Phillips, Elyse; Gazmararian, Julie

To determine whether specific state legislation has an effect on opioid overdose mortality rates compared to states without those types of legislation. Ecological study estimating opioid-related mortality in states with and without a prescription drug monitoring program (PDMP) and/or medical cannabis legislation. Opioid-related mortality rates for 50 states and Washington DC from 2011 to 2014 were obtained from CDC WONDER. PDMP data were obtained from the National Alliance for Model State Drug Laws, and data on medical cannabis legislation from the National Organization for the Reform of Marijuana Laws. The relationship between PDMPs with mandatory access provisions, medical cannabis legislation, and opioid-related mortality rates. Multivariate repeated measures analysis performed with software and services. Medical cannabis laws were associated with an increase of 21.7 percent in mean age-adjusted opioid-related mortality (p cannabis (p = 0.049) and 5.8 percent for states with a PDMP (p = 0.005). Interaction between both types of legislation produced a borderline significant decrease of 10.1 percent (p = 0.055). For every year states had both types of legislation, interaction resulted in a 0.6 percent decrease in rate (p = 0.013). When combined with the availability of medical cannabis as an alternative analgesic therapy, PDMPs may be more effective at decreasing opioid-related mortality.

Co-relationship between sexual dysfunction and high-risk sexual behavior in patients receiving buprenorphine and naltrexone maintenance therapy for opioid dependence

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Santosh Ramdurg

2015-01-01

Full Text Available Introduction: People suffering from substance dependence suffer from various sexual dysfunctions and are at risk for indulging in various high-risk sexual behaviors and thus are vulnerable to acquire various infections such as HIV/AIDS and other sexually transmitted infections. AIM: The aim of the study was to evaluate the correlation between sexual dysfunction and high-risk sexual behavior in opioid-dependent men receiving buprenorphine and naltrexone maintenance therapy. Materials and Methods: Semi-structured questionnaire, brief male sexual functioning inventory and HIV-risk taking behavior scale was administered to a sample of 60 sexually active men, receiving buprenorphine (n = 30 and naltrexone (n = 30 maintenance therapy for opioid dependence. Results: The main outcomes are correlation between severity of sexual dysfunction and HIV-risk taking behavior. The study results showed 83% of the men on buprenorphine and 90% on naltrexone reported at least one of the sexual dysfunction symptoms. There was a negative correlation between sexual dysfunction and HIV-risk taking behavior that suggest severe the dysfunction, higher the risk taking behavior. Significant correlation was present with overall sexual dysfunction and HIV-risk taking behavior (P = 0.028 and in naltrexone receiving group premature ejaculation versus HIV-risk taking behavior however, (P = 0.022, P < 0.05 there were no significant differences among both the groups except above findings. Conclusion: Conclusion was treatment is associated with sexual dysfunctions and HIV-risk taking behavior, which has clinical implication. Future research should explore this further using biochemical analyses.

Enhancing system-wide implementation of opioid prescribing guidelines in primary care: protocol for a stepped-wedge quality improvement project.

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Zgierska, Aleksandra E; Vidaver, Regina M; Smith, Paul; Ales, Mary W; Nisbet, Kate; Boss, Deanne; Tuan, Wen-Jan; Hahn, David L

2018-06-05

Systematic implementation of guidelines for opioid therapy management in chronic non-cancer pain can reduce opioid-related harms. However, implementation of guideline-recommended practices in routine care is subpar. The goal of this quality improvement (QI) project is to assess whether a clinic-tailored QI intervention improves the implementation of a health system-wide, guideline-driven policy on opioid prescribing in primary care. This manuscript describes the protocol for this QI project. A health system with 28 primary care clinics caring for approximately 294,000 primary care patients developed and implemented a guideline-driven policy on long-term opioid therapy in adults with opioid-treated chronic non-cancer pain (estimated N = 3980). The policy provided multiple recommendations, including the universal use of treatment agreements, urine drug testing, depression and opioid misuse risk screening, and standardized documentation of the chronic pain diagnosis and treatment plan. The project team drew upon existing guidelines, feedback from end-users, experts and health system leadership to develop a robust QI intervention, targeting clinic-level implementation of policy-directed practices. The resulting multi-pronged QI intervention included clinic-wide and individual clinician-level educational interventions. The QI intervention will augment the health system's "routine rollout" method, consisting of a single educational presentation to clinicians in group settings and a separate presentation for staff. A stepped-wedge design will enable 9 primary care clinics to receive the intervention and assessment of within-clinic and between-clinic changes in adherence to the policy items measured by clinic-level electronic health record-based measures and process measures of the experience with the intervention. Developing methods for a health system-tailored QI intervention required a multi-step process to incorporate end-user feedback and account for the needs of

Opioid-Induced Glial Activation: Mechanisms of Activation and Implications for Opioid Analgesia, Dependence, and Reward

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Mark R. Hutchinson

2007-01-01

Full Text Available This review will introduce the concept of toll-like receptor (TLR–mediated glial activation as central to all of the following: neuropathic pain, compromised acute opioid analgesia, and unwanted opioid side effects (tolerance, dependence, and reward. Attenuation of glial activation has previously been demonstrated both to alleviate exaggerated pain states induced by experimental pain models and to reduce the development of opioid tolerance. Here we demonstrate that selective acute antagonism of TLR4 results in reversal of neuropathic pain as well as potentiation of opioid analgesia. Attenuating central nervous system glial activation was also found to reduce the development of opioid dependence, and opioid reward at a behavioral (conditioned place preference and neurochemical (nucleus accumbens microdialysis of morphine-induced elevations in dopamine level of analysis. Moreover, a novel antagonism of TLR4 by (+- and (˗-isomer opioid antagonists has now been characterized, and both antiallodynic and morphine analgesia potentiating activity shown. Opioid agonists were found to also possess TLR4 agonistic activity, predictive of glial activation. Targeting glial activation is a novel and as yet clinically unexploited method for treatment of neuropathic pain. Moreover, these data indicate that attenuation of glial activation, by general or selective TLR antagonistic mechanisms, may also be a clinical method for separating the beneficial (analgesia and unwanted (tolerance, dependence, and reward actions of opioids, thereby improving the safety and efficacy of their use.

Opioid-induced constipation, use of laxatives, and health-related quality of life.

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Christensen, Helene Nordahl; Olsson, Urban; From, Jesper; Breivik, Harald

2016-04-01

Real-life data on laxative use in patients suffering from opioid-induced constipation (OIC) are very limited, and many OIC patients are only using over the counter laxatives to resolve their constipation. Our aim was to describe laxative utilization and quality of life in participants in Norway who ever experienced OIC. This was a cross-sectional online survey conducted between 27th of June and 3rd of July 2014 among participants above 18 years with self-reported OIC and who had agreed to receive information from the pharmacy chain (Boots A/S, Norway). The questionnaire comprised a series of multiple choice, close-ended, and free text questions on abdominal symptoms, laxative use and health-related quality of life. A total of 417 participants met the study eligibility criteria: (1) treated with opioid for a minimum of 4 weeks, (2) actively accepted participation, and (3) confirmed ever experiencing OIC and in addition completed the survey. Among the eligible participants, 86% were females, 85% were younger than 60 years of age, and 57% were currently suffering OIC. More than half of the currently constipated participants were experiencing moderate to very severe abdominal bloating (63%), abdominal pain (55%) and/or pain during bowel movement (50%). Less than every fourth participant (23%) had consulted health care professionals (HCPs) about their constipation. Up to 39% reported that they handled their OIC by self-management, e.g., bought laxative, reduced the dose and/or changed opioid without consulting HCP or pharmacy. Less than half (48%) of the laxative users were satisfied with the laxative they were using to relieve their constipation. The EQ-5D health-related quality of life score was mean (SD): 0.587 (0.272). Although not statistically significant (p=0.067), there was a tendency of lower quality of life among the participants who were currently constipated compared with those not currently constipated (difference of mean EQ-5D: 0.629-0.555=0.074). A

Chronic Opioid Use After Surgery: Implications for Perioperative Management in the Face of the Opioid Epidemic.

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Hah, Jennifer M; Bateman, Brian T; Ratliff, John; Curtin, Catherine; Sun, Eric

2017-11-01

Physicians, policymakers, and researchers are increasingly focused on finding ways to decrease opioid use and overdose in the United States both of which have sharply increased over the past decade. While many efforts are focused on the management of chronic pain, the use of opioids in surgical patients presents a particularly challenging problem requiring clinicians to balance 2 competing interests: managing acute pain in the immediate postoperative period and minimizing the risks of persistent opioid use after the surgery. Finding ways to minimize this risk is particularly salient in light of a growing literature suggesting that postsurgical patients are at increased risk for chronic opioid use. The perioperative care team, including surgeons and anesthesiologists, is poised to develop clinical- and systems-based interventions aimed at providing pain relief in the immediate postoperative period while also reducing the risks of opioid use longer term. In this paper, we discuss the consequences of chronic opioid use after surgery and present an analysis of the extent to which surgery has been associated with chronic opioid use. We follow with a discussion of the risk factors that are associated with chronic opioid use after surgery and proceed with an analysis of the extent to which opioid-sparing perioperative interventions (eg, nerve blockade) have been shown to reduce the risk of chronic opioid use after surgery. We then conclude with a discussion of future research directions.

Characteristics of opioid-users whose death was related to opioid-toxicity: a population-based study in Ontario, Canada.

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Parvaz Madadi

Full Text Available The impact of the prescription opioid public health crisis has been illustrated by the dramatic increase in opioid-related deaths in North America. We aimed to identify patterns and characteristics amongst opioid-users whose cause of death was related to opioid toxicity.This was a population-based study of Ontarians between the years 2006 and 2008. All drug-related deaths which occurred during this time frame were reviewed at the Office of the Chief Coroner of Ontario, and opioid-related deaths were identified. Medical, toxicology, pathology, and police reports were comprehensively reviewed. Narratives, semi-quantitative, and quantitative variables were extracted, tabulated, and analyzed.Out of 2330 drug-related deaths in Ontario, 58% were attributed either in whole or in part, to opioids (n = 1359. Oxycodone was involved in approximately one-third of all opioid-related deaths. At least 7% of the entire cohort used opioids that were prescribed for friends and/or family, 19% inappropriately self-administered opioids (injection, inhalation, chewed patch, 3% were recently released from jail, and 5% had been switched from one opioid to another near the time of death. Accidental deaths were significantly associated with personal history of substance abuse, enrollment in methadone maintenance programs, cirrhosis, hepatitis, and cocaine use. Suicides were significantly associated with mental illness, previous suicide attempts, chronic pain, and a history of cancer.These results identify novel, susceptible groups of opioid-users whose cause of death was related to opioids in Ontario and provide the first evidence to assist in quantifying the contribution of opioid misuse and diversion amongst opioid-related mortality in Canada. Multifaceted prevention strategies need to be developed based on subpopulations of opioid users.

Illicit Opioid Intoxication: Diagnosis and Treatment

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A. Fareed

2011-01-01

Full Text Available Opioid intoxications and overdose are associated with high rates of morbidity and mortality. Opioid overdose may occur in the setting of intravenous or intranasal heroin use, illicit use of diverted opioid medications, intentional or accidental misuse of prescription pain medications, or iatrogenic overdose. In this review, we focused on the epidemiology of illict opioid use in the United States and on the mechanism of action of opioid drugs. We also described the signs and symptoms, and diagnoses of intoxication and overdose. Lastly, we updated the reader about the most recent recommendations for treatment and prevention of opioid intoxications and overdose.

"I was a little surprised": Qualitative Insights from Patients Enrolled in a 12-Month Trial Comparing Opioids to Non-Opioid Medications for Chronic Musculoskeletal Pain.

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Marianne S Matthias; Donaldson, Melvin T; Jensen, Agnes C; Krebs, Erin E

2018-04-28

Chronic musculoskeletal pain is a major public health problem. Although opioid prescribing for chronic pain has increased dramatically since the 1990s, this practice has come under scrutiny because of increases in opioid-related harms and lack of evidence for long-term effectiveness. The Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) trial was a pragmatic 12-month randomized trial comparing benefits and harms of opioid versus non-opioid medications for chronic musculoskeletal pain. The current qualitative study was designed to better understand trial results by exploring patients' experiences, including perceptions of medications, experiences with the intervention, and whether expectations were met. Thirty-four participants who were purposefully sampled based on treatment group and intervention response participated in semi-structured interviews. The constant comparison method guided analysis. Results revealed that participants often held strong beliefs about opioid medications, which sometimes changed during the trial as they gained experience with medications; participants described a wide variety of experiences with treatment effectiveness, regardless of study group or their response to the intervention; and participants highly valued the personalized pain care model used in SPACE. SPACE trial results indicated no advantage for opioid over non-opioid medications. Qualitative findings suggest that, for patients in both treatment groups, pre-existing expectations of medications and of anticipated improvement in pain shaped experiences with and responses to medications. In addition, the personalized pain care model was described as contributing to positive outcomes in both groups. Copyright © 2018. Published by Elsevier Inc.

Impact of Chronic Pain on Treatment Prognosis for Patients with Opioid Use Disorder: A Systematic Review and Meta-analysis

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Brittany B. Dennis

2015-01-01

Full Text Available Background While a number of pharmacological interventions exist for the treatment of opioid use disorder, evidence evaluating the effect of pain on substance use behavior, attrition rate, and physical or mental health among these therapies has not been well established. We aim to evaluate these effects using evidence gathered from a systematic review of studies evaluating chronic non-cancer pain (CNCP in patients with opioid use disorder. Methods We searched the Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Database of Systematic Reviews, ProQuest Dissertations and theses Database, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform Search Portal, and National Institutes for Health Clinical Trials Registry databases to identify articles evaluating the impact of pain on addiction treatment outcomes for patients maintained on opioid agonist therapy. Results Upon screening 3,540 articles, 14 studies with a combined sample of 3,128 patients fulfilled the review inclusion criteria. Results from the meta-analysis suggest that pain has no effect on illicit opioid consumption [pooled odds ratio (pOR: 0.70, 95%CI 0.41–1.17; I 2 = 0.0] but a protective effect for reducing illicit non-opioid substance use (pOR: 0.57, 95%CI 0.41–0.79; I 2 = 0.0. Studies evaluating illicit opioid consumption using other measures demonstrate pain to increase the risk for opioid abuse. Pain is significantly associated with the presence of psychiatric disorders (pOR: 2.18; 95%CI 1.6, 2.9; I 2 = 0.0%. Conclusion CNCP may increase risk for continued opioid abuse and poor psychiatric functioning. Qualitative synthesis of the findings suggests that major methodological differences in the design and measurement of pain and treatment response outcomes are likely impacting the effect estimates.

Identifying Primary Care Skills and Competencies in Opioid Risk Management

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Chiauzzi, Emil; Trudeau, Kimberlee J.; Zacharoff, Kevin; Bond, Kathleen

2011-01-01

Introduction: Primary care physicians (PCPs) treat a high proportion of chronic pain patients but often lack training about how to assess and address issues associated with prescribing opioids when they are an appropriate component of therapy. The result may be that they may avoid treating these patients, which can lead to an undertreatment of…

Identifying and assessing the risk of opioid abuse in patients with cancer: an integrative review

Directory of Open Access Journals (Sweden)

Carmichael AN

2016-06-01

Full Text Available Ashley-Nicole Carmichael,1 Laura Morgan,1 Egidio Del Fabbro2 1School of Pharmacy, 2Division of Hematology, Oncology, and Palliative Care, Virginia Commonwealth University, Richmond, VA, USA Background: The misuse and abuse of opioid medications in many developed nations is a health crisis, leading to increased health-system utilization, emergency department visits, and overdose deaths. There are also increasing concerns about opioid abuse and diversion in patients with cancer, even at the end of life. Aims: To evaluate the current literature on opioid misuse and abuse, and more specifically the identification and assessment of opioid-abuse risk in patients with cancer. Our secondary aim is to offer the most current evidence of best clinical practice and suggest future directions for research. Materials and methods: Our integrative review included a literature search using the key terms “identification and assessment of opioid abuse in cancer”, “advanced cancer and opioid abuse”, “hospice and opioid abuse”, and “palliative care and opioid abuse”. PubMed, PsycInfo, and Embase were supplemented by a manual search. Results: We found 691 articles and eliminated 657, because they were predominantly noncancer populations or specifically excluded cancer patients. A total of 34 articles met our criteria, including case studies, case series, retrospective observational studies, and narrative reviews. The studies were categorized into screening questionnaires for opioid abuse or alcohol, urine drug screens to identify opioid misuse or abuse, prescription drug-monitoring programs, and the use of universal precautions. Conclusion: Screening questionnaires and urine drug screens indicated at least one in five patients with cancer may be at risk of opioid-use disorder. Several studies demonstrated associations between high-risk patients and clinical outcomes, such as aberrant behavior, prolonged opioid use, higher morphine-equivalent daily dose

Feeding Releases Endogenous Opioids in Humans.

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Tuulari, Jetro J; Tuominen, Lauri; de Boer, Femke E; Hirvonen, Jussi; Helin, Semi; Nuutila, Pirjo; Nummenmaa, Lauri

2017-08-23

The endogenous opioid system supports a multitude of functions related to appetitive behavior in humans and animals, and it has been proposed to govern hedonic aspects of feeding thus contributing to the development of obesity. Here we used positron emission tomography to investigate whether feeding results in hedonia-dependent endogenous opioid release in humans. Ten healthy males were recruited for the study. They were scanned with the μ-opioid-specific ligand [ 11 C]carfentanil three times, as follows: after a palatable meal, a nonpalatable meal, and after an overnight fast. Subjective mood, satiety, and circulating hormone levels were measured. Feeding induced significant endogenous opioid release throughout the brain. This response was more pronounced following a nonpalatable meal versus a palatable meal, and independent of the subjective hedonic responses to feeding. We conclude that feeding consistently triggers cerebral opioid release even in the absence of subjective pleasure associated with feeding, suggesting that metabolic and homeostatic rather than exclusively hedonic responses play a role in the feeding-triggered cerebral opioid release. SIGNIFICANCE STATEMENT The endogenous opioid system supports both hedonic and homeostatic functions. It has been proposed that overeating and concomitant opioid release could downregulate opioid receptors and promote the development of obesity. However, it remains unresolved whether feeding leads to endogenous opioid release in humans. We used in vivo positron emission tomography to test whether feeding triggers cerebral opioid release and whether this response is associated with pleasurable sensations. We scanned volunteers using the μ-opioid receptor-specific radioligand [ 11 C]carfentanil three times, as follows: after an overnight fast, after consuming a palatable meal, and after consuming a nonpalatable meal. Feeding led to significant endogenous opioid release, and this occurred also in the absence of feeding

Opioid-free anaesthesia in three dogs

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Donna M. White

2017-05-01

Full Text Available Opioid-free anaesthesia (OFA is a relatively new and growing field in human medicine. There are multiple motivations behind this emerging practice with the recognition of several serious potential opioid-related adverse effects including opioid induced hyperalgesia, opioid tolerance and immunomodulatory effects of opioids. Opioids have long been the mainstay of veterinary anaesthesia and pain management practice. The feasibility of OFA in veterinary patients is presented here. A case series of three dogs that underwent OFA for canine ovariohysterectomy is reported. The authors conclude OFA is possible in veterinary medicine; however the move away from the familiar effects of opioids perioperatively is challenging. Gaining experience with these types of protocols for standard procedures in healthy animals, such as neutering, will provide the anaesthetist with the building blocks for more invasive surgeries.

Pennsylvania State Core Competencies for Education on Opioids and Addiction.

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Ashburn, Michael A; Levine, Rachel L

2017-10-01

The objective of this project was to develop core competencies for education on opioids and addiction to be used in all Pennsylvania medical schools. The Pennsylvania Physician General created a task force that was responsible for the creation of the core competencies. A literature review was completed, and a survey of graduating medical students was conducted. The task force then developed, reviewed, and approved the core competencies. The competencies were grouped into nine domains: understanding core aspects of addiction; patient screening for substance use disorder; proper referral for specialty evaluation and treatment of substance use disorder; proper patient assessment when treating pain; proper use of multimodal treatment options when treating acute pain; proper use of opioids for the treatment of acute pain (after consideration of alternatives); the role of opioids in the treatment of chronic noncancer pain; patient risk assessment related to the use of opioids to treat chronic noncancer pain, including the assessment for substance use disorder or increased risk for aberrant drug-related behavior; and the process for patient education, initiation of treatment, careful patient monitoring, and discontinuation of therapy when using opioids to treat chronic noncancer pain. Specific competencies were developed for each domain. These competencies will be incorporated into the educational process at all Pennsylvania medical schools. It is hoped that these curriculum changes will improve student knowledge and attitudes in these areas, thus improving patient outcomes. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Interactions of the opioid and cannabinoid systems in reward: Insights from knockout studies

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Katia eBefort

2015-02-01

Full Text Available The opioid system consists of three receptors, mu, delta, and kappa, which are activated by endogenous opioid peptides (enkephalins, endorphins and dynorphins. The endogenous cannabinoid system comprises lipid neuromodulators (endocannabinoids, enzymes for their synthesis and their degradation and two well-characterized receptors, cannabinoid receptors CB1 and CB2. These systems play a major role in the control of pain as well as in mood regulation, reward processing and the development of addiction. Both opioid and cannabinoid receptors are coupled to G proteins and are expressed throughout the brain reinforcement circuitry. Extending classical pharmacology, research using genetically modified mice has provided important progress in the identification of the specific contribution of each component of these endogenous systems in vivo on reward process. This review will summarize available genetic tools and our present knowledge on the consequences of gene knockout on reinforced behaviors in both systems, with a focus on their potential interactions. A better understanding of opioid-cannabinoid interactions may provide novel strategies for therapies in addicted individuals.

Nonmedical opioid use among electronic dance music party attendees in New York City.

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Palamar, Joseph J; Le, Austin; Cleland, Charles M

2018-05-01

Nonmedical opioid use remains an epidemic in the United States. Electronic dance music (EDM) party attendees have been found to be at high risk for the use of drugs such as ecstasy, but little is known about nonmedical opioid use in this population. Using time-space sampling, we surveyed 954 individuals (ages 18-40) attending randomly selected EDM parties in New York City in 2017. Participants were asked about the use of 18 different opioids and about willingness to use if offered by a friend in the next 30 days. We estimated the prevalence of use in this population and examined correlates of past-year and past-month use. Almost a quarter (23.9%) of EDM party attendees are estimated to have used opioids non-medically in their lifetime, and one out of ten (9.8%) in the past year. 5% are estimated to be current users (reporting past-month use), and 16.4% are willing to use opioids non-medically if offered by a friend in the next 30 days. Past-year nonmedical benzodiazepine users were at high odds for reporting current nonmedical opioid use (aOR = 10.11, p < 0.001) and, on average, report using more different opioid drugs in the past year than non-past-year-users (p = 0.012). Nearly three-quarters (73.6%) of those who have used in the past year indicated that they would use again if offered by a friend in the next 30 days. Nonmedical opioid use is prevalent in the EDM scene and many attendees are willing to use if offered. Prevention efforts are needed in this high-risk population. Copyright © 2018 Elsevier B.V. All rights reserved.

Macroeconomic conditions and opioid abuse.

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Hollingsworth, Alex; Ruhm, Christopher J; Simon, Kosali

2017-12-01

We examine how deaths and emergency department (ED) visits related to use of opioid analgesics (opioids) and other drugs vary with macroeconomic conditions. As the county unemployment rate increases by one percentage point, the opioid death rate per 100,000 rises by 0.19 (3.6%) and the opioid overdose ED visit rate per 100,000 increases by 0.95 (7.0%). Macroeconomic shocks also increase the overall drug death rate, but this increase is driven by rising opioid deaths. Our findings hold when performing a state-level analysis, rather than county-level; are primarily driven by adverse events among whites; and are stable across time periods. Copyright © 2017 Elsevier B.V. All rights reserved.

Targinact--opioid pain relief without constipation?

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2010-12-01

Targinact (Napp Pharmaceuticals Ltd) is a modified-release combination product containing the strong opioid oxycodone plus the opioid antagonist naloxone. It is licensed for "severe pain, which can be adequately managed only with opioid analgesics".1 The summary of product characteristics (SPC) states that "naloxone is added to counteract opioid-induced constipation by blocking the action of oxycodone at opioid receptors locally in the gut". Advertising for the product claims "better pain relief", "superior GI [gastrointestinal] tolerability" and "improved quality of life" "compared to previous treatment in a clinical practice study (n=7836)". Here we consider whether Targinact offers advantages over using strong opioids plus laxatives where required.

Doctors and patients in pain: Conflict and collaboration in opioid prescription in primary care.

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Esquibel, Angela Y; Borkan, Jeffrey

2014-12-01

Use of chronic opioid therapy (COT) for chronic noncancer pain has dramatically increased in the United States. Patients seek compassionate care and relief while physicians struggle to manage patients' pain effectively without doing harm. This study explores the narratives of chronic noncancer pain patients receiving chronic opioid therapy and those of their physicians to better understand the effects of COT on the doctor-patient relationship. A mixed method study was conducted that included in-depth interviews and qualitative analysis of 21 paired patients with chronic pain and their physicians in the following groups: patients, physicians, and patient-physician pairs. Findings revealed that patients' narratives focus on suffering from chronic pain, with emphasis on the role of opioid therapy for pain relief, and physicians' narratives describe the challenges of treating patients with chronic pain on COT. Results elucidate the perceptions of ideal vs difficult patients and show that divergent patterns surrounding the consequences, utility, and goals of COT can negatively affect the doctor-patient relationship. The use of paired interviews through a narrative lens in this exploratory study offers a novel and informative approach for clinical practice and research. The findings have significant implications for improving doctor-patient communication and health outcomes by encouraging shared decision making and goal-directed health care encounters for physicians and patients with chronic pain on COT. This study found patterns of understanding pain, opioid pain medications, and the doctor-patient relationship for patients with chronic pain and their physicians using a narrative lens. Thematic findings in this exploratory study, which include a portrayal of collaborative vs conflictual relationships, suggest areas of future intervention and investigation. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Opioid use following gynecologic and pelvic reconstructive surgery.

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Hota, Lekha S; Warda, Hussein A; Haviland, Miriam J; Searle, Frances M; Hacker, Michele R

2017-09-09

Opioid use, addiction, and overdose are a growing epidemic in the USA. Our objective was to determine whether the amount of opioid medication prescribed following gynecologic and pelvic reconstructive surgery is insufficient, adequate, or in excess. We hypothesized that we were overprescribing postoperative opioids. Participants who were at least 18 years old and underwent gynecologic and/or pelvic reconstructive surgery from April through August 2016 were eligible to participate. Routine practice for pain management is to prescribe 30 tablets of opioids for major procedures and ten to 15 tablets for minor procedures. At the 2-week postoperative visit, participants completed a questionnaire regarding the number of tablets prescribed and used, postoperative pain control, and relevant medical history. Fisher's exact test was used to compare data. Sixty-five participants completed questionnaires. Half (49.1%) reported being prescribed more opioids than needed, while two (3.5%) felt the amount was less than needed. Though not significant, participants who underwent major surgeries were more likely to report being prescribed more than needed (53.5%) compared with participants who underwent minor surgeries (35.7%; p = 0.47). Though not significant, participants with anxiety were less likely to report being prescribed more tablets than needed compared with participants without anxiety (44.4% vs. 57.1%; p = 0.38). This was also true of participants with depression compared with those without (37.5% vs. 58.3%; p = 0.17), and those with chronic pain compared with those without (33.3% vs. 60.0%; p = 0.10). Our current opioid prescription practice for postoperative pain management may exceed what patients need.

Alternative Drugs in Pain Therapy

Directory of Open Access Journals (Sweden)

İlker Kelle

2006-01-01

Full Text Available Various treatment modalities of acute and chronic pain have been an area of interest of medicine and investigators for centuries. There are two major classes of drugs that are used to control pain: opioid and non-opioid analgesics. They could be used in the case of monotherapy or combination therapy in pain management. However, these agents are not accepted as ideal drugs in clinical approaches against pain because of their serious side effects such as development of tolerance and addiction, renal failure and gastrointestinal bleeding. As a consequent, developing new forms of pain relievers that are more safe and effective without any other side effects has became the main goal of researchers. In recent studies, it has been shown that conotoxin therapies are not addictive, and have tolerable indexes unlike opioids. In addition, conotoxins side effects are much milder and easier to manage than those of opioids. In this regard, it has been emphasized that biotoxins such as conotoxins obtained from marine creatures can be better choices in pain management for future prospects.

Carbon Nanotube Membranes for use in the Transdermal Treatment of Nicotine Addiction and Opioid Withdrawal Symptoms

Directory of Open Access Journals (Sweden)

Audra L. Stinchcomb

2009-01-01

Full Text Available Transdermal systems are attractive methods of drug administration specifically when treating patients for drug addiction. Current systems however are deficient in therapies that allow variable flux values of drug, such as nicotine for smoking cessation or complex dosing regimens using clonidine when treating opioid withdrawal symptoms. Through the use of functionalized carbon nanotube (CNT membranes, drug delivery to the skin can be controlled by applying a small electrical bias to create a programmable drug delivery system. Clearly, a transdermal patch system that can be tailored to an individual’s needs will increase patient compliance as well as provide much more efficient therapy. The purpose of this paper is to discuss the applicability of using carbon nanotube membranes in transdermal systems for treatment of drug abuse.

Variability in prescription opioid intake and reinforcement amongst 129 substrains.

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Jimenez, S M; Healy, A F; Coelho, M A; Brown, C N; Kippin, T E; Szumlinski, K K

2017-09-01

Opioid abuse in the United States has reached epidemic proportions, with treatment admissions and deaths associated with prescription opioid abuse quadrupling over the past 10 years. Although genetics are theorized to contribute substantially to inter-individual variability in the development, severity and treatment outcomes of opioid abuse/addiction, little direct preclinical study has focused on the behavioral genetics of prescription opioid reinforcement and drug-taking. Herein, we employed different 129 substrains of mice currently available from The Jackson Laboratory (129S1/SvlmJ, 129X1/SvJ, 129S4/SvJaeJ and 129P3/J) as a model system of genetic variation and assayed mice for oral opioid intake and reinforcement, as well as behavioral and somatic signs of dependence. All substrains exhibited a dose-dependent increase in oral oxycodone and heroin preference and intake under limited-access procedures and all, but 129S1/SvlmJ mice, exhibited oxycodone reinforcement. Relative to the other substrains, 129P3/J mice exhibited higher heroin and oxycodone intake. While 129X1/SvJ exhibited the highest anxiety-like behavior during natural opioid withdrawal, somatic and behavior signs of precipitated withdrawal were most robust in 129P3/J mice. These results demonstrate the feasibility and relative sensitivity of our oral opioid self-administration procedures for detecting substrain differences in drug reinforcement/intake among 129 mice, of relevance to the identification of genetic variants contributing to high vs. low oxycodone reinforcement and intake. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Opioids and breast cancer recurrence

DEFF Research Database (Denmark)

Cronin-Fenton, Deirdre P; Heide-Jørgensen, Uffe; Ahern, Thomas P

2015-01-01

BACKGROUND: Opioids may alter immune function, thereby potentially affecting cancer recurrence. The authors investigated the association between postdiagnosis opioid use and breast cancer recurrence. METHODS: Patients with incident, early stage breast cancer who were diagnosed during 1996 through...... 2008 in Denmark were identified from the Danish Breast Cancer Cooperative Group Registry. Opioid prescriptions were ascertained from the Danish National Prescription Registry. Follow-up began on the date of primary surgery for breast cancer and continued until breast cancer recurrence, death......, emigration, 10 years, or July 31, 2013, whichever occurred first. Cox regression models were used to compute hazard ratios and 95% confidence intervals associating breast cancer recurrence with opioid prescription use overall and by opioid type and strength, immunosuppressive effect, chronic use (≥6 months...

Women who abuse prescription opioids: findings from the Addiction Severity Index-Multimedia Version Connect prescription opioid database.

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Green, Traci C; Grimes Serrano, Jill M; Licari, Andrea; Budman, Simon H; Butler, Stephen F

2009-07-01

Evidence suggests gender differences in abuse of prescription opioids. This study aimed to describe characteristics of women who abuse prescription opioids in a treatment-seeking sample and to contrast gender differences among prescription opioid abusers. Data collected November 2005 to April 2008 derived from the Addiction Severity Index Multimedia Version Connect (ASI-MV Connect) database. Bivariate and multivariable logistic regression examined correlates of prescription opioid abuse stratified by gender. 29,906 assessments from 220 treatment centers were included, of which 12.8% (N=3821) reported past month prescription opioid abuse. Women were more likely than men to report use of any prescription opioid (29.8% females vs. 21.1% males, phistory of drug overdose. Men-specific correlates were age screen and identify those at highest risk of prescription opioid abuse. Prevention and intervention efforts with a gender-specific approach are warranted.

An educational strategy for treating chronic, noncancer pain with opioids: a pilot test.

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Elhwairis, Huda; Reznich, Christopher B

2010-12-01

Chronic pain is common and can be devastating to the patient and challenging to the health care provider. Despite the importance of the topic, pain management curricula are incomplete in health professionals' training. We developed a longitudinal curriculum to teach therapy for chronic noncancer pain over four units and pilot-tested the teaching of one unit (opioids) to internal medicine residents. The educational strategies we used included didactic sessions, write-up of a management plan following a model, case discussions, and role-play group activities. We pilot-tested one unit (opioid therapy) in March 2008. We performed learner evaluations, using a pretest and posttest, a write-up plan following a model, and a learner knowledge questionnaire. Results showed significant improvement in knowledge. Residents found the sessions and educational strategy to be excellent and reported higher confidence levels in managing patients with chronic noncancer pain. This article demonstrates that multiple teaching modalities-including didactic lectures, case discussions, write-up of a management plan following a model, and role-play group activities-are effective methods of teaching internal medicine residents how to use opioids to manage chronic noncancer pain. Copyright © 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.

Cannabis Use is Associated with Lower Odds of Prescription Opioid Analgesic Use Among HIV-Infected Individuals with Chronic Pain.

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Sohler, Nancy L; Starrels, Joanna L; Khalid, Laila; Bachhuber, Marcus A; Arnsten, Julia H; Nahvi, Shadi; Jost, John; Cunningham, Chinazo O

2018-01-17

Chronic pain is common in the United States and prescribed opioid analgesics use for noncancer pain has increased dramatically in the past two decades, possibly accounting for the current opioid addiction epidemic. Co-morbid drug use in those prescribed opioid analgesics is common, but there are few data on polysubstance use patterns. We explored patterns of use of cigarette, alcohol, and illicit drugs in HIV-infected people with chronic pain who were prescribed opioid analgesics. We conducted a secondary data analysis of screening interviews conducted as part of a parent randomized trial of financial incentives to improve HIV outcomes among drug users. In a convenience sample of people with HIV and chronic pain, we collected self-report data on demographic characteristics; pain; patterns of opioid analgesic use (both prescribed and illicit); cigarette, alcohol, and illicit drug use (including cannabis, heroin, and cocaine) within the past 30 days; and current treatment for drug use and HIV. Almost half of the sample of people with HIV and chronic pain reported current prescribed opioid analgesic use (N = 372, 47.1%). Illicit drug use was common (N = 505, 63.9%), and cannabis was the most commonly used illicit substance (N = 311, 39.4%). In multivariate analyses, only cannabis use was significantly associated with lower odds of prescribed opioid analgesic use (adjusted odds ratio = 0.57; 95% confidence interval: 0.38-0.87). Conclusions/Importance: Our data suggest that new medical cannabis legislation might reduce the need for opioid analgesics for pain management, which could help to address adverse events associated with opioid analgesic use.

Review of Opioid Pharmacogenetics and Considerations for Pain Management.

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Owusu Obeng, Aniwaa; Hamadeh, Issam; Smith, Michael

2017-09-01

Opioid analgesics are the standards of care for the treatment of moderate to severe nociceptive pain, particularly in the setting of cancer and surgery. Their analgesic properties mainly emanate from stimulation of the μ receptors, which are encoded by the OPRM1 gene. Hepatic metabolism represents the major route of elimination, which, for some opioids, namely codeine and tramadol, is necessary for their bioactivation into more potent analgesics. The highly polymorphic nature of the genes coding for phase I and phase II enzymes (pharmacokinetics genes) that are involved in the metabolism and bioactivation of opioids suggests a potential interindividual variation in their disposition and, most likely, response. In fact, such an association has been substantiated in several pharmacokinetic studies described in this review, in which drug exposure and/or metabolism differed significantly based on the presence of polymorphisms in these pharmacokinetics genes. Furthermore, in some studies, the observed variability in drug exposure translated into differences in the incidence of opioid-related adverse effects, particularly nausea, vomiting, constipation, and respiratory depression. Although the influence of polymorphisms in pharmacokinetics genes, as well as pharmacodynamics genes (OPRM1 and COMT) on response to opioids has been a subject of intense research, the results have been somehow conflicting, with some evidence insinuating for a potential role for OPRM1. The Clinical Pharmacogenetics Implementation Consortium guidelines provide CYP2D6-guided therapeutic recommendations to individualize treatment with tramadol and codeine. However, implementation guidelines for other opioids, which are more commonly used in real-world settings for pain management, are currently lacking. Hence, further studies are warranted to bridge this gap in our knowledge base and ultimately ascertain the role of pharmacogenetic markers as predictors of response to opioid analgesics. © 2017

Social Laughter Triggers Endogenous Opioid Release in Humans.

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Manninen, Sandra; Tuominen, Lauri; Dunbar, Robin I; Karjalainen, Tomi; Hirvonen, Jussi; Arponen, Eveliina; Hari, Riitta; Jääskeläinen, Iiro P; Sams, Mikko; Nummenmaa, Lauri

2017-06-21

The size of human social networks significantly exceeds the network that can be maintained by social grooming or touching in other primates. It has been proposed that endogenous opioid release after social laughter would provide a neurochemical pathway supporting long-term relationships in humans (Dunbar, 2012), yet this hypothesis currently lacks direct neurophysiological support. We used PET and the μ-opioid-receptor (MOR)-specific ligand [ 11 C]carfentanil to quantify laughter-induced endogenous opioid release in 12 healthy males. Before the social laughter scan, the subjects watched laughter-inducing comedy clips with their close friends for 30 min. Before the baseline scan, subjects spent 30 min alone in the testing room. Social laughter increased pleasurable sensations and triggered endogenous opioid release in thalamus, caudate nucleus, and anterior insula. In addition, baseline MOR availability in the cingulate and orbitofrontal cortices was associated with the rate of social laughter. In a behavioral control experiment, pain threshold-a proxy of endogenous opioidergic activation-was elevated significantly more in both male and female volunteers after watching laughter-inducing comedy versus non-laughter-inducing drama in groups. Modulation of the opioidergic activity by social laughter may be an important neurochemical pathway that supports the formation, reinforcement, and maintenance of human social bonds. SIGNIFICANCE STATEMENT Social contacts are vital to humans. The size of human social networks significantly exceeds the network that can be maintained by social grooming in other primates. Here, we used PET to show that endogenous opioid release after social laughter may provide a neurochemical mechanism supporting long-term relationships in humans. Participants were scanned twice: after a 30 min social laughter session and after spending 30 min alone in the testing room (baseline). Endogenous opioid release was stronger after laughter versus the

Group cognitive behavioral therapy to improve the quality of care to opioid-treated patients with chronic noncancer pain: a practice improvement project.

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Whitten, Stacey K; Stanik-Hutt, Julie

2013-07-01

To enhance outcomes of patients with chronic noncancer pain (CNCP) treated with opioids in a primary care setting by implementing an evidence-based quality improvement project. The project consisted of the implementation of a 6-week cognitive behavioral therapy (CBT) program. Twenty-two patients with CNCP completed the program. Impact of the project was evaluated by comparing pre- and postintervention participant self-reports of mood on the Beck Depression Inventory and functional status on the Brief Pain Inventory and Short Form-36. Patient perception of treatment benefit was also measured using the Patient Global Impression of Change. Qualitative provider perceptions of the program were also collected. Paired t-test statistics were used to analyze the data. Mood (including negative attitude, performance difficulty, and physical complaints), and patient impression of treatment benefit improved significantly after CBT was added. Primary care providers reported that the CBT supported their overall management of these complex patients. The addition of a CBT program improved selected outcomes in this self-selected sample of patients with CNCP treated with opioids. ©2012 The Author(s) ©2012 American Association of Nurse Practitioners.

Peripherally applied opioids for postoperative pain

DEFF Research Database (Denmark)

Nielsen, B N; Henneberg, S W; Schmiegelow, K

2015-01-01

BACKGROUND: Opioids applied peripherally at the site of surgery may produce postoperative analgesia with few side effects. We performed this systematic review to evaluate the analgesic effect of peripherally applied opioids for acute postoperative pain. METHODS: We searched PubMed (1966 to June...... 2013), Embase (1980 to June 2013), and the Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 6). Randomized controlled trials investigating the postoperative analgesic effect of peripherally applied opioids vs. systemic opioids or placebo, measured by pain intensity...... difference -5 mm, 95% CI: -7 to -3) for peripherally applied opioids vs. placebo and statistically significant increased time to first analgesic (mean difference 153 min, 95% CI: 41-265). When preoperative inflammation was reported (five studies), peripherally applied opioids significantly improved...

Can we predict addiction to opioid analgesics? A possible tool to estimate the risk of opioid addiction in patients with pain.

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Skala, Katrin; Reichl, Lukas; Ilias, Wilfried; Likar, Rudolf; Grogl-Aringer, Gabriele; Wallner, Christina; Schlaff, Golda; Herrmann, Peter; Lesch, Otto; Walter, Henriette

2013-01-01

The use of opioid analgesics in the treatment of chronic pain conditions has long been controversial. They have been reported to be relatively safe when prescribed with caution, but a brief and valid instrument to estimate a person's risk of addiction is still missing. The aim of this study was to investigate a self-rating questionnaire allowing an estimation of a person's risk of addiction to opioid analgesics. Retrospective review. Four Austrian hospitals. Seven hundred forty-one patients were interviewed. Of these, 634 patients were affected with chronic pain while 107 patients had a history of opioid addiction. Patients were interviewed about alcohol and nicotine consumption and family history of psychiatric disorders. Attitudes towards medication and the origin of pain were examined. We asked patients with an opioid addiction and patients suffering from chronic pain to complete a short questionnaire intended to help screen for addiction potential. Compared to the patients suffering from chronic pain, patients with an opioid addiction significantly more often had alcohol- and nicotine-related pathologies and psychiatric comorbidity. A family history of mental illness and developmental problems were significantly more frequent in this group. Compared to those not addicted, those with an opioid addiction had significantly higher expectations concerning the potential of medication to change one's mental state; they thought that psychological  factors might contribute to the pain they feel. The main limitation of this study is the use of a self-rating instrument which reduces objectivity and introduces the possibility of misreporting. Also, the 2 groups differ in number and are not homogenous. We found differences in questionnaire responses between patients with an opioid addiction and patients suffering from chronic pain to be dependent upon the prevalence of current or former addiction, psychiatric history, attitudes towards medication, and ideas about the

Needle syringe programmes and opioid substitution therapy for preventing hepatitis C transmission in people who inject drugs

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Platt, Lucy; Minozzi, Silvia; Reed, Jennifer; Vickerman, Peter; Hagan, Holly; French, Clare; Jordan, Ashly; Degenhardt, Louisa; Hope, Vivian; Hutchinson, Sharon; Maher, Lisa; Palmateer, Norah; Taylor, Avril; Bruneau, Julie; Hickman, Matthew

2017-01-01

Background Needle syringe programmes and opioid substitution therapy for preventing hepatitis C transmission in people who inject drugs Needle syringe programmes (NSP) and opioid substitution therapy (OST) are the primary interventions to reduce hepatitis C (HCV) transmission in people who inject drugs. There is good evidence for the effectiveness of NSP and OST in reducing injecting risk behaviour and increasing evidence for the effectiveness of OST and NSP in reducing HIV acquisition risk, but the evidence on the effectiveness of NSP and OST for preventing HCV acquisition is weak. Objectives To assess the effects of needle syringe programmes and opioid substitution therapy, alone or in combination, for preventing acquisition of HCV in people who inject drugs. Search methods We searched the Cochrane Drug and Alcohol Register, CENTRAL, the Cochrane Database of Systematic Reviews (CDSR), the Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment Database (HTA), the NHS Economic Evaluation Database (NHSEED), MEDLINE, Embase, PsycINFO, Global Health, CINAHL, and the Web of Science up to 16 November 2015. We updated this search in March 2017, but we have not incorporated these results into the review yet. Where observational studies did not report any outcome measure, we asked authors to provide unpublished data. We searched publications of key international agencies and conference abstracts. We reviewed reference lists of all included articles and topic-related systematic reviews for eligible papers. Selection criteria We included prospective and retrospective cohort studies, cross-sectional surveys, case-control studies and randomised controlled trials that measured exposure to NSP and/or OST against no intervention or a reduced exposure and reported HCV incidence as an outcome in people who inject drugs. We defined interventions as current OST (within previous 6 months), lifetime use of OST and high NSP coverage (regular attendance at

[The endogenous opioid system and drug addiction].

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Maldonado, R

2010-01-01

Drug addiction is a chronic brain disorder leading to complex adaptive changes within the brain reward circuits. Several neurotransmitters, including the endogenous opioid system are involved in these changes. The opioid system plays a pivotal role in different aspects of addiction. Thus, opioid receptors and endogenous opioid peptides are largely distributed in the mesolimbic system and modulate dopaminergic activity within the reward circuits. Opioid receptors and peptides are selectively involved in several components of the addictive processes induced by opioids, cannabinoids, psychostimulants, alcohol and nicotine. This review is focused on the contribution of each component of the endogenous opioid system in the addictive properties of the different drugs of abuse. Copyright 2010 Elsevier Masson SAS. All rights reserved.

42 CFR 8.11 - Opioid treatment program certification.

Science.gov (United States)

2010-10-01

... Substances Act (21 U.S.C. 823(g)(1)) to dispense opioid drugs in the treatment of opioid addiction. An OTP... opioid addiction. (2) To obtain certification from SAMHSA, an OTP must meet the Federal opioid treatment... governmental entities to regulate the use of opioid drugs in the treatment of opioid addiction. The provisions...

Reappraisal deficits promote craving and emotional distress among chronic pain patients at risk for prescription opioid misuse.

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Garland, Eric L; Hanley, Adam W; Bedford, Carter E; Zubieta, Jon-Kar; Howard, Matthew O; Nakamura, Yoshio; Donaldson, Gary W; Froeliger, Brett

2018-06-04

A subset of chronic pain patients misuse prescription opioids as a means of regulating negative emotions. However, opioid misuse may result in deficits in emotion regulation strategies like reappraisal by virtue of the deleterious effects of chronic opioid exposure. The aim of this study was to characterize differences in reappraisal use among chronic pain patients at risk for opioid misuse and those who report taking opioids as prescribed. A sample of 127 pain patients receiving chronic opioid analgesic pharmacotherapy were classified as at risk for opioid misuse (n = 62) or taking opioids as prescribed (n = 65) using the Current Opioid Misuse Measure (COMM). The Emotion Regulation Questionnaire (ERQ) characterized use of emotion regulation strategies including reappraisal and expressive suppression. Participants also reported levels of opioid craving, emotional distress, and pain severity. Patients at risk for opioid misuse reported significantly less reappraisal use (M = 25.31, SD = 7.33) than those who reportedly took opioids as prescribed (M = 30.28, SD = 7.50), p<.001, but did differ with regard to suppression strategies. Reduced reappraisal use was associated with higher opioid craving and emotional distress that mediated the association between reappraisal deficits and opioid misuse risk. Further, there was a significant indirect effect of opioid misuse on emotional distress via reappraisal use. Opioid misuse risk was associated with reduced use of reappraisal, which in turn was associated with dysregulated negative emotions and increased appetitive drive towards consuming opioids. Studying individual differences in emotion regulation may yield efficacious intervention and prevention approaches to stem the rising tide of the prescription opioid crisis.

Problematic Use of Prescription Opioids and Medicinal Cannabis Among Patients Suffering from Chronic Pain.

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Feingold, Daniel; Goor-Aryeh, Itay; Bril, Silviu; Delayahu, Yael; Lev-Ran, Shaul

2017-02-01

To assess prevalence rates and correlates of problematic use of prescription opioids and medicinal cannabis (MC) among patients receiving treatment for chronic pain. Cross-sectional study. Two leading pain clinics in Israel. Our sample included 888 individuals receiving treatment for chronic pain, of whom 99.4% received treatment with prescription opioids or MC. Problematic use of prescription opioids and MC was assessed using DSM-IV criteria, Portenoy’s Criteria (PC), and the Current Opioid Misuse Measure (COMM) questionnaire. Additional sociodemographic and clinical correlates of problematic use were also assessed. Among individuals treated with prescription opioids, prevalence of problematic use of opioids according to DSM-IV, PC, and COMM was 52.6%, 17.1%, and 28.7%, respectively. Among those treated with MC, prevalence of problematic use of cannabis according to DSM-IV and PC was 21.2% and 10.6%, respectively. Problematic use of opioids and cannabis was more common in individuals using medications for longer periods of time, reporting higher levels of depression and anxiety, and using alcohol or drugs. Problematic use of opioids was associated with higher self-reported levels of pain, and problematic use of cannabis was more common among individuals using larger amounts of MC. Problematic use of opioids is common among chronic pain patients treated with prescription opioids and is more prevalent than problematic use of cannabis among those receiving MC. Pain patients should be screened for risk factors for problematic use before initiating long-term treatment for pain-control.

Benzodiazepines, opioids and driving: an overview of the experimental research.

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Leung, Stefanie Y

2011-05-01

Road crashes contribute significantly to the total burden of injury in Australia, with the risk of injury being associated with the presence of drugs and/or alcohol in the driver's blood. Increasingly, some of the most commonly detected drugs include prescription medicines, the most notable of these being benzodiazepines and opioids. However, there is a paucity of experimental research into the effects of prescribed psychoactive drugs on driving behaviours. This paper provides an overview of experimental studies investigating the effects of prescribed doses of benzodiazepines and opioids on driving ability, and points to future directions for research. There is growing epidemiological evidence linking the therapeutic use of benzodiazepines and opioids to an increased crash risk. However, the current experimental literature remains unclear. Limitations to study methodologies have resulted in inconsistent findings. Limited experimental evidence exists to inform policy and guidelines regarding fitness-to-drive for patients taking prescribed benzodiazepines and opioids. Further experimental research is required to elucidate the effects of these medications on driving, under varying conditions and in different medical contexts. This will ensure that doctors prescribing benzodiazepines and opioids are well informed, and can appropriately advise patients of the risks associated with driving whilst taking these medications. © 2011 Australasian Professional Society on Alcohol and other Drugs.

Opioids, pain, the brain, and hyperkatifeia: a framework for the rational use of opioids for pain.

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Shurman, Joseph; Koob, George F; Gutstein, Howard B

2010-07-01

Opioids have relieved more human suffering than any other medication, but their use is still fraught with significant concerns of misuse, abuse, and addiction. This theoretical article explores the hypothesis that opioid misuse in the context of pain management produces a hypersensitivity to emotional distress, termed hyperkatifeia. In the misuse of opioids, neural substrates that mediate positive emotional states (brain reward systems) are compromised, and substrates mediating negative emotional states (brain stress systems) are enhanced. A reflection and early marker of such a nonhomeostatic state may be the development of opioid-induced hyperkatifeia, defined as the increased intensity of the constellation of negative emotional/motivational symptoms and signs observed during withdrawal from drugs of abuse (derived from the Greek "katifeia" for dejection or negative emotional state) and is most likely to occur in subjects in whom the opioid produces a break with homeostasis and less likely to occur when the opioid is restoring homeostasis, such as in effective pain treatment. When the opioid appropriately relieves pain, opponent processes are not engaged. However, if the opioid is administered in excess of need because of overdose, pharmacokinetic variables, or treating an individual without pain, then the body will react to that perturbation by engaging opponent processes in the domains of both pain (hyperalgesia) and negative emotional states (hyperkatifeia). Repeated engagement of opponent processes without time for the brain's emotional systems to reestablish homeostasis will further drive changes in emotional processes that may produce opioid abuse or addiction, particularly in individuals with genetic or environmental vulnerability.

Can variability in the effect of opioids on refractory breathlessness be explained by genetic factors?

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Currow, David C; Quinn, Stephen; Ekstrom, Magnus; Kaasa, Stein; Johnson, Miriam J; Somogyi, Andrew A; Klepstad, Päl

2015-01-01

Objectives Opioids modulate the perception of breathlessness with a considerable variation in response, with poor correlation between the required opioid dose and symptom severity. The objective of this hypothesis-generating, secondary analysis was to identify candidate single nucleotide polymorphisms (SNP) from those associated with opioid receptors, signalling or pain modulation to identify any related to intensity of breathlessness while on opioids. This can help to inform prospective studies and potentially lead to better tailoring of opioid therapy for refractory breathlessness. Setting 17 hospice/palliative care services (tertiary services) in 11 European countries. Participants 2294 people over 18 years of age on regular opioids for pain related to cancer or its treatment. Primary outcome measures The relationship between morphine dose, breathlessness intensity (European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire; EORTCQLQC30 question 8) and 112 candidate SNPs from 25 genes (n=588). Secondary outcome measures The same measures for people on oxycodone (n=402) or fentanyl (n=429). Results SNPs not in Hardy-Weinberg equilibrium or with allele frequencies (<5%) were removed. Univariate associations between each SNP and breathlessness intensity were determined with Benjamini-Hochberg false discovery rate set at 20%. Multivariable ordinal logistic regression, clustering over country and adjusting for available confounders, was conducted with remaining SNPs. For univariate morphine associations, 1 variant on the 5-hydroxytryptamine type 3B (HTR3B) gene, and 4 on the β-2-arrestin gene (ARRB2) were associated with more intense breathlessness. 1 SNP remained significant in the multivariable model: people with rs7103572 SNP (HTR3B gene; present in 8.4% of the population) were three times more likely to have more intense breathlessness (OR 2.86; 95% CIs 1.46 to 5.62; p=0.002). No associations were seen with fentanyl nor with

Creating opioid dependence in the emergency department.

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Upadhye, Suneel

2018-01-01

Clinical question What is the risk of creating opioid dependence from an ED opioid prescription? Article chosen Barnett ML, Olenski AR, Jena AB. Opioid-prescribing patterns of emergency physicians and risk of long-term use. N Engl J Med 2017;376:663-73, doi:10.1056/NEJMsa1610524. This study examined the risk of creating long-term opioid dependence from a prescription written in an opioid-naive patient in the ED.

CDC Vital Signs: Opioid Painkiller Prescribing

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... Mental Health Services Administration Medication-Assisted Treatment for Opioid Addiction: Facts for Families and Friends Opioid Overdose Prevention ... Abuse Drugs, Brains, and Behavior: The Science of Addiction Opioid and Pain Management CMEs/CEs Prescription Drugs U.S. ...

Electroconvulsive Therapy: A Current Review

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Gokben Hizli Sayar

2014-06-01

Full Text Available Most of the electroconvulsive therapy guidelines state that severe major depression with psychotic features, manic delirium, or catatonia are conditions where there is a clear consensus favoring early electroconvulsive therapy. The decision to administer electroconvulsive therapy is based on an evaluation of the risks and benefits for the individual patient and involves a combination of factors, including psychiatric diagnosis, type and severity of symptoms, prior treatment history and response, identification of possible alternative treatment options, and consumer preference. In this review history, mechanisms of action, side effects that have been referenced in the literature and clinical experience are discussed. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(2.000: 107-125

The long winding road of opioid substitution therapy implementation in South-East Asia: challenges to scale up

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Gary Reid

2014-03-01

Full Text Available The South-East Asia Region contains an estimated 400,000-500,000 people who inject drugs (PWID. HIV prevalence among PWID is commonly 20% or higher in Indonesia, Thailand, Myanmar and some regions of India. Opioid substitution therapy (OST is an important HIV prevention intervention in this part of the world. However, key challenges and barriers to scale up of OST exist, including: pervasive stigma and discrimination towards PWID; criminalisation of drug use overshadowing a public health response; lack of political will and national commitment; low financial investment; focus towards traditional treatment models of detoxification and rehabilitation; inadequate dosing of OST; and poor monitoring and evaluation of programmes. Our review of local evidence highlights that OST can be successful within the Asian context. Such evidence should be utilised more widely to advocate for policy change and increased political commitment to ensure OST reaches substantially more drug users.

School nurse experiences with prescription opioids in urban and rural schools: A cross-sectional survey.

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Pattison-Sharp, Ella; Estrada, Robin Dawson; Elio, Alice; Prendergast, Melissa; Carpenter, Delesha M

2017-01-01

Few studies have examined the use of prescription opioids in schools. The current study aimed to: (1) describe the context within which school nurses encounter student opioid prescriptions; (2) assess school nurses' preferences for training and student education; and (3) explore urban-rural differences in school nurses' experiences and training preferences. A convenience sample of school nurses (n = 633) from North Carolina and South Carolina participated in a brief, anonymous, online survey. Qualitative data were analyzed thematically and statistical tests (t-tests and Chi-square tests) were performed to investigate urban-rural differences. Many school nurses (40.3%) had encountered a student with an opioid prescription, but only 3.6% had naloxone available in case of an overdose. Most school nurses (69.9%), especially rural school nurses, believed students would benefit from opioid education (74.9 versus 66.6%, p = 0.03). The majority of school nurses (83.9%) were interested in opioid-related training. Many school nurses encounter students with prescription opioids and would like additional opioid-related training. The potential benefits of providing naloxone access to prevent opioid-related deaths at schools should be explored.

Relapse to opioid use in opioid-dependent individuals released from compulsory drug detention centres compared with those from voluntary methadone treatment centres in Malaysia: a two-arm, prospective observational study.

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Wegman, Martin P; Altice, Frederick L; Kaur, Sangeeth; Rajandaran, Vanesa; Osornprasop, Sutayut; Wilson, David; Wilson, David P; Kamarulzaman, Adeeba

2017-02-01

Detention of people who use drugs into compulsory drug detention centres (CDDCs) is common throughout East and Southeast Asia. Evidence-based pharmacological therapies for treating substance use disorders, such as opioid agonist treatments with methadone, are generally unavailable in these settings. We used a unique opportunity where CDDCs coexisted with voluntary drug treatment centres (VTCs) providing methadone in Malaysia to compare the timing and occurrence of opioid relapse (measured using urine drug testing) in individuals transitioning from CDDCs versus methadone maintenance in VTCs. We did a parallel, two-arm, prospective observational study of opioid-dependent individuals aged 18 years and older who were treated in Malaysia in the Klang Valley in two settings: CDDCs and VTCs. We used sequential sampling to recruit individuals. Assessed individuals in CDDCs were required to participate in services such as counselling sessions and manual labour. Assessed individuals in VTCs could voluntarily access many of the components available in CDDCs, in addition to methadone therapy. We undertook urinary drug tests and behavioural interviews to assess individuals at baseline and at 1, 3, 6, 9, and 12 months post-release. The primary outcome was time to opioid relapse post-release in the community confirmed by urinary drug testing in individuals who had undergone baseline interviewing and at least one urine drug test (our analytic sample). Relapse rates between the groups were compared using time-to-event methods. This study is registered at ClinicalTrials.gov (NCT02698098). Between July 17, 2012, and August 21, 2014, we screened 168 CDDC attendees and 113 VTC inpatients; of these, 89 from CDDCs and 95 from VTCs were included in our analytic sample. The baseline characteristics of the two groups were similar. In unadjusted analyses, CDDC participants had significantly more rapid relapse to opioid use post-release compared with VTC participants (median time to relapse

Hiperalgesia Inducida por Opioides

OpenAIRE

Jiménez Salazar, Andrés

2013-01-01

Los opioides producen analgesia a través de un efecto inhibitorio sobre el sistema nociceptivo principalmente. Hasta la fecha, los opioides siguen siendo los analgésicos más potentes para el manejo de dolor moderado a severo. La Asociación Internacional del Estudio del Dolor (IASP, en inglés) define hiperalgesia como "un aumento de la respuesta a un estímulo que normalmente es doloroso". En contraste, está bien establecido que la terapia crónica con opioides se asocia con el desarrollo de ...

Opioid and GABAB receptors differentially couple to an adenylyl cyclase/protein kinase A downstream effector after chronic morphine treatment.

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Elena Elizabeth Bagley

2014-06-01

Full Text Available Opioids are intensely addictive, and cessation of their chronic use is associated with a highly aversive withdrawal syndrome. A cellular hallmark of withdrawal is an opioid sensitive protein kinase A-dependent increase in GABA transporter-1 (GAT-1 currents in periaqueductal gray (PAG neurons. Elevated GAT-1 activity directly increases GABAergic neuronal excitability and synaptic GABA release, which will enhance GABAergic inhibition of PAG output neurons. This reduced activity of PAG output neurons to several brain regions, including the hypothalamus and medulla, contributes to many of the PAG-mediated signs of opioid withdrawal. The GABAB receptor agonist baclofen reduces some of the PAG mediated signs of opioid withdrawal. Like the opioid receptors the GABAB receptor is a Gi/Go coupled G-protein coupled receptor. This suggests it could be modulating GAT-1 activity in PAG neurons through its inhibition of the adenylyl cyclase/protein kinase A pathway. Opioid modulation of the GAT-1 activity can be detected by changes in the reversal potential of opioid membrane currents. We found that when opioids are reducing the GAT-1 cation conductance and increasing the GIRK conductance the opioid agonist reversal potential is much more negative than Ek. Using this approach for GABAB receptors we show that the GABAB receptor agonist, baclofen, does not couple to inhibition of GAT-1 currents during opioid withdrawal. It is possible this differential signaling of the two Gi/Go coupled G-protein coupled receptors is due to the strong compartmentalization of the GABAB receptor that does not favor signaling to the adenylyl cyclase/protein kinase A/GAT-1 pathway. This highlights the importance of studying the effects of G-protein coupled receptors in native tissue with endogenous G-protein coupled receptors and the full complement of relevant proteins and signaling molecules. This study suggests that baclofen reduces opioid withdrawal symptoms through a non-GAT-1

Analgesia for pain control during extracorporeal shock wave lithotripsy: Current status

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Narmada P Gupta

2008-01-01

Conclusion: The ideal analgesic, offering optimal pain control, minimal side effects, and cost-effectiveness is still elusive. Opioids administered using various techniques, provide effective analgesia, but require active monitoring of patient for potential adverse effects. Combination therapy (oral NSAID and occlusive dressing of EMLA, DMSO with lidocaine offers an effective alternative mode for achieving analgesia with minimal morbidity. This therapy avoids the need for general anesthesia, injectable analgesics, and opioids along with their side effects.

Prescription opioid abuse: pharmacists’ perspective and response

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Cochran G

2016-08-01

Full Text Available Gerald Cochran,1,2 Valerie Hruschak,2 Brooke DeFosse,3 Kenneth C Hohmeier3 1Department of Psychiatry, School of Medicine, 2School of Social Work, University of Pittsburgh, Pittsburgh, PA, 3Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee, Memphis, TN, USA Abstract: Opioid medication abuse and overdose are major concerns for public health, and a number of responses to address these issues have taken place across the US. Pharmacists and the pharmacy profession have made important contributions as a part of the response to this national crisis. This article provides a brief review of the antecedents, driving forces, and health status of patients involved in the opioid medication and overdose epidemic. This review further discusses pharmacy-based actions that have been undertaken to address this issue, including prescription drug monitoring, take-back, and naloxone training/distribution programs. This review likewise examines current efforts underway in the field to educate practitioners and needed future steps that must be taken by pharmacists in order to continue the profession’s pivotal role in working toward resolving this national public health problem. In particular, evidence and arguments are presented for proactively identifying and intervening with patients who abuse and/or are at risk for overdose. Continued and active engagement by pharmacists in these efforts has the potential to result in important reductions in opioid medication abuse and overdose and improvements for patient’s health. Keywords: opioid pain medication, addiction, pharmacy practice

Availability and utilization of opioids for pain management: global issues.

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Manjiani, Deepak; Paul, D Baby; Kunnumpurath, Sreekumar; Kaye, Alan David; Vadivelu, Nalini

2014-01-01

Pain can significantly influence an individual's health status and can have serious negative consequences: poor nutrition, decreased appetite, abnormal sleep patterns, fatigue, and impairment of daily living activities. Pain can cause psychological impairment and decrease healing and recovery from injuries and illness. A hallmark of many chronic conditions, pain affects more patients' lives than diabetes mellitus, heart disease, and cancer combined. However, many chronic sufferers do not have access to effective pain management for a variety of reasons, including limited access, restrictions, and personal and cultural biases. This review summarizes issues of access, distribution, and cultural bias with regard to opioid agents and seeks to clarify the challenges related to opioid delivery. The considerable negative physical and mental consequences of chronic pain are discussed for the general and palliative care population. Opioids are an effective treatment for various intractable painful conditions, but problems in global opioid access for safe and rational use in pain management contribute to unnecessary suffering. These problems persist despite increased understanding in recent years of the pathophysiology of pain. Comprehensive guidelines for goal-directed and patient-friendly chronic opiate therapy will potentially enhance the outlook for future chronic pain management. The improvement of pain education in undergraduate and postgraduate training will benefit patients and clinicians. The promise of new medications, along with the utilization of multimodal approaches, has the potential to provide effective pain relief to future generations of sufferers.

Genetic and Non-genetic Factors Associated With Constipation in Cancer Patients Receiving Opioids

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Laugsand, Eivor A; Skorpen, Frank; Kaasa, Stein; Sabatowski, Rainer; Strasser, Florian; Fayers, Peter; Klepstad, Pål

2015-01-01

Objectives: To examine whether the inter-individual variation in constipation among patients receiving opioids for cancer pain is associated with genetic or non-genetic factors. Methods: Cancer patients receiving opioids were included from 17 centers in 11 European countries. Intensity of constipation was reported by 1,568 patients on a four-point categorical scale. Non-genetic factors were included as covariates in stratified regression analyses on the association between constipation and 75 single-nucleotide polymorphisms (SNPs) within 15 candidate genes related to opioid- or constipation-signaling pathways (HTR3E, HTR4, HTR2A, TPH1, ADRA2A, CHRM3, TACR1, CCKAR, KIT, ARRB2, GHRL, ABCB1, COMT, OPRM1, and OPRD1). Results: The non-genetic factors significantly associated with constipation were type of laxative, mobility and place of care among patients receiving laxatives (N=806), in addition to Karnofsky performance status and presence of metastases among patients not receiving laxatives (N=762) (P<0.01). Age, gender, body mass index, cancer diagnosis, time on opioids, opioid dose, and type of opioid did not contribute to the inter-individual differences in constipation. Five SNPs, rs1800532 in TPH1, rs1799971 in OPRM1, rs4437575 in ABCB1, rs10802789 in CHRM3, and rs2020917 in COMT were associated with constipation (P<0.01). Only rs2020917 in COMT passed the Benjamini–Hochberg criterion for a 10% false discovery rate. Conclusions: Type of laxative, mobility, hospitalization, Karnofsky performance status, presence of metastases, and five SNPs within TPH1, OPRM1, ABCB1, CHRM3, and COMT may contribute to the variability in constipation among cancer patients treated with opioids. Knowledge of these factors may help to develop new therapies and to identify patients needing a more individualized approach to treatment. PMID:26087058

The Relative Potency of Inverse Opioid Agonists and a Neutral Opioid Antagonist in Precipitated Withdrawal and Antagonism of Analgesia and Toxicity

OpenAIRE

Sirohi, Sunil; Dighe, Shveta V.; Madia, Priyanka A.; Yoburn, Byron C.

2009-01-01

Opioid antagonists can be classified as inverse agonists and neutral antagonists. In the opioid-dependent state, neutral antagonists are significantly less potent in precipitating withdrawal than inverse agonists. Consequently, neutral opioid antagonists may offer advantages over inverse agonists in the management of opioid overdose. In this study, the relative potency of three opioid antagonists to block opioid analgesia and toxicity and precipitate withdrawal was exa...

Medicaid Coverage of Methadone Maintenance and the Use of Opioid Agonist Therapy Among Pregnant Women in Specialty Treatment.

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Bachhuber, Marcus A; Mehta, Pooja K; Faherty, Laura J; Saloner, Brendan

2017-12-01

Opioid agonist therapy (OAT) is the standard of care for pregnant women with opioid use disorder (OUD). Medicaid coverage policies may strongly influence OAT use in this group. To examine the association between Medicaid coverage of methadone maintenance and planned use of OAT in the publicly funded treatment system. Retrospective cross-sectional analysis of treatment admissions in 30 states extracted from the Treatment Episode Data Set (2013 and 2014). Medicaid-insured pregnant women with OUD (n=3354 treatment admissions). The main outcome measure was planned use of OAT on admission. The main exposure was state Medicaid coverage of methadone maintenance. Using multivariable logistic regression models adjusting for sociodemographic, substance use, and treatment characteristics, we compared the probability of planned OAT use in states with Medicaid coverage of methadone maintenance versus states without coverage. A total of 71% of pregnant women admitted to OUD treatment were 18-29 years old, 85% were white non-Hispanic, and 56% used heroin. Overall, 74% of admissions occurred in the 18 states with Medicaid coverage of methadone maintenance and 53% of admissions involved planned use of OAT. Compared with states without Medicaid coverage of methadone maintenance, admissions in states with coverage were significantly more likely to involve planned OAT use (adjusted difference: 32.9 percentage points, 95% confidence interval, 19.2-46.7). Including methadone maintenance in the Medicaid benefit is essential to increasing OAT among pregnant women with OUD and should be considered a key policy strategy to enhance outcomes for mothers and newborns.

Long-term course of opioid addiction.

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Hser, Yih-Ing; Evans, Elizabeth; Grella, Christine; Ling, Walter; Anglin, Douglas

2015-01-01

Opioid addiction is associated with excess mortality, morbidities, and other adverse conditions. Guided by a life-course framework, we review the literature on the long-term course of opioid addiction in terms of use trajectories, transitions, and turning points, as well as other factors that facilitate recovery from addiction. Most long-term follow-up studies are based on heroin addicts recruited from treatment settings (mostly methadone maintenance treatment), many of whom are referred by the criminal justice system. Cumulative evidence indicates that opioid addiction is a chronic disorder with frequent relapses. Longer treatment retention is associated with a greater likelihood of abstinence, whereas incarceration is negatively related to subsequent abstinence. Over the long term, the mortality rate of opioid addicts (overdose being the most common cause) is about 6 to 20 times greater than that of the general population; among those who remain alive, the prevalence of stable abstinence from opioid use is low (less than 30% after 10-30 years of observation), and many continue to use alcohol and other drugs after ceasing to use opioids. Histories of sexual or physical abuse and comorbid mental disorders are associated with the persistence of opioid use, whereas family and social support, as well as employment, facilitates recovery. Maintaining opioid abstinence for at least five years substantially increases the likelihood of future stable abstinence. Recent advances in pharmacological treatment options (buprenorphine and naltrexone) include depot formulations offering longer duration of medication; their impact on the long-term course of opioid addiction remains to be assessed.

Recognition and management of iatrogenically induced opioid dependence and withdrawal in children.

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Galinkin, Jeffrey; Koh, Jeffrey Lee

2014-01-01

Opioids are often prescribed to children for pain relief related to procedures, acute injuries, and chronic conditions. Round-the-clock dosing of opioids can produce opioid dependence within 5 days. According to a 2001 Consensus Paper from the American Academy of Pain Medicine, American Pain Society, and American Society of Addiction Medicine, dependence is defined as "a state of adaptation that is manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist." Although the experience of many children undergoing iatrogenically induced withdrawal may be mild or goes unreported, there is currently no guidance for recognition or management of withdrawal for this population. Guidance on this subject is available only for adults and primarily for adults with substance use disorders. The guideline will summarize existing literature and provide readers with information currently not available in any single source specific for this vulnerable pediatric population.

Provider and patient perspectives on opioids and alternative treatments for managing chronic pain: a qualitative study.

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Penney, Lauren S; Ritenbaugh, Cheryl; DeBar, Lynn L; Elder, Charles; Deyo, Richard A

2017-03-24

Current literature describes the limits and pitfalls of using opioid pharmacotherapy for chronic pain and the importance of identifying alternatives. The objective of this study was to identify the practical issues patients and providers face when accessing alternatives to opioids, and how multiple parties view these issues. Qualitative data were gathered to evaluate the outcomes of acupuncture and chiropractic (A/C) services for chronic musculoskeletal pain (CMP) using structured interview guides among patients with CMP (n = 90) and primary care providers (PCPs) (n = 25) purposively sampled from a managed care health care system as well as from contracted community A/C providers (n = 14). Focus groups and interviews were conducted patients with CMP with varying histories of A/C use. Plan PCPs and contracted A/C providers took part in individual interviews. All participants were asked about their experiences managing chronic pain and experience with and/or attitudes about A/C treatment. Audio recordings were transcribed and thematically coded. A summarized version of the focus group/interview guides is included in the Additional file 1. We identified four themes around opioid use: (1) attitudes toward use of opioids to manage chronic pain; (2) the limited alternative options for chronic pain management; (3) the potential of A/C care as a tool to help manage pain; and (4) the complex system around chronic pain management. Despite widespread dissatisfaction with opioid medications for pain management, many practical barriers challenged access to other options. Most of the participants' perceived A/C care as helpful for short term pain relief. We identified that problems with timing, expectations, and plan coverage limited A/C care potential for pain relief treatment. These results suggest that education about realistic expectations for chronic pain management and therapy options, as well as making A/C care more easily accessible, might lead to more

Ketamine as an Adjunct to Opioids for Acute Pain in the Emergency Department: A Randomized Controlled Trial.

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Bowers, Karen J; McAllister, Kelly B; Ray, Meredith; Heitz, Corey

2017-06-01

(mean ± SD = 9.95 ± 4.83 mg) compared to placebo (mean ± SD = 12.81 ± 6.81 mg; p = 0.02). Satisfaction did not differ between groups. Fewer patients in the ketamine group required additional opioid doses. More patients reported light-headedness and dizziness in the ketamine group. Ketamine, as an adjunct to opioid therapy, was more effective at reducing pain over 120 minutes and resulted in a lower total opioid dose as well as fewer repeat doses of analgesia. More side effects were reported in the ketamine group (51% vs. 19%), but the side effect profile appears tolerable. © 2017 by the Society for Academic Emergency Medicine.

Motives for using: a comparison of prescription opioid, marijuana and cocaine dependent individuals.

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Hartwell, Karen J; Back, Sudie E; McRae-Clark, Aimee L; Shaftman, Stephanie R; Brady, Kathleen T

2012-04-01

Identification of the motives for drug use is critical to the development of effective interventions. Furthermore, consideration of the differences in motives for drug use across substance dependent populations may assist in tailoring interventions. To date, few studies have systematically compared motives for substance use across drug classes. The current study examined motives for drug use between non-treatment seeking individuals with current prescription opioid, marijuana, or cocaine dependence. Participants (N=227) completed the Inventory of Drug-Taking Situations (IDTS; Annis, Turner & Sklar,1997), which contains eight subscales assessing motives for drug use. The findings revealed that prescription opioid dependent individuals scored significantly higher than all other groups on the Physical Discomfort, Testing Personal Control and Conflict with Others subscales. Both the prescription opioid and cocaine dependent groups scored significantly higher than the marijuana group on the Urges or a Temptation to Use subscale. In contrast, marijuana dependent individuals scored highest on the Pleasant Emotions and Pleasant Times with Others subscales. The marked differences revealed in motives for drug use could be used in the development and implementation of specific treatment interventions for prescription opioid, marijuana and cocaine dependent individuals. Published by Elsevier Ltd.

The opioid overdose epidemic: opportunities for pharmacists

Directory of Open Access Journals (Sweden)

Wu LT

2017-07-01

Full Text Available Li-Tzy Wu,1–4 Udi E Ghitza,5 Anne L Burns,6 Paolo Mannelli,1 1Department of Psychiatry and Behavioral Sciences, 2Department of Medicine, 3Duke Clinical Research Institute, Duke University School of Medicine, 4Center for Child and Family Policy, Sanford School of Public Policy, Duke University, Durham, NC, 5Center for Clinical Trials Network, National Institute on Drug Abuse, Bethesda, MD, 6American Pharmacists Association, Washington, DC, USA The USA is experiencing an opioid overdose epidemic. It has been driven largely by prescription opioids and intensified by a surge of illicit opioids (e.g., heroin and fentanyl.1,2 Drug-involved overdose, mainly opioids (e.g., prescription opioids and heroin, is a leading cause of accidental death in the USA. The opioid overdose epidemic has been escalating consistently for over a decade.2 Every day, an estimated 91 Americans die from opioid-related overdose.3 Opioid overdose appears to have disproportionally affected men, adults aged 25–64 years, and non-Hispanic whites.2

An unusual effect of interferential therapy.

LENUS (Irish Health Repository)

Keramat, Keramat Ullah

2012-11-01

In this report, a patient with severe shoulder pain was treated with interferential currents, a commonly used modality in physiotherapy for the management of pain. He reported loss of concentration, drowsiness, decreased alertness and gait disturbance, along with analgaesia, for 4-5 h after each treatment. He was regularly taking tramadol HCl for pain relief. Endogenous opioids produced in response to interferential therapy may be excessive or may interact with the tramadol HCl and potentiate its effect. There is no published report of interferential-induced symptoms, as described above, in the authors\\' knowledge. The clinician using interferential currents should be aware of this possible effect.

America's Opioid Epidemic: Supply and Demand Considerations.

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Clark, David J; Schumacher, Mark A

2017-11-01

America is in the midst of an opioid epidemic characterized by aggressive prescribing practices, highly prevalent opioid misuse, and rising rates of prescription and illicit opioid overdose-related deaths. Medical and lay public sentiment have become more cautious with respect to prescription opioid use in the past few years, but a comprehensive strategy to reduce our reliance on prescription opioids is lacking. Addressing this epidemic through reductions in unnecessary access to these drugs while implementing measures to reduce demand will be important components of any comprehensive solution. Key supply-side measures include avoiding overprescribing, reducing diversion, and discouraging misuse through changes in drug formulations. Important demand-side measures center around educating patients and clinicians regarding the pitfalls of opioid overuse and methods to avoid unnecessary exposure to these drugs. Anesthesiologists, by virtue of their expertise in the use of these drugs and their position in guiding opioid use around the time of surgery, have important roles to play in reducing patient exposure to opioids and providing education about appropriate use. Aside from the many immediate steps that can be taken, clinical and basic research directed at understanding the interaction between pain and opioid misuse is critical to identifying the optimal use of these powerful pain relievers in clinical practice.

Survey of Opioid and Barbiturate Prescriptions in Patients Attending a Tertiary Care Headache Center.

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Minen, Mia T; Lindberg, Kate; Wells, Rebecca E; Suzuki, Joji; Grudzen, Corita; Balcer, Laura; Loder, Elizabeth

2015-10-01

To educate physicians about appropriate acute migraine treatment guidelines by determining (1) where headache patients were first prescribed opioids and barbiturates, and (2) the characteristics of the patient population who had been prescribed opioids and barbiturates. Several specialty societies issued recommendations that caution against the indiscriminate use of opioids or barbiturate containing medications for the treatment of migraine. These medications are still being prescribed in various medical settings and could put headache specialists in a difficult position when patients request these agents. Patients presenting to a headache center comprised of eight physicians were asked to complete a survey that assessed headache types, comorbid conditions, and whether they had ever been prescribed opioids or barbiturates. If they responded affirmatively to the latter question, they were asked about the prescribing doctor, medication effectiveness, and whether they were currently on the medication. Data collection took place over a one month period. Two hundred forty-four patients were given the survey and 218 of these patients completed it. The predominant diagnosis was migraine (83.9%). More than half of the patients reported having been prescribed an opioid (54.8%) or a barbiturate (56.7%). About one fifth were on opioids (19.4%) or barbiturates (20.7%) at the time of completing the survey. Most patients reported being on opioids for more than 2 years (24.6%) or less than one week (32.1%). The reasons most frequently cited for stopping opioids were that the medications did not help (30.9%) or that they saw a new doctor who would not prescribe them (29.4%). Among patients who had previously been on barbiturates, 32.2% had been on these for over 2 years. Most patients (61.8%) stopped barbiturates because they did not find the medication helpful, while 17.6% said they saw a new doctor who would not prescribe them. The physician specialty most frequently cited as

Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: A two-phase randomized controlled trial*

Science.gov (United States)

Lofwall, Michelle R.; Babalonis, Shanna; Nuzzo, Paul A.; Siegel, Anthony; Campbell, Charles; Walsh, Sharon L.

2013-01-01

Background Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: 1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and 2) whether cessation of ER tramadol produces opioid withdrawal. Methods Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600 mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved. Results Use of breakthrough withdrawal medication differed significantly (popioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600 mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal. PMID:23755929

Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: a two-phase randomized controlled trial.

Science.gov (United States)

Lofwall, Michelle R; Babalonis, Shanna; Nuzzo, Paul A; Siegel, Anthony; Campbell, Charles; Walsh, Sharon L

2013-11-01

Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: (1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and (2) whether cessation of ER tramadol produces opioid withdrawal. Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600 mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved. Use of breakthrough withdrawal medication differed significantly (popioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600 mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

National consumption of opioid and nonopioid analgesics in Croatia: 2007–2013

Science.gov (United States)

Krnic, Darko; Anic-Matic, Andrea; Dosenovic, Svjetlana; Draganic, Pero; Zezelic, Sasa; Puljak, Livia

2015-01-01

Background The increased consumption of analgesics has been documented worldwide during the last 2 decades. The aim of the study was to examine the trends in opioid and nonopioid analgesic consumption in Croatia between 2007 and 2013. Methods Data on opioid consumption were extracted from the database of the national authority. All opioid and nonopioid analgesics were included in the analysis. Data were presented as defined daily doses per 1,000 inhabitants per day. Adequacy of opioid consumption was calculated using adequacy of consumption measure. Results During the examined 7-year period, the total consumption and total cost of all analgesics in Croatia showed continuous increase. In the M01A group (anti-inflammatory and antirheumatic products, nonsteroids), ibuprofen had an exponential increasing trend, and in 2011, it overtook diclofenac consumption. Ibuprofen and diclofenac had the highest consumption also in the M02A group of topical products for joint and muscular pain. Tramadol was by far the most consumed type of opioids (N02A group) and paracetamol in the group of other analgesics and antipyretics (N02B). The adequacy of consumption measure value was 0.19, indicating that Croatia is a country with a low opioid consumption. Conclusion Between 2007 and 2013, both consumption of analgesics and their cost in Croatia had an increasing trend. Comparisons with data from other countries, based on the published literature, indicate that analgesic consumption in Croatia is still relatively low. Calculation of the adequacy of opioid consumption indicated that Croatia is a country with low opioid consumption. Further studies are necessary for establishing whether current analgesic consumption in Croatia corresponds to patient needs. PMID:26357478

Barriers to Using Nonpharmacologic Approaches and Reducing Opioid Use in Primary Care.

Science.gov (United States)

Giannitrapani, Karleen F; Ahluwalia, Sangeeta C; McCaa, Matthew; Pisciotta, Maura; Dobscha, Steven; Lorenz, Karl A

2017-10-20

Opioid prescribing for chronic pain, including the potential for over-reliance and misuse, is a public health concern. In the context of Veterans Administration (VA) primary care team-based pain management, we aimed to understand providers' perceptions of barriers to reducing opioid use and improving the use of nonpharmacologic pain management therapies (NPTs) for chronic pain. A semistructured interview elucidated provider experiences with assessing and managing pain. Emergent themes were mapped to known dimensions of VA primary care access. Informants included 60 primary care providers, registered nurses, licensed practical nurses, clerks, psychologists, and social workers at two VA Medical Centers. Nine multidisciplinary focus groups. Provider perceptions of barriers to reducing opioids and improving use of NPTs for patients with chronic pain clustered around availability and access. Barriers to NPT access included the following subthemes: geographical (patient distance from service), financial (out-of-pocket cost to patient), temporal (treatment time delays), cultural (belief that NPTs increased provider workload, perception of insufficient training on NPTs, perceptions of patient resistance to change, confrontation avoidance, and insufficient leadership support), and digital (measure used for pain assessment, older patients hesitant to use technology, providers overwhelmed by information). Decreasing reliance on opioids for chronic pain requires a commitment to local availability and provider-facing strategies that increase efficacy in prescribing NPTs. Policies and interventions for decreasing utilization of opioids and increasing use of NPTs should comprehensively consider access barriers. 2017 American Academy of Pain Medicine. This work is written by US Government employees and is in the public domain in the US.

[11C]-MeJDTic: a novel radioligand for κ-opioid receptor positron emission tomography imaging

International Nuclear Information System (INIS)

Poisnel, Geraldine; Oueslati, Farhana; Dhilly, Martine; Delamare, Jerome; Perrio, Cecile; Debruyne, Daniele; Barre, Louisa

2008-01-01

Introduction: Radiopharmaceuticals that can bind selectively the κ-opioid receptor may present opportunities for staging clinical brain disorders and evaluating the efficiency of new therapies related to stroke, neurodegenerative diseases or opiate addiction. The N-methylated derivative of JDTic (named MeJDTic), which has been recently described as a potent and selective antagonist of κ-opioid receptor in vitro, was labeled with carbon-11 and evaluated for in vivo imaging the κ-opioid receptor in mice. Methods: [ 11 C]-MeJDTic was prepared by methylation of JDTic with [ 11 C]-methyl triflate. The binding of [ 11 C]-MeJDTic to κ-opioid receptor was investigated ex vivo by biodistribution and competition studies using nonfasted male CD1 mice. Results: [ 11 C]-MeJDTic exhibited a high and rapid distribution in peripheral organs. The uptake was maximal in lung where the κ receptor is largely expressed. [ 11 C]-MeJDTic rapidly crossed the blood-brain barrier and accumulated in the brain regions of interest (hypothalamus). The parent ligand remained the major radioactive compound in brain during the experiment. Chase studies with U50,488 (a κ referring agonist), morphine (a μ agonist) and naltrindole (a δ antagonist) demonstrated that this uptake was the result of specific binding to the κ-opioid receptor. Conclusion: These findings suggested that [ 11 C]-MeJDTic appeared to be a promising selective 'lead' radioligand for κ-opioid receptor PET imaging

Patient-reported opioid analgesic requirements after elective inguinal hernia repair: A call for procedure-specific opioid-administration strategies.

Science.gov (United States)

Mylonas, Konstantinos S; Reinhorn, Michael; Ott, Lauren R; Westfal, Maggie L; Masiakos, Peter T

2017-11-01

A better understanding of the analgesia needs of patients who undergo common operative procedures is necessary as we address the growing opioid public health crisis in the United States. The aim of this study was to evaluate patient experience with our opioid prescribing practice after elective inguinal hernia repairs. A prospective, observational study was conducted between October 1, 2015, and September 30, 2016, in a single-surgeon, high-volume, practice of inguinal hernia operation. Adult patients undergoing elective inguinal herniorrhaphy under local anesthesia with intravenous sedation were invited to participate. All patients were prescribed 10 opioid analgesic tablets postoperatively and were counseled to reserve opioids for pain not controlled by nonopioid analgesics. Their experience was captured by completing a questionnaire 2 to 3 weeks postoperatively during their postoperative visit. A total of 185 patients were surveyed. The majority of the participants were males (177, 95.7%) and ≥60 years old (96, 51.9%). Of the 185 patients, 159 (85.9%) reported using ≤4 opioid tablets; 110 patients (59.5%) reported that they used no opioid analgesics postoperatively. None of the patients was taking opioids within 7 days of their postoperative appointment. Of the 147 patients who were employed, 111 (75.5%) reported missing ≤3 work days, 57 of whom (51.4%) missed no work at all. Patients who were employed were more likely to take opioid analgesics postoperatively (P = .049). Patients who took no opioid analgesics experienced less maximum (P require any opioid analgesics, and nearly all of those who thought that they did need opioids used reserved.

Positron Emission Tomography (PET) Imaging of Opioid Receptors

NARCIS (Netherlands)

van Waarde, Aren; Absalom, Anthony; Visser, Anniek; Dierckx, Rudi; Dierckx, Rudi AJO; Otte, Andreas; De Vries, Erik FJ; Van Waarde, Aren; Luiten, Paul GM

2014-01-01

The opioid system consists of opioid receptors (which mediate the actions of opium), their endogenous ligands (the enkephalins, endorphins, endomorphins, dynorphin, and nociceptin), and the proteins involved in opioid production, transport, and degradation. PET tracers for the various opioid

Tolerance to non-opioid analgesics is opioid-sensitive in nucleus raphe magnus

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Merab G Tsagareli

2011-07-01

Full Text Available Repeated injection of opioid analgesics can lead to a progressive loss of its effect. This phenomenon is known as tolerance. Several lines of investigations have shown that systemic, intraperitoneal administration or the microinjection of non-opioid analgesics, non-steroidal anti-inflammatory drugs (NSAIDs in the midbrain periaqueductal gray matter induces antinociception with some effects of tolerance. Our recent study has revealed that microinjection of three drugs analgin, ketorolac and xefocam into the central nucleus of amygdala produce tolerance to them and cross-tolerance to morphine. Here we report that repeated administrations of these NSAIDs into the nucleus raphe magnus (NRM in the following four days result in progressively less antinociception, i.e. produce the development of tolerance to these drugs in mail rats. Special control experiments showed that post-treatment with μ-opioid antagonist naloxone in NRM significantly decreased antinociceptive effects of NSAIDs at the first day in behavioral tail flick reflex (TF and hot plate (HP latencies. At the second day, naloxone generally had trend effects in both TF and HP tests impeded the development of tolerance to the antinociceptive effect of non-opioid analgesics. These findings strongly support the suggestion on endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain control system. Moreover, repeated injections of NSAIDs progressively lead to tolerance to them, cross-tolerance to morphine and the risk of a withdrawal syndrome. Therefore, these results are important for human medicine too.

Breastfeeding and Opiate Substitution Therapy: Starting to Understand Infant Feeding Choices

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Lisa E. Graves

2016-01-01

Full Text Available Introduction Despite research demonstrating the safety and benefit of breastfeeding in opioid substitution therapy, few women in treatment breastfeed. Understanding the factors contributing to the choices women on opioid substitution therapy make about infant feeding is important. Objectives The aim of this study was to better understand and support infant feeding choices and breastfeeding experiences in women on opioid substitution therapy. Methods A systematic review was conducted on five databases: (1 Ovid MEDLINE(R without revisions, (2 Ovid MEDLINE(R In-Process & Other Non-Indexed Citations, (3 EMBASE, (4 CINAHL, and (5 FRANCIS. From 1081 articles, 46 articles were reviewed. Results The literature supports breastfeeding as an appropriate and safe option for women on opioid substitution treatment. Breastfeeding and rooming-in reduce neonatal abstinence. Women face barriers to breastfeeding due to societal stigma and the lack of patient and health-care provider education. Conclusions Efforts are needed to increase the knowledge that women and health-care professionals have about the safety and benefits of breastfeeding.

Drug interactions: volatile anesthetics and opioids.

Science.gov (United States)

Glass, P S; Gan, T J; Howell, S; Ginsberg, B

1997-09-01

Multiple drugs are used to provide anesthesia. Volatile anesthetics are commonly combined with opioids. Several studies have demonstrated that small doses of opioid (i.e., within the analgesic range) result in a marked reduction in minimum alveolar concentration (MAC) of the volatile anesthetic that will prevent purposeful movement in 50% of patients at skin incision). Further increases in opioid dose provide only a further small reduction in MAC. Thus, a ceiling effect of the opioid is observed at a MAC value of the volatile anesthetic equal to its MAC awake. Recovery from anesthesia when an opioid is combined with a volatile anesthetic is dependent on the rate of decrease of both drugs to their respective concentrations that are associated with adequate spontaneous ventilation and awakening. Through an understanding of the pharmacodynamic interaction of volatile anesthetics with opioids and the pharmacokinetic processes responsible for the recovery from drug effect, optimal dosing schemes can thus be developed. A review of these pharmacodynamic and pharmacokinetic principles that will allow clinicians to administer drugs to provide a more optimal anesthetic is provided.

DYNAMICS OF OPIOID SUBSTITUTION TREATMENTIN DIFFERENT INITIAL SUBSTANCE USER OPIOID DEPENDENT PATIENTS.

Science.gov (United States)

Todadze, Kh; Mosia, S

2016-05-01

Injecting drug user size estimation studies carried out in 2009, 2012 and 2015 revealed growing trends of drug abuse in Georgia:estimated number of people who inject drugs (PWID) have been increased from 40000 and 45000 to 50000. Since Soviet period the most popular injective narcotics have been opioids: home-made opium, heroine, buprenorphine and home-made desomorphine ("Krokodile") replacing each other on the black market. Self-made desomorphine typically contains big amounts of different toxic substances and causes significant somatic disorders, especially skin, bone, blood infections, liver and kidney failure; is highly addictive, associates with frequent injections that enhance injecting-related harm, including the risk of HIV transmission, in comparison with typical opioids. The aim of the study was to determine the effectiveness of opioid substitution treatment (OST) on depression and anxiety in opioid dependent clients with history of different opioid substance use. 104 opioid drug users undergoing OST with intensive psychological counseling have been divided in 5 groups according to the principal opioid drug that was abused during past 6 months before starting treatment: heroine, desomorphine, illicit methadone injectors, illicit buprenorphine injectors, and multiple drug abusers consuming opioids as primary drugs. Level of depression (Beck Depression Inventory), anxiety (Spielberger Anxiety Inventory) as well as clinical symptoms, risky behavior, quality of life (WHO), and other data were measured before starting and after 3, 9, 15, 21 months of treatment. The illegal use of psychotropic-narcotics was checked through random urine-testing 1-2 times per patient per month. In all five groups remarkable decrease of depression and anxiety was observed in comparison with the starting data. Before inclusion desomorphine and poly-drug users had the highest scores of depression and anxiety while buprenorphine users manifested the lowest rate. Improvement of

Effect Of A “No Superuser Opioid Prescription” Policy On ED Visits And Statewide Opioid Prescription

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Zachary P. Kahler

2017-07-01

Full Text Available Introduction: The U.S. opioid epidemic has highlighted the need to identify patients at risk of opioid abuse and overdose. We initiated a novel emergency department- (ED based interventional protocol to transition our superuser patients from the ED to an outpatient chronic pain program. The objective was to evaluate the protocol’s effect on superusers’ annual ED visits. Secondary outcomes included a quantitative evaluation of statewide opioid prescriptions for these patients, unique prescribers of controlled substances, and ancillary testing. Methods: Patients were referred to the program with the following inclusion criteria: ≥ 6 visits per year to the ED; at least one visit identified by the attending physician as primarily driven by opioid-seeking behavior; and a review by a committee comprising ED administration and case management. Patients were referred to a pain management clinic and informed that they would no longer receive opioid prescriptions from visits to the ED for chronic pain complaints. Electronic medical record (EMR alerts notified ED providers of the patient’s referral at subsequent visits. We analyzed one year of data pre- and post-referral. Results: A total of 243 patients had one year of data post-referral for analysis. Median annual ED visits decreased from 14 to 4 (58% decrease, 95% CI [50 to 66]. We also found statistically significant decreases for these patients’ state prescription drug monitoring program (PDMP opioid prescriptions (21 to 13, total unique controlled-substance prescribers (11 to 7, computed tomography imaging (2 to 0, radiographs (5 to 1, electrocardiograms (12 to 4, and labs run (47 to 13. Conclusion: This program and the EMR-based alerts were successful at decreasing local ED visits, annual opioid prescriptions, and hospital resource allocation for this population of patients. There is no evidence that these patients diverted their visits to neighboring EDs after being informed that they

Chronic ethanol consumption in rats produces opioid antinociceptive tolerance through inhibition of mu opioid receptor endocytosis.

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Li He

Full Text Available It is well known that the mu-opioid receptor (MOR plays an important role in the rewarding properties of ethanol. However, it is less clear how chronic ethanol consumption affects MOR signaling. Here, we demonstrate that rats with prolonged voluntary ethanol consumption develop antinociceptive tolerance to opioids. Signaling through the MOR is controlled at many levels, including via the process of endocytosis. Importantly, agonists at the MOR that promote receptor endocytosis, such as the endogenous peptides enkephalin and β-endorphin, show a reduced propensity to promote antinociceptive tolerance than do agonists, like morphine, which do not promote receptor endocytosis. These observations led us to examine whether chronic ethanol consumption produced opioid tolerance by interfering with MOR endocytosis. Indeed, here we show that chronic ethanol consumption inhibits the endocytosis of MOR in response to opioid peptide. This loss of endocytosis was accompanied by a dramatic decrease in G protein coupled receptor kinase 2 (GRK2 protein levels after chronic drinking, suggesting that loss of this component of the trafficking machinery could be a mechanism by which endocytosis is lost. We also found that MOR coupling to G-protein was decreased in ethanol-drinking rats, providing a functional explanation for loss of opioid antinociception. Together, these results suggest that chronic ethanol drinking alters the ability of MOR to endocytose in response to opioid peptides, and consequently, promotes tolerance to the effects of opioids.

Challenges to implementing opioid substitution therapy in Ukrainian prisons: Personnel attitudes toward addiction, treatment, and people with HIV/AIDS.

Science.gov (United States)

Polonsky, Maxim; Azbel, Lyuba; Wickersham, Jeffrey A; Taxman, Faye S; Grishaev, Evgeny; Dvoryak, Sergey; Altice, Frederick L

2015-03-01

Ukraine is experiencing one of the most volatile HIV epidemics globally, fueled primarily by people who inject drugs (PWIDs), and a parallel incarceration epidemic. Opioid substitution therapy (OST) is internationally recognized as one of the most effective forms of treatment for opioid dependence and is among the most effective HIV prevention strategies available, yet efforts to adopt it in Ukraine's Criminal Justice System (CJS) have been thwarted. To understand the reluctance of the Ukrainian CJS to adopt OST despite the overwhelming evidence pointing to its health benefits and improved criminal justice outcomes, we conducted the first survey of Ukrainian prison administrative, medical and custodial staff (N=243) attitudes towards addiction in general, OST, and people living with HIV/AIDS (PLWHA) in representative regions of Ukraine. Results revealed that Ukrainian CJS workers' attitudes toward OST, PLWHA, and drug addiction were universally negative, but differed substantially along geographic and occupational lines. Whereas geographic and cultural proximity to the European Union drove positive attitudes in the west, in the southern region we observed an identifiability effect, as workers who worked directly with prisoners held the most positive attitudes. We also found that knowledge mediated the effect of drug intolerance on OST attitudes. In Ukraine, adoption of OST is more influenced by myths, biases and ideological prejudices than by existing scientific evidence. By elucidating existing attitudes among CJS personnel, this study will help to direct subsequent interventions to address the barriers to implementing evidence-based HIV prevention treatments. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Global Supply and Demand of Opioids for Pain Management.

Science.gov (United States)

Kunnumpurath, Sreekumar; Julien, Natasha; Kodumudi, Gopal; Kunnumpurath, Anamika; Kodumudi, Vijay; Vadivelu, Nalini

2018-04-04

The goal of this review is to evaluate the global supply and demand of opioids used for pain management and discuss how it relates to the utilization of opioids around the world. The purpose of the review is also to determine the factors that contribute to inappropriate pain management. The total global production of opium for opioid manufacturing is enough to supply the growing global demands. However, licit opioids are only consumed by 20% of the world population. Most people throughout the world had no access to opioid analgesics for pain relief in case of need. Opioid misuse and abuse is not only a phenomena plague by the USA but globally across many countries. Many countries have a lack of availability of opioids, contributing factors being strict government regulations limiting access, lack of knowledge of the efficacy of opioid analgesics in treating acute and chronic pain and palliative care, and the stigma that opioids are highly addictive. For the countries in which opioids are readily available and prescribed heavily, diversion, misuse, abuse, and the resurgence of heroin have become problems leading to morbidity and mortality. It is pertinent to find a balance between having opioids accessible to patients in need, with ensuring that opioids are regulated along with other illicit drugs to decrease abuse potential.

Intentional intrathecal opioid detoxification in 3 patients: characterization of the intrathecal opioid withdrawal syndrome.

Science.gov (United States)

Jackson, Tracy P; Lonergan, Daniel F; Todd, R David; Martin, Peter R

2013-04-01

Intrathecal (IT) drug delivery systems for patients with chronic non-malignant pain are intended to improve pain and quality of life and reduce side effects of systemic use. A subset of patients may have escalating pain, functional decline, and/or intolerable side effects even as IT opioid doses are increased. Discontinuation of IT medications may represent a viable treatment option but strategies to accomplish this are needed. Three patients with intrathecal drug delivery systems (IDDS), inadequate pain control, and declining functionality underwent abrupt IT opioid cessation. This was accomplished through a standardized protocol with symptom-triggered administration of clonidine and buprenorphine, monitored using the clinical opiate withdrawal scale. Symptoms of IT withdrawal were similar in all patients and included diuresis, agitation, hyperalgesia, mild diarrhea, yawning, and taste and smell aversion. Hypertension and tachycardia were effectively controlled by clonidine administration. Classic symptoms of withdrawal, such as piloerection, chills, severe diarrhea, nausea, vomiting, diaphoresis, myoclonus, and mydriasis, were not noted. At 2 to 3 months follow-up, patients reported decreased, but ongoing pain, with improvements in functional capacity and quality of life. This preliminary work demonstrates the safety of abrupt IT opioid cessation utilizing standardized inpatient withdrawal protocols. To our knowledge, these are among the first reported cases of intentional, controlled IT opioid cessation without initiation of an opioid bridge: self-reported pain scores, functional capacity, and quality of life improved. The IT opioid withdrawal syndrome is characterized based upon our observations and a review of the literature. © 2012 The Authors. Pain Practice © 2012 World Institute of Pain.

Ketamine infusion for sickle cell pain crisis refractory to opioids: a case report and review of literature.

Science.gov (United States)

Uprety, Dipesh; Baber, Aurangzeb; Foy, Maria

2014-05-01

This article reports a rare case of the use of low-dose ketamine infusion as an adjuvant to opioids to treat pain in sickle cell disease. A 31-year-old African-American male with history of sickle cell disease presented to the emergency department with complaints of chest tightness, multiple joint pain, and headache for 1 week. His vital signs and physical examination were unremarkable. His admission lab included hemoglobin of 8.4 g/dl, reticulocyte count of 16.3%, bilirubin of 1.7 mg/dl, and LDH of 1,267 U/l. Chest X-ray showed middle and lower lobe opacity and interstitial thickening. He was treated for acute pain crisis and community-acquired pneumonia with intravenous fluids, supplemental oxygen, and intravenous levofloxacin. He was placed on fentanyl patient-controlled analgesia (PCA), oxycodone, ketorolac, and methadone with co-analgesic gabapentin and venlafaxine. Over the course of his hospitalization, his chest pain resolved, but the joint pains continued. He was then transferred to the ICU and was discharged a day later after 7 days of ketamine infusion. Ketamine is a noncompetitive antagonist at the N-methyl-D-aspartate (NMDA) receptor. This property has been shown to modulate opioid tolerance and opioid-induced hyperalgesia. There have been a very few published reports on the use of low-dose ketamine in sickle cell pain management. A PubMed search revealed four published articles (Table 1). Fourteen out of the 17 cases (82.35%) who received ketamine infusion showed improvement in self-reported pain intensity and significant reduction in opioid dosage. Only one patient (5.9%) developed serious side effect leading to discontinuation of the drug. A low-dose ketamine can be an option for pain control in sickle cell disease. Randomized trial is required to establish this benefit of ketamine over currently available therapies.

[{sup 11}C]-MeJDTic: a novel radioligand for {kappa}-opioid receptor positron emission tomography imaging

Energy Technology Data Exchange (ETDEWEB)

Poisnel, Geraldine; Oueslati, Farhana; Dhilly, Martine; Delamare, Jerome [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France); Perrio, Cecile [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)], E-mail: perrio@cyceron.fr; Debruyne, Daniele [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)], E-mail: debruyne@cyceron.fr; Barre, Louisa [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)

2008-07-15

Introduction: Radiopharmaceuticals that can bind selectively the {kappa}-opioid receptor may present opportunities for staging clinical brain disorders and evaluating the efficiency of new therapies related to stroke, neurodegenerative diseases or opiate addiction. The N-methylated derivative of JDTic (named MeJDTic), which has been recently described as a potent and selective antagonist of {kappa}-opioid receptor in vitro, was labeled with carbon-11 and evaluated for in vivo imaging the {kappa}-opioid receptor in mice. Methods: [{sup 11}C]-MeJDTic was prepared by methylation of JDTic with [{sup 11}C]-methyl triflate. The binding of [{sup 11}C]-MeJDTic to {kappa}-opioid receptor was investigated ex vivo by biodistribution and competition studies using nonfasted male CD1 mice. Results: [{sup 11}C]-MeJDTic exhibited a high and rapid distribution in peripheral organs. The uptake was maximal in lung where the {kappa} receptor is largely expressed. [{sup 11}C]-MeJDTic rapidly crossed the blood-brain barrier and accumulated in the brain regions of interest (hypothalamus). The parent ligand remained the major radioactive compound in brain during the experiment. Chase studies with U50,488 (a {kappa} referring agonist), morphine (a {mu} agonist) and naltrindole (a {delta} antagonist) demonstrated that this uptake was the result of specific binding to the {kappa}-opioid receptor. Conclusion: These findings suggested that [{sup 11}C]-MeJDTic appeared to be a promising selective 'lead' radioligand for {kappa}-opioid receptor PET imaging.

National consumption of opioid and nonopioid analgesics in Croatia: 2007–2013

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Krnic D

2015-08-01

Full Text Available Darko Krnic,1 Andrea Anic-Matic,2 Svjetlana Dosenovic,2 Pero Draganic,1 Sasa Zezelic,1 Livia Puljak2 1Agency for Medicinal Products and Medical Devices, Zagreb, 2Laboratory for Pain Research, School of Medicine, University of Split, Split, Croatia Background: The increased consumption of analgesics has been documented worldwide during the last 2 decades. The aim of the study was to examine the trends in opioid and nonopioid analgesic consumption in Croatia between 2007 and 2013. Methods: Data on opioid consumption were extracted from the database of the national authority. All opioid and nonopioid analgesics were included in the analysis. Data were presented as defined daily doses per 1,000 inhabitants per day. Adequacy of opioid consumption was calculated using adequacy of consumption measure. Results: During the examined 7-year period, the total consumption and total cost of all analgesics in Croatia showed continuous increase. In the M01A group (anti-inflammatory and antirheumatic products, nonsteroids, ibuprofen had an exponential increasing trend, and in 2011, it overtook diclofenac consumption. Ibuprofen and diclofenac had the highest consumption also in the M02A group of topical products for joint and muscular pain. Tramadol was by far the most consumed type of opioids (N02A group and paracetamol in the group of other analgesics and antipyretics (N02B. The adequacy of consumption measure value was 0.19, indicating that Croatia is a country with a low opioid consumption. Conclusion: Between 2007 and 2013, both consumption of analgesics and their cost in Croatia had an increasing trend. Comparisons with data from other countries, based on the published literature, indicate that analgesic consumption in Croatia is still relatively low. Calculation of the adequacy of opioid consumption indicated that Croatia is a country with low opioid consumption. Further studies are necessary for establishing whether current analgesic consumption in

Combined autoradiographic-immunocytochemical analysis of opioid receptors and opioid peptide neuronal systems in brain

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Lewis, M.E.; Khachaturian, H.; Watson, S.J.

1985-01-01

Using adjacent section autoradiography-immunocytochemistry, the distribution of (TH)naloxone binding sites was studied in relation to neuronal systems containing (Leu)enkephalin, dynorphin A, or beta-endorphin immunoreactivity in rat brain. Brain sections from formaldehyde-perfused rats show robust specific binding of (TH)naloxone, the pharmacological (mu-like) properties of which appear unaltered. In contrast, specific binding of the delta ligand (TH)D-Ala2,D-Leu5-enkephalin was virtually totally eliminated as a result of formaldehyde perfusion. Using adjacent section analysis, the authors have noted associations between (TH)naloxone binding sites and one, two, or all three opioid systems in different brain regions; however, in some areas, no apparent relationship could be observed. Within regions, the relationship was complex. The complexity of the association between (TH)naloxone binding sites and the multiple opioid systems, and previous reports of co-localization of mu and kappa receptors in rat brain, are inconsistent with a simple-one-to-one relationship between a given opioid precursor and opioid receptor subtype. Instead, since differential processing of the three precursors gives rise to peptides of varying receptor subtype potencies and selectivities, the multiple peptide-receptor relationships may point to a key role of post-translational processing in determining the physiological consequences of opioid neurotransmission.

When human immunodeficiency virus (HIV) treatment goals conflict with guideline-based opioid prescribing: A qualitative study of HIV treatment providers.

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Starrels, Joanna L; Peyser, Deena; Haughton, Lorlette; Fox, Aaron; Merlin, Jessica S; Arnsten, Julia H; Cunningham, Chinazo O

2016-01-01

Human immunodeficiency virus (HIV)-infected patients have a high prevalence of chronic pain and opioid use, making HIV care a critical setting for improving the safety of opioid prescribing. Little is known about HIV treatment providers' perspectives about opioid prescribing to patients with chronic pain. The authors administered a questionnaire and conducted semistructured telephone interviews with 18 HIV treatment providers (infectious disease specialists, general internists, family medicine physicians, nurse practitioners, and physician assistants) in Bronx, NY. Open-ended interview questions focused on providers' experiences, beliefs, and attitudes about opioid prescribing and about the use of guideline-based opioid prescribing practices (conservative prescribing, and monitoring for and responding to misuse). Transcripts were thematically analyzed using a modified grounded theory approach. Eighteen HIV treatment providers included 13 physicians, four nurse practitioners, and one physician assistant. They were 62% female, 56% white, and practiced as HIV treatment providers for a mean of 14.6 years. Most reported always or almost always using opioid treatment agreements (56%) and urine drug testing (61%) with their patients on long-term opioid therapy. HIV treatment providers tended to view opioid prescribing for chronic pain within the "HIV paradigm," a set of priorities and principles defined by three key themes: (1) primacy of HIV goals, (2) familiarity with substance use, and (3) the clinician as ally. The HIV paradigm sometimes supported, and sometimes conflicted with, guideline-based opioid prescribing practices. For HIV treatment providers, perceived alignment with the HIV paradigm determined whether and how guideline-based opioid prescribing practices were adopted. For example, the primacy of HIV goals superseded conservative opioid prescribing when providers prescribed opioids with the goal of retaining patients in HIV care. These findings highlight

Prescription opioid use: Patient characteristics and misuse in community pharmacy.

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Cochran, Gerald; Bacci, Jennifer L; Ylioja, Thomas; Hruschak, Valerie; Miller, Sharon; Seybert, Amy L; Tarter, Ralph

2016-01-01

Opioid pain medication misuse is a major concern for US public health. The purpose of this article is to: 1) describe the demographic and physical, behavioral, and mental health characteristics of patients who fill opioid medications in community pharmacy settings; and 2) describe the extent of opioid medication misuse behaviors among these patients. We recruited and screened a convenience sample of patients with the use of a tablet computer-based assessment protocol that examined behavioral, mental, and physical health. Descriptive and inferential statistics were calculated to describe respondents and their opioid medication misuse and health characteristics. Patients were screened in 2 urban and 2 rural community pharmacies in southwestern Pennsylvania. Survey participants were adult patients filling opioid pain medications who were not currently receiving treatment for a cancer diagnosis. None. Validated screening measures included the Prescription Opioid Misuse Index, Alcohol Use Disorders Identification Test C, Short Form 12, Drug Abuse Screening Test 10, Primary Care Post-traumatic Stress Disorder (PTSD) screen, and the Patient Health Questionnaire 2. A total of 333 patients were screened (71.2% response rate). Nearly the entire population reported pain above and general health below national norms. Hydrocodone (19.2%) and morphine (20.8%) were found to be the medications with the highest rates of misuse-with hydrocodone having more than 4 times higher odds of misuse compared with other medications (adjusted odds ratio [AOR] 4.48, 95% confidence interval [CI] 1.1-17.4). Patients with positive screens for illicit drug use (AOR 8.07, 95% CI 2.7-24.0), PTSD (AOR 5.88, 95% CI 2.3-14.7), and depression (AOR 2.44, 95% CI 1.0-5.9) also had significantly higher odds for misuse compared with those with negative screening results. These findings provide important foundational data that suggest implementation of regular opioid misuse screening protocols within

Differences in opioid prescribing in low back pain patients with and without depression: a cross-sectional study of a national sample from the United States

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Joyce A. Smith

2017-08-01

Conclusion:. Analysis of a nationwide sample of patients with LBP shows an association between depression and higher rates of opioid prescribing after controlling for several known cofounders. Clinicians prescribing opioids in LBP populations that rely on clinical trial results that exclude depressed patients may misjudge the risks and benefits of this class of therapy.

Resisting Prescribed Opioids: A Qualitative Study of Decision Making in Patients Taking Opioids for Chronic Noncancer Pain.

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Paterson, Charlotte; Ledgerwood, Kay; Arnold, Carolyn; Hogg, Malcolm; Xue, Charlie; Zheng, Zhen

2016-04-01

Opioids are increasingly prescribed for chronic noncancer pain across the developed world. Clinical guidelines for management of these patients focus on over-use. However, research into other types of long-term medication indicates that many patients minimize drug use whenever possible. To identify the varying influences on patients' decisions about their use of prescribed opioids and explore whether concepts of resistance and minimization of intake apply to these patients. A multiprofessional team performed a qualitative interview study using the constant-comparative method. Patient's decision making was explored in depth and with a thematic analysis utilizing a published "Model of medicine-taking." A purposive sample of 20 participants drawn from two pain clinics in Melbourne, Australia. The sample was biased toward patients interested in nonmedication pain management options. Patients' needs to obtain relief from severe pain, maintain function, and minimize side effects could lead to under-use as well as over-use of prescribed opioids. In keeping with the published Model of medicine-taking, resistance to taking opioids was a common and important influence on behavior. In the face of severe chronic pain, many participants used a variety of strategies to evaluate, avoid, reduce, self-regulate, and replace opioids. Furthermore, participants perceived a resistance to opioids within the system and among some healthcare professionals. This sometimes adversely affected their adherence. Both patients and doctors exhibit aspects of resistance to the use of prescribed opioids for chronic noncancer pain, suggesting that this shared concern could be the basis of a productive therapeutic alliance to improve communication and shared decision making. Clinical guidelines for opioids use for chronic noncancer pain focus on over-use. Our qualitative interview study found that many patients resisted and minimized the use of opioids. Using a published "Model of medicine-taking," we

Pleiotropic opioid regulation of spinal endomorphin 2 release and its adaptations to opioid withdrawal are sexually dimorphic.

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Chakrabarti, Sumita; Liu, Nai-Jiang; Zadina, James E; Sharma, Tarak; Gintzler, Alan R

2012-01-01

We studied adaptations to acute precipitated opioid withdrawal of spinal μ-opioid receptor (MOR)-coupled regulation of the release of endomorphin 2 (EM2). The release of this highly MOR-selective endogenous opioid from opioid-naive spinal tissue of male rats is subjected to MOR-coupled positive as well as negative modulation via cholera toxin-sensitive G(s) and pertussis toxin-sensitive G(i)/G(o), respectively. The net effect of this concomitant bidirectional modulation is inhibitory. MOR-coupled pleiotropic regulation of EM2 release is retained in opioid-withdrawn spinal tissue of male rats, but the balance of MOR-coupled inhibitory and facilitatory regulation shifted such that facilitatory regulation predominates. Augmented coupling of MOR to G(s) is causally associated with this change. Strikingly, pleiotropic characteristics of MOR-coupled regulation of spinal EM2 release and adaptations thereof to opioid withdrawal are male-specific. In females, MOR-coupled regulation of EM2 release from opioid-naive and -withdrawn spinal tissue does not have a significant G(s)-coupled facilitatory component, and MOR-coupled inhibition of EM2 release persists unabated in withdrawn preparations. The male-specific adaptations to chronic morphine that shift the relative predominance of opposing dual G protein-coupled MOR pathways provides a mechanism for mitigating inhibitory MOR signaling without losing MOR-coupled feedback regulation. These adaptations enable using endogenous EM2 as a substitute for morphine that had been precipitously removed. The sexually dimorphic functionality and regulation of spinal EM2/MOR-coupled signaling suggest the clinical utility of using sex-specific treatments for addiction that harness the activity of endogenous opioids.

Interactions between opioids and anabolic androgenic steroids: implications for the development of addictive behavior.

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Nyberg, Fred; Hallberg, Mathias

2012-01-01

Over the past decades, research on doping agents, such as anabolic androgenic steroids (AAS), has revealed that these compounds are often used in combination with other drugs of abuse. It seems that misuse of AAS probably involves more than a desire to enhance appearance or sports performance and studies have revealed that steroids are commonly connected with alcohol, opioids, tobacco, and psychotropic drugs. We have observed that AAS may interact with the endogenous opioids, excitatory amino acids, and dopaminergic pathways involved in the brain reward system. Furthermore, our studies provide evidence that AAS may induce an imbalance in these signal systems leading to an increased sensitivity toward opioid narcotics and central stimulants. In fact, studies performed in various clinics have shown that individuals taking AAS are likely to get addicted to opioids like heroin. This chapter reviews current knowledge on interactions between AAS and endogenous as well as exogenous opioids based not only on research in our laboratory but also on research carried out by several other clinical and preclinical investigators. Copyright © 2012 Elsevier Inc. All rights reserved.

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

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Christensen, Darren R; Landes, Reid D; Jackson, Lisa; Marsch, Lisa A; Mancino, Michael J; Chopra, Mohit P; Bickel, Warren K

2014-12-01

To examine the benefit of adding an Internet-delivered behavior therapy to a buprenorphine medication program and voucher-based motivational incentives. A block-randomized, unblinded, parallel, 12-week treatment trial was conducted with 170 opioid-dependent adult patients (mean age = 34.3 years; 54.1% male; 95.3% 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. Compared to those receiving CM-alone, CRA+ recipients exhibited, on average, 9.7 total days more of abstinence (95% confidence interval [CI = 2.3, 17.2]) and had a reduced hazard of dropping out of treatment (hazard ratio = 0.47; 95% CI [0.26, 0.85]). Prior treatment for opioid dependence significantly moderated the additional improvement of CRA+ for longest continuous days of abstinence. 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.

Secular trends in opioid prescribing in the USA

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Pezalla EJ

2017-02-01

Full Text Available Edmund J Pezalla,1 David Rosen,2 Jennifer G Erensen,2 J David Haddox,2,3 Tracy J Mayne2 1Bioconsult, LLC, Wethersfield, 2Purdue Pharma L.P., Stamford, CT, 3Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA Abstract: Opioid abuse and misuse in the USA is a public health crisis. The use of prescription opioid analgesics increased substantially from 2002 through 2010, then plateaued and began to decrease in 2011. This study examined prescriptions of branded and generic immediate- and extended-release opioid analgesics from 1992 to 2016. This was juxtaposed against state and federal policies designed to decrease overutilization and abuse, as well as the launch of new opioid products, including opioids with abuse-deterrent properties (OADPs. The data indicate that these health policies, including the utilization and reimbursement of OADPs, have coincided with decreased opioid utilization. The hypothesis that OADPs will paradoxically increase opioid prescribing is not supported. Keywords: OADP, prescription, utilization trends, legislation, opioids

Perspectives of patients, family caregivers and physicians about the use of opioids for refractory dyspnea in advanced chronic obstructive pulmonary disease.

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Rocker, Graeme; Young, Joanne; Donahue, Margaret; Farquhar, Morag; Simpson, Catherine

2012-06-12

A recent national practice guideline recommends the use of opioids for the treatment of refractory dyspnea in patients with advanced chronic obstructive pulmonary disease (COPD). We conducted two qualitative studies to explore the experiences of patients and family caregivers with opioids for refractory COPD-related dyspnea and the perspectives and attitudes of physicians toward opioids in this context. Patients (n = 8; 5 men, 3 women), their caregivers (n = 12; 5 men, 7 women) and physicians (n = 28, 17 men, 11 women) in Nova Scotia participated in the studies. Semistructured interviews were recorded, transcribed verbatim, coded conceptually and analyzed for emergent themes using interpretive description methodology. Patients reported that opioids provided a sense of calm and relief from severe dyspnea. Family caregivers felt that opioids helped patients to breathe more "normally," observed improvements in patients' symptoms of anxiety and depression, and experienced reductions in their own stress. Patients reported substantial improvements in their quality of life. All patients and family caregivers wanted opioid therapy to continue. Most physicians were reluctant to prescribe opioids for refractory dyspnea, describing a lack of related knowledge and experience, and fears related to the potential adverse effects and legal censure. Discrepancies between the positive experiences of patients and family caregivers with opioids and the reluctance of physicians to prescribe opioids for refractory dyspnea constitute an important gap in care. Bridging this gap will require initiatives to improve the uptake of practice guidelines and to increase confidence in prescribing opioids for dyspnea refractory to conventional treatment.

Amygdala mu-opioid receptors mediate the motivating influence of cue-triggered reward expectations.

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Lichtenberg, Nina T; Wassum, Kate M

2017-02-01

Environmental reward-predictive stimuli can retrieve from memory a specific reward expectation that allows them to motivate action and guide choice. This process requires the basolateral amygdala (BLA), but little is known about the signaling systems necessary within this structure. Here we examined the role of the neuromodulatory opioid receptor system in the BLA in such cue-directed action using the outcome-specific Pavlovian-to-instrumental transfer (PIT) test in rats. Inactivation of BLA mu-, but not delta-opioid receptors was found to dose-dependently attenuate the ability of a reward-predictive cue to selectively invigorate the performance of actions directed at the same unique predicted reward (i.e. to express outcome-specific PIT). BLA mu-opioid receptor inactivation did not affect the ability of a reward itself to similarly motivate action (outcome-specific reinstatement), suggesting a more selective role for the BLA mu-opioid receptor in the motivating influence of currently unobservable rewarding events. These data reveal a new role for BLA mu-opioid receptor activation in the cued recall of precise reward memories and the use of this information to motivate specific action plans. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

The relative potency of inverse opioid agonists and a neutral opioid antagonist in precipitated withdrawal and antagonism of analgesia and toxicity.

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Sirohi, Sunil; Dighe, Shveta V; Madia, Priyanka A; Yoburn, Byron C

2009-08-01

Opioid antagonists can be classified as inverse agonists and neutral antagonists. In the opioid-dependent state, neutral antagonists are significantly less potent in precipitating withdrawal than inverse agonists. Consequently, neutral opioid antagonists may offer advantages over inverse agonists in the management of opioid overdose. In this study, the relative potency of three opioid antagonists to block opioid analgesia and toxicity and precipitate withdrawal was examined. First, the potency of two opioid inverse agonists (naltrexone and naloxone) and a neutral antagonist (6beta-naltrexol) to antagonize fentanyl-induced analgesia and lethality was determined. The order of potency to block analgesia was naltrexone > naloxone > 6beta-naltrexol (17, 4, 1), which was similar to that to block lethality (13, 2, 1). Next, the antagonists were compared using withdrawal jumping in fentanyl-dependent mice. The order of potency to precipitate withdrawal jumping was naltrexone > naloxone 6beta-naltrexol (1107, 415, 1). The relative potencies to precipitate withdrawal for the inverse agonists compared with the neutral antagonist were dramatically different from that for antagonism of analgesia and lethality. Finally, the effect of 6beta-naltrexol pretreatment on naloxone-precipitated jumping was determined in morphine and fentanyl-dependent mice. 6beta-Naltrexol pretreatment decreased naloxone precipitated withdrawal, indicating that 6beta-naltrexol is a neutral antagonist. These data demonstrate that inverse agonists and neutral antagonists have generally comparable potencies to block opioid analgesia and lethality, whereas the neutral opioid antagonist is substantially less potent in precipitating opioid withdrawal. These results support suggestions that neutral antagonists may have advantages over inverse agonists in the management of opioid overdose.

Music therapy in palliative care: current perspectives.

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O'Kelly, Julian

2002-03-01

As the music therapy profession has developed internationally over the last 25 years, so has its role in palliative care. Music is a highly versatile and dynamic therapeutic modality, lending itself to a variety of music therapy techniques used to benefit both those living with life-threatening illnesses and their family members and caregivers. This article will give a broad overview of the historical roots of music therapy and introduce the techniques that are employed in current practice. By combining a review of mainstream music therapy practice involving musical improvisation, song-writing and receptive/recreational techniques with case material from my own experience, this article aims to highlight the potential music therapy holds as an effective holistic practice for palliative care, whatever the care setting.

Tolerance to Non-Opioid Analgesics is Opioid Sensitive in the Nucleus Raphe Magnus.

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Tsagareli, Merab G; Nozadze, Ivliane; Tsiklauri, Nana; Gurtskaia, Gulnaz

2011-01-01

Repeated injection of opioid analgesics can lead to a progressive loss of effect. This phenomenon is known as tolerance. Several lines of investigations have shown that systemic, intraperitoneal administration or the microinjection of non-opioid analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) into the midbrain periaqueductal gray matter induces antinociception with some effects of tolerance. Our recent study has revealed that microinjection of three drugs analgin, ketorolac, and xefocam into the central nucleus of amygdala produce tolerance to them and cross-tolerance to morphine. Here we report that repeated administrations of these NSAIDs into the nucleus raphe magnus (NRM) in the following 4 days result in progressively less antinociception compare to the saline control, i.e., tolerance develops to these drugs in male rats. Special control experiments showed that post-treatment with the μ-opioid antagonist naloxone into the NRM significantly decreased antinociceptive effects of NSAIDs on the first day of testing in the tail-flick (TF) reflex and hot plate (HP) latency tests. On the second day, naloxone generally had trend effects in both TF and HP tests and impeded the development of tolerance to the antinociceptive effect of non-opioid analgesics. These findings strongly support the suggestion of endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain-control system. Moreover, repeated injections of NSAIDs progressively lead to tolerance to them, cross-tolerance to morphine, and the risk of a withdrawal syndrome. Therefore, these results are important for human medicine too.

Acute toxicity in comprehensive head and neck radiation for nasopharynx and paranasal sinus cancers: cohort comparison of 3D conformal proton therapy and intensity modulated radiation therapy

International Nuclear Information System (INIS)

McDonald, Mark W.; Liu, Yuan; Moore, Michael G.; Johnstone, Peter A. S.

2016-01-01

To evaluate acute toxicity endpoints in a cohort of patients receiving head and neck radiation with proton therapy or intensity modulated radiation therapy (IMRT). Forty patients received comprehensive head and neck radiation including bilateral cervical nodal radiation, given with or without chemotherapy, for tumors of the nasopharynx, nasal cavity or paranasal sinuses, any T stage, N0-2. Fourteen received comprehensive treatment with proton therapy, and 26 were treated with IMRT, either comprehensively or matched to proton therapy delivered to the primary tumor site. Toxicity endpoints assessed included g-tube dependence at the completion of radiation and at 3 months after radiation, opioid pain medication requirement compared to pretreatment normalized as equivalent morphine dose (EMD) at completion of treatment, and at 1 and 3 months after radiation. In a multivariable model including confounding variables of concurrent chemotherapy and involved nodal disease, comprehensive head and neck radiation therapy using proton therapy was associated with a lower opioid pain requirement at the completion of radiation and a lower rate of gastrostomy tube dependence by the completion of radiation therapy and at 3 months after radiation compared to IMRT. Proton therapy was associated with statistically significant lower mean doses to the oral cavity, esophagus, larynx, and parotid glands. In subgroup analysis of 32 patients receiving concurrent chemotherapy, there was a statistically significant correlation with a greater opioid pain medication requirement at the completion of radiation and both increasing mean dose to the oral cavity and to the esophagus. Proton therapy was associated with significantly reduced radiation dose to assessed non-target normal tissues and a reduced rate of gastrostomy tube dependence and opioid pain medication requirements. This warrants further evaluation in larger studies, ideally with patient-reported toxicity outcomes and quality of life

Isobolographic analysis of the opioid-opioid interactions in a tonic and a phasic mouse model of induced nociceptive pain.

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Miranda, Hugo F; Noriega, Viviana; Zanetta, Pilar; Prieto, Juan Carlos; Prieto-Rayo, Juan Carlos; Aranda, Nicolás; Sierralta, Fernando

2014-07-15

Opioids have been used for the management of pain and coadministration of two opioids may induce synergism. In a model of tonic pain, the acetic acid writhing test and in a phasic model, the hot plate, the antinociceptive interaction between fentanyl, methadone, morphine, and tramadol was evaluated. The potency of opioids in the writhing test compared to the hot plate assay was from 2.5 (fentanyl) to 15.5 (morphine) times, respectively. The ED50 was used in a fixed ratio for each of the six pairs of opioid combinations, which, resulted in a synergistic antinociception except for methadone/tramadol and fentanyl/tramadol which were additive, in the hot plate. The opioid antagonists naltrexone, naltrindole and nor-binaltorphimine, suggests that the synergism of morphine combinations are due to the activation of MOR subtypes with partially contribution of DOR and KOR, however fentanyl and methadone combinations are partially due to the activation of MOR and DOR subtypes and KOR lack of participation. The antinociceptive effects of tramadol combinations, are partially due to the activation of MOR, DOR and KOR opioid subtypes. These results suggets that effectiveness and magnitude of the interactions between opioids are dependent on pain stimulus intensity.

Molecular characterization of opioid receptors

Energy Technology Data Exchange (ETDEWEB)

Howard, A.D.

1986-01-01

The aim of this research was to purify and characterize active opioid receptors and elucidate molecular aspects of opioid receptor heterogeneity. Purification to apparent homogeneity of an opioid binding protein from bovine caudate was achieved by solubilization in the non-ionic detergent, digitonin, followed by sequential chromatography on the opiate affinity matrix, ..beta..-naltrexylethylenediamine-CH-Sepharose 4B, and on the lectine affinity matrix, wheat germ agglutinin-agarose. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) followed by autoradiography revealed that radioiodinated purified receptor gave a single band. Purified receptor preparations showed a specific activity of 12,000-15,000 fmol of opiate bound per mg of protein. Radioiodinated human beta-endorphin (/sup 125/I-beta-end/sub H/) was used as a probe to investigate the ligand binding subunits of mu and delta opioid receptors. /sup 125/I-beta-end/sub H/ was shown to bind to a variety of opioid receptor-containing tissues with high affinity and specificity with preference for mu and delta sites, and with little, if any, binding to kappa sites. Affinity crosslinking techniques were employed to covalently link /sup 125/I-beta-end/sub H/ to opioid receptors, utilizing derivatives of bis-succinimidyl esters that are bifunctional crosslinkers with specificities for amino and sulfhydryl groups. This, and competition experiments with high type-selective ligands, permitted the assignment of two labeled peptides to their receptor types, namely a peptide of M/sub r/ = 65,000 for mu receptors and one of M/sub r/ = 53,000 for delta receptors.

Reiki therapy for postoperative oral pain in pediatric patients: pilot data from a double-blind, randomized clinical trial.

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Kundu, Anjana; Lin, Yuting; Oron, Assaf P; Doorenbos, Ardith Z

2014-02-01

To examine the effects of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients. This was a double-blind, randomized controlled study of children undergoing dental procedures. Participants were randomly assigned to receive either Reiki therapy or the control therapy (sham Reiki) preoperatively. Postoperative pain scores, opioid requirements, and side effects were assessed. Family members were also asked about perioperative care satisfaction. Multiple linear regressions were used for analysis. Thirty-eight children participated. The blinding procedure was successful. No statistically significant difference was observed between groups on all outcome measures. Our study provides a successful example of a blinding procedure for Reiki therapy among children in the perioperative period. This study does not support the effectiveness of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

Observational study to calculate addictive risk to opioids: a validation study of a predictive algorithm to evaluate opioid use disorder

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Brenton A

2017-05-01

Full Text Available Ashley Brenton,1 Steven Richeimer,2,3 Maneesh Sharma,4 Chee Lee,1 Svetlana Kantorovich,1 John Blanchard,1 Brian Meshkin1 1Proove Biosciences, Irvine, CA, 2Keck school of Medicine, University of Southern California, Los Angeles, CA, 3Departments of Anesthesiology and Psychiatry, University of Southern California, Los Angeles, CA, 4Interventional Pain Institute, Baltimore, MD, USA Background: Opioid abuse in chronic pain patients is a major public health issue, with rapidly increasing addiction rates and deaths from unintentional overdose more than quadrupling since 1999. Purpose: This study seeks to determine the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated single-nucleotide polymorphisms (SNPs. Patients and methods: The Proove Opioid Risk (POR algorithm determines the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated SNPs. In a validation study with 258 subjects with diagnosed opioid use disorder (OUD and 650 controls who reported using opioids, the POR successfully categorized patients at high and moderate risks of opioid misuse or abuse with 95.7% sensitivity. Regardless of changes in the prevalence of opioid misuse or abuse, the sensitivity of POR remained >95%. Conclusion: The POR correctly stratifies patients into low-, moderate-, and high-risk categories to appropriately identify patients at need for additional guidance, monitoring, or treatment changes. Keywords: opioid use disorder, addiction, personalized medicine, pharmacogenetics, genetic testing, predictive algorithm

Aripiprazole plus topiramate in opioid-dependent patients with schizoaffective disorder: an 8-week, open-label, uncontrolled, preliminary study.

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Bruno, Antonio; Romeo, Vincenzo M; Pandolfo, Gianluca; Scimeca, Giuseppe; Zoccali, Rocco A; Muscatello, Maria Rosaria A

2014-01-01

The aims of this study were to evaluate a combination of aripiprazole and topiramate in the treatment of opioid-dependent patients with schizoaffective disorder undergoing methadone maintenance therapy (MMT) and, further, to taper off patients from methadone treatment. Twenty patients who met DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria for opioid dependence and schizoaffective disorder receiving MMT (80 mg/day) were given aripiprazole (10 mg/day) plus topiramate (up to 200 mg/day) for 8 weeks. A methadone dose reduction of 3 mg/day until suspension at week 4 was established. Aripiprazole plus topiramate was effective in reducing clinical symptoms, and a rapid tapering off of MMT was achieved. Combining aripiprazole and topiramate may be effective in patients with a dual diagnosis of opioid dependency and schizoaffective disorder.

Suicidal ideation is associated with individual differences in prescription opioid craving and cue-reactivity among chronic pain patients.

Science.gov (United States)

Garland, Eric L; Riquino, Michael R; Priddy, Sarah E; Bryan, Craig J

2017-01-01

Given that chronic pain patients experience significant rates of suicidal ideation and suicide attempts, access to prescription opioids compounds the risk of death by suicide. These patients may experience heightened opioid craving and exhibit increased cue-reactivity to stimuli associated with past opioid use when suicidal ideation produces negative affective states. Because both opioids and suicidal behavior are used to alleviate emotional and physical pain through a process of negative reinforcement, elucidating factors that mediate this association may yield insight into suicide risk among chronic pain patients. This study examined the relationship between suicidal ideation and opioid craving and cue-reactivity, and tested opioid self-medication as a mediator of associations between those factors after controlling for the impact of pain severity. A sample of 115 chronic pain patients provided demographic and clinical information on the Obsessive Compulsive Drug Use Scale, the Current Opioid Misuse Measure, and the Brief Pain Inventory before completing an opioid dot probe task in which heart rate variability was recorded. As hypothesized, suicidal ideation was positively correlated with subjective opioid craving and physiological cue-reactivity. Self-medication significantly mediated the association between suicidal ideation, craving, and cue-reactivity. As opioids relieve the emotional pain linked with suicidal thoughts, chronic pain patients with higher levels of suicidal ideation may experience more intense opioid craving and exhibit heightened physiological cue-reactivity when compared to patients with low levels of suicidal ideation.

Police Officer, Deal-Maker, or Healthcare Provider? Moving to a Patient-Centered Framework for Chronic Opioid Management

Science.gov (United States)

Nicolaidis, Christina

2016-01-01

How we frame our thoughts about chronic opioid therapy greatly influences our ability to practice patient-centered care. Even providers who strive to be non-judgmental may approach clinical decision-making about opioids by considering if the pain is real or they can trust the patient. Not only does this framework potentially lead to poor or unshared decision-making, it likely adds to provider and patient discomfort by placing the provider in the position of a police officer or judge. Similarly, providers often find themselves making deals with patients using a positional bargaining approach. Even if a compromise is reached, this framework can potentially inadvertently weaken the therapeutic relationship by encouraging the idea that the patient and provider have opposing goals. Reframing the issue can allow the provider to be in a more therapeutic role. As recommended in the APS/AAPM guidelines, providers should decide whether the benefits of opioid therapy are likely to outweigh the harms for a specific patient (or sometimes, for society) at a specific time. This paper discusses how providers can use a benefit-to-harm framework to make and communicate decisions about the initiation, continuation, and discontinuation of opioids for managing chronic non-malignant pain. Such an approach focuses decisions and discussions on judging the treatment, not the patient. It allows the provider and the patient to ally together and make shared decisions regarding a common goal. Moving to a risk-benefit framework may allow providers to provide more patient-centered care, while also increasing provider and patient comfort with adequately monitoring for harm. PMID:21539703

Long-term evaluation of opioid treatment in fibromyalgia.

Science.gov (United States)

Peng, Xiaomei; Robinson, Rebecca L; Mease, Philip; Kroenke, Kurt; Williams, David A; Chen, Yi; Faries, Douglas; Wohlreich, Madelaine; McCarberg, Bill; Hann, Danette

2015-01-01

In a 12-month observational study, we evaluated the effect of opioid use on the outcomes in 1700 adult patients with fibromyalgia. Data were evaluated using propensity score matching after patients were divided into cohorts based on their baseline medication use: (1) taking an opioid (concurrent use of tramadol was permitted); (2) taking tramadol (but no opioids); and (3) not taking opioids or tramadol. Changes in outcomes were assessed using the Brief Pain Inventory for severity and pain-related interference (BPI-S, BPI-I), Fibromyalgia Impact Questionnaire (FIQ), Patient Health Questionnaire for depression (PHQ-8), Insomnia Severity Index (ISI), Sheehan Disability Scale (SDS), 7-item Generalized Anxiety Disorder Scale (GAD-7), and economic factors. Time-to-opioid or tramadol discontinuation was analyzed using Kaplan-Meier survival analyses. Compared with the opioid cohort, the nonopioid cohort demonstrated significantly greater reductions (PFIQ, PHQ-8, SDS, and ISI; the tramadol cohort compared with the opioid group showed greater reductions on FIQ and ISI. Reductions in BPI-S and GAD-7 did not differ significantly among cohorts. Compared with the opioid cohort, patients in the tramadol cohort had fewer outpatient visits to health care providers. Few significant differences were found between the tramadol and nonopioid cohorts across outcomes. Although pain severity was reduced over time in all cohorts, opioid users showed less improvement in pain-related interference with daily living, functioning, depression, and insomnia. Overall, the findings show little support for the long-term use of opioid medications in patients with fibromyalgia given the poorer outcomes across multiple assessment domains associated with this cohort.

Reduction of opioid withdrawal and potentiation of acute opioid analgesia by systemic AV411 (ibudilast).

Science.gov (United States)

Hutchinson, Mark R; Lewis, Susannah S; Coats, Benjamen D; Skyba, David A; Crysdale, Nicole Y; Berkelhammer, Debra L; Brzeski, Anita; Northcutt, Alexis; Vietz, Christine M; Judd, Charles M; Maier, Steven F; Watkins, Linda R; Johnson, Kirk W

2009-02-01

Morphine-induced glial proinflammatory responses have been documented to contribute to tolerance to opioid analgesia. Here, we examined whether drugs previously shown to suppress glial proinflammatory responses can alter other clinically relevant opioid effects; namely, withdrawal or acute analgesia. AV411 (ibudilast) and minocycline, drugs with distinct mechanisms of action that result in attenuation of glial proinflammatory responses, each reduced naloxone-precipitated withdrawal. Analysis of brain nuclei associated with opioid withdrawal revealed that morphine altered expression of glial activation markers, cytokines, chemokines, and a neurotrophic factor. AV411 attenuated many of these morphine-induced effects. AV411 also protected against spontaneous withdrawal-induced hyperactivity and weight loss recorded across a 12-day timecourse. Notably, in the spontaneous withdrawal study, AV411 treatment was delayed relative to the start of the morphine regimen so to also test whether AV411 could still be effective in the face of established morphine dependence, which it was. AV411 did not simply attenuate all opioid effects, as co-administering AV411 with morphine or oxycodone caused three-to-five-fold increases in acute analgesic potency, as revealed by leftward shifts in the analgesic dose response curves. Timecourse analyses revealed that plasma morphine levels were not altered by AV411, suggestive that potentiated analgesia was not simply due to prolongation of morphine exposure or increased plasma concentrations. These data support and extend similar potentiation of acute opioid analgesia by minocycline, again providing converging lines of evidence of glial involvement. Hence, suppression of glial proinflammatory responses can significantly reduce opioid withdrawal, while improving analgesia.

Pain management and opioid risk mitigation in the military.

Science.gov (United States)

Sharpe Potter, Jennifer; Bebarta, Vikhyat S; Marino, Elise N; Ramos, Rosemarie G; Turner, Barbara J

2014-05-01

Opioid analgesics misuse is a significant military health concern recognized as a priority issue by military leadership. Opioids are among those most commonly prescribed medications in the military for pain management. The military has implemented opioid risk mitigation strategies, including the Sole Provider Program and the Controlled Drug Management Analysis and Reporting Tool, which are used to identify and monitor for risk and misuse. However, there are substantial opportunities to build on these existing systems to better ensure safer opioid prescribing and monitor for misuse. Opioid risk mitigation strategies implemented by the civilian sector include establishing clinical guidelines for opioid prescribing and prescription monitoring programs. These strategies may help to inform opioid risk mitigation in the military health system. Reducing the risk of opioid misuse and improving quality of care for our Warfighters is necessary. This must be done through evidence-based approaches with an investment in research to improve patient care and prevent opioid misuse as well as its sequelae. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

A case of rhabdomyolysis associated with severe opioid withdrawal.

Science.gov (United States)

Gangahar, Deepali

2015-08-01

While the risk of opioid overdose is widely accepted, the dangers of opioid withdrawal are far less clearly defined. The purpose of this publication is to provide evidence against the erroneous clinical dictum that opioid withdrawal is never life-threatening. This case report (N = 1) illustrates an unfortunate, common scenario of a man abusing prescription opioids and heroin. His attempt at self-detoxification with buprenorphine-naloxone resulted in life-threatening opioid withdrawal. A detailed account of each day of his withdrawal period was documented by patient and family report and review of all medical records. The patient was contacted three months after hospitalization to verify information and determine progress in treatment and abstinence from drugs and alcohol. A review of the literature was completed on severe cases of precipitated and spontaneous opioid withdrawal followed by a discussion of the significance as it relates to this case. Given the widespread use of prescription opioids and opioid maintenance treatment, physicians should be aware of the complications of acute opioid withdrawal and should be equipped to treat these complications. © American Academy of Addiction Psychiatry.

Consumer attitudes about opioid addiction treatment: a focus group study in New York City.

Science.gov (United States)

Sohler, Nancy L; Weiss, Linda; Egan, James E; López, Carolina M; Favaro, Jamie; Cordero, Robert; Cunningham, Chinazo O

2013-01-01

To develop effective programs for people who are opioid dependent and to impact the opioid epidemic in New York City, it is crucial to monitor attitudes about opioid addiction treatments among opioid users who have experienced barriers to engagement and retention in addiction treatment. The authors conducted a qualitative study using focus groups. Six focus groups in three needle exchanges in New York City were audio recorded, transcribed, and systematically coded. The authors report on the main themes related to the study objectives. Participants of each needle exchange who were opioid dependent and had some knowledge of both methadone and buprenorphine were eligible. There were four main findings. Participants felt the following: 1) buprenorphine is an appropriate option for those heroin users who are motivated to stop using, 2) they have less control over their addiction treatment with methadone than they would have with buprenorphine, 3) buprenorphine treatment is not accessible to many New York City residents who would benefit from this treatment, and 4) lack of access to buprenorphine treatment is a cause of treatment-related diversion. Both methadone maintenance and buprenorphine treatment opportunities are necessary to address the diverse treatment needs of opioid-dependent people in New York City. However, the current medical model of buprenorphine treatment may be too restrictive for some opioid-dependent people and may be contributing to the use of illicit buprenorphine. New models to deliver buprenorphine treatment may address these problems.

Neurobiology of opioid dependence in creating addiction vulnerability [version 1; referees: 3 approved

Directory of Open Access Journals (Sweden)

Christopher J. Evans

2016-07-01

addiction is contributive to the current opioid epidemic in the USA.

Sustained Benefits of Exercise-based Motivational Interviewing, but Only among Nonusers of Opioids in Patients with Fibromyalgia.

Science.gov (United States)

Kim, Sunghye; Slaven, James E; Ang, Dennis C

2017-04-01

Given the known side effects of opioids and their potential effects on cognition, we sought to evaluate the benefits of motivational interviewing (MI) to promote physical activity on 2 subsets of participants with fibromyalgia (FM): nonusers and users of opioids. This was a secondary data analysis of a 36-week randomized controlled trial to assess the efficacy of MI to promote physical activity among participants with FM. Participants were randomized to 1 of 2 treatment arms: 6 phone-based MI sessions (n = 107) or 6 sessions of FM self-management instructions [attention control (AC), n = 109]. The primary outcomes were changes in physical function (Medical Outcomes Study Short Form-36), pain severity (Brief Pain Inventory), global FM symptom severity (Fibromyalgia Impact Questionnaire), and the amount of light to moderate physical activity (LMPA) from baseline to each followup visit. At study entry, subjects were categorized as opioid nonusers versus users. Repeated measures ANOVA was used to assess treatment effects adjusting for potential confounders. Of the 216 participants, 145 (67%) were nonusers and 71 (33%) were opioid users. Among nonusers, MI was associated with improved physical function, reduced pain severity, and global FM severity, and increased LMPA at 6-month followup. Among opioid users, there were no significant differences in any outcome measures between the MI and AC groups. Exercise-based MI was associated with sustained clinical benefits 6 months after completion of therapy, but only for those who were not taking opioids.

Towards safer use of opioids.

LENUS (Irish Health Repository)

Carson, R W R

2009-09-01

The main aim of our work was to improve the safety of opioid use in our institution, an acute generalhospital with 620 beds. Initially, all reported opioid errors from 2001 - 2006 were audited. The findings directed a range of multidisciplinary staff educational inputs to improve opioid prescribing and administration practice, and encourage drug error reporting. 448 drug errors were reported, of which 54 (12%) involved opioids; of these, 43 (79%) involved codeine, morphine or oxycodone. 31 of the errors (57%) were associated with administration, followed by 12 (22%) with dispensing and 11 (20%) with prescribing. There were 2 reports of definite patient harm. A subsequent audit examined a 17-month period following the introduction of the above teaching: 17 errors were noted, of which 14 (83%) involved codeine, morphine or oxycodone. Again, drug administration was most error-prone, comprising 11 (65%) of reports. However, just 2 (12%) of the reported errors now involved prescribing, which was a reduction.

Stress-opioid interactions: a comparison of morphine and methadone.

Science.gov (United States)

Taracha, Ewa; Mierzejewski, Paweł; Lehner, Małgorzata; Chrapusta, Stanisław J; Kała, Maria; Lechowicz, Wojciech; Hamed, Adam; Skórzewska, Anna; Kostowski, Wojciech; Płaźnik, Adam

2009-01-01

The utility of methadone and morphine for analgesia and of methadone for substitution therapy for heroin addiction is a consequence of these drugs acting as opioid receptor agonists.We compared the cataleptogenic and antinociceptive effects of single subcutaneous doses of methadone hydrochloride (1-4 mg/kg) and morphine sulfate (2.5-10 mg/kg) using catalepsy and hot-plate tests, and examined the effects of the highest doses of the drugs on Fos protein expression in selected brain regions in male Sprague-Dawley rats. Methadone had greater cataleptogenic and analgesic potency than morphine. Fos immunohistochemistry revealed substantial effects on the Fos response of both the stress induced by the experimental procedures and of the drug exposure itself. There were three response patterns identified: 1) drug exposure, but not stress, significantly elevated Fos-positive cell counts in the caudate-putamen; 2) stress alone and stress combined with drug exposure similarly elevated Fos-positive cell counts in the nucleus accumbens and cingulate cortex; and 3) methadone and morphine (to a lesser extent) counteracted the stimulatory effect of nonpharmacological stressors on Fos protein expression in the somatosensory cortex barrel field, and Fos-positive cell counts in this region correlated negatively with both the duration of catalepsy and the latency time in the hot-plate test. The overlap between brain regions reacting to nonpharmacological stressors and those responding to exogenous opioids suggests that stress contributes to opioid-induced neuronal activation.

Endogenous opioids encode relative taste preference.

Science.gov (United States)

Taha, Sharif A; Norsted, Ebba; Lee, Lillian S; Lang, Penelope D; Lee, Brian S; Woolley, Joshua D; Fields, Howard L

2006-08-01

Endogenous opioid signaling contributes to the neural control of food intake. Opioid signaling is thought to regulate palatability, the reward value of a food item as determined by orosensory cues such as taste and texture. The reward value of a food reflects not only these sensory properties but also the relative value of competing food choices. In the present experiment, we used a consummatory contrast paradigm to manipulate the relative value of a sucrose solution for two groups of rats. Systemic injection of the nonspecific opioid antagonist naltrexone suppressed sucrose intake; for both groups, however, this suppression was selective, occurring only for the relatively more valuable sucrose solution. Our results indicate that endogenous opioid signaling contributes to the encoding of relative reward value.

Dextromethorphan differentially affects opioid antinociception in rats

Science.gov (United States)

Chen, Shiou-Lan; Huang, Eagle Yi-Kung; Chow, Lok-Hi; Tao, Pao-Luh

2005-01-01

Opioid drugs such as morphine and meperidine are widely used in clinical pain management, although they can cause some adverse effects. A number of studies indicate that N-methyl-D-aspartate (NMDA) receptors may play a role in the mechanism of morphine analgesia, tolerance and dependence. Being an antitussive with NMDA antagonist properties, dextromethorphan (DM) may have some therapeutic benefits when coadministered with morphine. In the present study, we investigated the effects of DM on the antinociceptive effects of different opioids. We also investigated the possible pharmacokinetic mechanisms involved. The antinociceptive effects of the μ-opioid receptor agonists morphine (5 mg kg−1, s.c.), meperidine (25 mg kg−1, s.c.) and codeine (25 mg kg−1, s.c.), and the κ-opioid agonists nalbuphine (8 mg kg−1, s.c.) and U-50,488H (20 mg kg−1, s.c.) were studied using the tail-flick test in male Sprague–Dawley rats. Coadministration of DM (20 mg kg−1, i.p.) with these opioids was also performed and investigated. The pharmacokinetic effects of DM on morphine and codeine were examined, and the free concentration of morphine or codeine in serum was determined by HPLC. It was found that DM potentiated the antinociceptive effects of some μ-opioid agonists but not codeine or κ-opioid agonists in rats. DM potentiated morphine's antinociceptive effect, and acutely increased the serum concentration of morphine. In contrast, DM attenuated the antinociceptive effect of codeine and decreased the serum concentration of its active metabolite (morphine). The pharmacokinetic interactions between DM and opioids may partially explain the differential effects of DM on the antinociception caused by opioids. PMID:15655510

PSYCHIATRIC COMORBIDITY IN PATIENTS WITH OPIOID DEPENDENCE

Directory of Open Access Journals (Sweden)

Shihab Kattukulathil

2018-02-01

Full Text Available BACKGROUND Opioid dependence is a major public health problem in Kerala. Presence of psychiatric disorder among opioid dependent patients worsens the scenario. To date no attempts have been made to analyse the magnitude and pattern of comorbid psychiatric disorders in the state. MATERIALS AND METHODS We assessed 30 patients with ICD-10 diagnosis of opioid dependence syndrome for the presence of comorbid psychiatric disorders using structured clinical interview for DSM IV Axis 1 disorder (SCID-1. Patients with opioid withdrawal state, delirium and acute medical emergencies were excluded. RESULTS 56.7% of our subjects had a comorbid psychiatric disorder. Major depressive disorder was the most common one (n=7, 23.3%. Prevalence of other disorders were generalised anxiety disorder (n=6, 20%, bipolar affective disorder (n=3, 10% and schizophrenia (n=1, 3.3%. CONCLUSION Comorbid Psychiatric disorders are highly prevalent in opioid dependence. There is a need for further large sample studies in the areas of comorbidities and in the integrated strategies for the identification and management of both opioid dependence and comorbid psychiatric disorders.

ABCB1 genetic variability and methadone dosage requirements in opioid-dependent individuals.

Science.gov (United States)

Coller, Janet K; Barratt, Daniel T; Dahlen, Karianne; Loennechen, Morten H; Somogyi, Andrew A

2006-12-01

The most common treatment for opioid dependence is substitution therapy with another opioid such as methadone. The methadone dosage is individualized but highly variable, and program retention rates are low due in part to nonoptimal dosing resulting in withdrawal symptoms and further heroin craving and use. Methadone is a substrate for the P-glycoprotein transporter, encoded by the ABCB1 gene, which regulates central nervous system exposure. This retrospective study aimed to investigate the influence of ABCB1 genetic variability on methadone dose requirements. Genomic deoxyribonucleic acid was isolated from opioid-dependent subjects (n = 60) and non-opioid-dependent control subjects (n = 60), and polymerase chain reaction-restriction fragment length polymorphism and allele-specific polymerase chain reaction were used to determine the presence of single nucleotide polymorphisms at positions 61, 1199, 1236, 2677, and 3435. ABCB1 haplotypes were inferred with PHASE software (version 2.1). There were no significant differences in the allele or genotype frequencies of the individual single nucleotide polymorphisms or haplotypes between the 2 populations. ABCB1 genetic variability influenced daily methadone dose requirements, such that subjects carrying 2 copies of the wild-type haplotype required higher doses compared with those with 1 copy and those with no copies (98.3 +/- 10.4, 58.6 +/- 20.9, and 55.4 +/- 26.1 mg/d, respectively; P = .029). In addition, carriers of the AGCTT haplotype required significantly lower doses than noncarriers (38.0 +/- 16.8 and 61.3 +/- 24.6 mg/d, respectively; P = .04). Although ABCB1 genetic variability is not related to the development of opioid dependence, identification of variant haplotypes may, after larger prospective studies have been performed, provide clinicians with a tool for methadone dosage individualization.

Opioid use in palliative care | Hosking | Continuing Medical Education

African Journals Online (AJOL)

Continuing Medical Education. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 21, No 5 (2003) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Opioid use in palliative care. M Hosking. Abstract.

Variants of opioid system genes are associated with non-dependent opioid use and heroin dependence

NARCIS (Netherlands)

Randesi, Matthew; van den Brink, Wim; Levran, Orna; Blanken, Peter; Butelman, Eduardo R; Yuferov, Vadim; da Rosa, Joel Correa; Ott, Jurg; van Ree, Jan M; Kreek, Mary Jeanne

2016-01-01

BACKGROUND: Heroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence.

Variants of opioid system genes are associated with non-dependent opioid use and heroin dependence

NARCIS (Netherlands)

Randesi, Matthew; van den Brink, Wim; Levran, Orna; Blanken, Peter; Butelman, Eduardo R.; Yuferov, Vadim; da Rosa, Joel Correa; Ott, Jurg; van Ree, Jan M.; Kreek, Mary Jeanne

2016-01-01

Heroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence. Genetic

Methadone, commonly used as maintenance medication for outpatient treatment of opioid dependence, kills leukemia cells and overcomes chemoresistance.

Science.gov (United States)

Friesen, Claudia; Roscher, Mareike; Alt, Andreas; Miltner, Erich

2008-08-01

The therapeutic opioid drug methadone (d,l-methadone hydrochloride) is the most commonly used maintenance medication for outpatient treatment of opioid dependence. In our study, we found that methadone is also a potent inducer of cell death in leukemia cells and we clarified the unknown mechanism of methadone-induced cell killing in leukemia cells. Methadone inhibited proliferation in leukemia cells and induced cell death through apoptosis induction and activated apoptosis pathways through the activation of caspase-9 and caspase-3, down-regulation of Bcl-x(L) and X chromosome-linked inhibitor of apoptosis, and cleavage of poly(ADP-ribose) polymerase. In addition, methadone induced cell death not only in anticancer drug-sensitive and apoptosis-sensitive leukemia cells but also in doxorubicin-resistant, multidrug-resistant, and apoptosis-resistant leukemia cells, which anticancer drugs commonly used in conventional therapies of leukemias failed to kill. Depending on caspase activation, methadone overcomes doxorubicin resistance, multidrug resistance, and apoptosis resistance in leukemia cells through activation of mitochondria. In contrast to leukemia cells, nonleukemic peripheral blood lymphocytes survived after methadone treatment. These findings show that methadone kills leukemia cells and breaks chemoresistance and apoptosis resistance. Our results suggest that methadone is a promising therapeutic approach not only for patients with opioid dependence but also for patients with leukemias and provide the foundation for new strategies using methadone as an additional anticancer drug in leukemia therapy, especially when conventional therapies are less effective.

Efficacy and side-effect profiles of lactulose, docusate sodium, and sennosides compared to PEG in opioid-induced constipation: a systematic review.

Science.gov (United States)

Ruston, Teresa; Hunter, Kathleen; Cummings, Greta; Lazarescu, Adriana

2013-01-01

Opioid-induced constipation (OIC) is a side effect of opioid therapy that can affect quality of life, adherence to treatment, and morbidity and possibly mortality. To investigate whether docusate sodium, sennosides, and lactulose have equal efficacy and side effect profiles compared to PEG in the management of OIC in adults. A systematic review was undertaken. Randomized controlled trials of adults taking opioids for cancer or non-cancer pain were considered if they met inclusion criteria. Statistical pooling was not possible as no studies met inclusion criteria. Large, well-powered, randomized controlled trials are feasible. Standard definitions of OIC would assist with the execution of these studies and contribute to their internal and external validity. Further research is strongly encouraged.

Angina pectoris: current therapy and future treatment options.

Science.gov (United States)

Parikh, Raj; Kadowitz, Philip J

2014-02-01

Angina pectoris is the consequence of an inequality between the demand and supply of blood to the heart. Angina manifests itself as chest pain or discomfort and is a common complaint of patients in the hospital and in the clinic. There are, in fact, roughly half a million new cases of angina per year. Chest pain, while having many etiologies, is generally considered to be most lethal when related to a cardiac cause. In this review, the authors outline the current medical and surgical therapies that are used in the management of angina. Highlights of the various clinical trials that have assisted in the investigation of these therapies are summarized also. Then, the authors provide a focused review of the novel therapy options for angina that are currently being explored. From new medical treatments to revised surgical techniques to the discovery of stem cell therapy, many innovative options are being investigated for the treatment of angina.

Possible Opioid Shopping and its Correlates.

Science.gov (United States)

Walker, Alexander M; Weatherby, Lisa B; Cepeda, M Soledad; Bradford, Daniel; Yuan, Yingli

2017-11-01

We created an operational definition of possible opioid shopping in US commercial health insurance data and examined its correlates. The population consisted of 264,204 treatment courses in persons with a fill for an opioid or diuretic prescription in 2012 and a second within 18 months. We examined counts of prescribers and pharmacies and the numbers of fills and overlaps for ability to discriminate courses of opioids from diuretics, which were a negative control. The most discriminatory measure, indicating possible shopping behavior, was cross-tabulated against other prescriptions filled and diagnoses as found in insurance claims. The associations between claims characteristics and shopping behavior were assessed in a logistic regression. A definition that classified possible "moderate" or "extensive" shopping when a person obtained drug through at least 3 practices and at least 3 pharmacies over 18 months was highly discriminatory between opioid and diuretic treatment. Overlaps between fills and number of fills did not improve the discrimination. Data from insurance claims strongly predicted moderate-to-extensive levels of possible shopping (c=0.82). Prominent among 20 significant predictors were: state of residence; amount of opioid dispensed; self-payment; use of nonspecialist prescribers; high use of anxiolytics, hypnotics, psychostimulants, and antipsychotics; and use of both immediate release and extended-release or long-acting opioids. The use of ≥3 prescribing practices and ≥3 dispensing pharmacies over 18 months sharply discriminated courses of opioid treatment from courses of diuretics. This pattern of fills was additionally associated with the numbers of nonspecialist and self-paid fills, the total morphine milligram equivalents dispensed, and heavier use of drugs for anxiety, sleep, attention, and psychosis.

Using [11C]diprenorphine to image opioid receptor occupancy by methadone in opioid addiction: clinical and preclinical studies.

Science.gov (United States)

Melichar, Jan K; Hume, Susan P; Williams, Tim M; Daglish, Mark R C; Taylor, Lindsay G; Ahmad, Rabia; Malizia, Andrea L; Brooks, David J; Myles, Judith S; Lingford-Hughes, Anne; Nutt, David J

2005-01-01

Substitute methadone prescribing is one of the main modes of treatment for opioid dependence with established evidence for improved health and social outcomes. However, the pharmacology underpinning the effects of methadone is little studied despite controversies about dosing in relation to outcome. We therefore examined the relationship between methadone dose and occupation of opioid receptors in brain using the positron emission tomography (PET) radioligand [(11)C]diprenorphine in humans and rats. Eight opioid-dependent subjects stable on their substitute methadone (18-90 mg daily) had an [(11)C]diprenorphine PET scan at predicted peak plasma levels of methadone. These were compared with eight healthy controls. No difference in [(11)C]diprenorphine binding was found between the groups, with no relationship between methadone dose and occupancy. Adult male Sprague-Dawley rats that had been given an acute i.v. injection of methadone hydrochloride (0.35, 0.5, 0.7, or 1.0 mg kg(-1)) before [(11)C]diprenorphine showed a dose-dependent increase in biodistribution but no reduction in [(11)C]diprenorphine binding. We suggest that the lack of a dose-dependent relationship between methadone dose, either given chronically in human or acutely in rat, and occupancy of opioid receptor measured with [(11)C]diprenorphine PET is related to efficacy of this opioid agonist at very low levels of opioid receptor occupancy. This has implications for understanding the actions of methadone in comparison with other opioid drugs such as partial agonists and antagonists.

Current status of neutron capture therapy

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-05-01

There are about 6000 new glioblastoma multiform brain tumours diagnosed each year in the United States of America alone. This cancer is usually fatal within six months of diagnosis even with current standard treatments. Research on boron neutron capture therapy (BNCT) has been considered as a method of potentially curing such cancers. There is a great interest at under-utilised research reactors institutions to identify new medical utilization, attractive to the general public. Neutron capture therapy is a true multidisciplinary topic with a large variety of individuals involved. This publication attempts to provide current information for all those thinking about being involved with NCT, based on the knowledge and experience of those who have pioneered the treatment. It covers the whole range of NCT from designing reactor conversions or new facilities, through to clinical trials and their effectiveness. However, since most work has been done with boron capture therapy for brain tumours using modified thermal research reactors, this tends to be the focus of the report. One of the factors which need to be addressed at the beginning is the timing of the further development of NCT facilities. It should be emphasised that all current work is still at the research stage. Many of those now involved believe that there is little need for many more research facilities until such time as the treatment shows more promising results. For this and other reasons discussed in the report, very serious consideration should be given by research reactor owners and operators before spending large sums of money converting their facilities for NCT.

Current status of neutron capture therapy

International Nuclear Information System (INIS)

2001-05-01

There are about 6000 new glioblastoma multiform brain tumours diagnosed each year in the United States of America alone. This cancer is usually fatal within six months of diagnosis even with current standard treatments. Research on boron neutron capture therapy (BNCT) has been considered as a method of potentially curing such cancers. There is a great interest at under-utilised research reactors institutions to identify new medical utilization, attractive to the general public. Neutron capture therapy is a true multidisciplinary topic with a large variety of individuals involved. This publication attempts to provide current information for all those thinking about being involved with NCT, based on the knowledge and experience of those who have pioneered the treatment. It covers the whole range of NCT from designing reactor conversions or new facilities, through to clinical trials and their effectiveness. However, since most work has been done with boron capture therapy for brain tumours using modified thermal research reactors, this tends to be the focus of the report. One of the factors which need to be addressed at the beginning is the timing of the further development of NCT facilities. It should be emphasised that all current work is still at the research stage. Many of those now involved believe that there is little need for many more research facilities until such time as the treatment shows more promising results. For this and other reasons discussed in the report, very serious consideration should be given by research reactor owners and operators before spending large sums of money converting their facilities for NCT

Buprenorphine in the treatment of opioid addiction: opportunities, challenges and strategies.

Science.gov (United States)

Li, Xiaofan; Shorter, Daryl; Kosten, Thomas R

2014-10-01

Buprenorphine follows the success of methadone as another milestone in the history of treatment for opioid addiction. Buprenorphine can be used in an office-based setting where it is clearly effective, highly accepted by patients and has a favorable safety profile and less abuse potential. However, the adoption of buprenorphine treatment has been slow in the USA. This article first reviews the history of medication-assisted opioid addiction treatment and the current epidemic opioid addiction, followed by a review of the efficacy, pharmacology and clinical prescription of buprenorphine in office-based care. We then explore the possible barriers in using buprenorphine and the ways to overcome these barriers, including new formulations, educational programs and policy regulations that strike a balance between accessibility and reducing diversion. Buprenorphine can align addiction treatment with treatments for other chronic medical illnesses. However, preventing diversion will require graduate and continuing medical education and integrated care models for delivery of buprenorphine to those in need.

E-cigarette knowledge, attitudes, and use in opioid dependent smokers.

Science.gov (United States)

Stein, Michael D; Caviness, Celeste M; Grimone, Kristin; Audet, Daniel; Borges, Allison; Anderson, Bradley J

2015-05-01

Individuals in treatment for opioid dependence have smoking rates 3-5 times greater than the U.S. prevalence rate. Traditional smoking cessation strategies have been ineffective in this population. Novel approaches are needed as well as harm reduction avenues. E-cigarettes (e-cigs) may provide such a novel harm reduction and cessation opportunity, but little is known about the knowledge of, attitudes about, and usage of e-cigs in opioid dependent smokers. The current study enrolled 315 opioid dependent smokers (164 methadone, 151 buprenorphine), treated in the same health system in Fall River, Massachusetts. The sample was 49.7% male and 85.1% non-Latino White. Overall 98.7% had heard of e-cigs, 73.0% had ever tried e-cigs, and 33.8% had used e-cigs in the past 30 days. The most common reasons for use were curiosity (41.4%) and to quit all nicotine (26.0%). The proportion of opioid dependent smokers that had ever tried e-cigs and used them in the past month was substantially greater than that found in recent general population surveys. While e-cigs have been used to quit smoking, how to optimize their utility as a cessation tool remains undefined. E-cigs should be a part of smoking cessation discussions with this vulnerable, difficult-to-treat population. Copyright © 2015 Elsevier Inc. All rights reserved.

Criminal justice continuum for opioid users at risk of overdose.

Science.gov (United States)

Brinkley-Rubinstein, Lauren; Zaller, Nickolas; Martino, Sarah; Cloud, David H; McCauley, Erin; Heise, Andrew; Seal, David

2018-02-24

The United States (US) is in the midst of an epidemic of opioid use; however, overdose mortality disproportionately affects certain subgroups. For example, more than half of state prisoners and approximately two-thirds of county jail detainees report issues with substance use. Overdose is one of the leading causes of mortality among individuals released from correctional settings. Even though the criminal justice (CJ) system interacts with a disproportionately high number of individuals at risk of opioid use and overdose, few CJ agencies screen for opioid use disorder (OUD). Even less provide access to medication assisted treatment (e.g. methadone, buprenorphine, and depot naltrexone), which is one of the most effective tools to combat addiction and lower overdose risk. However, there is an opportunity to implement programs across the CJ continuum in collaboration with law enforcement, courts, correctional facilities, community service providers, and probation and parole. In the current paper, we introduce the concept of a "CJ Continuum of Care for Opioid Users at Risk of Overdose", grounded by the Sequential Intercept Model. We present each step on the CJ Continuum and include a general overview and highlight opportunities for: 1) screening for OUD and overdose risk, 2) treatment and/or diversion, and 3) overdose prevention and naloxone provision. Copyright © 2018 Elsevier Ltd. All rights reserved.

Nurses and opioids: results of a bi-national survey on mental models regarding opioid administration in hospitals.

Science.gov (United States)

Guest, Charlotte; Sobotka, Fabian; Karavasopoulou, Athina; Ward, Stephen; Bantel, Carsten

2017-01-01

Pain remains insufficiently treated in hospitals. Increasing evidence suggests human factors contribute to this, due to nurses failing to administer opioids. This behavior might be the consequence of nurses' mental models about opioids. As personal experience and conceptions shape these models, the aim of this prospective survey was to identify model-influencing factors. A questionnaire was developed comprising of 14 statements concerning ideations about opioids and seven questions concerning demographics, indicators of adult learning, and strength of religious beliefs. Latent variables that may underlie nurses' mental models were identified using undirected graphical dependence models. Representative items of latent variables were employed for ordinal regression analysis. Questionnaires were distributed to 1,379 nurses in two London, UK, hospitals (n=580) and one German (n=799) hospital between September 2014 and February 2015. A total of 511 (37.1%) questionnaires were returned. Mean (standard deviation) age of participants were 37 (11) years; 83.5% participants were female; 45.2% worked in critical care; and 51.5% had more than 10 years experience. Of the nurses, 84% were not scared of opioids, 87% did not regard opioids as drugs to help patients die, and 72% did not view them as drugs of abuse. More English (41%) than German (28%) nurses were afraid of criminal investigations and were constantly aware of side effects (UK, 94%; Germany, 38%) when using opioids. Four latent variables were identified which likely influence nurses' mental models: "conscious decision-making"; "medication-related fears"; "practice-based observations"; and "risk assessment". They were predicted by strength of religious beliefs and indicators of informal learning such as experience but not by indicators of formal learning such as conference attendance. Nurses in both countries employ analytical and affective mental models when administering the opioids and seem to learn from experience

Desensitization and Tolerance of Mu Opioid Receptors on Pontine Kölliker-Fuse Neurons.

Science.gov (United States)

Levitt, Erica S; Williams, John T

2018-01-01

Acute desensitization of mu opioid receptors is thought to be an initial step in the development of tolerance to opioids. Given the resistance of the respiratory system to develop tolerance, desensitization of neurons in the Kölliker-Fuse (KF), a key area in the respiratory circuit, was examined. The activation of G protein-coupled inwardly rectifying potassium current was measured using whole-cell voltage-clamp recordings from KF and locus coeruleus (LC) neurons contained in acute rat brain slices. A saturating concentration of the opioid agonist [Met 5 ]-enkephalin (ME) caused significantly less desensitization in KF neurons compared with LC neurons. In contrast to LC, desensitization in KF neurons was not enhanced by activation of protein kinase C or in slices from morphine-treated rats. Cellular tolerance to ME and morphine was also lacking in KF neurons from morphine-treated rats. The lack of cellular tolerance in KF neurons correlates with the relative lack of tolerance to the respiratory depressant effect of opioids. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Impulsivity but not sensation seeking is associated with opioid analgesic misuse risk in patients with chronic pain.

Science.gov (United States)

Marino, Elise N; Rosen, Kristen D; Gutierrez, Antonio; Eckmann, Maxim; Ramamurthy, Somayaji; Potter, Jennifer Sharpe

2013-05-01

Impulsivity and sensation seeking have been associated with substance use disorders, including opioid use disorders. This pilot study sought to examine whether impulsivity and sensation seeking, as measured by the Barratt Impulsiveness Scale (BIS) and Sensation Seeking Scale (SSS), were associated with opioid analgesic misuse risk in chronic, low-back pain patients prescribed opioid analgesics. Participants were 42 chronic, low-back pain patients enrolled in a larger study examining problematic opioid analgesic use. Impulsivity was assessed using the BIS, sensation seeking was measured using the SSS, and opioid analgesic misuse risk was assessed using the Current Opioid Misuse Measure (COMM). Significant bivariate associations were found between the COMM and the following predictor variables: age and the three BIS subscales: Attentional Impulsiveness, Non-planning Impulsiveness, and Motor Impulsiveness. Using a multivariate linear regression, after controlling for age, the BIS subscales accounted for 29.0% of the variance in the COMM. Attentional Impulsiveness was the only significant BIS subscale. These results suggest a potential relationship between impulsivity, but not sensation seeking, and risk for opioid analgesic misuse. Impulsivity is not a prominent trait observed in chronic pain patients; however, it may be an important risk factor for opioid analgesic misuse for a subset of individuals with chronic pain. As such, these findings suggest that additional exploration of this potential risk factor is warranted. Published by Elsevier Ltd.

Opioid mediated activity and expression of mu and delta opioid receptors in isolated human term non-labouring myometrium.

LENUS (Irish Health Repository)

Fanning, Rebecca A

2013-01-05

The existence of opioid receptors in mammalian myometrial tissue is now widely accepted. Previously enkephalin degrading enzymes have been shown to be elevated in pregnant rat uterus and a met-enkephalin analogue has been shown to alter spontaneous contractility of rat myometrium. Here we have undertaken studies to determine the effects of met-enkephalin on in vitro human myometrial contractility and investigate the expression of opioid receptors in pregnant myometrium. Myometrial biopsies were taken from women undergoing elective caesarean delivery at term. Organ bath experiments were used to investigate the effect of the met-enkephalin analogue [d-Ala 2, d-met 5] enkephalin (DAMEA) on spontaneous contractility. A confocal immunofluorescent technique and real time PCR were used to determine the expression of protein and mRNA, respectively for two opioid receptor subtypes, mu and delta. DAMEA had a concentration dependent inhibitory effect on contractile activity (1 × 10(-7)M-1 × 10(-4)M; 54% reduction in contractile activity, P<0.001 at 1 × 10(-4)M concentration). Mu and delta opioid receptor protein sub-types and their respective mRNA were identified in all tissues sampled. This is the first report of opioid receptor expression and of an opioid mediated uterorelaxant action in term human non-labouring myometrium in vitro.

Methadone versus buprenorphine for the treatment of opioid abuse in pregnancy: science and stigma.

Science.gov (United States)

Holbrook, Amber M

2015-01-01

The past decade has seen an increase in rates of opioid abuse during pregnancy. This clinical challenge has been met with debate regarding whether or not illicit and prescription opioid-dependent individuals require different treatment approaches; whether detoxification is preferable to maintenance; and the efficacy of methadone versus buprenorphine as treatment options during pregnancy. The clinical recommendations resulting from these discussions are frequently influenced by the comparative stigma attached to heroin abuse and methadone maintenance versus prescription opioid abuse and maintenance treatment with buprenorphine. While some studies have suggested that a subset of individuals who abuse prescription opioids may have different characteristics than heroin users, there is currently no evidence to suggest that buprenorphine is better suited to treatment of prescription opioid abuse than methadone. Similarly, despite its perennial popularity, there is no evidence to recommend detoxification as an efficacious approach to treatment of opioid dependence during pregnancy. While increased access to treatment is important, particularly in rural areas, there are multiple medical and psychosocial reasons to recommend comprehensive substance abuse treatment for pregnant women suffering from substance use disorders rather than office-based provision of maintenance medication. Both methadone and buprenorphine are important treatment options for opioid abuse during pregnancy. Methadone may still remain the preferred treatment choice for some women who require higher doses for stabilization, have a higher risk of treatment discontinuation, or who have had unsuccessful treatment attempts with buprenorphine. As treatment providers, we should advocate to expand available treatment options for pregnant women in all States.

Genetic and Non-genetic Factors Associated With Constipation in Cancer Patients Receiving Opioids.

Science.gov (United States)

Laugsand, Eivor A; Skorpen, Frank; Kaasa, Stein; Sabatowski, Rainer; Strasser, Florian; Fayers, Peter; Klepstad, Pål

2015-06-18

To examine whether the inter-individual variation in constipation among patients receiving opioids for cancer pain is associated with genetic or non-genetic factors. Cancer patients receiving opioids were included from 17 centers in 11 European countries. Intensity of constipation was reported by 1,568 patients on a four-point categorical scale. Non-genetic factors were included as covariates in stratified regression analyses on the association between constipation and 75 single-nucleotide polymorphisms (SNPs) within 15 candidate genes related to opioid- or constipation-signaling pathways (HTR3E, HTR4, HTR2A, TPH1, ADRA2A, CHRM3, TACR1, CCKAR, KIT, ARRB2, GHRL, ABCB1, COMT, OPRM1, and OPRD1). The non-genetic factors significantly associated with constipation were type of laxative, mobility and place of care among patients receiving laxatives (N=806), in addition to Karnofsky performance status and presence of metastases among patients not receiving laxatives (N=762) (Pconstipation. Five SNPs, rs1800532 in TPH1, rs1799971 in OPRM1, rs4437575 in ABCB1, rs10802789 in CHRM3, and rs2020917 in COMT were associated with constipation (Phospitalization, Karnofsky performance status, presence of metastases, and five SNPs within TPH1, OPRM1, ABCB1, CHRM3, and COMT may contribute to the variability in constipation among cancer patients treated with opioids. Knowledge of these factors may help to develop new therapies and to identify patients needing a more individualized approach to treatment.

Hiperalgesia asociada al tratamiento con opioides

OpenAIRE

A. Gil Martín; M. Moreno García; J. Sánchez-Rubio Ferrández; T. Molina García

2014-01-01

La hiperalgesia inducida por opioides es una reacción paradójica caracterizada por una percepción intensificada de dolor relacionada con el uso de estos medicamentos en ausencia de progresión de la enfermedad o de síndrome de retirada. A diferencia de los casos de tolerancia, definida como pérdida de potencia analgésica durante el uso prolongado de opioides, no se produce mejoría con el escalado de dosis. La hiperalgesia inducida por opioides se ha manifestado en pacientes con dosis de manten...

Bilateral Breast Reduction Without Opioid Analgesics: A Comparative Study.

Science.gov (United States)

Parsa, Fereydoun Don; Cheng, Justin; Stephan, Brad; Castel, Nikki; Kim, Leslie; Murariu, Daniel; Parsa, Alan A

2017-09-01

Breast reduction has traditionally been performed under general anesthesia with adjunct opioid use. However, opioids are associated with a wide variety of adverse effects, including nausea, vomiting, constipation, postoperative sedation, dizziness, and addiction. This study compares bilateral breast reduction using a multimodal opioid-free pain management regimen vs traditional general anesthesia with adjunct opioids. A total of 83 female patients were enrolled in this study. Group 1 includes a retrospective series of 39 patients that underwent breast reduction via general anesthesia with adjunct opioid use. This series was compared to 2 prospective groups of patients who did not receive opioids either preoperatively or intraoperatively. In group 2, twenty-six patients underwent surgery under intravenous sedation and local anesthesia. In group 3, eighteen patients underwent surgery with general anesthesia. All patients in groups 2 and 3 received preoperative gabapentin and celecoxib along with infiltration of local anesthetics during the operation and prior to discharge to the Post-Anesthesia Care Unit (PACU). Primary outcome measures included the duration of surgery, time from end of operation to discharge home, postoperative opioid and antiemetic use, and unplanned postoperative hospitalizations. When compared to group 1, groups 2 and 3 experienced a shorter time from end of operation to discharge home (P opioid use (P opioid-free bilateral breast reduction either under local or general anesthesia as an outpatient. This method resulted in significantly less morbidity, use of opioids postoperatively, as well as unplanned hospital admissions compared to "traditional" breast reduction under general anesthesia with the use of opioids. 3. © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

A randomized double-blind crossover comparison of continuous and intermittent subcutaneous administration of opioid for cancer pain.

Science.gov (United States)

Watanabe, Sharon; Pereira, Jose; Tarumi, Yoko; Hanson, John; Bruera, Eduardo

2008-05-01

ABSTRACT Although the preferred route of opioid administration is oral, patients with cancer often require an alternative route. Options include continuous subcutaneous infusion (CSCI) or regularly scheduled intermittent subcutaneous injections (ISCI). CSCI maintains steady drug levels, theoretically avoiding the "bolus effect" of nausea and sedation immediately post-dose, and breakthrough pain prior to the next dose. However, portable infusion pumps can be costly to use. The Edmonton Injector is an inexpensive portable device for ISCI. CSCI and ISCI have not been directly compared. The objective of this trial was to compare CSCI and ISCI of opioid for treatment of cancer pain. Patients were recruited from two tertiary palliative care units. Eligibility criteria included stable cancer pain requiring opioid therapy, need for parenteral route, and normal cognition. Patients were randomly assigned to receive opioid by CSCI by portable pump or ISCI by Edmonton Injector for 48 hours, followed by crossover to the alternative modality for 48 hours. During each phase, placebo was administered by the alternative modality. The study was closed after 12 patients were entered, due to slow accrual. Eleven patients completed the study. There were no differences between CSCI and ISCI in mean visual analogue score (VAS) for pain, nausea or drowsiness; categorical rating score of pain; number of breakthrough opioid doses per day; global rating of treatment effectiveness; or adverse effects. In all cases, patients and investigators expressed no preference for one modality over another. Further research is required to confirm that opioid administration by CSCI and ISCI provide similar analgesic and adverse effects.

Opioid Overdose

Science.gov (United States)

... Updated: 03/10/2016 Medications to Treat OPIOID ADDICTION Methadone Naltrexone Buprenorphine Related SAMHSA Resources Behavioral Health ... Systems Integration Health Disparities Health Financing Health Information Technology HIV, AIDS, and Viral Hepatitis Homelessness and Housing ...

Risk factors associated with iatrogenic opioid and benzodiazepine withdrawal in critically ill pediatric patients: a systematic review and conceptual model.

Science.gov (United States)

Best, Kaitlin M; Boullata, Joseph I; Curley, Martha A Q

2015-02-01

Analgesia and sedation are common therapies in pediatric critical care, and rapid titration of these medications is associated with iatrogenic withdrawal syndrome. We performed a systematic review of the literature to identify all common and salient risk factors associated with iatrogenic withdrawal syndrome and build a conceptual model of iatrogenic withdrawal syndrome risk in critically ill pediatric patients. Multiple databases, including PubMed/Medline, EMBASE, CINAHL, and the Cochrane Central Registry of Clinical Trials, were searched using relevant terms from January 1, 1980, to August 1, 2014. Articles were included if they were published in English and discussed iatrogenic withdrawal syndrome following either opioid or benzodiazepine therapy in children in acute or intensive care settings. Articles were excluded if subjects were neonates born to opioid- or benzodiazepine-dependent mothers, children diagnosed as substance abusers, or subjects with cancer-related pain; if data about opioid or benzodiazepine treatment were not specified; or if primary data were not reported. In total, 1,395 articles were evaluated, 33 of which met the inclusion criteria. To facilitate analysis, all opioid and/or benzodiazepine doses were converted to morphine or midazolam equivalents, respectively. A table of evidence was developed for qualitative analysis of common themes, providing a framework for the construction of a conceptual model. The strongest risk factors associated with iatrogenic withdrawal syndrome include duration of therapy and cumulative dose. Additionally, evidence exists linking patient, process, and system factors in the development of iatrogenic withdrawal syndrome. Most articles were prospective observational or interventional studies. Given the state of existing evidence, well-designed prospective studies are required to better characterize iatrogenic withdrawal syndrome in critically ill pediatric patients. This review provides data to support the

Behavioral intervention to reduce opioid overdose among high-risk persons with opioid use disorder: A pilot randomized controlled trial.

Directory of Open Access Journals (Sweden)

Phillip Oliver Coffin

Full Text Available The United States is amidst an opioid epidemic, including synthetic opioids that may result in rapid death, leaving minimal opportunity for bystander rescue. We pilot tested a behavioral intervention to reduce the occurrence of opioid overdose among opioid dependent persons at high-risk for subsequent overdose.We conducted a single-blinded randomized-controlled trial of a repeated dose motivational interviewing intervention (REBOOT to reduce overdose versus treatment as usual, defined as information and referrals, over 16 months at the San Francisco Department of Public Health from 2014-2016. Participants were 18-65 years of age, had opioid use disorder by Structured Clinical Interview, active opioid use, opioid overdose within 5 years, and prior receipt of naloxone kits. The intervention was administered at months 0, 4, 8, and 12, preceded by the assessment which was also administered at month 16. Dual primary outcomes were any overdose event and number of events, collected by computer-assisted personal interview, as well as any fatal overdose events per vital records.A total of 78 persons were screened and 63 enrolled. Mean age was 43 years, 67% were born male, 65% White, 17% African-American, and 14% Latino. Ninety-two percent of visits and 93% of counseling sessions were completed. At baseline, 33.3% of participants had experienced an overdose in the past four months, with a similar mean number of overdoses in both arms (p = 0.95; 29% overdosed during follow-up. By intention-to-treat, participants assigned to REBOOT were less likely to experience any overdose (incidence rate ratio [IRR] 0.62 [95%CI 0.41-0.92, p = 0.019 and experienced fewer overdose events (IRR 0.46, 95%CI 0.24-0.90, p = 0.023, findings that were robust to sensitivity analyses. There were no differences between arms in days of opioid use, substance use treatment, or naloxone carriage.REBOOT reduced the occurrence of any opioid overdose and the number of overdoses

Implementation of a Proactive Pilot Health Plan-Driven Opioid Tapering Program to Decrease Chronic Opioid Use for Conditions of the Back and Spine in a Medicaid Population.

Science.gov (United States)

Page, Julia; Traver, Robin; Patel, Sital; Saliba, Christopher

2018-03-01

In 2016, the Oregon Health Authority and the Health Evidence Review Commission implemented guidance for Oregon Medicaid members who were taking opioids for chronic pain related to conditions of the back and spine. This guidance required that an individualized taper plan be developed and initiated by January 1, 2017, and a discontinuation date for all chronic opioid therapy of January 1, 2018. This program evaluated the effect of a proactive and voluntary health plan-driven opioid tapering program on morphine equivalent daily dose (MEDD) before the implementation of governmental guidance. Two mailings were sent to the providers of the targeted members with a variety of resources to facilitate an opioid taper. Pharmacy claims were analyzed to measure member opioid use, in the form of MEDD, after the provider outreach to be compared with their MEDDs before the outreach. A total of 113 members met the study inclusion criteria for the second provider outreach. Of the 19 members' providers who submitted responses via fax to the health plan in response to this outreach, 6 indicated they would initiate taper plans. Of the 6 members with taper plans, 5 had decreases in MEDD (3.6%, 4.5%, 42.9%, 45.5%, and 46.1%) after the 3-month data collection period, while the sixth member had no change in MEDD. Of the 113 members, 16 members (14.2%) had a decrease in MEDD; 23 members (20.4%) had no change in MEDD; and 72 members (63.7%) had an increase in MEDD. This study demonstrated that when a physician agrees to enroll patients in a health-plan driven clinical program it may result in decreased opioid use as referenced by MEDD. However, the results also showed the progressive nature of opioid use in this population. While these initial taper results were promising, a larger sample size and longer follow-up duration are needed to validate long-term adherence to an opioid tapering program and confirm that these results are attributable to the program and not other factors. This study

Current therapy for Parkinson's disease

Directory of Open Access Journals (Sweden)

A. V. Obukhova

2014-01-01

Full Text Available The main goal of therapy for Parkinson's disease (PD is to correct dopamine deficiency in the nigrostriatal system. Levodopa preparations and dopamine receptor agonists (DRAs that are prescribed with regards to patient age and disease severity are mainly used now. Notwithstanding the fact that levodopa preparations are the gold standard of therapy, their long-term use gives rise to complications as motor fluctuations and drug-induced dyskinesias. The currently available DRAs are the drugs of choice for the therapy of early-stage PD as they are as effective as levodopa preparations. In extensive-stage PD, DRAs are used to enhance the therapy and correction of developed motor fluctuations and dyskinesias. Pramipexole is one of the most commonly used representatives of non-ergoline DRAs. The paper analyzes the efficacy of the medication used as both monotherapy and part of combined therapy, its effect on tremor and depression in PD. A novel extended-release formulation of pramipexole is considered separately. Both immediate- and extended-release pramipexole formulations contain the same active ingredient and have the same dopamine-receptor interaction profile, but differ in the tablet release rate of the active ingredient. The advantages of the novel formulation are its more steady-state plasma concentration and 24-hour action, which ensures continuous dopaminergic stimulation ofpostsynaptic receptors to prevent and treat already developed motor complications. The once-daily extended-release formulation of the drug makes its treatment regimen easier and patient compliance higher.

Induction of synaptic long-term potentiation after opioid withdrawal.

Science.gov (United States)

Drdla, Ruth; Gassner, Matthias; Gingl, Ewald; Sandkühler, Jürgen

2009-07-10

mu-Opioid receptor (MOR) agonists represent the gold standard for the treatment of severe pain but may paradoxically also enhance pain sensitivity, that is, lead to opioid-induced hyperalgesia (OIH). We show that abrupt withdrawal from MOR agonists induces long-term potentiation (LTP) at the first synapse in pain pathways. Induction of opioid withdrawal LTP requires postsynaptic activation of heterotrimeric guanine nucleotide-binding proteins and N-methyl-d-aspartate receptors and a rise of postsynaptic calcium concentrations. In contrast, the acute depression by opioids is induced presynaptically at these synapses. Withdrawal LTP can be prevented by tapered withdrawal and shares pharmacology and signal transduction pathways with OIH. These findings provide a previously unrecognized target to selectively combat pro-nociceptive effects of opioids without compromising opioid analgesia.

Intranasal naloxone and related strategies for opioid overdose intervention by nonmedical personnel: a review

Directory of Open Access Journals (Sweden)

Lewis CR

2017-10-01

Full Text Available Christa R Lewis,1,2 Hoa T Vo,1 Marc Fishman1,3 1Maryland Treatment Centers, Baltimore, MD, USA; 2Department of Psychology, Towson University, Towson, MD, USA; 3Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD, USA Abstract: Deaths due to prescription and illicit opioid overdose have been rising at an alarming rate, particularly in the USA. Although naloxone injection is a safe and effective treatment for opioid overdose, it is frequently unavailable in a timely manner due to legal and practical restrictions on its use by laypeople. As a result, an effort spanning decades has resulted in the development of strategies to make naloxone available for layperson or “take-home” use. This has included the development of naloxone formulations that are easier to administer for nonmedical users, such as intranasal and autoinjector intramuscular delivery systems, efforts to distribute naloxone to potentially high-impact categories of nonmedical users, as well as efforts to reduce regulatory barriers to more widespread distribution and use. Here we review the historical and current literature on the efficacy and safety of naloxone for use by nonmedical persons, provide an evidence-based discussion of the controversies regarding the safety and efficacy of different formulations of take-home naloxone, and assess the status of current efforts to increase its public distribution. Take-home naloxone is safe and effective for the treatment of opioid overdose when administered by laypeople in a community setting, shortening the time to reversal of opioid toxicity and reducing opioid-related deaths. Complementary strategies have together shown promise for increased dissemination of take-home naloxone, including 1 provision of education and training; 2 distribution to critical populations such as persons with opioid addiction, family members, and first responders; 3 reduction of prescribing barriers to access; and 4 reduction of legal

Access to opioids: a global pain management crisis.

Science.gov (United States)

Buitrago, Rosa

2013-03-01

The lack of availability of opioids in many countries has created a pain management crisis. Because the Single Convention on Narcotic Drugs requires governments to report annual opioid statistics, there is a need for methods to calculate individual nations' opioid needs. Ways to address this need are discussed.

The opioid ketobemidone has a NMDA blocking effect

DEFF Research Database (Denmark)

Andersen, S; Dickenson, A H; Kohn, M

1996-01-01

There are clinical observations that neurogenic pain can respond well to the opioid ketobemidone, in contrast to pethidine and morphine. This has led us to the hypothesis that the analgesic effect of ketobemidone in neurogenic pain may be due to both opioid as well as additional non-opioid effect...

Computational opioid prescribing: a novel application of clinical pharmacokinetics.

Science.gov (United States)

Linares, Oscar A; Linares, Annemarie L

2011-01-01

We implemented a pharmacokinetics-based mathematical modeling technique using algebra to assist prescribers with point-of-care opioid dosing. We call this technique computational opioid prescribing (COP). Because population pharmacokinetic parameter values are needed to estimate drug dosing regimen designs for individual patients using COP, and those values are not readily available to prescribers because they exist scattered in the vast pharmacology literature, we estimated the population pharmacokinetic parameter values for 12 commonly prescribed opioids from various sources using the bootstrap resampling technique. Our results show that opioid dosing regimen design, evaluation, and modification is feasible using COP. We conclude that COP is a new technique for the quantitative assessment of opioid dosing regimen design evaluation and adjustment, which may help prescribers to manage acute and chronic pain at the point-of-care. Potential benefits include opioid dose optimization and minimization of adverse opioid drug events, leading to potential improvement in patient treatment outcomes and safety.

Killing two birds with one stone: successful opioid monotherapy in intractable migraine-triggered epilepsy, a case series.

Science.gov (United States)

Derakhshan, Iraj

2017-01-01

The novel concept explored in this case series is the primacy of headaches in generating seizures in those patients who suffer from migraine-triggered epilepsy. In this series, once the migraine headaches were fully suppressed, via daily scheduled opioid therapy, the seizures also stopped. Seizures returned, however, after the patients stopped the opiate regimen for any reason. The above pharmacological scenario is reminiscent of a similar but naturalistic course of events reported on the salutary effects of ketogenic diet, or changes in life style, in similar cases of migraine-triggered epilepsy. The primacy of migraine in treating what has been named 'seizure headaches' is seen in two other scenarios (i.e. the salutary effect of ketogenic diet and lifestyle changes resulting in restoration of one's sleeping pattern) thus stopping the migraine as well as the seizures associated with the same. This case series recounts the same phenomenon via utilizing around-the-clock maintenance opioid therapy.

Differences in the Association between Depression and Opioid Misuse in Chronic Low Back Pain versus Chronic Pain at Other Locations

Directory of Open Access Journals (Sweden)

Arpana Jaiswal

2016-06-01

Full Text Available Patients with chronic pain and depression are more likely to develop opioid abuse compared to patients without depression. It is not known if this association differs by pain location. We compared the strength of association between depression and opioid misuse in patients with chronic low back pain (CLBP vs. chronic pain of other location (CPOL. Chart abstracted data was obtained from 166 patients seeking care in a family medicine clinic. Depression was measured by the PHQ-9 and opioid misuse was measured using the Current Opioid Misuse Measure. Pain severity and interference questions came from the Brief Pain Inventory. Cross-tabulations were computed to measure the association between depression and opioid misuse stratified on pain location. Exploratory logistic regression modeled the association between depression and opioid misuse after adjusting for pain location and pain severity and interference. Depression was significantly associated with opioid misuse in CPOL but not in CLBP. Regression results indicate pain interference partly accounts for the depression–opioid misuse association. These preliminary results from a small patient sample suggest depression may co-occur with opioid misuse more often in CPOL than in CLBP. Further research is needed to compare this comorbidity in specific pain diagnoses such as arthritis, fibromyalgia and CLBP.

Characterizing the Use of Telepsychiatry for Patients with Opioid Use Disorder and Cooccurring Mental Health Disorders in Ontario, Canada

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Brittanie LaBelle

2018-01-01

Full Text Available Rural patients with opioid use disorder (OUD face a variety of barriers when accessing opioid agonist therapy (OAT and psychiatric services, due to the limited supply of physicians and the vast geographic area. The telemedicine allows for contact between patients and their physician—regardless of physical distance. Objective. We characterize the usage of telemedicine to deliver psychiatric services to patients with OUD in Ontario, as well as traits of treatment-seeking patients with opioid dependence and concurrent psychiatric disorders. Methodology. A retrospective cohort study was conducted using an administrative database for patients who received psychiatric services via telemedicine between 2008 and 2014 and who also had OUD. Results. We identified 9,077 patients with concurrent opioid use and other mental health disorders who had received psychiatric services via telemedicine from 2008 to 2014; 7,109 (78.3% patients lived in Southern Ontario and 1,968 (21.7% in Northern Ontario. Telemedicine was used more frequently to provide mental health services to patients residing in Northern Ontario than Southern Ontario. Conclusion. Telemedicine is increasingly being utilized throughout Ontario for delivering mental health treatment. There is an opportunity to increase access to psychiatric services for patients with opioid dependence and concurrent psychiatric disorders through the use of the telemedicine.

The Combination Very Low-Dose Naltrexone–Clonidine in the Management of Opioid Withdrawal

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Mannelli, Paolo; Peindl, Kathleen; Wu, Li-Tzy; Patkar, Ashwin A.; Gorelick, David A.

2013-01-01

Background The management of withdrawal absorbs substantial clinical efforts in opioid dependence (OD). The real challenge lies in improving current pharmacotherapies. Although widely used, clonidine causes problematic adverse effects and does not alleviate important symptoms of opioid withdrawal, alone or in combination with the opioid antagonist naltrexone. Very low-dose naltrexone (VLNTX) has been shown to attenuate withdrawal intensity and noradrenaline release following opioid agonist taper, suggesting a combination with clonidine may result in improved safety and efficacy. Objectives We investigated the effects of a VLNTX–clonidine combination in a secondary analysis of data from a double-blind, randomized opioid detoxification trial. Methods Withdrawal symptoms and treatment completion were compared following VLNTX (.125 or .25 mg/day) and clonidine (.1–.2 mg q6h) in 127 individuals with OD undergoing 6-day methadone inpatient taper at a community program. Results VLNTX was more effective than placebo or clonidine in reducing symptoms and signs of withdrawal. The use of VLNTX in combination with clonidine was associated with attenuated subjective withdrawal compared with each medication alone, favoring detoxification completion in comparison with clonidine or naltrexone placebo. VLNTX/clonidine was effective in reducing symptoms that are both undertreated and well controlled with clonidine treatment and was not associated with significant adverse events compared with other treatments. Conclusions and Scientific Significance Preliminary results elucidate neurobiological mechanisms of OD and support the utility of controlled studies on a novel VLNTX + low-dose clonidine combination for the management of opioid withdrawal. PMID:22233189

Healthy Adult Male Facial Skin Surface Lipid Pheromone p.o. to Treat Opioid Addiction

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2018-03-20

Opioid Addiction; Opioid Abuse, Continuous Use; Opioid Use; Opioid-Related Disorders; Paternal Pheromone Deficiency; Opioid Dependence; Opioid Abuse; Opioid-use Disorder; Opioid Intoxication; Opioid Abuse, Episodic

Opioids Increase Sexual Dysfunction in Patients With Non-Cancer Pain.

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Ajo, Raquel; Segura, Ana; Inda, María M; Planelles, Beatriz; Martínez, Luz; Ferrández, Guillermina; Sánchez, Angel; César Margarit; Peiró, Ana-María

2016-09-01

Long-term opioid therapy has been found to have a strong impact on the hypothalamic-pituitary-gonadal axis that can be manifested clinically by sexual dysfunction (SD). This event is rarely reported and thus unnoticed and undertreated. To analyze the presence of SD in a large group of patients receiving long-term opioids. A descriptive, cross-sectional pilot study of sexual health was conducted for 2 years in 750 consecutive ambulatory patients with chronic non-cancer pain (CNP) receiving opioids for at least 12 months. Cases that reported SD and matched controls were included. Standardized questionnaires and medical record reviews were used to assess rates of pain at diagnosis, daily morphine equivalent doses, and opioid adverse effects. Sexual function was determined by the Female Sexual Function Index (FSFI; scores = 2-36) and the International Index of Erectile Function erectile function domain (IIEF-EF; scores = 1-30). Thirty-three percent of 33% of 750 patients with CNP recorded SD based on their spontaneous notification at the pain unit. Men reported SD significantly more frequently than women (33% vs 25%, respectively, P sexually active life (69% vs 34%, respectively, P = .00) significantly more often. FSFI scores were significantly influenced by sexual activity in lubrication and arousal. IIEF scores were significantly determined by age in satisfaction with sexual intercourse and overall satisfaction. The morphine equivalent dose was significant higher in men than in women (38%; median = 70 mg/d, interquartile range = 43.1-170, 115.5 ± 110.3 mg/d vs median = 60 mg/d, interquartile range = 30-100.6, 76.67 ± 63.79 mg/d, P = .016) at the same mean intensity of pain (P = .54), which correlated to FSFI scores (r = -0.313, P = .01). SD is prevalent in patients with CNP and higher in men who received a significantly higher mean opioid dose at the same intensity pain level than women. The morphine equivalent dose was correlated to SD intensity

Pain in the management of opioid use disorder

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Sirohi S

2016-11-01

Full Text Available Sunil Sirohi,1 Amit K Tiwari21Laboratory of Endocrine and Neuropsychiatric Disorders, Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, LA, 2Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USAOpioids remain the drug of choice for the clinical management of moderate to severe pain. However, in addition to their most effective analgesic actions, opioids also produce a sense of well-being and euphoria, which may trigger significant concerns associated with their use.1 In fact, there has been an alarming increase in prescription opioid use, abuse and illicit use; and according to the National Center for Health Statistics, the total number of deaths related to opioid overdose has more than tripled from 2011 to 2014.2–5 Although representing 5.0 % of the global population, studies report that Americans consume 80% of the global opioid supply,3 and the United States is experiencing an opioid abuse epidemic.6 Considering this unprecedented rise in opioid consumption, the United States Centers for Disease Control and Prevention has listed prescription opioid overdose among one of the 10 most important public health problems in all the 50 states.7

Opioid Addiction

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... breathing rate nausea, vomiting constipation physical agitation poor decision making abandoning responsibilities slurred speech sleeping more or less than normal mood swings euphoria (feeling high) irritability depression lowered motivation anxiety attacks. Symptoms of opioid overdose An overdose ...

Estimating the health care burden of prescription opioid abuse in five European countries

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Shei A

2015-09-01

Full Text Available Amie Shei,1 Matthew Hirst,2 Noam Y Kirson,1 Caroline J Enloe,1 Howard G Birnbaum,1 William C N Dunlop21Analysis Group, Inc., Boston, MA, USA; 2Mundipharma International Limited, Cambridge, UK Background: Opioid abuse, including abuse of prescription opioids (“RxOs” and illicit substances like heroin, is a serious public health issue in Europe. Currently, there is limited data on the magnitude of RxO abuse in Europe, despite increasing public and scientific interest in the issue. The purpose of this study was to use the best-available data to derive comparable estimates of the health care burden of RxO abuse in France, Germany, Italy, Spain, and the United Kingdom (EU5. Methods: Published data on the prevalence of problem opioid use and the share of opioid abuse patients reporting misuse of non-heroin opioids were used to estimate the prevalence of RxO abuse in the EU5 countries. The costs of RxO abuse were calculated by applying published estimates of the incremental health care costs of opioid abuse to country-specific estimates of the costs of chronic pain conditions. These estimates were input into an economic model that quantified the health care burden of RxO abuse in each of the EU5 countries. Sensitivity analyses examined key assumptions. Results: Based on best-available current data, prevalence estimates of RxO abuse ranged from 0.7 to 13.7 per 10,000 individuals across the EU5 countries. Estimates of the incremental health care costs of RxO abuse ranged from €900 to €2,551 per patient per year. The annual health care cost burden of RxO abuse ranged from €6,264 to €279,927 per 100,000 individuals across the EU5 countries. Conclusion: This study suggests that RxO abuse imposes a cost burden on health systems in the five largest European countries. The extent of RxO abuse in Europe should be monitored given the potential for change over time. Continued efforts should be made to collect reliable data on the prevalence and costs

The development of [18F]cyclofoxy as a ligand for imaging opioid receptors in the CNS of conscious humans

International Nuclear Information System (INIS)

Rice, K.C.; Newman, A.H.; Ostrowski, N.L.; Cohen, R.M.; Pert, A.; Pert, C.B.; Burke, T.R. Jr.; McLellan, C.A.; Channing, M.A.; Finn, R.D.; Dunn, B.; Simpson, N.; Carson, R.W.; Larson, S.M.; Eckelman, W.C.; Bennett, J.M.; Kawai, R.; Sawada, Y.; Herscovitch, P.; Yolles, P.S.; Nordhal, T.; Gross, M.; Blasberg, R.

1989-01-01

Positron emission tomography (PET) is a unique, noninvasive technique applicable to real time visualization and quantitation of drug receptor occupancy in the brain of conscious humans. Such studies with the normal and abnormal human CNS can potentially provide insight into the biochemical basis of disease states and the effects of drug therapy. The (-)-enantiomer of cyclofoxy, a fluorinated, potent narcotic antagonist derived from naltrexone, has been developed at NIH as an agent for study of the opioid receptor-endorphin system using PET. The development and current status of this program is described, including application of the NIH Opiate Total Synthesis for production the pharmacologically inert (+)-[ 18 F]cyclofoxy required for quantitation of receptor occupancy

Is there a role for opioids in the treatment of fibromyalgia?

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Littlejohn, Geoffrey O; Guymer, Emma K; Ngian, Gene-Siew

2016-05-01

The use of opioids for chronic pain has increased significantly due to a combination of the high patient burden of pain and the more widespread availability of a range of long-acting opioid preparations. This increased opioid use has translated into the care of many patients with fibromyalgia. The pain mechanism in fibromyalgia is complex but does not seem to involve disturbance of opioid analgesic functions. Hence, there is general concern about the harms in the absence of benefits of opioids in this setting. There is no evidence that pure opioids are effective in fibromyalgia but there is some evidence that opioids with additional actions on the norepinephrine-related pain modulatory pathways, such as tramadol, can be clinically useful in some patients. Novel actions of low-dose opioid antagonists may lead to better understanding of the role of opioid function in fibromyalgia.

Endogenous opioids regulate moment-to-moment neuronal communication and excitability

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Winters, Bryony L.; Gregoriou, Gabrielle C.; Kissiwaa, Sarah A.; Wells, Oliver A.; Medagoda, Danashi I.; Hermes, Sam M.; Burford, Neil T.; Alt, Andrew; Aicher, Sue A.; Bagley, Elena E.

2017-01-01

Fear and emotional learning are modulated by endogenous opioids but the cellular basis for this is unknown. The intercalated cells (ITCs) gate amygdala output and thus regulate the fear response. Here we find endogenous opioids are released by synaptic stimulation to act via two distinct mechanisms within the main ITC cluster. Endogenously released opioids inhibit glutamate release through the δ-opioid receptor (DOR), an effect potentiated by a DOR-positive allosteric modulator. Postsynaptically, the opioids activate a potassium conductance through the μ-opioid receptor (MOR), suggesting for the first time that endogenously released opioids directly regulate neuronal excitability. Ultrastructural localization of endogenous ligands support these functional findings. This study demonstrates a new role for endogenously released opioids as neuromodulators engaged by synaptic activity to regulate moment-to-moment neuronal communication and excitability. These distinct actions through MOR and DOR may underlie the opposing effect of these receptor systems on anxiety and fear. PMID:28327612

The challenge of perioperative pain management in opioid-tolerant patients

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Coluzzi, Flaminia; Bifulco, Francesca; Cuomo, Arturo; Dauri, Mario; Leonardi, Claudio; Melotti, Rita Maria; Natoli, Silvia; Romualdi, Patrizia; Savoia, Gennaro; Corcione, Antonio

2017-01-01

The increasing number of opioid users among chronic pain patients, and opioid abusers among the general population, makes perioperative pain management challenging for health care professionals. Anesthesiologists, surgeons, and nurses should be familiar with some pharmacological phenomena which are typical of opioid users and abusers, such as tolerance, physical dependence, hyperalgesia, and addiction. Inadequate pain management is very common in these patients, due to common prejudices and fears. The target of preoperative evaluation is to identify comorbidities and risk factors and recognize signs and symptoms of opioid abuse and opioid withdrawal. Clinicians are encouraged to plan perioperative pain medications and to refer these patients to psychiatrists and addiction specialists for their evaluation. The aim of this review was to give practical suggestions for perioperative management of surgical opioid-tolerant patients, together with schemes of opioid conversion for chronic pain patients assuming oral or transdermal opioids, and patients under maintenance programs with methadone, buprenorphine, or naltrexone. PMID:28919771

Effect of electroacupuncture on opioid consumption in patients with chronic musculoskeletal pain: protocol of a randomised controlled trial

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Xue Charlie CL

2012-09-01

Full Text Available Abstract Background Chronic musculoskeletal pain is common and has been increasingly managed by opioid medications, of which the long-term efficacy is unknown. Furthermore, there is evidence that long-term use of opioids is associated with reduced pain control, declining physical function and quality of life, and could hinder the goals of integrated pain management. Electroacupuncture (EA has been shown to be effective in reducing postoperative opioid consumption. Limited evidence suggests that acupuncture could assist patients with chronic pain to reduce their requirements for opioids. The proposed research aims to assess if EA is an effective adjunct therapy to standard pain and medication management in reducing opioids use by patients with chronic musculoskeletal pain. Methods In this multicentre, randomised, sham-acupuncture controlled, three-arm clinical trial, 316 patients regularly taking opioids for pain control and meeting the defined selection criteria will be recruited from pain management centres and clinics of primary care providers in Victoria, Australia. After a four-week run-in period, the participants are randomly assigned to one of three treatment groups to receive EA, sham EA or no-EA with a ratio of 2:1:1. All participants receive routine pain medication management delivered and supervised by the trial medical doctors. Twelve sessions of semi-structured EA or sham EA treatment are delivered over 10 weeks. Upon completion of the acupuncture treatment period, there is a 12-week follow-up. In total, participants are involved in the trial for 26 weeks. Outcome measures of opioid and non-opioid medication consumption, pain scores and opioid-related adverse events are documented throughout the study. Quality of life, depression, function, and attitude to pain medications are also assessed. Discussion This randomised controlled trial will determine whether EA is of significant clinical value in assisting the management of

Preventing Opioid Use Disorders among Fishing Industry Workers

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Angela Wangari Walter

2018-03-01

Full Text Available Fishing industry workers are at high risk for work-related musculoskeletal disorders (MSDs and injuries. Prescription opioids used to treat pain injuries may put these workers at increased risk for developing substance disorders. Using a Community-Based Participatory Research approach, formative research was conducted to inform the eventual development of relevant interventions to prevent and reduce opioid use disorders among fishing industry workers. Qualitative interviews (n = 21 were conducted to assess: knowledge and attitudes about opioid use disorders; features of fishing work that might affect use and/or access to treatment; and community and organizational capacity for prevention and treatment. Participants reported numerous pathways connecting commercial fishing with opioid use. The combination of high stress and physically tasking job duties requires comprehensive workplace interventions to prevent chronic pain and MSDs, in addition to tailored and culturally responsive treatment options to address opioid use disorders in this population. Public health programs must integrate workplace health and safety protection along with evidence-based primary, secondary, and tertiary interventions in order to address opioid use disorders, particularly among workers in strenuous jobs.

Knowledge of Opioid Overdose and Attitudes to Supply of Take-Home Naloxone Among People with Chronic Noncancer Pain Prescribed Opioids.

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Nielsen, Suzanne; Peacock, Amy; Lintzeris, Nicholas; Bruno, Raimondo; Larance, Briony; Degenhardt, Louisa

2018-03-01

Take-home naloxone (THN) is recommended in response to pharmaceutical opioid-related mortality. Some health professionals are reluctant to discuss THN for fear of causing offense. The aims of this study were to assess knowledge of opioid overdose and attitudes toward THN for opioid overdose reversal in people with chronic noncancer pain (CNCP). Prospective cohort study. Australia, September to October 2015. A subset of participants (N = 208) from a cohort of people prescribed restricted opioids for CNCP. Questions added in the two-year telephone interviews examined knowledge of overdose symptoms and attitudes toward community supply of naloxone. Associations with overdose risk factors and naloxone supply eligibility criteria with attitudes toward naloxone were explored. Fourteen percent reported ever experiencing opioid overdose symptoms. Participants correctly identified fewer than half of the overdose signs and symptoms. After receiving information on naloxone, most participants (60%), thought it was a "good" or "very good" idea. Few participants reported that they would be "a little" (N = 21, 10%) or "very" offended (N = 7, 3%) if their opioid prescriber offered them naloxone. Positive attitudes toward THN were associated with male gender (odds ratio [OR] = 1.96, 95% confidence interval [CI] = 1.09-3.50), past year cannabis use (OR = 2.52, 95% CI = 1.03-6.16), and past year nicotine use (OR = 2.11, 95% CI = 1.14-3.91). Most participants had positive attitudes toward THN but low knowledge about opioid overdose symptoms. Strategies for educating patients and their caregivers on opioid toxicity are needed. THN may be best targeted toward those with risk factors in terms of overdose prevention and acceptability.

A Trigger for Opioid Misuse: Chronic Pain and Stress Dysregulate the Mesolimbic Pathway and Kappa Opioid System.