Opioid Dependence Treatment: Options In Pharmacotherapy

PubMed Central

Stotts, Angela L.; Dodrill, Carrie L.; Kosten, Thomas R.

2010-01-01

The development of effective treatments for opioid dependence is of great importance given the devastating consequences of the disease. Pharmacotherapies for opioid addiction include opioid agonists, partial agonists, opioid antagonists, and alpha-2-adrenergic agonists, which are targeted toward either detoxification or long-term agonist maintenance. Agonist maintenance therapy is currently the recommended treatment for opioid dependence due to its superior outcomes relative to detoxification. Detoxification protocols have limited long term efficacy and patient discomfort remains a significant therapy challenge. Buprenorphine’s effectiveness relative to methadone remains a controversy and may be most appropriate for patients in need of low doses of agonist treatment. Buprenorphine appears superior to alpha-2 agonists, however, and office-based treatment with buprenorphine in the US is gaining support. Studies of sustained-release formulations of naltrexone suggest improved effectiveness for retention and sustained abstinence, however, randomized clinical trials are needed. PMID:19538000

Increased Opioid Dependence in a Mouse Model of Panic Disorder

PubMed Central

Gallego, Xavier; Murtra, Patricia; Zamalloa, Teresa; Canals, Josep Maria; Pineda, Joseba; Amador-Arjona, Alejandro; Maldonado, Rafael; Dierssen, Mara

2009-01-01

Panic disorder is a highly prevalent neuropsychiatric disorder that shows co-occurrence with substance abuse. Here, we demonstrate that TrkC, the high-affinity receptor for neurotrophin-3, is a key molecule involved in panic disorder and opiate dependence, using a transgenic mouse model (TgNTRK3). Constitutive TrkC overexpression in TgNTRK3 mice dramatically alters spontaneous firing rates of locus coeruleus (LC) neurons and the response of the noradrenergic system to chronic opiate exposure, possibly related to the altered regulation of neurotrophic peptides observed. Notably, TgNTRK3 LC neurons showed an increased firing rate in saline-treated conditions and profound abnormalities in their response to met5-enkephalin. Behaviorally, chronic morphine administration induced a significantly increased withdrawal syndrome in TgNTRK3 mice. In conclusion, we show here that the NT-3/TrkC system is an important regulator of neuronal firing in LC and could contribute to the adaptations of the noradrenergic system in response to chronic opiate exposure. Moreover, our results indicate that TrkC is involved in the molecular and cellular changes in noradrenergic neurons underlying both panic attacks and opiate dependence and support a functional endogenous opioid deficit in panic disorder patients. PMID:20204153

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

PubMed Central

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

Cue-Induced Craving in Dependence Upon Prescription Opioids and Heroin

PubMed Central

McHugh, R. Kathryn; Park, Sara; Weiss, Roger D.

2014-01-01

Background and Objectives Cues associated with heroin use (e.g., needles, powder) elicit robust craving responses in individuals dependent upon heroin. Elevated cue-induced craving may be a risk factor for relapse and can persist after periods of drug abstinence. Despite the growing prevalence of opioid dependence involving prescription opioids, published studies have yet to examine whether cue-induced craving is also present in prescription opioid dependence. Methods A sample of 50 adults diagnosed with opioid dependence (20 prescription opioid users, 25 heroin users, and 5 mixed opioid users) completed a cue reactivity assessment. Participants were administered a series of 90 pictures, including heroin-specific, prescription opioid-specific, and neutral images, and were asked to rate craving and cue salience after each image. Results Both the prescription opioid and heroin groups experienced significantly more craving to drug than to neutral stimuli. The prescription opioid group reported significantly less craving to prescription opioid stimuli than the heroin group to heroin stimuli; however, this effect was smaller and non-significant when controlling for group differences in cue salience. Discussion and Conclusions This study found evidence for cue-induced craving in individuals dependent upon prescription opioids. Further research is needed to better understand the role of cue reactivity in the course and treatment of opioid dependence involving prescription opioid use. Scientific Significance As elevated craving reactivity to drug cues may reflect a risk factor for relapse, understanding the nature of cue-induced craving in individuals with opioid dependence is important to improving treatments for this population. PMID:24628912

Current and Potential Pharmacological Treatment Options for Maintenance Therapy in Opioid-Dependent Individuals

PubMed Central

Tetrault, Jeanette M.; Fiellin, David A.

2013-01-01

Opioid dependence, manifesting as addiction to heroin and pharmaceutical opioids is increasing. Internationally, there are an estimated 15.6 million illicit opioid users. The global economic burden of opioid dependence is profound both in terms of HIV and hepatitis C virus transmission, direct healthcare costs, and indirectly through criminal activity, absenteeism and lost productivity. Opioid agonist medications, such as methadone and buprenorphine, that stabilize neuronal systems and provide narcotic blockade are the most effective treatments. Prolonged provision of these medications, defined as maintenance treatment, typically produces improved outcomes when compared with short-duration tapers and withdrawal. The benefits of opioid agonist maintenance include decreased illicit drug use, improved retention in treatment, decreased HIV risk behaviours and decreased criminal behaviour. While regulations vary by country, these medications are becoming increasingly available internationally, especially in regions experiencing rapid transmission of HIV due to injection drug use. In this review, we describe the rationale for maintenance treatment of opioid dependence, discuss emerging uses of opioid antagonists such as naltrexone, and sustained-release formulations of naltrexone and buprenorphine, and provide a description of the experimental therapies. PMID:22235870

Increases in Drug and Opioid Overdose Deaths--United States, 2000-2014.

PubMed

Rudd, Rose A; Aleshire, Noah; Zibbell, Jon E; Gladden, R Matthew

2016-01-01

The United States is experiencing an epidemic of drug overdose (poisoning) deaths. Since 2000, the rate of deaths from drug overdoses has increased 137%, including a 200% increase in the rate of overdose deaths involving opioids (opioid pain relievers and heroin). CDC analyzed recent multiple cause-of-death mortality data to examine current trends and characteristics of drug overdose deaths, including the types of opioids associated with drug overdose deaths. During 2014, a total of 47,055 drug overdose deaths occurred in the United States, representing a 1-year increase of 6.5%, from 13.8 per 100,000 persons in 2013 to 14.7 per 100,000 persons in 2014. The rate of drug overdose deaths increased significantly for both sexes, persons aged 25-44 years and ≥55 years, non-Hispanic whites and non-Hispanic blacks, and in the Northeastern, Midwestern, and Southern regions of the United States. Rates of opioid overdose deaths also increased significantly, from 7.9 per 100,000 in 2013 to 9.0 per 100,000 in 2014, a 14% increase. Historically, CDC has programmatically characterized all opioid pain reliever deaths (natural and semisynthetic opioids, methadone, and other synthetic opioids) as "prescription" opioid overdoses (1). Between 2013 and 2014, the age-adjusted rate of death involving methadone remained unchanged; however, the age-adjusted rate of death involving natural and semisynthetic opioid pain relievers, heroin, and synthetic opioids, other than methadone (e.g., fentanyl) increased 9%, 26%, and 80%, respectively. The sharp increase in deaths involving synthetic opioids, other than methadone, in 2014 coincided with law enforcement reports of increased availability of illicitly manufactured fentanyl, a synthetic opioid; however, illicitly manufactured fentanyl cannot be distinguished from prescription fentanyl in death certificate data. These findings indicate that the opioid overdose epidemic is worsening. There is a need for continued action to prevent opioid

Haloperidol Disrupts Opioid-Antinociceptive Tolerance and Physical Dependence

PubMed Central

Yang, Cheng; Chen, Yan; Tang, Lei

2011-01-01

Previous studies from our laboratory and others have implicated a critical role of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in opioid tolerance and dependence. Translational research targeting the CaMKII pathway is challenging, if not impossible, because of a lack of selective inhibitors. We discovered in a preliminary study that haloperidol, a butyrophenone antipsychotic drug, inhibited CaMKII, which led us to hypothesize that haloperidol can attenuate opioid tolerance and dependence by inhibiting CaMKII. The hypothesis was tested in two rodent models of opioid tolerance and dependence. Pretreatment with haloperidol (0.2–1.0 mg/kg i.p.) prevented the development of morphine tolerance and dependence in a dose-dependent manner. Short-term treatment with haloperidol (0.06–0.60 mg/kg i.p.) dose-dependently reversed the established morphine-antinociceptive tolerance and physical dependence. Correlating with behavioral effects, pretreatment or short-term treatment with haloperidol dose-dependently inhibited morphine-induced up-regulation of supraspinal and spinal CaMKIIα activity. Moreover, haloperidol given orally was also effective in attenuating morphine-induced CaMKIIα activity, antinociceptive tolerance, and physical dependence. Taken together, these data suggest that haloperidol attenuates opioid tolerance and dependence by suppressing CaMKII activity. Because haloperidol is a clinically used drug that can be taken orally, we propose that the drug may be of use in attenuating opioid tolerance and dependence. PMID:21436292

[Comorbid neurotic disorders in opioid-dependent patients].

PubMed

Zobin, M L; Iarovoĭ, V S

2012-01-01

Necessity of distinguishing between psychopathology of opioid dependence itself and co-occurred neurotic (ICD-10 item F4) disorders is caused by the need to choose an adequate therapy. The prevalence and types of comorbid neurotic disorders among opioid-dependent patients in sustained full and partial remission are described.

Comorbid Post-Traumatic Stress Disorder and Opioid Dependence.

PubMed

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.

Epigenetic regulation of opioid-induced hyperalgesia, dependence, and tolerance in mice.

PubMed

Liang, De-Yong; Li, XiangQi; Clark, J David

2013-01-01

Repeated administration of opioids such as morphine induces persistent behavioral changes including opioid-induced hyperalgesia (OIH), tolerance, and physical dependence. In the current work we explored how the balance of histone acetyltransferase (HAT) versus histone deacetylase (HDAC) might regulate these morphine-induced changes. Nociceptive thresholds, analgesia, and physical dependence were assessed during and for a period of several weeks after morphine exposure. To probe the roles of histone acetylation, the HAT inhibitor curcumin or a selective HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) was administered daily to groups of animals. Histone acetylation in spinal cord was assessed by Western blot and immunohistochemistry. Concurrent administration of curcumin with morphine for 4 days significantly reduced development of opioid-induced mechanical allodynia, thermal hyperalgesia, tolerance, and physical dependence. Conversely, the HDAC inhibitor SAHA enhanced these responses. Interestingly, SAHA treatment after the termination of opioid administration sustained these behavioral changes for at least 4 weeks. Histone H3 acetylation in the dorsal horn of the spinal cord was increased after chronic morphine treatment, but H4 acetylation was unchanged. Moreover, we observed a decrease in HDAC activity in the spinal cords of morphine-treated mice while overall HAT activity was unchanged, suggesting a shift toward a state of enhanced histone acetylation. The current study indicates that epigenetic mechanisms play a crucial role in opioid-induced long-lasting neuroplasticity. These results provide new sight into understanding the mechanisms of opioid-induced neuroplasticity and suggest new strategies to limit opioid abuse potential and increase the value of these drugs as analgesics. Copyright © 2013 American Pain Society. All rights reserved.

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

PubMed

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, p<.001) and a greater proportion of their income on drugs (OR=1.31, p<.001) were more likely to use opioids during treatment. Individual differences in drug reinforcement value, as indicated by pre-treatment allocation of economic 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.

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

PubMed Central

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

2015-01-01

Background 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. Methods 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. Results 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, p < .001) and a greater proportion of their income on drugs (OR = 1.31, p < .001) were more likely to use opioids during treatment. Conclusions Individual differences in drug reinforcement value, as indicated by pre-treatment allocation of economic 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. PMID:25622776

Measuring quality of life in opioid-dependent people: a systematic review of assessment instruments.

PubMed

Strada, Lisa; Vanderplasschen, Wouter; Buchholz, Angela; Schulte, Bernd; Muller, Ashley E; Verthein, Uwe; Reimer, Jens

2017-12-01

Opioid dependence is a chronic relapsing disorder. Despite increasing research on quality of life (QOL) in people with opioid dependence, little attention has been paid to the instruments used. This systematic review examines the suitability of QOL instruments for use in opioid-dependent populations and the instruments' quality. A systematic search was performed in the databases Medline, PsycInfo, The Cochrane Library, and CINAHL. Articles were eligible if they assessed QOL of opioid-dependent populations using a validated QOL instrument. Item content relevance to opioid-dependent people was evaluated by means of content analysis, and instrument properties were assessed using minimum standards for patient-reported outcome measures. Eighty-nine articles were retrieved, yielding sixteen QOL instruments, of which ten were assessed in this review. Of the ten instruments, six were disease specific, but none for opioid dependence. Two instruments had good item content relevance. The conceptual and measurement model were described in seven instruments. Four instruments were developed with input from the respective target population. Eight instruments had low respondent and administrator burden. Psychometric properties were either not assessed in opioid-dependent populations or were inconclusive or moderate. No instrument scored perfectly on both the content and properties. The limited suitability of instruments for opioid-dependent people hinders accurate and sensitive measurement of QOL in this population. Future research is in need of an opioid dependence-specific QOL instrument to measure the true impact of the disease on people's lives and to evaluate treatment-related services.

Gray matter abnormalities in opioid-dependent patients: A neuroimaging meta-analysis.

PubMed

Wollman, Scott C; Alhassoon, Omar M; Hall, Matthew G; Stern, Mark J; Connors, Eric J; Kimmel, Christine L; Allen, Kenneth E; Stephan, Rick A; Radua, Joaquim

2017-09-01

Prior research utilizing whole-brain neuroimaging techniques has identified structural differences in gray matter in opioid-dependent individuals. However, the results have been inconsistent. The current study meta-analytically examines the neuroimaging findings of studies published before 2016 comparing opioid-dependent individuals to drug-naïve controls. Exhaustive search of five databases yielded 12 studies that met inclusion criteria. Anisotropic Effect-Size Seed-Based d Mapping (AES-SDM) was used to analyze the data extracted by three independent researchers. Voxel-based AES-SDM distinguishes increases and decreases in brain matter significant at the whole-brain level. AES-SDM identified the fronto-temporal region, bilaterally, as being the primary site of gray matter deficits associated with opioid use. Moderator analysis revealed that length of opioid use was negatively associated with gray matter in the left cerebellar vermis and the right Rolandic operculum, including the insula. Meta-regression revealed no remaining significant areas of gray matter reductions, except in the precuneus, following longer abstinence from opioids. Opioid-dependent individuals had significantly less gray matter in several regions that play a key role in cognitive and affective processing. The findings provide evidence that opioid dependence may result in the breakdown of two distinct yet highly overlapping structural and functional systems. These are the fronto-cerebellar system that might be more responsible for impulsivity, compulsive behaviors, and affective disturbances and the fronto-insular system that might account more for the cognitive and decision-making impairments.

Tramadol for maintenance in opioid dependence: A retrospective chart review.

PubMed

Sarkar, Siddharth; Lal, Rakesh; Varshney, Mohit; Balhara, Yatan Pal Singh

Tramadol is an opioid agonist which can be potentially used for maintenance treatment of patients with opioid use disorders. This chart review presents the characteristics of individuals with an ICD 10 diagnosis of opioid dependence who were maintained on tramadol for a period of at least 6 months. Records of patients seeking treatment for opioid dependence from the outpatient clinic of the National Drug Dependence Treatment Centre, Ghaziabad, India were screened. One hundred consecutive patients who received tramadol for more than 6 months were included. The sample comprised exclusively of males and had a mean age of 40.9 years. The median dose of tramadol at initiation and continuation was 300 mg/day. Sixty-two patients achieved complete abstinence during the course of treatment. Greater age, longer duration of opioid use, and better follow-up adherence were associated with abstinent status. The rates of abstinence were higher among those presenting with natural opioid use as compared to others (prescription opioid use or heroin use). Tramadol can be an alternative medication for harm reduction in select group of patients with opioid dependence. Further research is required to strengthen the evidence base of rational use of tramadol for maintenance treatment of patients with opioid dependence.

Delayed Ego Strength Development in Opioid Dependent Adolescents and Young Adults.

PubMed

Abramoff, Benjamin A; Lange, Hannah L H; Matson, Steven C; Cottrill, Casey B; Bridge, Jeffrey A; Abdel-Rasoul, Mahmoud; Bonny, Andrea E

2015-01-01

Objective. To evaluate ego strengths, in the context of Erikson's framework, among adolescents and young adults diagnosed with opioid dependence as compared to non-drug using youth. Methods. Opioid dependent (n = 51) and non-drug using control (n = 31) youth completed the self-administered Psychosocial Inventory of Ego Strengths (PIES). The PIES assesses development in the framework of Erikson's ego strength stages. Multivariate linear regression modeling assessed the independent association of the primary covariate (opioid dependent versus control) as well as potential confounding variables (e.g., psychiatric comorbidities, intelligence) with total PIES score. Results. Mean total PIES score was significantly lower in opioid dependent youth (231.65 ± 30.39 opioid dependent versus 270.67 ± 30.06 control; p < 0.01). Evaluation of the PIES subscores found significant (p < 0.05) delays in all ego strength areas (hope, will, purpose, competence, fidelity, love, care, and wisdom). When adjusting for potential confounders, opioid dependence remained a significant (p < 0.001) independent predictor of total PIES score. Conclusion. Adolescents with opioid dependence demonstrated significant delays in ego strength development. A treatment approach acknowledging this delay may be needed in the counseling and treatment of adolescents with opioid dependence.

Delayed Ego Strength Development in Opioid Dependent Adolescents and Young Adults

PubMed Central

Abramoff, Benjamin A.; Lange, Hannah L. H.; Matson, Steven C.; Cottrill, Casey B.; Bridge, Jeffrey A.; Abdel-Rasoul, Mahmoud; Bonny, Andrea E.

2015-01-01

Objective. To evaluate ego strengths, in the context of Erikson's framework, among adolescents and young adults diagnosed with opioid dependence as compared to non-drug using youth. Methods. Opioid dependent (n = 51) and non-drug using control (n = 31) youth completed the self-administered Psychosocial Inventory of Ego Strengths (PIES). The PIES assesses development in the framework of Erikson's ego strength stages. Multivariate linear regression modeling assessed the independent association of the primary covariate (opioid dependent versus control) as well as potential confounding variables (e.g., psychiatric comorbidities, intelligence) with total PIES score. Results. Mean total PIES score was significantly lower in opioid dependent youth (231.65 ± 30.39 opioid dependent versus 270.67 ± 30.06 control; p < 0.01). Evaluation of the PIES subscores found significant (p < 0.05) delays in all ego strength areas (hope, will, purpose, competence, fidelity, love, care, and wisdom). When adjusting for potential confounders, opioid dependence remained a significant (p < 0.001) independent predictor of total PIES score. Conclusion. Adolescents with opioid dependence demonstrated significant delays in ego strength development. A treatment approach acknowledging this delay may be needed in the counseling and treatment of adolescents with opioid dependence. PMID:26664819

Psychiatric disorders in opioid dependants.

PubMed

Ahmadi, Jamshid; Toobaee, Shahin; Kharras, Mohammad; Radmehr, Mohammad

2003-09-01

Psychiatric disorders are common among substance dependants. The objectives of this study were to assess the rate of neurotic disorders among opioid addicts, and reassess the rate of those neurotic disorders two weeks after complete detoxification of the patients. Data were gathered from 500 (496 men and 4 women) opioid dependants, using DSM-IV criteria. The Middlesex Hospital Questionnaire (MHQ) was used to measure free-floating anxiety, depression, phobia, obsession, hysteria and somatization. Four hundred and ninety-six (99.2%) of the subjects were men of whom the majority (65.2%) were married, 26.4% single and the others were divorced or separated. Three hundred and thirty-four (66.8%) were in age range of 20 to 39 years. Of the subjects 154 (30.8) were self-employed, 116 (23.2%) were factory workers, 100 (20%) unemployed, 64 (12.8%) employees and 32 (6.4%) retailers. The majority, 322 (64.4%), reported elementary and high school as their level of education and only 20 (4%) were illiterate. The means for neurotic disorders (using the MHQ) before and two weeks after detoxification were 10.12 and 9.98 for anxiety, 7.54 and 7.41 for phobia, 10.10 and 9.76 for depression, 11.11 and 11.05 for obsession, 8.47 and 8.49 for hysteria and 9.82 and 9.46 for somatization, respectively. The mean difference was significant only for depression. Present findings indicated that the rate of neurotic disorders in opioid dependants is high and (except for depression) was not significantly different before detoxification and two weeks after detoxification. Opium was found to be the most prevalent form of opioid used. Also it can be concluded that during the last years some demographic characteristics of Iranian opioid addicts in this sample have changed. Cultural attitudes toward substance use quite likely affect the pattern of substance use. These findings can be considered when planning preventive and therapeutic programs.

The Neurobiology of Opioid Dependence: Implications for Treatment

PubMed Central

Kosten, Thomas R.; George, Tony P.

2002-01-01

Opioid tolerance, dependence, and addiction are all manifestations of brain changes resulting from chronic opioid abuse. The opioid abuser’s struggle for recovery is in great part a struggle to overcome the effects of these changes. Medications such as methadone, LAAM, buprenorphine, and naltrexone act on the same brain structures and processes as addictive opioids, but with protective or normalizing effects. Despite the effectiveness of medications, they must be used in conjunction with appropriate psychosocial treatments. PMID:18567959

Peripheral Sensitization Increases Opioid Receptor Expression and Activation by Crotalphine in Rats

PubMed Central

Zambelli, Vanessa Olzon; Fernandes, Ana Carolina de Oliveira; Gutierrez, Vanessa Pacciari; Ferreira, Julio Cesar Batista; Parada, Carlos Amilcar; Mochly-Rosen, Daria; Cury, Yara

2014-01-01

Inflammation enhances the peripheral analgesic efficacy of opioid drugs, but the mechanisms involved in this phenomenon have not been fully elucidated. Crotalphine (CRP), a peptide that was first isolated from South American rattlesnake C.d. terrificus venom, induces a potent and long-lasting anti-nociceptive effect that is mediated by the activation of peripheral opioid receptors. Because the high efficacy of CRP is only observed in the presence of inflammation, we aimed to elucidate the mechanisms involved in the CRP anti-nociceptive effect induced by inflammation. Using real-time RT-PCR, western blot analysis and ELISA assays, we demonstrate that the intraplantar injection of prostaglandin E2 (PGE2) increases the mRNA and protein levels of the µ- and κ-opioid receptors in the dorsal root ganglia (DRG) and paw tissue of rats within 3 h of the injection. Using conformation state-sensitive antibodies that recognize activated opioid receptors, we show that PGE2, alone does not increase the activation of these opioid receptors but that in the presence of PGE2, the activation of specific opioid receptors by CRP and selective µ- and κ-opioid receptor agonists (positive controls) increases. Furthermore, PGE2 down-regulated the expression and activation of the δ-opioid receptor. CRP increased the level of activated mitogen-activated protein kinases in cultured DRG neurons, and this increase was dependent on the activation of protein kinase Cζ. This CRP effect was much more prominent when the cells were pretreated with PGE2. These results indicate that the expression and activation of peripheral opioid receptors by opioid-like drugs can be up- or down-regulated in the presence of an acute injury and that acute tissue injury enhances the efficacy of peripheral opioids. PMID:24594607

Treating opioid dependence. Growing implications for primary care.

PubMed

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.

Age at onset typology in opioid dependent men: an exploratory study.

PubMed

De, Biswajit; Mattoo, Surendra K; Basu, Debasish

2002-04-01

This study attempted to apply age at onset typology in ICD-10 diagnosed opioid dependence. The sample comprised 80 men seeking treatment at an addiction clinic. The measures included socio-demographic and clinical profile, Severity of Opioid Dependence Questionnaire, Modified Sensation Seeking Scale, Multiphasic Personality Questionnaire (MPQ) and Family History Assessment Module. A cut-off age of 20/21 years for an early-onset late-onset typology of opioid dependence was obtained using two methods - the modal age at onset method and one-third sample by age at onset method. The early onset group showed significant differences in terms of it being more often younger, urban, unmarried, wage earning or students, using oral opioids (not heroin or injectables), showing higher lifetime use and dependence of sedatives, earlier onset of use and dependence of sedatives and tobacco, and higher global psychopathology in terms of MPQ. The early onset group also showed statistically insignificant trends for lesser use and dependence of alcohol, higher severity of opioid dependence, more legal and less social complications, higher sensation seeking (except boredom susceptibility), and more frequent substance dependence in first degree relatives. The age at onset typology in opioid dependence appears to be feasible and having some similarities to similar typology in alcoholism.

Risk factors for drug dependence among out-patients on opioid therapy in a large US health-care system.

PubMed

Boscarino, Joseph A; Rukstalis, Margaret; Hoffman, Stuart N; Han, John J; Erlich, Porat M; Gerhard, Glenn S; Stewart, Walter F

2010-10-01

Our study sought to assess the prevalence of and risk factors for opioid drug dependence among out-patients on long-term opioid therapy in a large health-care system. Using electronic health records, we identified out-patients receiving 4+ physician orders for opioid therapy in the past 12 months for non-cancer pain within a large US health-care system. We completed diagnostic interviews with 705 of these patients to identify opioid use disorders and assess risk factors. Preliminary analyses suggested that current opioid dependence might be as high as 26% [95% confidence interval (CI) = 22.0-29.9] among the patients studied. Logistic regressions indicated that current dependence was associated with variables often in the medical record, including age <65 [odds ratio (OR) = 2.33, P = 0.001], opioid abuse history (OR = 3.81, P < 0.001), high dependence severity (OR = 1.85, P = 0.001), major depression (OR = 1.29, P = 0.022) and psychotropic medication use (OR = 1.73, P = 0.006). Four variables combined (age, depression, psychotropic medications and pain impairment) predicted increased risk for current dependence, compared to those without these factors (OR = 8.01, P < 0.001). Knowing that the patient also had a history of severe dependence and opioid abuse increased this risk substantially (OR = 56.36, P < 0.001). Opioid misuse and dependence among prescription opioid patients in the United States may be higher than expected. A small number of factors, many documented in the medical record, predicted opioid dependence among the out-patients studied. These preliminary findings should be useful in future research efforts. © 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.

Fatal and non-fatal opioid overdose in opioid dependent patients treated with methadone, buprenorphine or implant naltrexone.

PubMed

Kelty, Erin; Hulse, Gary

2017-08-01

Illicit opioid use is associated with high rates of fatal and non-fatal opioid overdose. This study aims to compare rates of fatal and serious but non-fatal opioid overdose in opioid dependent patients treated with methadone, buprenorphine or implant naltrexone, and to identify risk factors for fatal opioid overdose. Opioid dependent patients treated with methadone (n=3515), buprenorphine (n=3250) or implant naltrexone (n=1461) in Western Australia for the first time between 2001 and 2010, were matched against state mortality and hospital data. Rates of fatal and non-fatal serious opioid overdoses were calculated and compared for the three treatments. Risk factors associated with fatal opioid overdose were examined using multivariate cox proportional hazard models. No significant difference was observed between the three groups in terms of crude rates of fatal or non-fatal opioid overdoses. During the first 28days of treatment, rates of non-fatal opioid overdose were high in all three groups, as were fatal opioid overdoses in patients treated with methadone. However, no fatal opioid overdoses were observed in buprenorphine or naltrexone patients during this period. Following the first 28 days, buprenorphine was shown to be protective, particularly in terms of non-fatal opioid overdoses. After the cessation of treatment, rates of fatal and non-fatal opioid overdoses were similar between the groups, with the exception of lower rates of non-fatal opioid overdose in the naltrexone treated patients compared with the methadone treated patients. After the commencement of treatment, gender, and hospitalisations with a diagnosis of opioid poisoning, cardiovascular or mental health problems were significant predictors of subsequent fatal opioid overdose. Rates of fatal and non-fatal opioid overdose were not significantly different in patients treated with methadone, buprenorphine or implant naltrexone. Gender and prior cause-specific hospitalisations can be used to identify

Curcumin Attenuates Opioid Tolerance and Dependence by Inhibiting Ca2+/Calmodulin-Dependent Protein Kinase II α Activity

PubMed Central

Hu, Xiaoyu; Huang, Fang; Szymusiak, Magdalena

2015-01-01

Chronic use of opioid analgesics has been hindered by the development of opioid addiction and tolerance. We have reported that curcumin, a natural flavonoid from the rhizome of Curcuma longa, attenuated opioid tolerance, although the underlying mechanism remains unclear. In this study, we tested the hypothesis that curcumin may inhibit Ca2+/calmodulin-dependent protein kinase II α (CaMKIIα), a protein kinase that has been previously proposed to be critical for opioid tolerance and dependence. In this study, we used state-of-the-art polymeric formulation technology to produce poly(lactic-co-glycolic acid) (PLGA)-curcumin nanoparticles (nanocurcumin) to overcome the drug’s poor solubility and bioavailability, which has made it extremely difficult for studying in vivo pharmacological actions of curcumin. We found that PLGA-curcumin nanoparticles reduced the dose requirement by 11- to 33-fold. Pretreatment with PLGA-curcumin (by mouth) prevented the development of opioid tolerance and dependence in a dose-dependent manner, with ED50 values of 3.9 and 3.2 mg/kg, respectively. PLGA-curcumin dose-dependently attenuated already-established opioid tolerance (ED50 = 12.6 mg/kg p.o.) and dependence (ED50 = 3.1 mg/kg p.o.). Curcumin or PLGA-curcumin did not produce antinociception by itself or affect morphine (1–10 mg/kg) antinociception. Moreover, we found that the behavioral effects of curcumin on opioid tolerance and dependence correlated with its inhibition of morphine-induced CaMKIIα activation in the brain. These results suggest that curcumin may attenuate opioid tolerance and dependence by suppressing CaMKIIα activity. PMID:25515789

Predictors of social anxiety in an opioid dependent sample and a control sample.

PubMed

Shand, Fiona L; Degenhardt, Louisa; Nelson, Elliot C; Mattick, Richard P

2010-01-01

Compared to other mental health problems, social anxiety is under-acknowledged amongst opioid dependent populations. This study aimed to assess levels of social anxiety and identify its predictors in an opioid dependent sample and a matched control group. Opioid dependent participants (n=1385) and controls (n=417) completed the Social Interaction Anxiety Scale (SIAS), the Social Phobia Scale (SPS) and a diagnostic interview. Regression analyses were used to test a range of predictors of social anxiety. Opioid dependent cases had higher mean scores on both scales compared to controls. Predictors of social anxiety centred on emotional rejection in childhood, either by parents or peers. For opioid dependent cases, but not controls, lifetime non-opioid substance dependence (cannabis, sedatives, and tobacco) was associated with higher levels of social anxiety. However, much of the variance in social anxiety remains unexplained for this population.

Predictors of social anxiety in an opioid dependent sample and a control sample

PubMed Central

Shand, Fiona L.; Degenhardt, Louisa; Nelson, Elliot C.; Mattick, Richard P.

2010-01-01

Compared to other mental health problems, social anxiety is under-acknowledged amongst opioid dependent populations. This study aimed to assess levels of social anxiety and identify its predictors in an opioid dependent sample and a matched control group. Opioid dependent participants (n = 1385) and controls (n = 417) completed the Social Interaction Anxiety Scale (SIAS), the Social Phobia Scale (SPS) and a diagnostic interview. Regression analyses were used to test a range of predictors of social anxiety. Opioid dependent cases had higher mean scores on both scales compared to controls. Predictors of social anxiety centred on emotional rejection in childhood, either by parents or peers. For opioid dependent cases, but not controls, lifetime non-opioid substance dependence (cannabis, sedatives, and tobacco) was associated with higher levels of social anxiety. However, much of the variance in social anxiety remains unexplained for this population. PMID:19775865

The effectiveness of opioid substitution treatments for patients with opioid dependence: a systematic review and multiple treatment comparison protocol

PubMed Central

2014-01-01

Background Opioids are psychoactive analgesic drugs prescribed for pain relief and palliative care. Due to their addictive potential, effort and vigilance in controlling prescriptions is needed to avoid misuse and dependence. Despite the effort, the prevalence of opioid use disorder continues to rise. Opioid substitution therapies are commonly used to treat opioid dependence; however, there is minimal consensus as to which therapy is most effective. Available treatments include methadone, heroin, buprenorphine, as well as naltrexone. This systematic review aims to assess and compare the effect of all available opioid substitution therapies on the treatment of opioid dependence. Methods/Design The authors will search Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry, World Health Organization International Clinical Trials Registry Platform Search Portal, and the National Institutes for Health Clinical Trials Registry. The title, abstract, and full-text screening will be completed in duplicate. When appropriate, multiple treatment comparison Bayesian meta-analytic methods will be performed to deduce summary statistics estimating the effectiveness of all opioid substitution therapies in terms of retention and response to treatment (as measured through continued opioid abuse). Discussion Using evidence gained from this systematic review, we anticipate disseminating an objective review of the current available literature on the effectiveness of all opioid substitution therapies for the treatment of opioid use disorder. The results of this systematic review are imperative to the further enhancement of clinical practice in addiction medicine. Systematic review registration PROSPERO CRD42013006507. PMID:25239213

Assessing Craving and its Relationship to Subsequent Prescription Opioid Use Among Treatment-Seeking Prescription Opioid Dependent Patients

PubMed Central

McHugh, R. Kathryn; Fitzmaurice, Garrett M.; Carroll, Kathleen M.; Griffin, Margaret L.; Hill, Kevin P.; Wasan, Ajay D.; Weiss, Roger D.

2014-01-01

Background Craving is viewed as a core feature of substance use disorders and has been shown to predict future drug use, particularly over the short term. Accordingly, craving is often assessed in treatment settings as a marker of risk for subsequent drug use. The identification of the briefest measure that maintains predictive validity is of particular value for both clinical and research settings to minimize assessment burden while maintaining utility for the prediction of use. Methods Data from a multi-site clinical trial of treatment for prescription opioid dependence were examined to evaluate whether a brief, 3-item craving scale administered each week predicted urine-confirmed self report of prescription opioid use in the subsequent week. Logistic regression models examining the association between craving and presence or absence of opioid use in the following week were conducted, controlling for opioid use in the previous week, treatment condition, and lifetime history of heroin use. Results Greater craving was associated with a higher odds of prescription opioid use in the following week. For each one-unit increase on this 10-point scale, the odds of using opioids in the subsequent week was 17% higher. In addition to an item assessing urges, items assessing cue-induced craving and perceived likelihood of relapse in an environment where drugs were previously used contributed uniquely to this association. Conclusions A brief measure of prescription opioid craving predicted prescription opioid use among individuals in treatment. This measure offers an efficient strategy to inform the assessment of risk for use in this population. PMID:25454409

Prescription Opioid Abuse and Dependence: Assessment Strategies for Counselors

ERIC Educational Resources Information Center

Weigel, Daniel J.; Donovan, Kimberly A.; Krug, Kevin S.; Dixon, Wayne A.

2007-01-01

The authors review the article "Prescription Drug Use and Abuse: Risk Factors, Red Flags, and Prevention Strategies" (J. H. Isaacson, J. A. Hopper, D. P. Alford, & T. Parran, 2005), which provides an overview of the recent increase in prescription opioid abuse and dependence from the physician's perspective. In the present article, the authors…

Evidence that anhedonia is a symptom of opioid dependence associated with recent use.

PubMed

Garfield, Joshua B B; Cotton, Sue M; Allen, Nicholas B; Cheetham, Ali; Kras, Marni; Yücel, Murat; Lubman, Dan I

2017-08-01

Anhedonia is prevalent among substance-dependent populations. The hedonic allostasis model suggests this is due to the effects of addictive substances on neural substrates of reward processing. However, previous research may have been confounded by other factors likely to influence anhedonia, including tobacco use, psychopathology, and history of trauma and other stressors. Thus it remains unclear whether elevated anhedonia in substance-dependent populations is caused by substance use itself, or is due to other correlates of substance dependence. Multivariate analysis of covariance was conducted to test whether opioid-dependent participants' anhedonia scores were elevated, relative to a non-dependent control group, after controlling for psychosocial factors likely to influence anhedonia. Correlational analyses within opioid-dependent participants were also conducted to examine whether anhedonia was associated with recent illicit opioid use or duration of abstinence. There was a modest, but significant, elevation in anhedonia in opioid-dependent participants, relative to controls (Partial η 2 =0.034, p=0.041) after controlling for psychosocial variables that were associated with anhedonia. Depressive symptoms and history of post-traumatic stress disorder also remained significantly associated with anhedonia in the adjusted model. Among participants on opioid pharmacotherapy, there were significant associations between frequency of recent illicit opioid use and scores on anhedonia measures (all r s >0.25, p<0.013), but among abstinent opioid-dependent participants, relationships between duration of abstinence and anhedonia were not significant (all r s <0.24, p>0.22). These findings support the hypothesis that use of opioids can cause anhedonia, although other psychosocial factors may also contribute to the high prevalence of anhedonia among opioid-dependent populations. Copyright © 2017 Elsevier B.V. All rights reserved.

Cue-Induced Craving to Paraphernalia and Drug Images in Opioid Dependence

PubMed Central

McHugh, R. Kathryn; Fulciniti, Francesca; Mashhoon, Yasmin; Weiss, Roger D.

2016-01-01

Background and Objectives Stimuli that are repeatedly paired with substance use, such as drug paraphernalia, can themselves elicit drug craving. The aim of this study was to examine whether particular cue types elicit greater craving responses than others among individuals with opioid dependence. Methods Participants seeking inpatient treatment for opioid dependence were recruited for a study of cue-induced craving. This sample (N=50), included 25 primary heroin users, 20 primary prescription opioid users, and 5 users of heroin and prescription opioids equally. Participants completed a cue reactivity task, in which images of drug-related stimuli were presented on a computer screen, each followed by a question assessing state drug craving. Results Overall, participants reported higher craving following paraphernalia stimuli relative to drug stimuli. However, this was moderated by opioid type; there was significantly higher craving in response to images of paraphernalia cues in the heroin group, and higher craving in response to drug cues in the prescription opioid group. Discussion and Conclusions These findings highlight potential differences in cue reactivity to opioid paraphernalia and drug cues, which appears to be moderated by drug type. Scientific Significance Cue-induced craving is an important factor in relapse. This study adds further to the literature on cue-induced craving in opioid dependence, suggesting that craving may vary based on both cue type and opioid type. Future studies designed to discriminate the impact of substance of abuse, route of administration, and cue type will help to further understand cue-induced craving in this population. PMID:26848719

A call for evidence-based medical treatment of opioid dependence in the United States and Canada.

PubMed

Nosyk, Bohdan; Anglin, M Douglas; Brissette, Suzanne; Kerr, Thomas; Marsh, David C; Schackman, Bruce R; Wood, Evan; Montaner, Julio S G

2013-08-01

Despite decades of experience treating heroin or prescription opioid dependence with methadone or buprenorphine--two forms of opioid substitution therapy--gaps remain between current practices and evidence-based standards in both Canada and the United States. This is largely because of regulatory constraints and pervasive suboptimal clinical practices. Fewer than 10 percent of all people dependent on opioids in the United States are receiving substitution treatment, although the proportion may increase with expanded health insurance coverage as a result of the Affordable Care Act. In light of the accumulated evidence, we recommend eliminating restrictions on office-based methadone prescribing in the United States; reducing financial barriers to treatment, such as varying levels of copayment in Canada and the United States; reducing reliance on less effective and potentially unsafe opioid detoxification; and evaluating and creating mechanisms to integrate emerging treatments. Taking these steps can greatly reduce the harms of opioid dependence by maximizing the individual and public health benefits of treatment.

Factors associated with opioid dose increases: a chart review of patients’ first year on long-term opioids

PubMed Central

Bautista, Christopher A.; Iosif, Ana-Maria; Wilsey, Barth L.; Melnikow, Joy A.; Crichlow, Althea; Henry, Stephen G.

2016-01-01

OBJECTIVE To examine encounter-level factors associated with opioid dose increases during patients’ first year on opioid therapy for chronic pain. DESIGN Case-control study analyzing all opioid prescriptions for patients with chronic pain during their first year after opioid initiation. Cases were patients who experienced an overall dose escalation of ≥30 mg morphine equivalents over the 1-year period; controls did not experience overall dose escalation. Main measures were encounter type; opioid dose change; documented prescribing rationale; documentation of guideline-concordant opioid prescribing practices. Two coders reviewed all encounters associated with opioid prescriptions. Analysis of factors associated with dose increases and provider documentation of prescribing rationale was conducted using multiple logistic regression. RESULTS 674 encounters were coded for 66 patients (22 cases, 44 controls). Fifty-three percent of opioid prescriptions were associated with telephone encounters; 13% were associated with email encounters. No prescribing rationale was documented for 43% of all opioid prescriptions and 25% of dose increases. Likelihood of dose increase and documentation of prescribing rationale did not significantly differ for cases versus controls. Compared to face-to-face encounters, dose increases were significantly less likely for telephone (OR 0.18, 95%CI 0.11 – 0.28) and email (OR 0.23, 95%CI 0.12 – 0.47) encounters; documentation of prescribing rationale was significantly more likely for email (OR 5.06, 95%CI 1.87–13.72) and less likely for telephone (OR 0.30, 95%CI 0.18–0.51) encounters. CONCLUSION Most opioid prescriptions were written without face-to-face encounters. One quarter of dose increases contained no documented prescribing rationale. Documented encounter-level factors were not significantly associated with overall opioid dose escalation. PMID:27477581

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

PubMed

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

Adjunctive Counseling During Brief and Extended Buprenorphine-Naloxone Treatment for Prescription Opioid Dependence

PubMed Central

Weiss, Roger D.; Potter, Jennifer Sharpe; Fiellin, David A.; Byrne, Marilyn; Connery, Hilary S.; Dickinson, William; Gardin, John; Griffin, Margaret L.; Gourevitch, Marc N.; Haller, Deborah L.; Hasson, Albert L.; Huang, Zhen; Jacobs, Petra; Kosinski, Andrzej S.; Lindblad, Robert; McCance-Katz, Elinore F.; Provost, Scott E.; Selzer, Jeffrey; Somoza, Eugene C.; Sonne, Susan C.; Ling, Walter

2012-01-01

Context No randomized trials have examined treatments for prescription opioid dependence, despite its increasing prevalence. Objective To evaluate the efficacy of brief and extended buprenorphine-naloxone treatment, with different counseling intensities, for patients dependent upon prescription opioids. Setting, Participants 653 treatment-seeking outpatients dependent on prescription opioids, at 10 U.S. sites from June 2006-July 2009. Design Multi-site, randomized clinical trial, using a two-phase adaptive treatment research design. Brief treatment (Phase 1) included 2-week buprenorphine-naloxone stabilization, 2-week taper, and 8-week post-medication follow-up. Patients with successful opioid use outcomes exited the study; unsuccessful patients entered Phase 2: extended (12-week) buprenorphine-naloxone treatment, 4-week taper, and 8-week post-medication follow-up. Main outcome measures Pre-defined “successful outcome” in each phase: composite measures indicating minimal or no opioid use, based on urine-confirmed self-reports. Interventions In both phases, patients were randomized to Standard Medical Management (SMM) or SMM+Opioid Drug Counseling (ODC); all received buprenorphine-naloxone. Results During Phase 1, only 6.6% (43/653) of patients had successful outcomes, with no difference between the SMM and SMM+ODC. In contrast, 49.2% (177/360) attained successful outcomes in Phase 2 during extended buprenorphine-naloxone treatment (week 12), with no difference between counseling conditions. Success rates 8 weeks after completing the buprenorphine-naloxone taper (Phase 2, week 24) dropped sharply to 8.6% (31/360), again with no counseling difference. In secondary analyses, successful Phase 2 outcomes were far more common while taking buprenorphine-naloxone than 8 weeks post-taper (49.2% (177/360) vs. 8.6% (31/360), p<0.001). Chronic pain did not affect opioid use outcomes; a history of ever using heroin was associated with lower Phase 2 success rates while

Attitudes toward buprenorphine and methadone among opioid-dependent individuals

PubMed Central

Schwartz, Robert P.; Kelly, Sharon M.; O'Grady, Kevin E.; Mitchell, Shannon Gwin; Peterson, James A.; Reisinger, Heather Schacht; Agar, Michael H.; Brown, Barry S.

2009-01-01

Attitudes and beliefs about drug abuse treatment have long been known to shape response to that treatment. Two major pharmacological alternatives are available for opioid dependence: methadone, which has been available for the past 40 years, and buprenorphine, a recently-introduced medication. This mixed methods study examined the attitudes of opioid-dependent individuals toward methadone and buprenorphine. A total of 195 participants (n = 140 who were enrolling in one of 6 Baltimore area methadone programs and n = 55 who were out-of-treatment) were administered the Attitudes toward Methadone and toward Buprenorphine Scales and a subset (n = 46) received an ethnographic interview. In-treatment group had significantly more positive attitudes toward methadone than did the out-of-treatment group (p < .001), while they did not differ in their attitudes toward buprenorphine. Both groups had significantly more positive attitudes toward buprenorphine than methadone. Addressing these attitudes may increase treatment entry and retention. PMID:18770082

Psychological and physiological stress negatively impacts early engagement and retention of opioid-dependent individuals on methadone maintenance

PubMed Central

Jaremko, Kellie M.; Sterling, Robert C.; Van Bockstaele, Elisabeth J.

2014-01-01

The present study investigated whether psychological and/or physiological measures of stress would impede induction onto methadone maintenance and predict early (<6 months) discontinuation. Compared with controls, opioid-dependent subjects displayed increased distress on the perceived stress scale (PSS) and post-traumatic stress disorder checklist (PCLC); 60% exhibited abnormal cortisol. Addiction severity index (ASI), drug-use, and stress indices explained between 17–37% of the variance in engagement including attendance, opioid abstinence, and methadone stabilization. Participants who discontinued treatment displayed poor engagement, abnormal cortisol, elevated withdrawal symptoms, higher distress, and increased ongoing opioid use versus compliant individuals. Discontinuation was initially related to drug-use severity; however, by 6 months, retention depended primarily upon cortisol abnormalities, which increased an individual’s discontinuation risk by 7.7-fold. These findings support admission screening with the ASI/cortisol for drop out, and stress/drug-use indices for engagement that together may enable clinically-relevant early recognition and interventions for prevention of stress-induced relapse in opioid-dependent populations. PMID:25239858

Psychological and physiological stress negatively impacts early engagement and retention of opioid-dependent individuals on methadone maintenance.

PubMed

Jaremko, Kellie M; Sterling, Robert C; Van Bockstaele, Elisabeth J

2015-01-01

The present study investigated whether psychological and/or physiological measures of stress would impede induction onto methadone maintenance and predict early (<6 months) discontinuation. Compared with controls, opioid-dependent subjects displayed increased distress on the perceived stress scale (PSS) and post-traumatic stress disorder checklist (PCLC); 60% exhibited abnormal cortisol. Addiction severity index (ASI), drug-use, and stress indices explained between 17 and 37% of the variance in engagement including attendance, opioid abstinence, and methadone stabilization. Participants who discontinued treatment displayed poor engagement, abnormal cortisol, elevated withdrawal symptoms, higher distress, and increased ongoing opioid use versus compliant individuals. Discontinuation was initially related to drug-use severity; however, by 6 months, retention depended primarily upon cortisol abnormalities, which increased an individual's discontinuation risk by 7.7-fold. These findings support admission screening with the ASI/cortisol for drop out, and stress/drug-use indices for engagement that together may enable clinically-relevant early recognition and interventions for prevention of stress-induced relapse in opioid-dependent populations. Copyright © 2014 Elsevier Inc. All rights reserved.

Treatment of Opioid Dependent Pregnant Women: Clinical and Research Issues

PubMed Central

Jones, H.E.; Martin, P.R.; Heil, S.H.; Stine, S.M.; Kaltenbach, K.; Selby, P.; Coyle, M.G.; O’Grady, K.E.; Arria, A.M.; Fischer, G.

2008-01-01

This paper addresses common questions that clinicians face when treating pregnant women with opioid dependence. Guidance is provided to aid clinical decision-making, based on both research evidence and the collective clinical experience of the authors which include investigators in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) project. MOTHER is a double-blind, double-dummy, flexible–dosing, parallel-group clinical trial examining the comparative safety and efficacy of methadone and buprenorphine for the opioid dependence treatment among pregnant women and their neonates. The paper begins with a discussion of appropriate assessment during pregnancy, and then addresses clinical management stages, including maintenance medication selection, induction and stabilization, opioid agonist medication management before, during and after delivery, pain management, breast-feeding, and transfer to aftercare. Lastly, other important clinical issues including managing co-occurring psychiatric disorders and medication interactions are discussed. PMID:18248941

Memantine improves buprenorphine/naloxone treatment for opioid dependent young adults.

PubMed

Gonzalez, Gerardo; DiGirolamo, Gregory; Romero-Gonzalez, Mauricio; Smelson, David; Ziedonis, Douglas; Kolodziej, Monika

2015-11-01

Opioid use disorders are considered a serious public health problem among young adults. Current treatment is limited to long-term opioid substitution therapy, with high relapse rates after discontinuation. This study evaluated the co-administration of memantine to brief buprenorphine pharmacotherapy as a treatment alternative. 13-week double-blind placebo-controlled trial evaluating 80 young adult opioid dependent participants treated with buprenorphine/naloxone 16-4mg/day and randomized to memantine (15mg or 30mg) or placebo. Primary outcomes were a change in the weekly mean proportion of opioid use, and cumulative abstinence rates after rapid buprenorphine discontinuation on week 9. Treatment retention was not significantly different between groups. The memantine 30mg group was significantly less likely to relapse and to use opioids after buprenorphine discontinuation. Among participants abstinent on week 8, those in the memantine 30mg group (81.9%) were significantly less likely to relapse after buprenorphine was discontinued compared to the placebo group (30%) (p<0.025). Also, the memantine 30mg group had significantly reduced opioid use (mean=0, SEM±0.00) compared to the placebo group (mean=0.33, SEM±0.35; p<0.004) during the last 2 weeks of study participation. Memantine 30mg significantly improved short-term treatment with buprenorphine/naloxone for opioid dependent young adults by reducing relapse and opioid use after buprenorphine discontinuation. Combined short-term treatment with buprenorphine/naloxone may be an effective alternative treatment to long-term methadone or buprenorphine maintenance in young adults. Published by Elsevier Ireland Ltd.

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

PubMed

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.

Tobacco withdrawal among opioid-dependent smokers.

PubMed

Streck, Joanna M; Heil, Sarah H; Higgins, Stephen T; Bunn, Janice Y; Sigmon, Stacey C

2018-04-01

Prevalence of cigarette smoking among opioid-dependent individuals is 6-fold that of the general U.S. adult population and their quit rates are notoriously poor. One possible reason for the modest cessation outcomes in opioid-dependent smokers may be that they experience more severe tobacco withdrawal upon quitting. In this secondary analysis, we evaluated tobacco withdrawal in opioid-dependent (OD) smokers versus smokers without co-occurring substance use disorders (SUDs). Participants were 47 methadone- or buprenorphine-maintained smokers and 25 non-SUD smokers who completed 1 of several 2-week studies involving daily visits for biochemical monitoring, delivery of financial incentives contingent on smoking abstinence, and assessment of withdrawal via the Minnesota Nicotine Withdrawal Scale (MNWS). Prior to quitting smoking, OD smokers presented with higher baseline withdrawal scores than non-SUD smokers (1.7 ± 0.2 vs. 0.7 ± 0.2, respectively; F [1, 63] = 7.31, p < .001). Withdrawal scores in both groups decreased over the subsequent 2-week period with no group differences, F (1, 910) = 0.50, p = .48. A similar pattern was observed on craving (i.e., Desire to Smoke item of MNWS), although the trajectory of decrease over time on this item was also moderated by gender. Overall, there was no difference in withdrawal during biochemically verified smoking abstinence between OD and non-SUD smokers, suggesting that elevated withdrawal severity following quitting may not be a major factor contributing to the poor cessation outcomes consistently observed among OD smokers. Further scientific efforts are needed to improve our understanding of the high smoking rates and modest cessation outcomes in this challenging population. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Probuphine® (buprenorphine implant): a promising candidate in opioid dependence

PubMed Central

Barnwal, Preeti; Das, Saibal; Mondal, Somnath; Ramasamy, Anand; Maiti, Tanay; Saha, Arunava

2016-01-01

Opioid dependence leads to physical dependence and addiction which finally results in profound medical, psychological and social dysfunction. One of the useful medications for opioid dependence is buprenorphine, the partial opioid agonist, which is used alone or in combination with naloxone. However, buprenorphine is the victim of its own success due to its illicit use and accidental poisoning in children. Also, buprenorphine typically requires daily self-administration and its effectiveness heavily depends on patient adherence. So, poor treatment adherence results in ineffective treatment manifesting as craving and withdrawal symptoms. Short-term use of buprenorphine in opioid dependence is also often followed by relapse. Buprenorphine when used sublingually often results in inadequate or fluctuating blood concentrations and poorer treatment retention compared with methadone. All of these led to the development of Probuphine®, a polymeric matrix composed of ethylene vinyl acetate and buprenorphine in the form of implants, that are implanted subdermally in office practice and deliver the active drug over 6 months. Buprenorphine release from such implant is fairly consistent, avoiding plasma peaks and troughs, and the implant is also reported to be safe. In this review article, we have highlighted these aspects of treatment of opioid addiction, stressing on the pharmacology of buprenorphine and Probuphine®, and relevant clinical trials addressing the efficacy and safety of Probuphine®. This sustained-release implantable formulation of buprenorphine has the potential to be a suitable alternative to daily or alternate day sublingual buprenorphine which can thereby eliminate the need for daily supervision, minimizing fluctuations in plasma concentrations, and allowing these patients to reduce clinic or pharmacy visits. PMID:28348732

Probuphine® (buprenorphine implant): a promising candidate in opioid dependence.

PubMed

Barnwal, Preeti; Das, Saibal; Mondal, Somnath; Ramasamy, Anand; Maiti, Tanay; Saha, Arunava

2017-03-01

Opioid dependence leads to physical dependence and addiction which finally results in profound medical, psychological and social dysfunction. One of the useful medications for opioid dependence is buprenorphine, the partial opioid agonist, which is used alone or in combination with naloxone. However, buprenorphine is the victim of its own success due to its illicit use and accidental poisoning in children. Also, buprenorphine typically requires daily self-administration and its effectiveness heavily depends on patient adherence. So, poor treatment adherence results in ineffective treatment manifesting as craving and withdrawal symptoms. Short-term use of buprenorphine in opioid dependence is also often followed by relapse. Buprenorphine when used sublingually often results in inadequate or fluctuating blood concentrations and poorer treatment retention compared with methadone. All of these led to the development of Probuphine®, a polymeric matrix composed of ethylene vinyl acetate and buprenorphine in the form of implants, that are implanted subdermally in office practice and deliver the active drug over 6 months. Buprenorphine release from such implant is fairly consistent, avoiding plasma peaks and troughs, and the implant is also reported to be safe. In this review article, we have highlighted these aspects of treatment of opioid addiction, stressing on the pharmacology of buprenorphine and Probuphine®, and relevant clinical trials addressing the efficacy and safety of Probuphine®. This sustained-release implantable formulation of buprenorphine has the potential to be a suitable alternative to daily or alternate day sublingual buprenorphine which can thereby eliminate the need for daily supervision, minimizing fluctuations in plasma concentrations, and allowing these patients to reduce clinic or pharmacy visits.

Increased use of heroin as an initiating opioid of abuse.

PubMed

Cicero, Theodore J; Ellis, Matthew S; Kasper, Zachary A

2017-11-01

Given the relatively recent growth in access to heroin and a more permissive atmosphere surrounding its use, we hypothesized that an increasing number of persons with limited experience and tolerance to opioids would experiment with heroin as their first opioid rather than more common prescription opioid analgesics. Individuals entering substance abuse treatment for an opioid use disorder in the period 2010-2016 (N=5885) were asked about the specific opioid they first regularly used to get high. To limit long-term recall and survival bias, analyses was restricted to opioid initiation that occurred in the past ten years (2005-2015). In 2005, only 8.7% of opioid initiators started with heroin, but this sharply increased to 33.3% (p<0.001) in 2015, with no evidence of stabilization. The use of commonly prescribed opioids, oxycodone and hydrocodone, dropped from 42.4% and 42.3% of opioid initiators, respectively, to 24.1% and 27.8% in 2015, such that heroin as an initiating opioid was now more frequently endorsed than prescription opioid analgesics. Our data document that, as the most commonly prescribed opioids - hydrocodone and oxycodone - became less accessible due to supply-side interventions, the use of heroin as an initiating opioid has grown at an alarming rate. Given that opioid novices have limited tolerance to opioids, a slight imprecision in dosing inherent in heroin use is likely to be an important factor contributing to the growth in heroin-related over dose fatalities in recent years. Copyright © 2017. Published by Elsevier Ltd.

Risk-Taking Propensity as a Predictor of Induction onto Naltrexone Treatment for Opioid Dependence

PubMed Central

Aklin, Will M.; Severtson, S. Geoffrey; Umbricht, Annie; Fingerhood, Michael; Bigelow, George E.; Lejuez, C. W.; Silverman, Kenneth

2014-01-01

Objective Heroin addiction is a chronic relapsing disorder that has devastating social, medical, and economic consequences. Naltrexone is an antagonist that blocks opioid effects and could be an effective medication for the treatment of opioid dependence. However, its clinical utility has been limited partly because of poor adherence and acceptability. Given the importance of compliance to naltrexone treatment for opioid dependence, the goal of the current study was to examine predictors involved in successful induction onto naltrexone treatment. Method Parametric and nonparametric statistical tests were performed on data from a sample of 64 individuals entering treatment who met DSM-IV criteria for opioid dependence. The relationship between naltrexone induction (i.e., inducted- vs. not-inducted onto naltrexone) and risk-taking propensity, as indexed by riskiness on the Balloon Analogue Risk Task (BART) was examined. Participants were recruited from local detoxification programs, inpatient drug treatment, and other Baltimore programs that provided services to opioid dependent adults (e.g., Baltimore Needle Exchange Program) during the period from August 2007 to September 2008. Results Positive association between risk-taking propensity and odds of naltrexone induction. Specifically, each five point increase in the total BART score was associated with a 25% decrease in odds of naltrexone induction (OR=0.76, 95% CI: 0.58–0.99, p = .041). This association remained statistically significant even after adjusting for potential confounds, including injection drug use and cocaine positive urine results (p = .05). After adjusting for the covariates, each five point increase in BART score was associated with 28% decrease in the odds of achieving the maintenance dose (AOR=0.73, 95% CI: 0.54–0.99, p = .046). Conclusions Risk taking propensity was predictive of induction onto naltrexone treatment, above and beyond injection drug use and cocaine-positive urine samples. PMID

Buprenorphine implants for treatment of opioid dependence: a randomized controlled trial.

PubMed

Ling, Walter; Casadonte, Paul; Bigelow, George; Kampman, Kyle M; Patkar, Ashwin; Bailey, Genie L; Rosenthal, Richard N; Beebe, Katherine L

2010-10-13

Limitations of existing pharmacological treatments for opioid dependence include low adherence, medication diversion, and emergence of withdrawal symptoms. To determine the efficacy of buprenorphine implants that provide a low, steady level of buprenorphine over 6 months for the treatment of opioid dependence. A randomized, placebo-controlled, 6-month trial conducted at 18 sites in the United States between April 2007 and June 2008. One hundred sixty-three adults, aged 18 to 65 years, diagnosed with opioid dependence. One hundred eight were randomized to receive buprenorphine implants and 55 to receive placebo implants. After induction with sublingual buprenorphine-naloxone tablets, patients received either 4 buprenorphine implants (80 mg per implant) or 4 placebo implants. A fifth implant was available if a threshold for rescue use of sublingual buprenorphine-naloxone treatment was exceeded. Standardized individual drug counseling was provided to all patients. The percentage of urine samples negative for illicit opioids for weeks 1 through 16 and for weeks 17 through 24. The buprenorphine implant group had significantly more urine samples negative for illicit opioids during weeks 1 through 16 (P = .04). Patients with buprenorphine implants had a mean percentage of urine samples that tested negative for illicit opioids across weeks 1 through 16 of 40.4% (95% confidence interval [CI], 34.2%-46.7%) and a median of 40.7%; whereas those in the placebo group had a mean of 28.3% (95% CI, 20.3%-36.3%) and a median of 20.8%. A total of 71 of 108 patients (65.7%) who received buprenorphine implants completed the study vs 17 of 55 (30.9%) who received placebo implants (P < .001). Those who received buprenorphine implants also had fewer clinician-rated (P <.001) and patient-rated (P = .004) withdrawal symptoms, had lower patient ratings of craving (P <.001), and experienced a greater change on clinician global ratings of severity of opioid dependence (P<.001) and on the

Effectiveness of low-dose naltrexone in the post-detoxification treatment of opioid dependence.

PubMed

Mannelli, Paolo; Patkar, Ashwin A; Peindl, Kathleen; Murray, Heather W; Wu, Li-Tzy; Hubbard, Robert

2007-10-01

The clinical use of naltrexone (NTX) in the treatment of opioid dependence has been limited because of poor compliance and inconsistent outcomes. In particular, the therapeutic benefit of extended treatment with NTX after opioid detoxification is unclear. The present study evaluated whether the augmentation with low-dose NTX during the post-detoxification treatment of opioid dependence would improve outcomes. In an open-label naturalistic design, 435 opioid-dependent patients who had completed inpatient detoxification were offered the choice of entering 1 of the 2 outpatient treatment arms: clonidine extended treatment (CET) (clonidine + psychosocial treatment), or enhanced extended treatment (EET) (oral NTX [1-10 mg/d] + CET) for 21 days. The primary outcome measure was retention in treatment. Secondary outcomes included abstinence from opioids, dropouts, and adherence to postdischarge care. One hundred sixty-two patients (37.2%) accepted EET. Subjects receiving EET stayed longer in the program (F = 64.4; P = 0.000), were less likely to drop out, used less opioids, and followed through with referral to long-term outpatient treatment in a higher number, compared with patients in the CET arm (P = 0.000 in each case). The NTX + clonidine combination was safe and well tolerated. This preliminary study indicates the potential benefit of augmentation with low-dose NTX to improve outcomes after opioid detoxification for a preferred group of patients. Randomized controlled trials are necessary to further evaluate the role of low-dose NTX in the outpatient treatment of opioid dependence.

Advances in the delivery of buprenorphine for opioid dependence.

PubMed

Rosenthal, Richard N; Goradia, Viral V

2017-01-01

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.

Perceived stigma and social support in treatment for pharmaceutical opioid dependence.

PubMed

Cooper, Sasha; Campbell, Gabrielle; Larance, Briony; Murnion, Bridin; Nielsen, Suzanne

2018-02-01

The dramatic increase in pharmaceutical opioid (PO) use in high-income countries is a growing public health concern. Stigma and social support are important as they may influence treatment uptake and outcomes, yet few studies exist regarding perceived stigma and social support among people with PO dependence. The aims of the study are to: (i) compare characteristics of those with PO dependence from iatrogenic and non-iatrogenic causes; (ii) document perceived stigma and its correlates in people in treatment for PO dependence; and (iii) examine correlates of social support in people in treatment for PO dependence. This prospective cohort study included (n = 108) PO-dependent people referred from treatment services. Telephone interviews were conducted at baseline, 3, 12 and 24 months. Multivariate linear regression was used to examine correlations. Mean age was 41 (SD = 10.5). Half (n = 56, 52%) were female. Two in five met the criteria for iatrogenic dependence (n = 41, 38%), with iatrogenic dependence associated with chronic pain, and no history of injection or heroin use. One quarter of study subjects reported past month unsanctioned opioid use (n = 25, 23%). Being married/de facto or female was associated with higher levels of perceived stigma. Unsanctioned opioid use, iatrogenic dependence and mental health conditions were associated with lower social support. Stigma affects all people in treatment. Those who are married/de facto and female may benefit from interventions to address stigma. The association of low social support with poorer mental health and ongoing substance use indicate that treatment could focus more on this area. © 2017 Australasian Professional Society on Alcohol and other Drugs.

What factors are associated with increased risk for prolonged postoperative opioid usage after colorectal surgery?

PubMed

Stafford, Caitlin; Francone, Todd; Roberts, Patricia L; Ricciardi, Rocco

2018-02-06

Opioid-related deaths have increased substantially over the last 10 years placing clinician's prescription practices under intense scrutiny. Given the substantial risk of opioid dependency after colorectal surgery, we sought to analyze risk of postoperative prolonged opioid use after colorectal resections. Between 2008 and 2014, patients undergoing abdominopelvic procedure with intestinal resection at a tertiary care facility were retrospectively identified. Patient's postoperative narcotic usage including their prescriptions on discharge and their total opioid medication use was recorded. Patient variables such as demographics, surgical characteristics, and prescription use were evaluated. Finally, we developed multivariate models to identify risk factors for prolonged opioid use (> 30 days after incident surgical procedure). We identified 9423 recorded procedures of which 2173 consisted of abdominopelvic procedures with intestinal resection and survived > 1 year. Of these, 91% (n = 1981) were discharged on opioids, and 98% (n = 1955) of those patients filled only one prescription. A total of 92 (4%) patients remained on opioids beyond 30 days, and from this group, 25% (n = 23 patients) remained at 90 days. We found no association between postoperative complications, stoma formation, and patient's sex with risk of prolonged opioid use. However, younger age and history of chronic pain were associated with an increased risk of prolonged opioid use. The use of minimally invasive techniques also attenuated the risk of prolonged opioid use (Table 2). A small but considerable proportion of patients remain on opioids beyond 30 days. Predictors of opioid use for greater than 30 days include a history of chronic pain and younger age. The use of minimally invasive techniques reduced the risk of prolonged opioid use. We identified several immutable risk factors that predicted prolonged postoperative opioid use; however, surgeons may be able to attenuate

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

PubMed

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.

Advances in the delivery of buprenorphine for opioid dependence

PubMed Central

Rosenthal, Richard N; Goradia, Viral V

2017-01-01

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. PMID:28894357

A cross-sectional study of correlates of imprisonment in opioid-dependent men and women in New South Wales, Australia.

PubMed

Larney, Sarah; Cama, Elena; Nelson, Elliot; Larance, Briony; Degenhardt, Louisa

2016-11-01

Involvement in the criminal justice system is common among opioid-dependent people. This study aimed to determine prevalence and adolescent-onset correlates of adult imprisonment among opioid-dependent men and women in New South Wales, Australia. Participants were recruited from opioid substitution therapy clinics and completed a face-to-face, structured interview. Data were collected on demographic characteristics, family history, substance dependence and psychiatric disorders. Adolescent-onset correlates of adult incarceration (including interactions with gender) were examined using logistic regression. Opioid-dependent men were significantly more likely than opioid-dependent women to report adult imprisonment (66% vs 40%; P < 0.001). In a multivariable logistic regression model, older age, male gender, having completed high school education only, having dependent children or living independently prior to age 18 years, a history of juvenile detention and adolescent-onset opioid dependence were all significantly associated with increased odds of adult imprisonment. Adolescent-onset depression was associated with a halving of odds of adult imprisonment. The only variable for which we observed an interaction with gender was juvenile detention, which had a significantly greater impact on the odds of imprisonment for men than women. More than half of this sample of opioid dependent adults had a history of imprisonment. Variables that are associated with imprisonment in the general population, such as childhood maltreatment, were not important in predicting imprisonment in this sample. Further study is required to understand the interaction between sex and juvenile detention in predicting adult imprisonment. [Larney S, Cama E, Nelson E, Larance B, Degenhardt L. A cross-sectional study of correlates of imprisonment in opioid-dependent men and women in New South Wales, Australia. Drug Alcohol Rev 2016;35:686-692]. © 2015 Australasian Professional Society on

Changes in Religious Coping and Relapse to Drug Use Among Opioid-Dependent Patients Following Inpatient Detoxification

PubMed Central

Skalski, Linda M.; Meade, Christina S.

2013-01-01

Relapse rates remain high among people with opioid dependence. Identifying psychosocial factors associated with outcomes is important for informing behavioral treatments. This study examined religious coping, opioid use, and 12-step participation among 45 participants receiving inpatient opioid detoxification at baseline and follow-up. At baseline, higher positive coping was related to less frequent opioid use pre-admission (β = −.44, p < .001) and history of 12-step participation (OR = 2.33, p < .05). Decreases in negative coping after discharge predicted less opioid use (β = .55, p < .001), and increases in positive coping predicted more frequent 12-step program participation (β = .42, p < .05). Positive religious coping may be protective, while negative religious coping may be a barrier to treatment. PMID:21125425

Analysis of opioid efficacy, tolerance, addiction and dependence from cell culture to human.

PubMed

Morgan, Michael M; Christie, MacDonald J

2011-10-01

Opioid agonists are the most effective treatment for pain, but their use is limited by side effects, tolerance and fears of addiction and dependence. A major goal of opioid research is to develop agonists that have high analgesic efficacy and a low profile for side effects, tolerance, addiction and dependence. Unfortunately, there is a serious lack of experimental data comparing the degree to which different opioids produce these effects in humans. In contrast, a wide range of experimental techniques from heterologous expression systems to behaviour assessment in whole animals have been developed to study these problems. The objective of this review is to describe and evaluate these techniques as they are used to study opioid efficacy, tolerance, addiction and dependence. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Inflammatory Pain Promotes Increased Opioid Self-Administration: Role of Dysregulated Ventral Tegmental Area μ Opioid Receptors

PubMed Central

Hipólito, Lucia; Wilson-Poe, Adrianne; Campos-Jurado, Yolanda; Zhong, Elaine; Gonzalez-Romero, Jose; Virag, Laszlo; Whittington, Robert; Comer, Sandra D.; Carlton, Susan M.; Walker, Brendan M.; Bruchas, Michael R.

2015-01-01

Pain management in opioid abusers engenders ethical and practical difficulties for clinicians, often resulting in pain mismanagement. Although chronic opioid administration may alter pain states, the presence of pain itself may alter the propensity to self-administer opioids, and previous history of drug abuse comorbid with chronic pain promotes higher rates of opioid misuse. Here, we tested the hypothesis that inflammatory pain leads to increased heroin self-administration resulting from altered mu opioid receptor (MOR) regulation of mesolimbic dopamine (DA) transmission. To this end, the complete Freund's adjuvant (CFA) model of inflammation was used to assess the neurochemical and functional changes induced by inflammatory pain on MOR-mediated mesolimbic DA transmission and on rat intravenous heroin self-administration under fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. In the presence of inflammatory pain, heroin intake under an FR schedule was increased for high, but attenuated for low, heroin doses with concomitant alterations in mesolimbic MOR function suggested by DA microdialysis. Consistent with the reduction in low dose FR heroin self-administration, inflammatory pain reduced motivation for a low dose of heroin, as measured by responding under a PR schedule of reinforcement, an effect dissociable from high heroin dose PR responding. Together, these results identify a connection between inflammatory pain and loss of MOR function in the mesolimbic dopaminergic pathway that increases intake of high doses of heroin. These findings suggest that pain-induced loss of MOR function in the mesolimbic pathway may promote opioid dose escalation and contribute to opioid abuse-associated phenotypes. SIGNIFICANCE STATEMENT This study provides critical new insights that show that inflammatory pain alters heroin intake through a desensitization of MORs located within the VTA. These findings expand our knowledge of the interactions between

Dependence to legally prescribed opioid analgesics in a university hospital in Medellin-Colombia: an observational study.

PubMed

Garcia-Orjuela, Maria G; Alarcon-Franco, Lineth; Sanchez-Fernandez, Juan C; Agudelo, Yuli; Zuluaga, Andres F

2016-09-14

In some countries the misuse and diversion of prescribed opioid analgesic is increasing considerably, but there is no official data regarding the situation in Colombia. The aim of this study was to identify all dependent to opioid analgesics legally prescribed patients that were treated in a University Hospital in Medellin, Colombia during 4 years and to characterize this population. Observational study in a University Hospital in Medellin, Colombia, searching for patients with ICD-10 codes related with opioid related disorders, adverse events or pain and treated between January 2011 and December 2014. Sixty patients with opioid dependence according to DSM-IV criteria were found from 3332 clinical charts reviewed. The median age was 43 years. Although all patients met the DSM-IV criteria, 33 % of patients were wrongly diagnosed by other ICD-10 codes. Almost all patient (88 %) initiated opioids after medical prescription although the adherence to pain scale was low (25 %). The median time of consumption was 48 months. Tramadol was the opioid more frequently used by patients, followed by morphine and oxycodone. A statistically significant higher consumption of other psychotropic substances was observed in male than female (P = 0.005 by Fisher's test). After be diagnosed, 55 % of patients gone a methadone-based replacement therapy. Legally prescribed opioid dependence was belatedly diagnosed in 60 patients in a University hospital, after prolonged use of drugs to treat chronic pain and with low adherence to pain scale or guidelines. This is the first report in Colombia.

Driving and legal status of Spanish opioid-dependent patients.

PubMed

Roncero, Carlos; Álvarez, F Javier; Barral, Carmen; Gómez-Baeza, Susana; Gonzalvo, Begoña; Rodríguez-Cintas, Laia; Brugal, M Teresa; Jacas, Carlos; Romaguera, Anna; Casas, Miguel

2013-06-03

Opioid dependent patients have legal problems, driving violations and accidents more frequently than the general population. We have hypothesized that those patients currently driving may have better legal outcomes than those who do not possess a valid driving license. With this aim we have analyzed the information gathered in the PROTEUS study regarding the legal and driving statuses and assessed the possible association between them. The PROTEUS study was an observational, cross-sectional, descriptive, multicenter nationwide representative study, conducted in Spanish healthcare centers for opioid dependent patients. The driving and legal statuses of a population of opioid dependent patients ≥ 18 years and enrolled in Opioid Agonist Therapy treatment centers in Spain, were assessed using a short specific questionnaire and the EuropASI questionnaire to highlight distinct individual clinical needs. 621 patients were evaluable (84% men, 24.5% active workers). 321 patients (52%) drove on a regular basis. Nineteen percent of patients had some problem with the criminal justice system. There was a significant difference (p = 0.0433) in status, according to the criminal justice system, between patients who drove on a regular basis and those who did not, with a higher percentage of patients with non-pending charges among usual drivers. Regular drivers showed fewer legal problems than non-regular drivers, with the exception of those related to driving (driving violations and drunk driving). Driving is a good prognostic factor for the social integration of the patients and policies should be implemented to enable these patients to drive safely under medical authorization. The legal description will be useful to assess treatment efficacy.

The Economic Burden of Prescription Opioid Overdose, Abuse, and Dependence in the United States, 2013.

PubMed

Florence, Curtis S; Zhou, Chao; Luo, Feijun; Xu, Likang

2016-10-01

It is important to understand the magnitude and distribution of the economic burden of prescription opioid overdose, abuse, and dependence to inform clinical practice, research, and other decision makers. Decision makers choosing approaches to address this epidemic need cost information to evaluate the cost effectiveness of their choices. To estimate the economic burden of prescription opioid overdose, abuse, and dependence from a societal perspective. Incidence of fatal prescription opioid overdose from the National Vital Statistics System, prevalence of abuse and dependence from the National Survey of Drug Use and Health. Fatal data are for the US population, nonfatal data are a nationally representative sample of the US civilian noninstitutionalized population ages 12 and older. Cost data are from various sources including health care claims data from the Truven Health MarketScan Research Databases, and cost of fatal cases from the WISQARS (Web-based Injury Statistics Query and Reporting System) cost module. Criminal justice costs were derived from the Justice Expenditure and Employment Extracts published by the Department of Justice. Estimates of lost productivity were based on a previously published study. Calendar year 2013. Monetized burden of fatal overdose and abuse and dependence of prescription opioids. The total economic burden is estimated to be $78.5 billion. Over one third of this amount is due to increased health care and substance abuse treatment costs ($28.9 billion). Approximately one quarter of the cost is borne by the public sector in health care, substance abuse treatment, and criminal justice costs. These estimates can assist decision makers in understanding the magnitude of adverse health outcomes associated with prescription opioid use such as overdose, abuse, and dependence.

Predictors of attrition with buprenorphine/naloxone treatment in opioid dependent youth.

PubMed

Warden, Diane; Subramaniam, Geetha A; Carmody, Thomas; Woody, George E; Minhajuddin, Abu; Poole, Sabrina A; Potter, Jennifer; Fishman, Marc; Bogenschutz, Michael; Patkar, Ashwin; Trivedi, Madhukar H

2012-09-01

In opioid dependent youth there is substantial attrition from medication-assisted treatment. If youth at risk for attrition can be identified at treatment entry or early in treatment, they can be targeted for interventions to help retain them in treatment. Opioid dependent adolescents and young adults (n=152), aged 15-21, were randomized to 12 weeks (BUP, n=74) or 2 weeks of detoxification (DETOX, n=78) with buprenorphine/naloxone (Bup/Nal), both in combination with 12 weeks of psychosocial treatment. Baseline and early treatment related predictors of treatment attrition were identified in each group using bivariate and multivariate logistic regression. In the DETOX group 36% left between weeks 2 and 4, at the end of the dose taper, while in the BUP group only 8% left by week 4. In the BUP group, early adherence to Bup/Nal, early opioid negative urines, use of any medications in the month prior to treatment entry, and lifetime non-heroin opioid use were associated with retention while prior 30-day hallucinogen use was associated with attrition. In the DETOX group, only use of sleep medications was associated with retention although not an independent predictor. A broad range of other pre-treatment characteristics was unrelated to attrition. Prompt attention to those with early non-adherence to medication or an early opioid positive urine, markers available in the first 2 weeks of treatment, may improve treatment retention. Extended Bup/Nal treatment appeared effective in improving treatment retention for youth with opioid dependence across a wide range of demographics, and pre-treatment clinical characteristics. Copyright © 2012 Elsevier Ltd. All rights reserved.

Predictors of attrition with buprenorphine/naloxone treatment in opioid dependent youth☆

PubMed Central

Warden, Diane; Subramaniam, Geetha A.; Carmody, Thomas; Woody, George E.; Minhajuddin, Abu; Poole, Sabrina A.; Potter, Jennifer; Fishman, Marc; Bogenschutz, Michael; Patkar, Ashwin; Trivedi, Madhukar H.

2012-01-01

Background In opioid dependent youth there is substantial attrition from medication-assisted treatment. If youth at risk for attrition can be identified at treatment entry or early in treatment, they can be targeted for interventions to help retain them in treatment. Methods Opioid dependent adolescents and young adults (n=152), aged 15–21, were randomized to 12 weeks (BUP, n=74) or 2 weeks of detoxification (DETOX, n=78) with buprenorphine/naloxone (Bup/Nal), both in combination with 12 weeks of psychosocial treatment. Baseline and early treatment related predictors of treatment attrition were identified in each group using bivariate and multivariate logistic regression. Results In the DETOX group 36% left between weeks 2 and 4, at the end of the dose taper, while in the BUP group only 8% left by week 4. In the BUP group, early adherence to Bup/Nal, early opioid negative urines, use of any medications in the month prior to treatment entry, and lifetime non-heroin opioid use were associated with retention while prior 30-day hallucinogen use was associated with attrition. In the DETOX group, only use of sleep medications was associated with retention although not an independent predictor. A broad range of other pre-treatment characteristics was unrelated to attrition. Conclusions Prompt attention to those with early non-adherence to medication or an early opioid positive urine, markers available in the first 2 weeks of treatment, may improve treatment retention. Extended Bup/ Nal treatment appeared effective in improving treatment retention for youth with opioid dependence across a wide range of demographics, and pre-treatment clinical characteristics. PMID:22626890

Neurobiological mechanisms involved in nicotine dependence and reward: participation of the endogenous opioid system

PubMed Central

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

2010-01-01

Nicotine is the primary component of tobacco that maintains the smoking habit and develops addiction. The adaptive changes of nicotinic acetylcholine receptors produced by repeated exposure to nicotine play a crucial role in the establishment of dependence. However, other neurochemical systems also participate in the addictive effects of nicotine including glutamate, cannabinoids, GABA and opioids. This review will cover the involvement of these neurotransmitters in nicotine addictive properties, with a special emphasis on the endogenous opioid system. Thus, endogenous enkephalins and beta-endorphins acting on mu-opioid receptors are involved in nicotine rewarding effects, whereas opioid peptides derived from prodynorphin participate in nicotine aversive responses. An upregulation of mu-opioid receptors has been reported after chronic nicotine treatment that could counteract the development of nicotine tolerance, whereas the downregulation induced on kappa-opioid receptors seems to facilitate nicotine tolerance. Endogenous enkephalins acting on mu-opioid receptors also play a role in the development of physical dependence to nicotine. In agreement with these actions of the endogenous opioid system, the opioid antagonist naltrexone has shown to be effective for smoking cessation in certain subpopulations of smokers. PMID:20170672

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

PubMed

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.

Development of dependence following treatment with opioid analgesics for pain relief: a systematic review.

PubMed

Minozzi, Silvia; Amato, Laura; Davoli, Marina

2013-04-01

To assess the incidence or prevalence of opioid dependence syndrome in adults (with and without previous history of substance abuse) following treatment with opioid analgesics for pain relief. Medline, Embase, CINHAL and the Cochrane Library were searched up to January 2011. Systematic reviews and primary studies were included if they reported data about incidence or prevalence of opioid dependence syndrome (as defined by DSM-IV or ICD-10) in patients receiving strong opioids (or opioid-type analgesics) for treatment of acute or chronic pain due to any physical condition. The data were abstracted, and the methodological quality was assessed using validated checklists. Data were extracted from 17 studies involving a total of 88 235 participants. The studies included three systematic reviews, one randomized controlled trial, eight cross-sectional studies and four uncontrolled case series. Most studies included adult patients with chronic non-malignant pain; two also included patients with cancer pain; only one included patients with a previous history of dependence. Incidence ranged from 0 to 24% (median 0.5%); prevalence ranged from 0 to 31% (median 4.5%). The available evidence suggests that opioid analgesics for chronic pain conditions are not associated with a major risk for developing dependence. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

Increases in Drug and Opioid-Involved Overdose Deaths - United States, 2010-2015.

PubMed

Rudd, Rose A; Seth, Puja; David, Felicita; Scholl, Lawrence

2016-12-30

The U.S. opioid epidemic is continuing, and drug overdose deaths nearly tripled during 1999-2014. Among 47,055 drug overdose deaths that occurred in 2014 in the United States, 28,647 (60.9%) involved an opioid (1). Illicit opioids are contributing to the increase in opioid overdose deaths (2,3). In an effort to target prevention strategies to address the rapidly changing epidemic, CDC examined overall drug overdose death rates during 2010-2015 and opioid overdose death rates during 2014-2015 by subcategories (natural/semisynthetic opioids, methadone, heroin, and synthetic opioids other than methadone).* Rates were stratified by demographics, region, and by 28 states with high quality reporting on death certificates of specific drugs involved in overdose deaths. During 2015, drug overdoses accounted for 52,404 U.S. deaths, including 33,091 (63.1%) that involved an opioid. There has been progress in preventing methadone deaths, and death rates declined by 9.1%. However, rates of deaths involving other opioids, specifically heroin and synthetic opioids other than methadone (likely driven primarily by illicitly manufactured fentanyl) (2,3), increased sharply overall and across many states. A multifaceted, collaborative public health and law enforcement approach is urgently needed. Response efforts include implementing the CDC Guideline for Prescribing Opioids for Chronic Pain (4), improving access to and use of prescription drug monitoring programs, enhancing naloxone distribution and other harm reduction approaches, increasing opioid use disorder treatment capacity, improving linkage into treatment, and supporting law enforcement strategies to reduce the illicit opioid supply.

Driving and legal status of Spanish opioid-dependent patients

PubMed Central

2013-01-01

Background Opioid dependent patients have legal problems, driving violations and accidents more frequently than the general population. We have hypothesized that those patients currently driving may have better legal outcomes than those who do not possess a valid driving license. With this aim we have analyzed the information gathered in the PROTEUS study regarding the legal and driving statuses and assessed the possible association between them. The PROTEUS study was an observational, cross-sectional, descriptive, multicenter nationwide representative study, conducted in Spanish healthcare centers for opioid dependent patients. Findings The driving and legal statuses of a population of opioid dependent patients ≥18 years and enrolled in Opioid Agonist Therapy treatment centers in Spain, were assessed using a short specific questionnaire and the EuropASI questionnaire to highlight distinct individual clinical needs. 621 patients were evaluable (84% men, 24.5% active workers). 321 patients (52%) drove on a regular basis. Nineteen percent of patients had some problem with the criminal justice system. There was a significant difference (p = 0.0433) in status, according to the criminal justice system, between patients who drove on a regular basis and those who did not, with a higher percentage of patients with non-pending charges among usual drivers. Conclusions Regular drivers showed fewer legal problems than non-regular drivers, with the exception of those related to driving (driving violations and drunk driving). Driving is a good prognostic factor for the social integration of the patients and policies should be implemented to enable these patients to drive safely under medical authorization. The legal description will be useful to assess treatment efficacy. PMID:23731546

Determinants of Fentanyl and other Potent μ Opioid Agonist Misuse in Opioid-Dependent Individuals

PubMed Central

Cicero, Theodore J.; Ellis, Matthew S.; Paradis, Alethea; Ortbal, Zachary

2010-01-01

Purpose Based on preclinical and clinical abuse liability assessments, fentanyl and other potent μ opioid agonists (e.g. hydromorphone and morphine) should be the most misused opioids if accessibility in the real world were not an issue. Since the latter is seldom true, we postulated that there would be a significant mismatch between actual and predicted rates of misuse. Methods We recruited 1,818 prescription-opioid dependent patients entering drug treatment programs to complete an anonymous survey, covering drug use and health related issues. Results Hydrocodone and oxycodone products were the drugs of choice in 75% of patients, whereas potent μ opioid agonists (fentanyl, hydromorphone and morphine), with the greatest predicted abuse potential, were very rarely chosen (<5% each). Most unexpectedly, the rank order of the actual drug of choice and the preferred drug in an ideal world were highly correlated. The reason most commonly given for the failure to endorse fentanyl, for example, as an actual or preferred drug, was fear of toxicity and overdose. We found few differences in drug use patterns between a subset of high-risk, impaired health care professionals (N=196) and all other patients other than source of drug, (forged prescriptions and doctors more common and dealers much less common in the HC sample). Conclusions These results indicate that it should not be assumed- particularly for new drug formulations- that a high potential for abuse will result in actual abuse; and, most importantly, that the hesitancy to use potent opioids because of fears of abuse may be misguided. PMID:20597128

Buprenorphine-naloxone buccal soluble film for the treatment of opioid dependence: current update.

PubMed

Soyka, Michael

2015-02-01

Opioid dependence is a severe medical disorder with a high psychiatric and somatic comorbidity and mortality rate. The opioid agonist methadone, mixed agonist-antagonist buprenorphine and the combination of buprenorphine with the opioid antagonist naloxone are the first-line maintenance treatments for opioid dependence. Risk of diversion and accidental intoxications, especially in children, are of great concern. To lower these risks, a novel buprenorphine-naloxone film has been developed and introduced in the USA and Australia. This review evaluates the available preclinical and clinical data on the novel buprenorphine-naloxone film for treatment of opioid dependence. Literature was identified through a comprehensive PubMed search. Data sources also included official FDA information and material made public by the manufacturer. Few preclinical and clinical data on safety and efficacy have been published. The pharmacological differences between the novel film and the conventional buprenorphine/naloxone are small. In an experimental study, the new formulation suppressed symptoms of opioid withdrawal. The spectrum of adverse events seems to be similar to that of the conventional sublingual tablet. Recent data show that patients prefer the novel film over the conventional sublingual tablet. Emerging surveillance data indicate a lower risk of accidental poisoning in children compared with the conventional formulation. Further clinical and preclinical data are needed to explore additional possible advantages of the new formulation.

Analysis of opioid efficacy, tolerance, addiction and dependence from cell culture to human

PubMed Central

Morgan, Michael M; Christie, MacDonald J

2011-01-01

Opioid agonists are the most effective treatment for pain, but their use is limited by side effects, tolerance and fears of addiction and dependence. A major goal of opioid research is to develop agonists that have high analgesic efficacy and a low profile for side effects, tolerance, addiction and dependence. Unfortunately, there is a serious lack of experimental data comparing the degree to which different opioids produce these effects in humans. In contrast, a wide range of experimental techniques from heterologous expression systems to behaviour assessment in whole animals have been developed to study these problems. The objective of this review is to describe and evaluate these techniques as they are used to study opioid efficacy, tolerance, addiction and dependence. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21434879

Utilizing buprenorphine–naloxone to treat illicit and prescription-opioid dependence

PubMed Central

Mauger, Sofie; Fraser, Ronald; Gill, Kathryn

2014-01-01

Objectives To review current evidence on buprenorphine–naloxone (bup/nx) for the treatment of opioid-use disorders, with a focus on strategies for clinical management and office-based patient care. Quality of evidence Medline and the Cochrane Database of Systematic Reviews were searched. Consensus reports, guidelines published, and other authoritative sources were also included in this review. Apart from expert guidelines, data included in this review constitute level 1 evidence. Findings Bup/nx is a partial μ-opioid agonist combined with the opioid antagonist naloxone in a 4:1 ratio. It has a lower abuse potential, carries less stigma, and allows for more flexibility than methadone. Bup/nx is indicated for both inpatient and ambulatory medically assisted withdrawal (acute detoxification) and long-term substitution treatment (maintenance) of patients who have a mild-to-moderate physical dependence. A stepwise long-term substitution treatment with regular monitoring and follow-up assessment is usually preferred, as it has better outcomes in reducing illicit opioid use, minimizing concomitant risks such as human immunodeficiency virus and hepatitis C transmission, retaining patients in treatment and improving global functioning. Conclusion Bup/nx is safe and effective for opioid detoxification and substitution treatment. Its unique pharmaceutical properties make it particularly suitable for office-based maintenance treatment of opioid-use disorder. PMID:24741316

Baclofen for maintenance treatment of opioid dependence: A randomized double-blind placebo-controlled clinical trial [ISRCTN32121581

PubMed Central

Assadi, Seyed Mohammad; Radgoodarzi, Reza; Ahmadi-Abhari, Seyed Ali

2003-01-01

Background Results of preclinical studies suggest that the GABAB receptor agonist baclofen may be useful in treatment of opioid dependence. This study was aimed at assessing the possible efficacy of baclofen for maintenance treatment of opioid dependence. Methods A total of 40 opioid-dependent patients were detoxified and randomly assigned to receive baclofen (60 mg/day) or placebo in a 12-week, double blind, parallel-group trial. Primary outcome measure was retention in treatment. Secondary outcome measures included opioids and alcohol use according to urinalysis and self-report ratings, intensity of opioid craving assessed with a visual analogue scale, opioid withdrawal symptoms as measured by the Short Opiate Withdrawal Scale and depression scores on the Hamilton inventory. Results Treatment retention was significantly higher in the baclofen group. Baclofen also showed a significant superiority over placebo in terms of opiate withdrawal syndrome and depressive symptoms. Non-significant, but generally favorable responses were seen in the baclofen group with other outcome measures including intensity of opioid craving and self-reported opioid and alcohol use. However, no significant difference was seen in the rates of opioid-positive urine tests. Additionally, the drug side effects of the two groups were not significantly different. Conclusion The results support further study of baclofen in the maintenance treatment of opioid dependence. PMID:14624703

A systematic review of health economic models of opioid agonist therapies in maintenance treatment of non-prescription opioid dependence.

PubMed

Chetty, Mersha; Kenworthy, James J; Langham, Sue; Walker, Andrew; Dunlop, William C N

2017-02-24

Opioid dependence is a chronic condition with substantial health, economic and social costs. The study objective was to conduct a systematic review of published health-economic models of opioid agonist therapy for non-prescription opioid dependence, to review the different modelling approaches identified, and to inform future modelling studies. Literature searches were conducted in March 2015 in eight electronic databases, supplemented by hand-searching reference lists and searches on six National Health Technology Assessment Agency websites. Studies were included if they: investigated populations that were dependent on non-prescription opioids and were receiving opioid agonist or maintenance therapy; compared any pharmacological maintenance intervention with any other maintenance regimen (including placebo or no treatment); and were health-economic models of any type. A total of 18 unique models were included. These used a range of modelling approaches, including Markov models (n = 4), decision tree with Monte Carlo simulations (n = 3), decision analysis (n = 3), dynamic transmission models (n = 3), decision tree (n = 1), cohort simulation (n = 1), Bayesian (n = 1), and Monte Carlo simulations (n = 2). Time horizons ranged from 6 months to lifetime. The most common evaluation was cost-utility analysis reporting cost per quality-adjusted life-year (n = 11), followed by cost-effectiveness analysis (n = 4), budget-impact analysis/cost comparison (n = 2) and cost-benefit analysis (n = 1). Most studies took the healthcare provider's perspective. Only a few models included some wider societal costs, such as productivity loss or costs of drug-related crime, disorder and antisocial behaviour. Costs to individuals and impacts on family and social networks were not included in any model. A relatively small number of studies of varying quality were found. Strengths and weaknesses relating to model structure, inputs and approach were identified across

Ondansetron does not prevent physical dependence in patients taking opioid medications chronically for pain control.

PubMed

Chu, Larry F; Rico, Tom; Cornell, Erika; Obasi, Hannah; Encisco, Ellen M; Vertelney, Haley; Gamble, Jamison G; Crawford, Clayton W; Sun, John; Clemenson, Anna; Erlendson, Matthew J; Okada, Robin; Carroll, Ian; Clark, J David

2018-02-01

In this study, we investigated the co-administration of ondansetron with morphine, and whether it could prevent the development of physical dependence in patients taking opioids for the treatment of chronic pain. A total of 48 chronic back pain patients (N = 48) participated in this double-blinded, placebo-controlled, randomized study. Patients were titrated onto sustained-release oral morphine and randomized to take 8 mg ondansetron or placebo three times daily concurrently with morphine during the 30-day titration. Following titration, patients underwent Naloxone induced opioid withdrawal. Opioid withdrawal signs and symptoms were then assessed by a blinded research assistant (objective opioid withdrawal score: OOWS) and by the research participant (subjective opioid withdrawal score: SOWS). We observed clinically significant signs of naloxone-precipitated opioid withdrawal in all participants (ΔOOWS = 4.3 ± 2.4, p < 0.0001; ΔSOWS = 14.1 ± 11.7, p < 0.0001), however no significant differences in withdrawal scores were detected between treatment groups. We hypothesized that ondansetron would prevent the development of physical dependence in human subjects when co-administered with opioids, but found no difference in naloxone-precipitated opioid withdrawal scores between ondansetron and placebo treatment groups. These results suggest that further studies are needed to determine if 5HT 3 receptor antagonists are useful in preventing opioid physical dependence. Copyright © 2017 Elsevier B.V. All rights reserved.

Recent Increases in Cocaine-Related Overdose Deaths and the Role of Opioids.

PubMed

McCall Jones, Christopher; Baldwin, Grant T; Compton, Wilson M

2017-03-01

To assess trends in cocaine overdose deaths and examine the role opioids play in these deaths. We used data on drug overdose deaths in the United States from 2000 to 2015 collected in the National Vital Statistics System to calculate annual rates and numbers of cocaine-related overdose deaths overall and deaths both involving and not involving opioids. We assessed statistically significant changes in trends with joinpoint regression. Rates of cocaine-related overdose deaths increased significantly from 1.26 to 2.50 per 100 000 population from 2000 to 2006, declined to 1.35 in 2010, and increased to 2.13 in 2015. Cocaine-related overdose deaths involving opioids increased from 0.37 to 0.91 from 2000 to 2006, declined to 0.57 in 2010, and then increased to 1.36 in 2015. Cocaine-related overdose deaths not involving opioids increased from 0.89 to 1.59 from 2000 to 2006 and then declined to 0.78 in 2015. Opioids, primarily heroin and synthetic opioids, have been driving the recent increase in cocaine-related overdose deaths. This corresponds to the growing supply and use of heroin and illicitly manufactured fentanyl in the United States.

Systematic review of prospective studies investigating "remission" from amphetamine, cannabis, cocaine or opioid dependence.

PubMed

Calabria, Bianca; Degenhardt, Louisa; Briegleb, Christina; Vos, Theo; Hall, Wayne; Lynskey, Michael; Callaghan, Bridget; Rana, Umer; McLaren, Jennifer

2010-08-01

To review and summarize existing prospective studies reporting on remission from dependence upon amphetamines, cannabis, cocaine or opioids. Systematic searches of the peer-reviewed literature were conducted to identify prospective studies reporting on remission from amphetamines, cannabis, cocaine or opioid dependence. Searches were limited to publication between 1990 and 2009. Reference lists of review articles and important studies were searched to identify additional studies. Remission was defined as no longer meeting diagnostic criteria for drug dependence or abstinence from drug use; follow-up periods of at least three years were investigated. The remission rate was estimated for each drug type, allowing pooling across studies with varying follow-up times. There were few studies examining the course of psychostimulant dependence that met inclusion criteria (one for amphetamines and four for cocaine). There were ten studies of opioid and three for cannabis dependence. Definitions of remission varied and most did not clearly assess remission from dependence. Amphetamine dependence had the highest remission rate (0.4477; 95%CI 0.3991, 0.4945), followed by opioid (0.2235; 95%CI 0.2091, 0.2408) and cocaine dependence (0.1366; 95%CI 0.1244, 0.1498). Conservative estimates of remission rates followed the same pattern with cannabis dependence (0.1734; 95%CI 0.1430, 0.2078) followed by amphetamine (0.1637; 95%CI 0.1475, 0.1797), opioid (0.0917; 95%CI 0.0842, 0.0979) and cocaine dependence (0.0532; 95%CI 0.0502, 0.0597). The limited prospective evidence suggests that "remission" from dependence may occur relatively frequently but rates may differ across drugs. There is very little research on remission from drug dependence; definitions used are often imprecise and inconsistent across studies and there remains considerable uncertainty about the longitudinal course of dependence upon these most commonly used illicit drugs. Copyright 2010 Elsevier Ltd. All rights reserved.

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

PubMed

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.

Creating a Community of Support for Children and Families Affected by Opioid Dependence: Identifying and Addressing Gaps in Maternal-Fetal Care

ERIC Educational Resources Information Center

Fragassi, Philip A.; Bora, Geetanjali

2018-01-01

The last decade has seen an exponential increase in the use of illicit and prescription opioids during pregnancy. Opioid dependency during pregnancy increases the risks of obstetric complications for mothers and potential dangers for newborns during infancy and later in life. The mother-child dyad faces specific hurdles when it comes to getting…

Impact of treatment for opioid dependence on fatal drug‐related poisoning: a national cohort study in England

PubMed Central

Pierce, Matthias; Bird, Sheila M.; Hickman, Matthew; Marsden, John; Dunn, Graham; Jones, Andrew

2015-01-01

Abstract Aims To compare the change in illicit opioid users’ risk of fatal drug‐related poisoning (DRP) associated with opioid agonist pharmacotherapy (OAP) and psychological support, and investigate the modifying effect of patient characteristics, criminal justice system (CJS) referral and treatment completion. Design National data linkage cohort study of the English National Drug Treatment Monitoring System and the Office for National Statistics national mortality database. Data were analysed using survival methods. Setting All services in England that provide publicly funded, structured treatment for illicit opioid users. Participants Adults treated for opioid dependence during April 2005 to March 2009: 151 983 individuals; 69% male; median age 32.6 with 442 950 person‐years of observation. Measurements The outcome was fatal DRP occurring during periods in or out of treatment, with adjustment for age, gender, substances used, injecting status and CJS referral. Findings There were 1499 DRP deaths [3.4 per 1000 person‐years, 95% confidence interval (CI) = 3.2–3.6]. DRP risk increased while patients were not enrolled in any treatment [adjusted hazard ratio (aHR) = 1.73, 95% CI = 1.55–1.92]. Risk when enrolled only in a psychological intervention was double that during OAP (aHR = 2.07, 95% CI = 1.75–2.46). The increased risk when out of treatment was greater for men (aHR = 1.88, 95% CI = 1.67–2.12), illicit drug injectors (aHR = 2.27, 95% CI = 1.97–2.62) and those reporting problematic alcohol use (aHR = 2.37, 95% CI = 1.90–2.98). Conclusions Patients who received only psychological support for opioid dependence in England appear to be at greater risk of fatal opioid poisoning than those who received opioid agonist pharmacotherapy. PMID:26452239

Impact of treatment for opioid dependence on fatal drug-related poisoning: a national cohort study in England.

PubMed

Pierce, Matthias; Bird, Sheila M; Hickman, Matthew; Marsden, John; Dunn, Graham; Jones, Andrew; Millar, Tim

2016-02-01

To compare the change in illicit opioid users' risk of fatal drug-related poisoning (DRP) associated with opioid agonist pharmacotherapy (OAP) and psychological support, and investigate the modifying effect of patient characteristics, criminal justice system (CJS) referral and treatment completion. National data linkage cohort study of the English National Drug Treatment Monitoring System and the Office for National Statistics national mortality database. Data were analysed using survival methods. All services in England that provide publicly funded, structured treatment for illicit opioid users. Adults treated for opioid dependence during April 2005 to March 2009: 151,983 individuals; 69% male; median age 32.6 with 442,950 person-years of observation. The outcome was fatal DRP occurring during periods in or out of treatment, with adjustment for age, gender, substances used, injecting status and CJS referral. There were 1499 DRP deaths [3.4 per 1000 person-years, 95% confidence interval (CI) = 3.2-3.6]. DRP risk increased while patients were not enrolled in any treatment [adjusted hazard ratio (aHR) = 1.73, 95% CI = 1.55-1.92]. Risk when enrolled only in a psychological intervention was double that during OAP (aHR = 2.07, 95% CI = 1.75-2.46). The increased risk when out of treatment was greater for men (aHR = 1.88, 95% CI = 1.67-2.12), illicit drug injectors (aHR = 2.27, 95% CI = 1.97-2.62) and those reporting problematic alcohol use (aHR = 2.37, 95% CI = 1.90-2.98). Patients who received only psychological support for opioid dependence in England appear to be at greater risk of fatal opioid poisoning than those who received opioid agonist pharmacotherapy. © 2015 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Increasing pregnancy-related use of prescribed opioid analgesics

PubMed Central

Epstein, Richard A.; Bobo, William V.; Martin, Peter R.; Morrow, James A.; Wang, Wei; Chandrasekhar, Rameela; Cooper, William O.

2013-01-01

Purpose To quantify the prevalence of prescribed opioid analgesics among pregnant women enrolled in Tennessee Medicaid from 1995 to 2009. Methods Retrospective cohort study of 277,555 pregnancies identified from birth and fetal death certificates, and linked to previously-validated computerized pharmacy records. Poisson regression was used to estimate trends over time, rate ratios and 95% confidence intervals. Results During the study period, 29% of pregnant women filled a prescription for an opioid analgesic. From 1995 to 2009, any pregnancy-related use increased 1.90-fold (95% CI = 1.83, 1.98), first trimester use increased 2.27-fold (95% CI = 2.14, 2.41), and second or third trimester use increased 2.02-fold (95% CI = 1.93, 2.12), after adjusting for maternal characteristics. Any pregnancy-related, first trimester, and second or third trimester use were each more likely among mothers who were at least 21 years old, white, non-Hispanic, prima gravid, resided in non-urban areas, enrolled in Medicaid due to disability, and who had less than a high school education. Conclusions Opioid analgesic use by Tennessee Medicaid-insured pregnant women increased nearly 2-fold from 1995 to 2009. Additional study is warranted in order to understand the implications of this increased use. PMID:23889859

Use and dependence on opioid drugs in the Spanish population with chronic pain: Prevalence and differences according to sex.

PubMed

Coloma-Carmona, A; Carballo, J L; Rodríguez-Marín, J; Pérez-Carbonell, A

To analyse the prevalence in the use and dependence on opioid drugs in the Spanish population with chronic pain and evaluate the differences according to sex. The demographic variables, opioid treatment characteristics and use of other substances were assessed in 229 users of opioid drugs. A descriptive bivariate analysis of the data was performed. Forty-six percent of the patients met the criteria of dependence on opioid drugs (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition [DSM-IV-TR]). Alcohol and cannabis consumption was greater in the men. The rates of dependence on the use of opioid drugs were significantly higher in the extended treatments. Planning for treatments with opioids and strategies for preventing inappropriate use should not depend on the patient's sex. We need further studies on the medical and psychological variables related to the use of and dependence on opioids. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Introduction to the College on Problems of Drug Dependence special issue: contemporary advances in opioid neuropharmacology.

PubMed

Walsh, Sharon L; Unterwald, Ellen M; Izenwasser, Sari

2010-05-01

Opioid receptors are critical therapeutic targets for medications development relevant to the treatment of drug dependence and pain. With recent advances in molecular neurobiology, it has become evident that the functional activity of opioid receptors, as ligand-regulated protein complexes, is modulated by multifarious intracellular and extracellular events, that there is genetic variation in coding for receptors, and that the activity of endogenous opioid systems may underlie actions common to other addictive disorders. This supplemental issue of Drug and Alcohol Dependence, arising from an invited symposium at the 71st Annual Meeting of the College on Problems of Drug Dependence, provides a series of contemporary reviews focused on recent advances in opioid neuropharmacology. Each speaker provides herein an invited comprehensive review of the state of knowledge on a specific topic in opioid neuropharmacology. Evans and colleagues describe the multi-faceted control of the opioid G-protein coupled receptor as a dynamic "sensor" complex and identify novel targets for drug development. von Zastrow focuses on opioid receptor-mediated events regulated by endocytosis and membrane trafficking through the endocytic pathway and differential responses to opioid agonists. Blendy and colleague provide a review of human association studies on the functional relevance of the mu opioid receptor variant, A118G, and presents data from the A112G knock-in model, an analogous mouse variant to A118G. Finally, Maldonado and colleagues provide a broader systems review from genetic, pharmacologic and behavioral studies implicating the endogenous opioid systems as a substrate for the mediation of substance use disorders spanning pharmacological classes.

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

PubMed

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

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

PubMed

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.

Failure to identify or effectively manage prescription opioid dependence acted as a gateway to heroin use-buprenorphine/naloxone treatment and recovery in a surgical patient.

PubMed

Conroy, Stephen; Hill, Duncan

2014-12-17

The prescribing of opioid pain medication has increased markedly in recent years, with strong opioid dispensing increasing 18-fold in Tayside, Scotland since 1995. Despite this, little data is available to quantify the problem of opioid pain medication dependence (OPD) and until recently there was little guidance on best-practice treatment. We report the case of a young mother prescribed dihydrocodeine for postoperative pain relief who became opioid dependent. When her prescription was stopped without support, she briefly used heroin to overcome her withdrawal. After re-exposure to dihydrocodeine following surgery 9 years later and treatment with methadone for dependency, she was transferred to buprenorphine/naloxone. In our clinical experience and in agreement with Department of Health and Royal College of General Practitioner guidance, buprenorphine/naloxone is the preferred opioid substitution treatment for OPD. Our patient remains within her treatment programme and has returned to work on buprenorphine 16 mg/naloxone 4 mg in conjunction with social and psychological support. 2014 BMJ Publishing Group Ltd.

Intraoperative ketamine reduces immediate postoperative opioid consumption after spinal fusion surgery in chronic pain patients with opioid dependency: a randomized, blinded trial.

PubMed

Nielsen, Rikke Vibeke; Fomsgaard, Jonna Storm; Siegel, Hanna; Martusevicius, Robertas; Nikolajsen, Lone; Dahl, Jørgen Berg; Mathiesen, Ole

2017-03-01

Perioperative handling of surgical patients with opioid dependency represents an important clinical problem. Animal studies suggest that ketamine attenuates central sensitization and hyperalgesia and thereby reduces postoperative opioid tolerance. We hypothesized that intraoperative ketamine would reduce immediate postoperative opioid consumption compared with placebo in chronic pain patients with opioid dependency undergoing lumbar spinal fusion surgery. Primary outcome was morphine consumption 0 to 24 hours postoperatively. Secondary outcomes were acute pain at rest and during mobilization 2 to 24 hours postoperatively (visual analogue scale), adverse events, and persistent pain 6 months postoperatively. One hundred fifty patients were randomly assigned to intraoperative S-ketamine bolus 0.5 mg/kg and infusion 0.25 mg·kg·h or placebo. Postoperatively, patients received their usual opioids, paracetamol and IV patient-controlled analgesia with morphine. In the final analyses, 147 patients were included. Patient-controlled analgesia IV morphine consumption 0 to 24 hours postoperatively was significantly reduced in the ketamine group compared with the placebo group: 79 (47) vs 121 (53) mg IV, mean difference 42 mg (95% confidence interval -59 to -25), P < 0.001. Sedation was significantly reduced in the ketamine group 6 and 24 hours postoperatively. There were no significant differences regarding acute pain, nausea, vomiting, hallucinations, or nightmares. Back pain at 6 months postoperatively compared with preoperative pain was significantly more improved in the ketamine group compared with the placebo group, P = 0.005. In conclusion, intraoperative ketamine significantly reduced morphine consumption 0 to 24 hours after lumbar fusion surgery in opioid-dependent patients. The trend regarding less persistent pain 6 months postoperatively needs further investigation.

Predictors of transition to heroin use among initially non-opioid dependent illicit pharmaceutical opioid users: A natural history study

PubMed Central

Carlson, Robert G.; Nahhas, Ramzi W.; Martins, Silvia S.; Daniulaityte, Raminta

2016-01-01

Background Increases in illicit pharmaceutical opioid (PO) use have been associated with risk for transition to heroin use. We identify predictors of transition to heroin use among young, illicit PO users with no history of opioid dependence or heroin use at baseline. Methods Respondent-driven sampling recruited 383 participants; 362 returned for at least one biannual structured interview over 36 months. Cox regression was used to test for associations between lagged predictors and hazard of transition to heroin use. Potential predictors were based on those suggested in the literature. We also computed population attributable risk (PAR) and the rate of heroin transition. Results Over 36 months, 27 (7.5%) participants initiated heroin use; all were white, and the rate of heroin initiation was 2.8% per year (95% CI=1.9%–4.1%). Mean length of PO at first reported heroin use was 6.2 years (SD=1.9). Lifetime PO dependence (AHR=2.39, 95% CI= 1.07–5.48; PAR=32%, 95% CI=−2%–64%), early age of PO initiation (AHR=3.08, 95%; CI= 1.26–7.47; PAR=30%, 95% CI=2%–59%), using illicit POs to get high but not to self-medicate a health problem (AHR=4.83, 95% CI= 2.11–11.0; PAR=38%, 95% CI=12%–65%), and ever using PO non-orally most often (AHR=6.57, 95% CI=2.81–17.2; PAR=63%, 95% CI=31%–86%) were significant predictors. Conclusion This is one of the first prospective studies to test observations from previous cross-sectional and retrospective research on the relationship between illicit PO use and heroin initiation among young, initially non-opioid dependent PO users. The results provide insights into targets for the design of urgently needed prevention interventions. PMID:26785634

Activation of Peripheral κ-Opioid Receptors Normalizes Caffeine Effects Modified in Nicotine-Dependent Rats during Nicotine Withdrawal.

PubMed

Sudakov, S K; Bogdanova, N G

2016-10-01

The study examined the effect of peripheral (intragastric) ICI-204,448, an agonist of gastric κ-opioid receptors, on the psychostimulating and anxiolytic effects of caffeine in nicotinedependent rats at the stage of nicotine withdrawal. In these rats, the effects of caffeine (10 mg/kg) were perverted. In nicotine-dependent rats, caffeine produced an anxiolytic effect accompanied by pronounced stimulation of motor activity, in contrast to anxiogenic effect induced by caffeine in intact rats without nicotine dependence. During nicotine withdrawal, nicotine-dependent rats demonstrated enhanced sensitivity to nicotine. Intragastric administration of κ-opioid receptor agonist ICI-204,448 normalized the effect of caffeine in nicotinedependent rats. We have previously demonstrated that activation of peripheral κ-opioid receptors inhibited central κ-opioid activity and eliminated manifestations of nicotine withdrawal syndrome in nicotine-dependent rats, e.g. metabolism activation, stimulation of motor activity, and enhancement of food consumption. In its turn, inhibition of central κ-opioid structures activates the brain adenosine system, which can attenuate the caffeine-induced effects in nicotine-dependent rats.

Use of Pharmacotherapies in the Treatment of Alcohol Use Disorders and Opioid Dependence in Primary Care

PubMed Central

Lee, Jinhee; Kresina, Thomas F.; Campopiano, Melinda; Lubran, Robert; Clark, H. Westley

2015-01-01

Substance-related and addictive disorders are chronic relapsing conditions that substantially impact public health. Effective treatments for these disorders require addressing substance use/dependence comprehensively as well as other associated comorbidities. Comprehensive addressing of substance use in a medical setting involves screening for substance use, addressing substance use directly with the patient, and formulating an appropriate intervention. For alcohol dependence and opioid dependence, pharmacotherapies are available that are safe and effective when utilized in a comprehensive treatment paradigm, such as medication assisted treatment. In primary care, substance use disorders involving alcohol, illicit opioids, and prescription opioid abuse are common among patients who seek primary care services. Primary care providers report low levels of preparedness and confidence in identifying substance-related and addictive disorders and providing appropriate care and treatment. However, new models of service delivery in primary care for individuals with substance-related and addictive disorders are being developed to promote screening, care and treatment, and relapse prevention. The education and training of primary care providers utilizing approved medications for the treatment of alcohol use disorders and opioid dependence in a primary care setting would have important public health impact and reduce the burden of alcohol abuse and opioid dependence. PMID:25629034

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

PubMed

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 < 0.05 for both). PDMPs may be helpful in identifying patients with certain aberrant drug-related behavior, but are unable to detect many patients with opioid use disorder. The majority of ED patients with opioid use disorder were not captured by the PDMP, highlighting the importance of using additional methods such as screening and clinical history to identify opioid use disorders in ED patients and the

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

PubMed

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.

Prescription opioid abuse, pain and addiction: Clinical issues and implications

PubMed Central

LING, WALTER; MOONEY, LARISSA; HILLHOUSE, MAUREEN

2014-01-01

Issues 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. Approach 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. Implications Physicians should strive to find a reasonable balance between minimising potential adverse effects of opioid medications without diminishing legitimate access to opioids for analgesia. Conclusions 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. PMID:21545561

Presence or Absence of QTc Prolongation in Buprenorphine-Naloxone Among Youth With Opioid Dependence.

PubMed

Poole, Sabrina A; Pecoraro, Anna; Subramaniam, Geetha; Woody, George; Vetter, Victoria L

2016-01-01

The aim of the study was to evaluate buprenorphine-naloxone effects on the QTc in youth with opioid dependence. Buprenorphine is a partial agonist that is an effective treatment for opioid dependence. Compared with methadone, it has a lower risk of QTc prolongation in adults, but is less studied in the youth. It may also reduce the risk of torsades de pointes (TdP)--an uncommon variant of polymorphic ventricular tachycardia--that can result in syncope, ventricular fibrillation, and sudden death. Secondary analysis of the electrocardiogram data from 95 individuals who participated in a multisite trial for youth with opioid dependence. The participants were randomized to a 2-week (DETOX) or a 12-week course of buprenorphine-naloxone (BUP). At baseline, 12-lead electrocardiograms were done at weeks 4 and 12, and QTc intervals were hand-measured and calculated using Bazett formula. Increases above 60 milliseconds were considered clinically significant, and readings above 450 milliseconds (in men) and 470 milliseconds (in women) indicated a prolonged QTc. Mean QTc intervals were higher for BUP than for DETOX participants at baseline, week 4, and week 12 (P = 0.045), and women had longer mean QTc intervals than men (P < 0.0005). Variations in the QTc intervals were observed in some; however, none were above 500 milliseconds--the level at which risk for TdP becomes more significant. In this randomized trial, the mean QTc at baseline, before randomization, was higher in BUP than in DETOX patients. Minimal changes in the QTc were seen at 4 and 12 weeks in a few patients in both groups. There was no evidence that buprenorphine-naloxone alone increased the QTc to a level that increased the risk for TdP.

Sex work involvement among women with long-term opioid injection drug dependence who enter opioid agonist treatment.

PubMed

Marchand, Kirsten; Oviedo-Joekes, Eugenia; Guh, Daphne; Marsh, David C; Brissette, Suzanne; Schechter, Martin T

2012-01-25

Substitution with opioid-agonists (e.g., methadone) has shown to be an effective treatment for chronic long-term opioid dependency. Survival sex work, very common among injection drug users, has been associated with poor Opioid Agonist Treatment (OAT) engagement, retention and response. Therefore, this study was undertaken to determine factors associated with engaging in sex work among long-term opioid dependent women receiving OAT. Data from a randomized controlled trial, the North American Opiate Medication Initiative (NAOMI), conducted in Vancouver and Montreal (Canada) between 2005-2008, was analyzed. The NAOMI study compared the effectiveness of oral methadone to injectable diacetylmorphine or injectable hydromorphone, the last two on a double blind basis, over 12 months. A research team, independent of the clinic services, obtained outcome evaluations at baseline and follow-up (3, 6, 9, 12, 18 and 24 months). A total 53.6% of women reported engaging in sex work in at least one of the research visits. At treatment initiation, women who were younger and had fewer years of education were more likely to be engaged in sex work. The multivariate logistic generalized estimating equation regression analysis determined that psychological symptoms, and high illicit heroin and cocaine use correlated with women's involvement in sex work during the study period. After entering OAT, women using injection drugs and engaging in sex work represent a particularly vulnerable group showing poorer psychological health and a higher use of heroin and cocaine compared to women not engaging in sex work. These factors must be taken into consideration in the planning and provision of OAT in order to improve treatment outcomes. NCT00175357.

Catastrophic thinking and increased risk for prescription opioid misuse in patients with chronic pain

PubMed Central

Martel, MO; Wasan, AD; Jamison, RN; Edwards, RR

2013-01-01

Background As a consequence of the substantial rise in the prescription of opioids for the treatment of chronic noncancer pain, greater attention has been paid to the factors that may be associated with an increased risk for prescription opioid misuse. Recently, a growing number of studies have shown that patients with high levels of catastrophizing are at increased risk for prescription opioid misuse. Objective The primary objective of this study was to examine the variables that might underlie the association between catastrophizing and risk for prescription opioid misuse in patients with chronic pain. Methods Patients with chronic musculoskeletal pain (n = 115) were asked to complete the SOAPP-R, a validated self-report questionnaire designed to identify patients at risk for prescription opioid misuse. Patients were also asked to complete self-report measures of pain intensity, catastrophizing, anxiety, and depression. Results Consistent with previous research, we found that catastrophizing was associated with an increased risk for prescription opioid misuse. Results also revealed that the association between catastrophizing and risk for opioid misuse was partially mediated by patients’ levels of anxiety. Follow-up analyses, however, indicated that catastrophizing remained a significant ‘unique’ predictor of risk for opioid misuse even when controlling for patients’ levels of pain severity, anxiety and depressive symptoms. Discussion Discussion addresses the factors that might place patients with high levels of catastrophizing at increased risk for prescription opioid misuse. The implications of our findings for the management of patients considered for opioid therapy are also discussed. PMID:23618767

Opioid-receptor subtype agonist-induced enhancements of sucrose intake are dependent upon sucrose concentration.

PubMed

Ruegg, H; Yu, W Z; Bodnar, R J

1997-07-01

Selective mu ([D-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin (DAMGO)), delta1 ([D-Pen2, D-Pen5]-enkephalin (DPDPE)), delta2 ([D-Ala2, Glu4]-Deltorphin (Delt II)), kappa1 (U50488H) and kappa3 (naloxone benzoylhydrazone (NalBzOH)) opioid agonists each stimulate food intake in rats. Whereas studies with selective opioid antagonists implicate mu and kappa1 receptors in the mediation of sucrose intake, studies with selective opioid agonists implicate mu and delta receptors in the mediation of saccharin intake. The present study determined if specific delta1, delta2, kappa1, kappa3 and mu opioid-receptor subtype agonists produced similar alterations in sucrose intake as a function of sucrose concentration (0.5%, 2.5%, 10%) across a 1-h time-course. Each of these agonists significantly increased sucrose intake with variations in pattern, magnitude, and consistency as a function of sucrose concentration. Whereas the mu opioid agonist, DAMGO, and the delta1 opioid agonist, DPDPE, each enhanced sucrose intake at higher (2.5%, 10%), but not lower (0.5%), concentrations, the delta2 opioid agonist, Delt II, increased sucrose intake at lower (0.5%, 2.5%), but not higher (10%), concentrations. Kappa opioid agonists produced less consistent effects. The kappa1 opioid agonist, U50488H, increased sucrose intake at high (10%) concentrations and decreased sucrose intake at low (0.5%) concentrations, and the kappa3 opioid agonist, NalBzOH, inconsistently increased sucrose intake at the 0.5% (20 microg) and 10% (1 microg) concentrations. Thus, these data further implicate mu, delta1, and delta2 opioid mediation of palatable intake, particularly of its orosensory characteristics.

The Presence or Absence of QTc Prolongation in Buprenorphine-Naloxone Among Youth with Opioid Dependence

PubMed Central

Poole, Sabrina A.; Pecoraro, Anna; Subramaniam, Geetha; Woody, George; Vetter, Victoria L

2015-01-01

Objective To evaluate buprenorphine-naloxone effects on the QTc in youth with opioid dependence. Buprenorphine is a partial agonist that is an effective treatment for opioid dependence. Compared to methadone it has a lower risk of QTc prolongation in adults but is less well studied in youth. It may also reduce the risk for torsades de pointes (TdP) an uncommon variant of polymorphic ventricular tachycardia, that can result in syncope, ventricular fibrillation, and sudden death. Methods Secondary analysis of ECG data from 95 subjects who participated in a multi-site trial for youth with opioid dependence. Subjects were randomized to a 2-week (DETOX), or a 12-week course of buprenorphine-naloxone (BUP). 12-lead ECGs were done at baseline, weeks 4 and 12, and QTc intervals were hand measured and calculated using Bazett's formula. Increases > 60 milliseconds (ms) were considered clinically significant, and readings > 450 ms (males) and 470 ms (females) indicated a prolonged QTc. Results Mean QTc intervals were higher for BUP than DETOX participants at baseline, week 4, and week 12 (p = 0.045), and females had longer mean QTc intervals than males (p < 0.0005). Variations in QTc intervals were observed in some, however none were above 500 ms, the level at which risk for TdP becomes more significant. Conclusion In this randomized trial, the mean QTc at baseline, before randomization, was higher in BUP than DETOX patients. Minimal changes in the QTc were seen at 4 and 12-weeks in a few patients in both groups. There was no evidence that buprenorphine-naloxone alone increased the QTc to a level that increased the risk for TdP. PMID:26690291

Injectable, sustained-release naltrexone for the treatment of opioid dependence: a randomized, placebo-controlled trial

PubMed Central

Comer, Sandra D.; Sullivan, Maria A.; Yu, Elmer; Rothenberg, Jami L.; Kleber, Herbert D.; Kampman, Kyle; Dackis, Charles; O'Brien, Charles P.; Chiang, C. Nora; Hawks, Richard L.

2013-01-01

recalculated without the assumption that missing urine samples were positive, however, a main effect of group was not found for any of the drugs tested with the exception of cocaine, where the percentage of cocaine-negative urines was lower in the placebo group. Adverse events were minimal and generally mild in severity. This sustained-release formulation of naltrexone was well tolerated and produced a robust and dose-related increase in treatment retention. Conclusion The present data provide exciting new evidence for the feasibility, efficacy, and tolerability of long-lasting antagonist treatments for opioid dependence. PMID:16461865

Long term outcomes of pharmacological treatments for opioid dependence: does methadone still lead the pack?

PubMed Central

Garcia-Portilla, Maria Paz; Bobes-Bascaran, Maria Teresa; Bascaran, Maria Teresa; Saiz, Pilar Alejandra; Bobes, Julio

2014-01-01

The aim of this review was to update and summarize the scientific knowledge on the long term outcomes of the different pharmacological treatment options for opioid dependence currently available and to provide a critical discussion on the different treatment options based on these results. We performed a literature search using the PubMed databases and the reference lists of the identified articles. Data from research show that the three pharmacological options reviewed are effective treatments for opioid dependence with positive long term outcomes. However, each one has its specific target population and setting. While methadone and buprenorphine are first line options, heroin-assisted treatment is a second line option for those patients refractory to treatment with methadone with concomitant severe physical, mental, social and/or functional problems. Buprenorphine seems to be the best option for use in primary care offices. The field of opioid dependence treatment is poised to undergo a process of reinforcement and transformation. Further efforts from researchers, clinicians and authorities should be made to turn new pharmacological options into clinical reality and to overcome the structural and functional obstacles that maintenance programmes face in combatting opioid dependence. PMID:23145768

Child maltreatment as a risk factor for opioid dependence: Comparison of family characteristics and type and severity of child maltreatment with a matched control group.

PubMed

Conroy, Elizabeth; Degenhardt, Louisa; Mattick, Richard P; Nelson, Elliot C

2009-06-01

To examine the prevalence, characteristics and risk factors for child maltreatment among opioid-dependent persons compared to a community sample of similar social disadvantage. The study employed a case-control design. Cases had a history of opioid pharmacotherapy. Controls were frequency matched to cases with regard to age, sex and unemployment and were restricted to those with a lifetime opioid use of less than five times. The interview covered child maltreatment, family environment, drug use and psychiatric history. This study found a high prevalence of child maltreatment among both cases and controls. Despite the elevated prevalence among controls, opioid-dependent males had a higher prevalence of physical and emotional abuse; female cases had a higher prevalence and greater severity of sexual abuse. The prevalence of neglect was similar for both groups. Early parental separation was more prevalent among female cases compared to female controls; otherwise the prevalence of the risk factors was comparable for both groups. The risk factors significantly associated with child maltreatment were also similar for both cases and controls. Given the documented association between child maltreatment and adult mental disorder, child maltreatment may be an important antecedent of current psychological distress in persons presenting to treatment for opioid dependence. Apart from a possible association between early parental separation and sexual abuse among female cases, the increased prevalence of child maltreatment associated with opioid dependence did not appear to be related to differences in early childhood risk factors considered in this paper. Other risk factors may be more pertinent for those with opioid dependence. The high prevalence of child maltreatment among the opioid-dependent sample has implications for the assessment and treatment of clients presenting with opioid dependence. Assessment of child maltreatment history could help inform the development of

Fibromyalgia survey criteria are associated with increased postoperative opioid consumption in women undergoing hysterectomy.

PubMed

Janda, Allison M; As-Sanie, Sawsan; Rajala, Baskar; Tsodikov, Alex; Moser, Stephanie E; Clauw, Daniel J; Brummett, Chad M

2015-05-01

The current study was designed to test the hypothesis that the fibromyalgia survey criteria would be directly associated with increased opioid consumption after hysterectomy even when accounting for other factors previously described as being predictive for acute postoperative pain. Two hundred eight adult patients undergoing hysterectomy between October 2011 and December 2013 were phenotyped preoperatively with the use of validated self-reported questionnaires including the 2011 fibromyalgia survey criteria, measures of pain severity and descriptors, psychological measures, preoperative opioid use, and health information. The primary outcome was the total postoperative opioid consumption converted to oral morphine equivalents. Higher fibromyalgia survey scores were significantly associated with worse preoperative pain characteristics, including higher pain severity, more neuropathic pain, greater psychological distress, and more preoperative opioid use. In a multivariate linear regression model, the fibromyalgia survey score was independently associated with increased postoperative opioid consumption, with an increase of 7-mg oral morphine equivalents for every 1-point increase on the 31-point measure (Estimate, 7.0; Standard Error, 1.7; P < 0.0001). In addition to the fibromyalgia survey score, multivariate analysis showed that more severe medical comorbidity, catastrophizing, laparotomy surgical approach, and preoperative opioid use were also predictive of increased postoperative opioid consumption. As was previously demonstrated in a total knee and hip arthroplasty cohort, this study demonstrated that increased fibromyalgia survey scores were predictive of postoperative opioid consumption in the posthysterectomy surgical population during their hospital stay. By demonstrating the generalizability in a second surgical cohort, these data suggest that patients with fibromyalgia-like characteristics may require a tailored perioperative analgesic regimen.

Ibogaine treatment outcomes for opioid dependence from a twelve-month follow-up observational study.

PubMed

Noller, Geoffrey E; Frampton, Chris M; Yazar-Klosinski, Berra

2018-01-01

The psychoactive indole alkaloid ibogaine has been associated with encouraging treatment outcomes for opioid dependence. The legal status of ibogaine in New Zealand provides a unique opportunity to evaluate durability of treatment outcomes. To examine longitudinal treatment effects over a 12-month period among individuals receiving legal ibogaine treatment for opioid dependence. This observational study measured addiction severity as the primary outcome in 14 participants (50% female) over 12 months post-treatment using the Addiction Severity Index-Lite (ASI-Lite) following a single ibogaine treatment by either of two treatment providers. Secondary effects on depression were assessed via the Beck Depression Inventory-II (BDI-II). The Subjective Opioid Withdrawal Scale (SOWS) was collected before and immediately after treatment to measure opioid withdrawal symptoms. Nonparametric comparisons via Friedman Test between baseline and 12-month follow-up for participants completing all interviews (n = 8) showed a significant reduction for the ASI-Lite drug use (p = 0.002) composite score. Reductions in BDI-II scores from baseline to 12-month follow-up were also significant (p < 0.001). Significant reductions in SOWS scores for all participants (n = 14) were also observed acutely after treatment (p = 0.015). Patients with partial data (n = 4) also showed reductions in ASI-Lite drug use scores and family/social status problems. One patient enrolled in the study died during treatment. A single ibogaine treatment reduced opioid withdrawal symptoms and achieved opioid cessation or sustained reduced use in dependent individuals as measured over 12 months. Ibogaine's legal availability in New Zealand may offer improved outcomes where legislation supports treatment providers to work closely with other health professionals.

Training HIV Physicians to Prescribe Buprenorphine for Opioid Dependence

ERIC Educational Resources Information Center

Sullivan, Lynn E.; Tetrault, Jeanette; Bangalore, Deepa; Fiellin, David A.

2006-01-01

Few HIV physicians are trained to provide buprenorphine treatment. We conducted a cross-sectional survey to assess the impact of an eight-hour course on the treatment of opioid dependence on HIV physicians' preparedness to prescribe buprenorphine. One hundred thirteen of 257 trained physicians (44%) provided HIV care. Post-course, the majority of…

Integrated Psychosocial and Opioid-Antagonist Treatment for Alcohol Dependence: A Systematic Review of Controlled Evaluations

ERIC Educational Resources Information Center

Vaughn, Michael G.; Howard, Matthew O.

2004-01-01

Methodological characteristics and outcomes of 14 controlled clinical investigations of integrated psychosocial and opioid-antagonist alcohol dependence treatment were evaluated. The 14 studies were identified through computerized bibliographic and manual literature searches. Clients receiving integrated psychosocial and opioid-antagonist…

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

PubMed Central

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

Ethical and Human Rights Imperatives to Ensure Medication-Assisted Treatment for Opioid Dependence in Prisons and Pre-trial Detention

PubMed Central

Bruce, R. Douglas; Schleifer, Rebecca A.

2008-01-01

Opioid dependence is a complex medical condition affecting neurocognitive and physical functioning. Forced or abrupt opioid withdrawal may cause profound physical and psychological suffering, including nausea, vomiting, diarrhea, extreme agitation and/or anxiety. Opioid dependent individuals are especially vulnerable at the time of arrest or initial detention, when they may, as a result of their chemical dependency, be coerced into providing incriminating testimony, or be driven to engage in risky behavior (such as sharing needles in detention) in order to avoid painful withdrawal symptoms Upon incarceration, many opioid dependent prisoners are forced to undergo abrupt opioid withdrawal (both from legally prescribed agonist therapy such as methadone as well as illicit opioids). Physical and psychological symptoms attendant to withdrawal may impair capacity to make informed legal decisions, and cause prisoners to risk HIV and other bloodborne diseases by sharing injection equipment. Although prisons must provide at least the standard of care to prisoners that is available in the general population, medication-assisted treatment, endorsed by international health and drug agencies as an integral part of HIV prevention and care strategies for opioid dependent drug users, is unavailable to most prisoners. Medication-assisted treatment is a well-studied and validated pharmacological therapy for the medical condition known as opioid dependence. The failure to ensure prisoner access to this medical therapy threatens fundamental human rights protections against cruel, inhuman or degrading treatment and rights to health and to life. It also poses serious ethical problems for health care providers, violating basic principles of beneficence and non-maleficence (i.e., do good/do no harm). Governments must take immediate action to ensure access to opioid substitution to prisoners to ensure fulfillment of ethical and human rights obligations. PMID:18226517

Ethical and human rights imperatives to ensure medication-assisted treatment for opioid dependence in prisons and pre-trial detention.

PubMed

Bruce, R Douglas; Schleifer, Rebecca A

2008-02-01

Opioid dependence is a complex medical condition affecting neurocognitive and physical functioning. Forced or abrupt opioid withdrawal may cause profound physical and psychological suffering, including nausea, vomiting, diarrhoea, extreme agitation and/or anxiety. Opioid-dependent individuals are especially vulnerable at the time of arrest or initial detention, when they may, as a result of their chemical dependency, be coerced into providing incriminating testimony, or be driven to engage in risky behaviour (such as sharing needles in detention) in order to avoid painful withdrawal symptoms. Upon incarceration, many opioid-dependent prisoners are forced to undergo abrupt opioid withdrawal (both from legally prescribed agonist therapy such as methadone as well as illicit opioids). Physical and psychological symptoms attendant to withdrawal may impair capacity to make informed legal decisions, and cause prisoners to risk HIV and other blood-borne diseases by sharing injection equipment. Although prisons must provide at least the standard of care to prisoners that is available in the general population, medication-assisted treatment, endorsed by international health and drug agencies as an integral part of HIV prevention and care strategies for opioid-dependent drug users, is unavailable to most prisoners. Medication-assisted treatment is a well-studied and validated pharmacological therapy for the medical condition known as opioid dependence. The failure to ensure prisoner access to this medical therapy threatens fundamental human rights protections against cruel, inhuman or degrading treatment and rights to health and to life. It also poses serious ethical problems for health care providers, violating basic principles of beneficence and non-maleficence (i.e., do good/do no harm). Governments must take immediate action to ensure access to opioid substitution to prisoners to ensure fulfilment of ethical and human rights obligations.

Does naltrexone affect craving in abstinent opioid-dependent patients?

PubMed

Dijkstra, Boukje A G; De Jong, Cor A J; Bluschke, Sarah M; Krabbe, Paul F M; van der Staak, Cees P F

2007-06-01

Naltrexone blocks the opioid receptors that modulate the release of dopamine in the brain reward system and therefore blocks the rewarding effects of heroin and alcohol. It is generally assumed that naltrexone leads to reduction of craving, but few studies have been performed to prove this. The purpose of the present study was to examine the effect of the administration of naltrexone on craving level after rapid opioid detoxification induced by naltrexone. A naturalistic study was carried out in which patients were followed during 10 months after rapid detoxification. Data about abstinence, relapse, and naltrexone use were collected by means of urine specimens. Craving was measured by the visual analogue scale craving, the Obsessive Compulsive Drug Use Scale, and the Desires for Drug Questionnaire. Results showed that patients who relapsed in opioid use experienced obviously more craving than abstinent people. Patients who took naltrexone did not experience significant less craving than those who did not. These results suggest that the use of opioids is associated with increased craving and that abstinence for opioids is associated with less craving, independent of the use of naltrexone. This is in contrast to the general opinion. Because of the naturalistic design of the study, no firm conclusions can be drawn, but the results grounded the needs of an experimental study.

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

PubMed

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

PubMed Central

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

2015-01-01

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. PMID:26877751

Brief early handling increases morphine dependence in adult rats.

PubMed

Vazquez, Vincent; Penit-Soria, Jacqueline; Durand, Claudette; Besson, Marie-Jo; Giros, Bruno; Daugé, Valérie

2006-06-30

Short early manipulations of rodent postnatal environment may trigger long-term effects on neurobiological and behavioural phenotypes in adulthood. However, little is known about such effects of handling on the vulnerability to develop drug dependence. The present study aimed to analyze the long-term effects of a brief handling (1 min) on morphine and ethanol dependence and on the preproenkephalin (PPE) mRNA and mu opioid receptor levels. Handled rats showed a significant increase in morphine (25mg/l) but not ethanol (10%) consumption and preference after 7 weeks and no difference in morphine (2 and 5mg/kg) conditioned place preference. No difference of preproenkephalin mRNA and mu opioid receptor levels was detected in the mesolimbic system between both groups. These data emphasize that human brief handling, which can lead to morphine dependence development, constitutes in itself an experimental treatment and not a control condition.

Factors Affecting Drug Use During Incarceration: A Cross-Sectional Study of Opioid-Dependent Persons from India.

PubMed

Rao, Ravindra; Mandal, Piyali; Gupta, Rishab; Ramshankar, Prashanth; Mishra, Ashwani; Ambekar, Atul; Jhanjee, Sonali; Dhawan, Anju

2016-02-01

Substance abuse and criminality share a complex relationship. The rates of substance use among the prisoners, and that of criminal acts among substance users in community setting are high. Data from South Asian countries, including from India are inadequate. This study aimed to assess the pattern of criminal acts among opioid-dependent subjects and their substance use pattern in the month before, during and after imprisonment. Using a cross-sectional study design and purposive sampling, opioid-dependent subjects (n=101) attending two community drug treatment clinics who have had any contact with the law were assessed using a specifically-designed tool to record criminal acts and substance use before, during and after last imprisonment. Most subjects (93%) had committed illegal acts in their lifetime. Physical assault was the most common illegal act, while 23% reported selling drugs and 9% reported committing serious crimes. About 95% were arrested and 92% had spent time in police lockups. About 29% were arrested for drugs possession or drug use, and 3% of injecting drug users arrested for carrying injection equipment. About 85% had been imprisoned at least once, of whom 88% used psychoactive substances in the 1-month period before their last imprisonment. Opioids were the most common substances used daily (68%), followed by cannabis (34%) and alcohol (22%). Ninety-seven percent reported the availability of substances in prisons, and 65% also used substances during their last imprisonment. Cannabis (35%) was the most common substances used in prison followed by opioids (19%). Seventy-six percent used substances soon after prison release, and 13% of opioid users experienced opioid overdose soon after prison release. Use of cannabis, injecting drugs, and opioid use before imprisonment were predictors of substance use in prison. Opioid-dependent people have various contacts with the law, including imprisonment. Many users are dependent on substances during prison

Co-administration of delta- and mu-opioid receptor agonists promotes peripheral opioid receptor function

PubMed Central

Schramm, Cicely L.; Honda, Christopher N.

2010-01-01

Enhancement of peripheral opioid analgesia following tissue injury or inflammation in animal models is well-documented, but clinical results of peripheral opioid therapy remain inconsistent. Previous studies in the central nervous system have shown that co-administration of μ- and δ-opioid receptor agonists can enhance analgesic outcomes; however, less is known about the functional consequences of opioid receptor interactions in the periphery. The present study examines the effects of intraplantar injection of the μ- and δ-opioid receptor agonists, morphine and deltorphin, alone and in combination on behavioral tests of nociception in naïve rats and on potassium-evoked release of CGRP from sciatic nerves of naïve rats. Neither drug alone affected nociceptive behaviors or CGRP release. Two separate measures of mechanical nociceptive sensitivity remained unchanged after co-administration of the two drugs. In contrast, when deltorphin was co-injected with morphine, dose-dependent and peripherally-restricted increases in paw withdrawal latencies to radiant heat were observed. Similarly, concentration-dependent inhibition of CGRP release was observed when deltorphin and morphine were administered in sequence prior to potassium stimulation. However, no inhibition was observed when morphine was administered prior to deltorphin. All combined opioid effects were blocked by co-application of antagonists. Deltorphin exposure also enhanced the in vivo and in vitro effects of another μ-opioid receptor agonist, DAMGO. Together, these results suggest that under normal conditions, δ-opioid receptor agonists enhance the effect of μ-opioid receptor agonists in the periphery, and local co-administration of δ- and μ-opioid receptor agonists may improve results of peripheral opioid therapy for the treatment of pain. PMID:20970925

Molecular Mechanisms of Opioid Receptor-Dependent Signaling and Behavior

PubMed Central

Al-Hasani, Ream; Bruchas, Michael R.

2013-01-01

Opioid receptors have been targeted for the treatment of pain and related disorders for thousands of years, and remain the most widely used analgesics in the clinic. Mu (μ), kappa (κ), and delta (δ) opioid receptors represent the originally classified receptor subtypes, with opioid receptor like-1 (ORL1) being the least characterized. All four receptors are G-protein coupled, and activate inhibitory G-proteins. These receptors form homo- and hetereodimeric complexes, signal to kinase cascades, and scaffold a variety of proteins. In this review, we discuss classical mechanisms and developments in understanding opioid tolerance, opioid receptor signaling, and highlight advances in opioid molecular pharmacology, behavioral pharmacology, and human genetics. We put into context how opioid receptor signaling leads to the modulation of behavior with the potential for therapeutic intervention. Finally, we conclude that there is a continued need for more translational work on opioid receptors in vivo. PMID:22020140

Blunted endogenous opioid release following an oral dexamphetamine challenge in abstinent alcohol-dependent individuals.

PubMed

Turton, Samuel; Myers, James Fm; Mick, Inge; Colasanti, Alessandro; Venkataraman, Ashwin; Durant, Claire; Waldman, Adam; Brailsford, Alan; Parkin, Mark C; Dawe, Gemma; Rabiner, Eugenii A; Gunn, Roger N; Lightman, Stafford L; Nutt, David J; Lingford-Hughes, Anne

2018-06-25

Addiction has been proposed as a 'reward deficient' state, which is compensated for with substance use. There is growing evidence of dysregulation in the opioid system, which plays a key role in reward, underpinning addiction. Low levels of endogenous opioids are implicated in vulnerability for developing alcohol dependence (AD) and high mu-opioid receptor (MOR) availability in early abstinence is associated with greater craving. This high MOR availability is proposed to be the target of opioid antagonist medication to prevent relapse. However, changes in endogenous opioid tone in AD are poorly characterised and are important to understand as opioid antagonists do not help everyone with AD. We used [ 11 C]carfentanil, a selective MOR agonist positron emission tomography (PET) radioligand, to investigate endogenous opioid tone in AD for the first time. We recruited 13 abstinent male AD and 15 control participants who underwent two [ 11 C]carfentanil PET scans, one before and one 3 h following a 0.5 mg/kg oral dose of dexamphetamine to measure baseline MOR availability and endogenous opioid release. We found significantly blunted dexamphetamine-induced opioid release in 5 out of 10 regions-of-interest including insula, frontal lobe and putamen in AD compared with controls, but no significantly higher MOR availability AD participants compared with HC in any region. This study is comparable to our previous results of blunted dexamphetamine-induced opioid release in gambling disorder, suggesting that this dysregulation in opioid tone is common to both behavioural and substance addictions.

Family burden in opioid dependence syndrome in tertiary care centre.

PubMed

Shyangwa, P M; Tripathi, B M; Lal, R

2008-01-01

This is a cross-sectional, hospital based study conducted in De-Addiction centre under department of psychiatry, AIIMS, New Delhi, India. Patients and their spouses fulfilling inclusion criteria were enrolled in the study after taking informed consent. A diagnosis of Opioid Dependence Syndrome (ODS) was made based on ICD-10 criteria and the assessment of severity of ODS was determined by Addiction Severity Index (Hindi version). Subsequently the family burden, perceived by spouses was assessed using Family Burden Interview Schedule (FBIS). Most of the subjects were from urban or semi-urban areas, mostly from around the service facility. The maximum number of subjects was of age group 31-40 years with majority of having below high school level education. Both subjective and objective family burden was perceived as "severe" by subjects' spouses. The relationship between spouses' perceived burden and socio-demographic variables including duration of substance abuse were not correlated. Hence it was found that opioid dependent subjects cause considerable amount of distress to their care providers.

Endogenous opioids: role in prostaglandin-dependent and -independent fever.

PubMed

Fraga, Daniel; Machado, Renes R; Fernandes, Luíz C; Souza, Glória E P; Zampronio, Aleksander R

2008-02-01

This study evaluated the participation of mu-opioid-receptor activation in body temperature (T(b)) during normal and febrile conditions (including activation of heat conservation mechanisms) and in different pathways of LPS-induced fever. The intracerebroventricular treatment of male Wistar rats with the selective opioid mu-receptor-antagonist cyclic d-Phe-Cys-Try-d-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP; 0.1-1.0 microg) reduced fever induced by LPS (5.0 microg/kg) but did not change T(b) at ambient temperatures of either 20 degrees C or 28 degrees C. The subcutaneous, intracerebroventricular, and intrahypothalamic injection of morphine (1.0-10.0 mg/kg, 3.0-30.0 microg, and 1-100 ng, respectively) produced a dose-dependent increase in T(b). Intracerebroventricular morphine also produced a peripheral vasoconstriction. Both effects were abolished by CTAP. CTAP (1.0 microg icv) reduced the fever induced by intracerebroventricular administration of TNF-alpha (250 ng), IL-6 (300 ng), CRF (2.5 microg), endothelin-1 (1.0 pmol), and macrophage inflammatory protein (500 pg) and the first phase of the fever induced by PGF(2alpha) (500.0 ng) but not the fever induced by IL-1beta (3.12 ng) or PGE(2) (125.0 ng) or the second phase of the fever induced by PGF(2alpha). Morphine-induced fever was not modified by the cyclooxygenase (COX) inhibitor indomethacin (2.0 mg/kg). In addition, morphine injection did not induce the expression of COX-2 in the hypothalamus, and CTAP did not modify PGE(2) levels in cerebrospinal fluid or COX-2 expression in the hypothalamus after LPS injection. In conclusion, our results suggest that LPS and endogenous pyrogens (except IL-1beta and prostaglandins) recruit the opioid system to cause a mu-receptor-mediated fever.

Acute opioid withdrawal is associated with increased neural activity in reward-processing centers in healthy men: A functional magnetic resonance imaging study.

PubMed

Chu, Larry F; Lin, Joanne C; Clemenson, Anna; Encisco, Ellen; Sun, John; Hoang, Dan; Alva, Heather; Erlendson, Matthew; Clark, J David; Younger, Jarred W

2015-08-01

Opioid analgesics are frequently prescribed for chronic pain. One expected consequence of long-term opioid use is the development of physical dependence. Although previous resting state functional magnetic resonance imaging (fMRI) studies have demonstrated signal changes in reward-associated areas following morphine administration, the effects of acute withdrawal on the human brain have been less well-investigated. In an earlier study by our laboratory, ondansetron was shown to be effective in preventing symptoms associated with opioid withdrawal. The purpose of this current study was to characterize neural activity associated with acute opioid withdrawal and examine whether these changes are modified by ondansetron. Ten participants were enrolled in this placebo-controlled, randomized, double-blind, crossover study and attended three acute opioid withdrawal sessions. Participants received either placebo or ondansetron (8Ymg IV) before morphine administration (10Ymg/70Ykg IV). Participants then underwent acute naloxone-precipitated withdrawal during a resting state fMRI scan. Objective and subjective opioid withdrawal symptoms were assessed. Imaging results showed that naloxone-precipitated opioid withdrawal was associated with increased neural activity in several reward processing regions, including the right pregenual cingulate, putamen, and bilateral caudate, and decreased neural activity in networks involved in sensorimotor integration. Ondansetron pretreatment did not have a significant effect on the imaging correlates of opioid withdrawal. This study presents a preliminary investigation of the regional changes in neural activity during acute opioid withdrawal. The fMRI acute opioid withdrawal model may serve as a tool for studying opioid dependence and withdrawal in human participants. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

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

PubMed

Garami, Julia; Haber, Paul; Myers, Catherine E; Allen, Michael T; Misiak, Blazej; Frydecka, Dorota; Moustafa, Ahmed A

2017-01-01

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.

Hepatitis Infection in the Treatment of Opioid Dependence and Abuse

PubMed Central

Kresina, Thomas F; Sylvestre, Diana; Seeff, Leonard; Litwin, Alain H; Hoffman, Kenneth; Lubran, Robert; Clark, H Westley

2008-01-01

Many new and existing cases of viral hepatitis infections are related to injection drug use. Transmission of these infections can result directly from the use of injection equipment that is contaminated with blood containing the hepatitis B or C virus or through sexual contact with an infected individual. In the latter case, drug use can indirectly contribute to hepatitis transmission through the dis-inhibited at-risk behavior, that is, unprotected sex with an infected partner. Individuals who inject drugs are at-risk for infection from different hepatitis viruses, hepatitis A, B, or C. Those with chronic hepatitis B virus infection also face additional risk should they become co-infected with hepatitis D virus. Protection from the transmission of hepatitis viruses A and B is best achieved by vaccination. For those with a history of or who currently inject drugs, the medical management of viral hepatitis infection comprising screening, testing, counseling and providing care and treatment is evolving. Components of the medical management of hepatitis infection, for persons considering, initiating, or receiving pharmacologic therapy for opioid addiction include: testing for hepatitis B and C infections; education and counseling regarding at-risk behavior and hepatitis transmission, acute and chronic hepatitis infection, liver disease and its care and treatment; vaccination against hepatitis A and B infection; and integrative primary care as part of the comprehensive treatment approach for recovery from opioid abuse and dependence. In addition, participation in a peer support group as part of integrated medical care enhances treatment outcomes. Liver disease is highly prevalent in patient populations seeking recovery from opioid addiction or who are currently receiving pharmacotherapy for opioid addiction. Pharmacotherapy for opioid addiction is not a contraindication to evaluation, care, or treatment of liver disease due to hepatitis virus infection. Successful

Crosswalk between DSM-IV Dependence and DSM-5 Substance Use Disorders for Opioids, Cannabis, Cocaine and Alcohol

PubMed Central

Compton, Wilson M.; Dawson, Deborah A.; Goldstein, Risë B.; Grant, Bridget F.

2013-01-01

Background Ascertaining agreement between DSM-IV and DSM-5 is important to determine the applicability of treatments for DSM-IV conditions to persons diagnosed according to the proposed DSM-5. Methods Data from a nationally representative sample of US adults were used to compare concordance of past-year DSM-IV Opioid, Cannabis, Cocaine and Alcohol Dependence with past-year DSM-5 disorders at thresholds of 3+, 4+ 5+ and 6+ positive DSM-5 criteria among past-year users of opioids (n=264), cannabis (n=1,622), cocaine (n=271) and alcohol (n=23,013). Substance-specific 2×2 tables yielded overall concordance (kappa), sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV). Results For DSM-IV Alcohol, Cocaine and Opioid Dependence, optimal concordance occurred when 4+ DSM-5 criteria were endorsed, corresponding to the threshold for moderate DSM-5 Alcohol, Cocaine and Opioid Use Disorders. Maximal concordance of DSM-IV Cannabis Dependence and DSM-5 Cannabis Use Disorder occurred when 6+ criteria were endorsed, corresponding to the threshold for severe DSM-5 Cannabis Use Disorder. At these optimal thresholds, sensitivity, specificity, PPV and NPV generally exceeded 85% (>75% for cannabis). Conclusions Overall, excellent correspondence of DSM-IV Dependence with DSM-5 Substance Use Disorders was documented in this general population sample of alcohol, cannabis, cocaine and opioid users. Applicability of treatments tested for DSM-IV Dependence is supported by these results for those with a DSM-5 Alcohol, Cocaine or Opioid Use Disorder of at least moderate severity or Severe Cannabis Use Disorder. Further research is needed to provide evidence for applicability of treatments for persons with milder substance use disorders. PMID:23642316

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

PubMed

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.

Effects of opioid- and non-opioid analgesics on responses to psychosocial stress in humans.

PubMed

Bershad, Anya K; Miller, Melissa A; Norman, Greg J; de Wit, Harriet

2018-06-01

Both preclinical and clinical evidence suggests that the endogenous opioid system is involved in responses to stress. For example, in animal models opioid agonists reduce isolation distress whereas opioid antagonists increase isolation distress. We recently reported that the mixed mu agonist and kappa antagonist buprenorphine dampened responses to acute psychosocial stress in humans. Now we extend this to study the effects of a pure mu-opioid agonist, hydromorphone, and a non-opioid analgesic, acetaminophen, on response to social stress. We compared the effect of hydromorphone (2 and 4 mg), acetaminophen (1000 mg) to a placebo using a between subject design. Healthy adult volunteers were randomly assigned to receive placebo (N = 13), 2 mg hydromorphone (N = 12), 4 mg hydromorphone (N = 12), or 1000 mg acetaminophen (paracetamol; N = 13) under double-blind conditions before undergoing a stress task or a control task on two separate sessions. The stress task, consisting of a standardized speaking task and the non-stressful control task were presented in counterbalanced order. Dependent measures included mood ratings, subjective appraisal of the stress (or no-stress) task, salivary cortisol, pupil diameter, heart rate, and blood pressure. The stress task produced its expected increase in heart rate, blood pressure, salivary cortisol, pupil diameter, and subjective ratings of anxiety and negative mood. Hydromorphone dose-dependently dampened cortisol responses to stress, and decreased ratings of how "challenging" participants found the task. Acetaminophen did not affect physiological responses, but, like hydromorphone, decreased ratings of how "challenging" the task was. The hydromorphone results support the idea that the mu-opioid system is involved in physiological responses to acute stress in humans, in line with results from preclinical studies. The non-opioid analgesic acetaminophen did not dampen physiological responses, but did reduce

Alcohol-Induced Changes in Opioid Peptide Levels in Adolescent Rats Are Dependent on Housing Conditions

PubMed Central

Palm, Sara; Nylander, Ingrid

2014-01-01

Background Endogenous opioids are implicated in the mechanism of action of alcohol and alcohol affects opioids in a number of brain areas, although little is known about alcohol's effects on opioids in the adolescent brain. One concern, in particular when studying young animals, is that alcohol intake models often are based on single housing that may result in alcohol effects confounded by the lack of social interactions. The aim of this study was to investigate short- and long-term alcohol effects on opioids and the influence of housing conditions on these effects. Methods In the first part, opioid peptide levels were measured after one 24-hour session of single housing and 2-hour voluntary alcohol intake in adolescent and adult rats. In the second part, a model with a cage divider inserted during 2-hour drinking sessions was tested and the effects on opioids were examined after 6 weeks of adolescent voluntary intake in single-and pair-housed rats, respectively. Results The effects of single housing were age specific and affected Met-enkephalin-Arg6Phe7 (MEAP) in particular. In adolescent rats, it was difficult to distinguish between effects induced by alcohol and single housing, whereas alcohol-specific effects were seen in dynorphin B (DYNB), beta-endorphin (BEND), and MEAP levels in adults. Voluntary drinking affected several brain areas and the majority of alcohol-induced effects were not dependent on housing. However, alcohol effects on DYNB and BEND in the amygdala were dependent on housing. Housing alone affected MEAP in the cingulate cortex. Conclusions Age-specific housing- and alcohol-induced effects on opioids were found. In addition, prolonged voluntary alcohol intake under different housing conditions produced several alcohol-induced effects independent of housing. However, housing-dependent effects were found in areas implicated in stress, emotionality, and alcohol use disorder. Housing condition and age may therefore affect the reasons and

Child maltreatment as a risk factor for opioid dependence: comparison of family characteristics and type and severity of child maltreatment with a matched control group

PubMed Central

Conroy, Elizabeth; Degenhardt, Louisa; Mattick, Richard P.; Nelson, Elliot C.

2009-01-01

Objective To examine the prevalence, characteristics and risk factors for child maltreatment among opioid-dependent persons compared to a community sample of similar social disadvantage. Method The study employed a case-control design. Cases had a history of opioid pharmacotherapy. Controls were frequency matched to cases with regard to age, sex and unemployment and were restricted to those with a lifetime opioid use of less than five times. The interview covered child maltreatment, family environment, drug use and psychiatric history. Results This study found a high prevalence of child maltreatment among both cases and controls. Despite the elevated prevalence among controls, opioid-dependent males had a higher prevalence of physical and emotional abuse; female cases had a higher prevalence and greater severity of sexual abuse. The prevalence of neglect was similar for both groups. Early parental separation was more prevalent among female cases compared to female controls; otherwise the prevalence of the risk factors was comparable for both groups. The risk factors significantly associated with child maltreatment were also similar for both cases and controls. Conclusions Given the documented association between child maltreatment and adult mental disorder, child maltreatment may be an important antecedent of current psychological distress in persons presenting to treatment for opioid dependence. Apart from a possible association between early parental separation and sexual abuse among female cases, the increased prevalence of child maltreatment associated with opioid-dependence did not appear to be related to differences in early childhood risk factors considered in this paper. Other risk factors may be more pertinent for those with opioid dependence. Practice Implications The high prevalence of child maltreatment among the opioid-dependent sample has implications for the assessment and treatment of clients presenting with opioid dependence. Assessment of child

“Listening” and “talking” to neurons: Implications of immune activation for pain control and increasing the efficacy of opioids

PubMed Central

Watkins, Linda R.; Hutchinson, Mark R.; Milligan, Erin D.; Maier, Steven F.

2008-01-01

It is recently become clear that activated immune cells and immune-like glial cells can dramatically alter neuronal function. By increasing neuronal excitability, these non-neuronal cells are now implicated in the creation and maintenance of pathological pain, such as occurs in response to peripheral nerve injury. Such effects are exerted at multiple sites along the pain pathway, including at peripheral nerves, dorsal root ganglia, and spinal cord. In addition, activated glial cells are now recognized as disrupting the pain suppressive effects of opioid drugs and contributing to opioid tolerance and opioid dependence/withdrawal. While this review focuses on regulation of pain and opioid actions, such immune-neuronal interactions are broad in their implications. Such changes in neuronal function would be expected to occur wherever immune-derived substances come in close contact with neurons. PMID:17706291

Opioid Analgesics.

PubMed

Jamison, Robert N; Mao, Jianren

2015-07-01

Chronic pain is an international health issue of immense importance that is influenced by both physical and psychological factors. Opioids are useful in treating chronic pain but have accompanying complications. It is important for clinicians to understand the basics of opioid pharmacology, the benefits and adverse effects of opioids, and related problematic issues of tolerance, dependence, and opioid-induced hyperalgesia. In this article, the role of psychiatric comorbidity and the use of validated assessment tools to identify individuals who are at the greatest risk for opioid misuse are discussed. Additionally, interventional treatment strategies for patients with chronic pain who are at risk for opioid misuse are presented. Specific behavioral interventions designed to improve adherence with prescription opioids among persons treated for chronic pain, such as frequent monitoring, periodic urine screens, opioid therapy agreements, opioid checklists, and motivational counseling, are also reviewed. Use of state-sponsored prescription drug monitoring programs is also encouraged. Areas requiring additional investigation are identified, and the future role of abuse-deterrent opioids and innovative technology in addressing issues of opioid therapy and pain are presented. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Psychiatric comorbidity is associated prospectively with diminished opioid analgesia and increased opioid misuse in patients with chronic low back pain

PubMed Central

Wasan, Ajay, D.; Michna, Edward; Edwards, Robert, R.; Katz, Jeff, N.; Nedeljkovic, Srdjan, S.; Dolman, Andrew, J.; Janfaza, David; Isaac, Zach; Jamison, Robert, N.

2015-01-01

Background Opioids are frequently prescribed for chronic low back pain (CLBP), but there is little prospective data on which patient subgroups may benefit. Psychiatric comorbidity, such as high levels of depression and anxiety symptoms (termed, comorbid negative affect [NA]) is a common presentation and may predict diminished opioid analgesia and/or increased opioid misuse. Methods We conducted a 6½-month prospective cohort study of oral opioid therapy, with an active drug/placebo run-in period, in 81 CLBP patients with low, moderate, and high levels of NA. Treatment included an opioid titration phase with a prescribing physician blinded to NA group assignment, and a 4-month continuation phase, during which subjects recorded daily pain levels using an electronic diary. The primary outcome was the percent improvement in average daily pain, summarized weekly. Results There was an overall 25% drop out rate. Despite the high NA group being prescribed a higher average daily dose of morphine equivalents, linear mixed model analysis revealed that the 24 study completers in each of the high and low NA groups had an average 21% vs. 39% improvement in pain, respectively (p<.01). The high NA group also had a significantly greater rate of opioid misuse (39% vs. 8%, p<.05), and significantly more and intense opioid side effects (p<.01). Conclusions These results indicate that the benefit and risk considerations in CLBP patients with high vs. low NA are distinctly different. Thus, negative affect is an important phenotypic variable to characterize at baseline, prior to deciding whether to prescribe opioids for CLBP. PMID:26375824

Possible evidence for re-regulation of HPA axis and brain reward systems over time in treatment in prescription opioid-dependent patients.

PubMed

Bunce, Scott C; Harris, Jonathan D; Bixler, Edward O; Taylor, Megan; Muelly, Emilie; Deneke, Erin; Thompson, Kenneth W; Meyer, Roger E

2015-01-01

There is growing evidence for a neuroadaptive model underlying vulnerability to relapse in opioid dependence. The purpose of this study was to evaluate clinical measures hypothesized to mirror elements of allostatic dysregulation in patients dependent on prescription opioids at 2 time points after withdrawal, compared with healthy control participants. Recently withdrawn (n = 7) prescription opioid-dependent patients were compared with the patients in supervised residential care for 2 to 3 months (extended care; n = 7) and healthy controls (n = 7) using drug cue reactivity, affect-modulated startle response tasks, salivary cortisol, and 8 days of sleep actigraphy. Prefrontal cortex was monitored with functional near-infrared spectroscopy during the cue reactivity task. Startle response results indicated reduced hedonic response to natural rewards among patients recently withdrawn from opioids relative to extended care patients. The recently withdrawn patients showed increased activation to pill stimuli in right dorsolateral prefrontal cortex relative to extended care patients. Cortisol levels were elevated among recently withdrawn patients and intermediate for extended care relative to healthy controls. Actigraphy indicated disturbed sleep between recently withdrawn patients and extended care patients; extended care patients were similar to controls. Dorsolateral prefrontal cortex activation to drug and natural reward cues, startle responses to natural reward cues, day-time cortisol levels, time in bed, and total time spent sleeping were all correlated with the number of days since last drug use (ie, time in supervised residential treatment). These results suggest possible re-regulation of dysregulated hypothalamic-pituitary-adrenal axis and brain reward systems in prescription opioid-dependent patients over the drug-free period in residential treatment.

Moderate- vs high-dose methadone in the treatment of opioid dependence: a randomized trial.

PubMed

Strain, E C; Bigelow, G E; Liebson, I A; Stitzer, M L

1999-03-17

Methadone hydrochloride treatment is the most common pharmacological intervention for opioid dependence, and recent interest has focused on expanding methadone treatment availability beyond traditional specially licensed clinics. However, despite recommendations regarding effective dosing of methadone, controlled clinical trials of higher-dose methadone have not been conducted. To compare the relative clinical efficacy of moderate- vs high-dose methadone in the treatment of opioid dependence. A 40-week randomized, double-blind clinical trial starting in June 1992 and ending in October 1995. Outpatient substance abuse treatment research clinic at the Johns Hopkins University Bayview Campus, Baltimore, Md. One hundred ninety-two eligible clinic patients. Daily oral methadone hydrochloride in the dose range of 40 to 50 mg (n = 97) or 80 to 100 mg (n = 95), with concurrent substance abuse counseling. Opioid-positive urinalysis results and retention in treatment. By intent-to-treat analysis through week 30 patients in the high-dose group had significantly lower rates of opioid-positive urine samples compared with patients in the moderate-dose group (53.0% [95% confidence interval [CI], 46.9%-59.2%] vs 61.9% [95% CI, 55.9%-68.0%]; P = .047. These differences persisted during withdrawal from methadone. Through day 210 no significant difference was evident between dose groups in treatment retention (high-dose group mean retention, 159 days; moderate-dose group mean retention, 157 days). Nineteen (33%) of 57 patients in the high-dose group and 11 (20%) of 54 patients in the moderate-dose group completed detoxification. Both moderate- and high-dose methadone treatment resulted in decreased illicit opioid use during methadone maintenance and detoxification. The high-dose group had significantly greater decreases in illicit opioid use.

Predictors of Abstinence: NIDA Multi-site Buprenorphine/Naloxone Treatment Trial in Opioid Dependent Youth

PubMed Central

Subramaniam, Geetha A.; Warden, Diane; Minhajuddin, Abu; Fishman, Marc J.; Stitzer, Maxine L.; Adinoff, Bryon; Trivedi, Madhukar; Weiss, Roger; Potter, Jennifer; Poole, Sabrina A.; Woody, George E.

2013-01-01

Objective To examine predictors of opioid abstinence in buprenorphine/naloxone (Bup/Nal) assisted psychosocial treatment for opioid dependent youth Method Secondary analyses of data from 152 youth (ages 15–21) randomly assigned to 12 weeks of extended Bup/Nal therapy or up to 2 weeks of Bup/Nal detoxification, both with weekly individual and group drug counseling. Logistic regression models were constructed to identify baseline and during-treatment predictors of opioid positive urines (OPU) at week-12. Predictors were selected based on significance or trend toward significance (i.e. p<0.1) and backward stepwise selection was used, controlling for treatment group, to produce final independent predictors at p ≤ 0.05. Results Youth presenting to treatment with past 30-day injection drug use (IDU) and more active medical/psychiatric problems were less likely to have a week-12 OPU. Those with early treatment opioid abstinence (i.e. weeks 1 and 2); and those who received additional non-study treatments during the study were less likely to have a week-12 OPU; and those not completing 12 weeks of treatment were more likely to have an OPU. Conclusions Youth with advanced illness (i.e. reporting IDU and additional health problems), and those receiving ancillary treatments to augment study treatment were more likely to have lower opioid use. Treatment success in the first 2 weeks and completion of 12 weeks of treatment were associated with lower rates of OPU. These findings suggest that youth with advanced illness respond well to Bup/Nal treatment, and identify options for tailoring treatment for opioid-dependent youth presenting at community-based settings. PMID:22024000

Role of opioid receptors in the reinstatement of opioid-seeking behavior: an overview.

PubMed

Fattore, Liana; Fadda, Paola; Antinori, Silvia; Fratta, Walter

2015-01-01

Opioid abuse in humans is characterized by discontinuous periods of drug use and abstinence. With time, the probability of falling into renewed drug consumption becomes particularly high and constitutes a considerable problem in the management of heroin addicts. The major problem in the treatment of opioid dependence still remains the occurrence of relapse, to which stressful life events, renewed use of heroin, and exposure to drug-associated environmental cues are all positively correlated. To study the neurobiology of relapse, many research groups currently use the reinstatement animal model, which greatly contributed to disentangle the mechanisms underlying relapse to drug-seeking in laboratory animals. The use of this model is becoming increasingly popular worldwide, and new versions have been recently developed to better appreciate the differential contribution of each opioid receptor subtype to the relapse phenomenon. In this chapter we review the state of the art of our knowledge on the specific role of the opioid receptors as unrevealed by the reinstatement animal model of opioid-seeking behavior.

Effect of Buprenorphine Implants on Illicit Opioid Use Among Abstinent Adults With Opioid Dependence Treated With Sublingual Buprenorphine: A Randomized Clinical Trial.

PubMed

Rosenthal, Richard N; Lofwall, Michelle R; Kim, Sonnie; Chen, Michael; Beebe, Katherine L; Vocci, Frank J

2016-07-19

The effectiveness of buprenorphine treatment of opioid dependence is limited by suboptimal medication adherence, abuse, and diversion. To determine whether 6-month buprenorphine implants are noninferior to daily sublingual buprenorphine as maintenance treatment for opioid-dependent patients with stable abstinence. Outpatient, randomized, active-controlled, 24-week, double-blind, double-dummy study conducted at 21 US sites from June 26, 2014, through May 18, 2015. Outpatients were prescribed daily sublingual buprenorphine for 6 months or more, were abstinent while taking 8 mg/d or less of sublingual buprenorphine for 90 days or longer, and were determined to be clinically stable by their physician. Participants were randomized to receive sublingual buprenorphine plus 4 placebo implants or sublingual placebo plus four 80-mg buprenorphine hydrochloride implants (expected efficacy, 24 weeks). The primary end point was between-group difference in proportion of responders (≥4 of 6 months without opioid-positive urine test result [monthly and 4 times randomly] and self-report). The noninferiority established for the lower bound of the 95% confidence interval was greater than -0.20 (P < .025). Secondary end points included cumulative percentage of negative opioid urine results, abstinence, and time to first illicit opioid use. Safety was assessed by adverse event reporting. Of 177 participants (mean age, 39 years; 40.9% female), 90 were randomized to sublingual buprenorphine with placebo implants and 87 to buprenorphine implants with sublingual placebo; 165 of 177 (93.2%) completed the trial. Eighty-one of 84 (96.4%) receiving buprenorphine implants and 78 of 89 (87.6%) receiving sublingual buprenorphine were responders, an 8.8% difference (1-sided 97.5% CI, 0.009 to ∞; P < .001 for noninferiority). Over 6 months, 72 of 84 (85.7%) receiving buprenorphine implants and 64 of 89 (71.9%) receiving sublingual buprenorphine maintained opioid abstinence (hazard ratio

Fentanyl Law Enforcement Submissions and Increases in Synthetic Opioid-Involved Overdose Deaths - 27 States, 2013-2014.

PubMed

Gladden, R Matthew; Martinez, Pedro; Seth, Puja

2016-08-26

In March and October 2015, the Drug Enforcement Administration (DEA) and CDC, respectively, issued nationwide alerts identifying illicitly manufactured fentanyl (IMF) as a threat to public health and safety (1,2). IMF is unlawfully produced fentanyl, obtained through illicit drug markets, includes fentanyl analogs, and is commonly mixed with or sold as heroin (1,3,4). Starting in 2013, the production and distribution of IMF increased to unprecedented levels, fueled by increases in the global supply, processing, and distribution of fentanyl and fentanyl-precursor chemicals by criminal organizations (3). Fentanyl is a synthetic opioid 50-100 times more potent than morphine (2).* Multiple states have reported increases in fentanyl-involved overdose (poisoning) deaths (fentanyl deaths) (2). This report examined the number of drug products obtained by law enforcement that tested positive for fentanyl (fentanyl submissions) and synthetic opioid-involved deaths other than methadone (synthetic opioid deaths), which include fentanyl deaths and deaths involving other synthetic opioids (e.g., tramadol). Fentanyl deaths are not reported separately in national data. Analyses also were conducted on data from 27 states(†) with consistent death certificate reporting of the drugs involved in overdoses. Nationally, the number of fentanyl submissions and synthetic opioid deaths increased by 426% and 79%, respectively, during 2013-2014; among the 27 analyzed states, fentanyl submission increases were strongly correlated with increases in synthetic opioid deaths. Changes in fentanyl submissions and synthetic opioid deaths were not correlated with changes in fentanyl prescribing rates, and increases in fentanyl submissions and synthetic opioid deaths were primarily concentrated in eight states (high-burden states). Reports from six of the eight high-burden states indicated that fentanyl-involved overdose deaths were primarily driving increases in synthetic opioid deaths. Increases in

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

PubMed Central

Haber, Paul; Myers, Catherine E.; Allen, Michael T.; Misiak, Blazej; Frydecka, Dorota; Moustafa, Ahmed A.

2017-01-01

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. PMID:28759635

Management of opioid painkiller dependence in primary care: ongoing recovery with buprenorphine/naloxone

PubMed Central

Hard, Bernadette

2014-01-01

Opioid painkiller dependence is a growing problem and best-practice management is not well defined. We report a case of a young woman exhibiting dependence on codeine, originally prescribed for myalgic encephalopathy, after escalating use over a 10-year period. In 2012, a consultation with a new general practitioner, who had extensive experience of patients with substance abuse, revealed the underlying dependence. After building trust for 6 months, she was able to admit to medication abuse, and was referred to the community drug and alcohol team. On presentation to the team, the patient had no pain issues and the dihydrocodeine use—600 tablets/week—solely reflected her dependence. The patient successfully underwent rapid induction with buprenorphine/naloxone as opioid substitution treatment over 2 days. She is currently stable, engaged with recovery support services and psychosocial counselling, and has just returned to work. She is maintained on a therapeutic dose of buprenorphine 10 mg/naloxone 2.5 mg. PMID:25432908

Extended-release intramuscular naltrexone (VIVITROL®): a review of its use in the prevention of relapse to opioid dependence in detoxified patients.

PubMed

Syed, Yahiya Y; Keating, Gillian M

2013-10-01

Naltrexone is a μ-opioid receptor antagonist that blocks the euphoric effects of heroin and prescription opioids. In order to improve treatment adherence, a once-monthly, intramuscular, extended-release formulation of naltrexone (XR-NTX) [VIVITROL(®)] has been developed, and approved in the USA and Russia for the prevention of relapse to opioid dependence, after opioid detoxification. The clinical efficacy of this formulation in patients with opioid dependence was demonstrated in a 24-week, randomized, double-blind, placebo-controlled, multicentre, phase III trial (ALK21-013; n = 250). In this trial, opioid-detoxified patients receiving XR-NTX 380 mg once every 4 weeks, in combination with psychosocial support, had a significantly higher median proportion of weeks of confirmed opioid abstinence during weeks 5-24, compared with those receiving placebo (primary endpoint). A significantly higher proportion of patients receiving XR-NTX achieved total confirmed abstinence during this period than those receiving placebo. XR-NTX was also associated with a significantly greater reduction in opioid craving and a significantly longer treatment retention period than placebo. XR-NTX was generally well tolerated in the phase III trial. The most common (incidence ≥5 %) treatment-emergent adverse events that also occurred more frequently with XR-NTX than with placebo were hepatic enzyme abnormalities, nasopharyngitis, insomnia, hypertension, influenza and injection-site pain. Thus, XR-NTX is a useful treatment option for the prevention of relapse to opioid dependence, following opioid detoxification.

Continuous opioid treatment for chronic noncancer pain: a time for moderation in prescribing.

PubMed

Colameco, Stephen; Coren, Joshua S; Ciervo, Carman A

2009-07-01

Physicians have embraced the concept of long-term opioid treatment for chronic noncancer pain (CNCP), as evidenced by increased prescribing. Many patients have benefited from more liberal opioid prescribing, but many have not, and prescription opioid abuse has risen significantly coincident with increased prescribing. Because of the potentially serious adverse effects of opioids, physicians must balance potential benefits against risks, especially in individuals at risk for opioid misuse, abuse, or dependence. This article reviews long-term, continuous opioid treatment of CNCP, current treatment guidelines, addiction risk stratification, opioid-induced hyperalgesia, and endocrine dysfunction.

Are Prescription Opioids Driving the Opioid Crisis? Assumptions vs Facts.

PubMed

Rose, Mark Edmund

2018-04-01

Sharp increases in opioid prescriptions, and associated increases in overdose deaths in the 2000s, evoked widespread calls to change perceptions of opioid analgesics. Medical literature discussions of opioid analgesics began emphasizing patient and public health hazards. Repetitive exposure to this information may influence physician assumptions. While highly consequential to patients with pain whose function and quality of life may benefit from opioid analgesics, current assumptions about prescription opioid analgesics, including their role in the ongoing opioid overdose epidemic, have not been scrutinized. Information was obtained by searching PubMed, governmental agency websites, and conference proceedings. Opioid analgesic prescribing and associated overdose deaths both peaked around 2011 and are in long-term decline; the sharp overdose increase recorded in 2014 was driven by illicit fentanyl and heroin. Nonmethadone prescription opioid analgesic deaths, in the absence of co-ingested benzodiazepines, alcohol, or other central nervous system/respiratory depressants, are infrequent. Within five years of initial prescription opioid misuse, 3.6% initiate heroin use. The United States consumes 80% of the world opioid supply, but opioid access is nonexistent for 80% and severely restricted for 4.1% of the global population. Many current assumptions about opioid analgesics are ill-founded. Illicit fentanyl and heroin, not opioid prescribing, now fuel the current opioid overdose epidemic. National discussion has often neglected the potentially devastating effects of uncontrolled chronic pain. Opioid analgesic prescribing and related overdoses are in decline, at great cost to patients with pain who have benefited or may benefit from, but cannot access, opioid analgesic therapy.

Alcohol-induced changes in opioid peptide levels in adolescent rats are dependent on housing conditions.

PubMed

Palm, Sara; Nylander, Ingrid

2014-12-01

Endogenous opioids are implicated in the mechanism of action of alcohol and alcohol affects opioids in a number of brain areas, although little is known about alcohol's effects on opioids in the adolescent brain. One concern, in particular when studying young animals, is that alcohol intake models often are based on single housing that may result in alcohol effects confounded by the lack of social interactions. The aim of this study was to investigate short- and long-term alcohol effects on opioids and the influence of housing conditions on these effects. In the first part, opioid peptide levels were measured after one 24-hour session of single housing and 2-hour voluntary alcohol intake in adolescent and adult rats. In the second part, a model with a cage divider inserted during 2-hour drinking sessions was tested and the effects on opioids were examined after 6 weeks of adolescent voluntary intake in single-and pair-housed rats, respectively. The effects of single housing were age specific and affected Met-enkephalin-Arg(6) Phe(7) (MEAP) in particular. In adolescent rats, it was difficult to distinguish between effects induced by alcohol and single housing, whereas alcohol-specific effects were seen in dynorphin B (DYNB), beta-endorphin (BEND), and MEAP levels in adults. Voluntary drinking affected several brain areas and the majority of alcohol-induced effects were not dependent on housing. However, alcohol effects on DYNB and BEND in the amygdala were dependent on housing. Housing alone affected MEAP in the cingulate cortex. Age-specific housing- and alcohol-induced effects on opioids were found. In addition, prolonged voluntary alcohol intake under different housing conditions produced several alcohol-induced effects independent of housing. However, housing-dependent effects were found in areas implicated in stress, emotionality, and alcohol use disorder. Housing condition and age may therefore affect the reasons and underlying mechanisms for drinking and

Association of Opioids and Sedatives with Increased Risk of In-Hospital Cardiopulmonary Arrest from an Administrative Database

PubMed Central

Overdyk, Frank J.; Dowling, Oonagh; Marino, Joseph; Qiu, Jiejing; Chien, Hung-Lun; Erslon, Mary; Morrison, Neil; Harrison, Brooke; Dahan, Albert; Gan, Tong J.

2016-01-01

Background While opioid use confers a known risk for respiratory depression, the incremental risk of in-hospital cardiopulmonary arrest, respiratory arrest, or cardiopulmonary resuscitation (CPRA) has not been studied. Our aim was to investigate the prevalence, outcomes, and risk profile of in-hospital CPRA for patients receiving opioids and medications with central nervous system sedating side effects (sedatives). Methods A retrospective analysis of adult inpatient discharges from 2008–2012 reported in the Premier Database. Patients were grouped into four mutually exclusive categories: (1) opioids and sedatives, (2) opioids only, (3) sedatives only, and (4) neither opioids nor sedatives. Results Among 21,276,691 inpatient discharges, 53% received opioids with or without sedatives. A total of 96,554 patients suffered CPRA (0.92 per 1000 hospital bed-days). Patients who received opioids and sedatives had an adjusted odds ratio for CPRA of 3.47 (95% CI: 3.40–3.54; p<0.0001) compared with patients not receiving opioids or sedatives. Opioids alone and sedatives alone were associated with a 1.81-fold and a 1.82-fold (p<0.0001 for both) increase in the odds of CPRA, respectively. In opioid patients, locations of CPRA were intensive care (54%), general care floor (25%), and stepdown units (15%). Only 42% of patients survived CPRA and only 22% were discharged home. Opioid patients with CPRA had mean increased hospital lengths of stay of 7.57 days and mean increased total hospital costs of $27,569. Conclusions Opioids and sedatives are independent and additive risk factors for in-hospital CPRA. The impact of opioid sparing analgesia, reduced sedative use, and better monitoring on CPRA incidence deserves further study. PMID:26913753

Increases in the use of prescription opioid analgesics and the lack of improvement in disability metrics among users.

PubMed

Sites, Brian D; Beach, Michael L; Davis, Matthew A

2014-01-01

In the United States, use of oral opioid analgesics has been associated with increasing rates of addiction, abuse, and diversion. However, little is known about the recent national use of non-illicit prescription opioid analgesics (those prescribed in a physician-patient relationship), the primary source of these drugs for the general US population. Our primary objective was to examine trends in the use of prescription opioid analgesics in the United States and to identify defining characteristics of patient users of prescribed opioids from 2000 to 2010. We used the nationally representative Medical Expenditure Panel Survey to examine trends in prescription oral opioid analgesic use from 2000 to 2010. We used survey design methods to make national estimates of adults (18 years and older) who reported receiving an opioid analgesic prescription (referred to as opioid users) and used logistic regression to examine predictors of opioid analgesic use. Our primary outcome measures were national estimates of total users of prescription opioid analgesics and total number of prescriptions. Our secondary outcome was that of observing changes in the disability and health of the users. The estimated total number of opioid analgesic prescriptions in the United States increased by 104%, from 43.8 million in 2000 to 89.2 million in 2010. In 2000, an estimated 7.4% (95% confidence interval, 6.9-7.9) of adult Americans were prescription opioid users compared with 11.8% (95% confidence interval, 11.2-12.4) in 2010. On the basis of estimates adjusted for changes in the general population, each year was associated with a 6% increase in the likelihood of receiving an opioid prescription from 2000 to 2010. Despite the apparent increase in use, there were no demonstrable improvements in the age- or sex-adjusted disability and health status measures of opioid users. The use of prescription opioid analgesics among adult Americans has increased in recent years, and this increase does not

Increases in the Use of Prescription Opioid Analgesics and the Lack of Improvement in Disability Metrics Among Users

PubMed Central

Sites, Brian D.; Beach, Michael L.; Davis, Matthew

2014-01-01

Background and Objectives In the United States, use of oral opioid analgesics has been associated with increasing rates of addiction, abuse, and diversion. However, little is known about recent national use of non-illicit prescription opioid analgesics (those prescribed in a doctor-patient relationship), the primary source of these drugs for the general US population. Our primary objective was to examine trends in the use of prescription opioid analgesics in the United States and to identify defining characteristics of patient users of prescribed opioids from 2000 to 2010. Methods We used the nationally representative Medical Expenditure Panel Survey to examine trends in prescription oral opioid analgesic use from 2000 to 2010. We used survey design methods to make national estimates of adults (18 years and older) who reported receiving an opioid analgesic prescription (referred to as opioid users) and used logistic regression to examine predictors of opioid analgesic use. Our primary outcome measures were national estimates of total users of prescription opioid analgesics and total number of prescriptions. Our secondary outcome was that of observing changes in the disability and health of the users. Results The estimated total number of opioid analgesic prescriptions in the United States increased by 104%, from 43.8 million in 2000 to 89.2 million in 2010. In 2000, an estimated 7.4% (95% CI, 6.9–7.9) of adult Americans were prescription opioid users compared with 11.8% (95% CI, 11.2–12.4) in 2010. Based on estimates adjusted for changes in the general population, each year was associated with a 6% increase in the likelihood of receiving an opioid prescription from 2000 to 2010. Despite the apparent increase in use, there were no demonstrable improvements in the age- or sex-adjusted disability and health status measures of opioid users. Conclusions The use of prescription opioid analgesics among adult Americans has increased in recent years, and this increase

Problem drinking and low-dose naltrexone-assisted opioid detoxification.

PubMed

Mannelli, Paolo; Peindl, Kathleen; Patkar, Ashwin A; Wu, Li-Tzy; Tharwani, Haresh M; Gorelick, David A

2011-05-01

The influence of alcohol use on opioid dependence is a major problem that warrants a search for more effective treatment strategies. The addition of very-low-dose naltrexone (VLNTX) to methadone taper was recently associated with reduced withdrawal intensity during detoxification. In a secondary analysis of these data, we sought to determine whether problem drinking affects detoxification outcomes and whether symptoms are influenced by VLNTX use. Opioid-dependent patients (N = 174) received naltrexone (0.125 or 0.250 mg/day) or placebo in a double-blind, randomized design during methadone-based, 6-day inpatient detoxification. Alcohol consumption was assessed at admission using the Addiction Severity Index and selfreport. Outcome measures were opioid withdrawal intensity, craving, and retention in treatment. Problem drinking-opioid dependent patients (n = 79) showed episodic heavy alcohol use and reported increased subjective opioid withdrawal intensity (p = .001), craving (p = .001), and significantly lower rate of retention in treatment (p = .02). Individuals with problem drinking and opioid dependence who were treated with VLNTX (n = 55) showed reduced withdrawal (p = .05) and a lower rate of treatment discontinuation (p = .03), resuming alcohol intake in smaller numbers the day following discharge (p = .03). Treatment effects were more pronounced on anxiety, perspiration, shakiness, nausea, stomach cramps, and craving. There were no group differences in use of adjuvant medications and no treatment-related adverse events. Heavy drinking is associated with worse opioid detoxification outcomes. The addition of VLNTX is safe and is associated with reduced withdrawal symptoms and better completion rate in these patients. Further studies should explore the use of VLNTX in detoxification and long-term treatment of combined alcohol-opioid dependence and alcohol dependence alone.

Neonatal opioid withdrawal and antenatal opioid prescribing

PubMed Central

Gomes, Tara; Camacho, Ximena; Yao, Zhan; Guttmann, Astrid; Mamdani, Muhammad M.; Juurlink, David N.; Dhalla, Irfan A.

2015-01-01

Background The incidence of neonatal opioid withdrawal is increasing in both Canada and the United States. However, the degree to which the treatment of pain with opioids, rather than the misuse of prescription opioids or heroin, contributes to the prevalence of neonatal opioid withdrawal remains unknown. Methods We conducted a retrospective, population-based, cross-sectional study between 1992 and 2011 in Ontario with 2 objectives. First, we determined the annual incidence of neonatal abstinence syndrome. Second, using data from a subset of women eligible for publicly funded prescription drugs, we determined what proportion of women who deliver an infant with neonatal abstinence syndrome were given a prescription for an opioid before and during pregnancy. Results The incidence of neonatal abstinence syndrome in Ontario increased 15-fold during the study period, from 0.28 per 1000 live births in 1992 to 4.29 per 1000 live births in 2011. During the final 5 years of the study, we identified 927 deliveries of infants with neonatal abstinence syndrome to mothers who were public drug plan beneficiaries. Of these mothers, 67% had received an opioid prescription in the 100 days preceding delivery, including 53.3% who received methadone, an increase from 28.6% in the interval spanning 1 to 2 years before delivery (p < 0.001). Prescription for nonmethadone opioids decreased from 38% to 17% (p < 0.001). Interpretation The incidence of neonatal opioid withdrawal in Ontario has increased substantially over the last 20 years. Most of the women in this cohort who delivered an infant with neonatal abstinence syndrome had received a prescription for an opioid both before and during their pregnancy. PMID:25844370

Clinical Management of the Breast-Feeding Mother-Infant Dyad in Recovery From Opioid Dependence.

PubMed

Busch, Deborah W

2016-01-01

Human milk is one of the most health-promoting and cost-effective nutritional substances known to humankind. Breastmilk provides substantial and remarkable physiological and psychological health benefits. Within the last decade, there has been a resurgence of breast-feeding in the United States and worldwide and an increased awareness of the immense health benefits for mothers, infants, and societies that support it. Each mother-baby dyad is a unique pair, with distinct relationships, biases, barriers, and obstacles. This article aims to address clinical management for the opioid-recovering breast-feeding dyad and to translate current evidenced-based practice findings, recommendations, and resources to best support this unique population. The recovering breast-feeding mother and newborn with opioid dependence deserve special consideration and expert care to foster their recovery and breast-feeding efforts. It is our moral and ethical responsibility as healthcare professionals to enable, foster, and promote breast-feeding among all families, especially those who stand to benefit the greatest. Substance recovery cannot be treated in isolation, nor can breast-feeding efforts; an interdisciplinary professional team effort promises the greatest chances for recovery success. With appropriate evidence-based practice support, training, and intervention by knowledgeable professionals, many women can overcome the biases and obstacles associated with opioid recovery to successfully breast-feed their babies.

Ascending Single-Dose, Double-Blind, Placebo-Controlled Safety Study of Noribogaine in Opioid-Dependent Patients.

PubMed

Glue, Paul; Cape, Gavin; Tunnicliff, Donna; Lockhart, Michelle; Lam, Fred; Hung, Noelyn; Hung, C Tak; Harland, Sarah; Devane, Jane; Crockett, R S; Howes, John; Darpo, Borje; Zhou, Meijian; Weis, Holger; Friedhoff, Lawrence

2016-11-01

Ibogaine is a psychoactive substance that may reduce opioid withdrawal symptoms. This was the first clinical trial of noribogaine, ibogaine's active metabolite, in patients established on methadone opioid substitution therapy (OST). In this randomized, double-blind, placebo-controlled single ascending-dose study, we evaluated the safety, tolerability, and pharmacokinetics of noribogaine in 27 patients seeking to discontinue methadone OST who had been switched to morphine during the previous week. Noribogaine doses were 60, 120, or 180 mg (n = 6/dose level) or matching placebo (n = 3/dose level). Noribogaine was well tolerated. The most frequent treatment-emergent adverse events were noneuphoric changes in light perception ∼1 hour postdose, headache, and nausea. Noribogaine had dose-linear increases for AUC and C max and was slowly eliminated (mean t 1/2 range, 24-30 hours). There was a concentration-dependent increase in QTcI (0.17 ms/ng/mL), with the largest observed mean effect of ∼16, 28, and 42 milliseconds in the 60-, 120-, and 180-mg groups, respectively. Noribogaine showed a nonstatistically significant trend toward decreased total score in opioid withdrawal ratings, most notably at the 120-mg dose; however, the study design may have confounded evaluations of time to resumption of OST. Future exposure-controlled multiple-dose noribogaine studies are planned that will address these safety and design issues. © 2016, The American College of Clinical Pharmacology.

Pain and Opioid Addiction: A Systematic Review and Evaluation of Pain Measurement in Patients with Opioid Dependence on Methadone Maintenance Treatment.

PubMed

Dennis, B B; Bawor, M; Paul, J; Plater, C; Pare, G; Worster, A; Varenbut, M; Daiter, J; Marsh, D C; Desai, D; Thabane, L; Samaan, Z

2016-01-01

While chronic pain has been said to impact patient's response to methadone maintenance treatment for opioid dependence, the reported findings are inconsistent. These discrepancies may be a direct result of variations in the measurement of chronic pain or definitions of response to methadone treatment. The goal of this study is to evaluate the association between pain and substance use behaviour to determine the real impact of comorbid pain in the methadone population. We also aim to examine sources of variation across the literature with a specific focus on the measurement of pain. We performed a systematic review using an electronic search strategy across CINAHL, MEDLINE, Web of Science, PsychINFO, EMBASE, and the Cochrane Library including Cochrane Reviews and the Cochrane Central Register of Controlled Trials databases. Title, abstract, as well as full text screening and extraction were performed in duplicate. Studies evaluating the association between chronic pain and methadone maintenance treatment response were eligible for inclusion in this review. Using a sample of 297 methadone patients from the Genetics of Opioid Addiction (GENOA) research collaborative, we assessed the reliability of patient self-reported pain and the validated Brief Pain Inventory (BPI) assessment tool. After screening 826 articles we identified five studies eligible for full text extraction, of which three showed a significant relationship between the presence of pain and the increase in substance abuse among patients on methadone for the treatment of opioid dependence. Studies varied largely in the definitions and measurement of both pain and response to treatment. Results from our validation of pain measurement in the GENOA sample (n=297) showed the use of a simple self-reported pain question is highly correlated to the use of the BPI. Simply asking patients whether they have pain showed a 44.2% sensitivity, 88.8% specificity, 84.4% PPV and 53.6% NPV to the BPI. The area under the

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

PubMed Central

Wachholtz, Amy; Gonzalez, Gerardo

2014-01-01

Introduction 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. Method 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. Results A Kaplan-Meier-Cox survival analysis showed group differences for both pain sensitivity (Log rank=15.50; p<.001) and tolerance (Log rank=20.11; p<.001). Current or historical use of opioid maintenance resulted in differing pain sensitivity compared to opioid naïve (p’s<.01). However, tolerance to pain was better among those with a history of opioid maintenance compared to active methadone patients (p<.05), with the highest tolerance found among opioid naïve control group participants (p’s<.001). Correlations within the prolonged abstinent group indicated pain tolerance was significantly improved as length of opioid abstinence increased (R=.37; p<.05); but duration of abstinence did not alter sensitivity (ns). Conclusion Among individuals with a history of prolonged 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. PMID:25456326

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

PubMed

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 < .001) and tolerance (log rank = 20.11; p < .001). Current or historical use of opioid maintenance resulted in differing pain sensitivity compared to opioid naïve (p's < .01). However, tolerance to pain was better among those with a history of opioid maintenance compared to active methadone patients (p < .05), with the highest tolerance found among opioid naïve control group participants (p's < .001). Correlations within the prolonged abstinent group indicated pain tolerance was significantly improved as length of opioid abstinence increased (R = .37; p < .05); but duration of abstinence did not alter sensitivity (ns). Among individuals with a history of prolonged 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.

Comparison of efficacy between buprenorphine and tramadol in the detoxification of opioid (heroin)-dependent subjects.

PubMed

Chawla, Jatinder Mohan; Pal, Hemraj; Lal, Rakesh; Jain, Raka; Schooler, Nina; Balhara, Yatan Pal Singh

2013-01-01

Tramadol is a synthetic opiate and a centrally acting weak m-opioid receptor agonist. The potential advantages of tramadol include ease of administration, low abuse potential, and being nonscheduled. This study compared tramadol and buprenorphine for controlling withdrawal symptoms in patients with opioid dependence syndrome. Consenting male subjects between 20 and 45 years of age who fulfilled the ICD-10-DCR criteria for opiate dependence syndrome were randomly assigned in a double-blind, double-dummy placebo-controlled trial for detoxification. Those with multiple drug dependence, abnormal cardiac, renal and hepatic functions, psychosis, or organic mental illness were excluded. Assessments included Subjective Opiate Withdrawal Scale (SOWS), Objective Opiate Withdrawal Scale (OOWS), Visual Analog Scale (VAS), and Side Effect Check List. Subjects were evaluated daily and study duration was 10 days. Sixty two subjects were enrolled. The mean SOWS and OOWS and VAS were significantly lower in the buprenorphine group on second and third day of detoxification as compared to the tramadol group. Although the retention rate was higher for buprenorphine group throughout the study, when compared with tramadol the difference was not significant on any day. Three subjects in the tramadol group had seizures. Tramadol was found to have limited detoxification efficacy in moderate to severe opioid withdrawal and substantial risk of seizures as compared to buprenorphine. Further studies are warranted to examine its efficacy in mild opioid withdrawal symptoms and its potential use in outpatient settings where its administration advantages may be valuable.

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

PubMed

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.

Design considerations for point-of-care clinical trials comparing methadone and buprenorphine treatment for opioid dependence in pregnancy and for neonatal abstinence syndrome.

PubMed

Winhusen, Theresa; Wilder, Christine; Wexelblatt, Scott L; Theobald, Jeffrey; Hall, Eric S; Lewis, Daniel; Van Hook, James; Marcotte, Michael

2014-09-01

In recent years, the U.S. has experienced a significant increase in the prevalence of pregnant opioid-dependent women and of neonatal abstinence syndrome (NAS), which is caused by withdrawal from in-utero drug exposure. While methadone-maintenance currently is the standard of care for opioid dependence during pregnancy, research suggests that buprenorphine-maintenance may be associated with shorter infant hospital lengths of stay (LOS) relative to methadone-maintenance. There is no "gold standard" treatment for NAS but there is evidence that buprenorphine, relative to morphine or methadone, treatment may reduce LOS and length of treatment. Point-of-care clinical trial (POCCT) designs, maximizing external validity while reducing cost and complexity associated with classic randomized clinical trials, were selected for two planned trials to compare methadone to buprenorphine treatment for opioid dependence during pregnancy and for NAS. This paper describes design considerations for the Medication-assisted treatment for Opioid-dependent expecting Mothers (MOMs; estimated N = 370) and Investigation of Narcotics for Ameliorating Neonatal abstinence syndrome on Time in hospital (INFANTs; estimated N = 284) POCCTs, both of which are randomized, intent-to-treat, two-group trials. Outcomes would be obtained from participants' electronic health record at three participating hospitals. Additionally, a subset of infants in the INFANTs POCCT would be from mothers in the MOMs POCCT and, thus, potential interaction between medication treatment of mother and infant could be evaluated. This pair of planned POCCTs would evaluate the comparative effectiveness of treatments for opioid dependence during pregnancy and for NAS. The results could have a significant impact on practice. Copyright © 2014 Elsevier Inc. All rights reserved.

Delay discounting in opioid use disorder: Differences between heroin and prescription opioid users.

PubMed

Karakula, Sterling L; Weiss, Roger D; Griffin, Margaret L; Borges, Allison M; Bailey, Allen J; McHugh, R Kathryn

2016-12-01

Among those with opioid use disorder, heroin use is associated with poorer prognosis relative to use of prescription opioids alone. However, relatively little is known about distinguishing features between those who use heroin relative to those who use prescription opioids. In the present study we evaluated differences in delay discounting in those with opioid use disorder based on primary opioid of use. Delay discounting is associated with a range of negative outcomes and is an important therapeutic target in this population. Treatment-seeking adults with opioid dependence completed self-report measures including past-month opioid use and the Monetary Choice Questionnaire (Kirby and Marakovic, 1996; Kirby et al., 1999), a measure of delay discounting. Participants were divided into two groups based on whether they used any heroin in the past 30days or only prescription opioids, and delay discounting scores were compared between the groups. Group differences in sociodemographic or clinical variables were included in the analysis as covariates. Results from a forward stepwise linear regression indicated that heroin use was associated with significantly higher delay discounting (B=-0.99, SE B =0.34, t=-2.88, p=0.005), even when considering covariates. Adults with opioid dependence who exclusively used prescription opioids had lower delay discounting relative to those who used heroin. This finding contributes further to the literature suggesting that heroin use is associated with greater clinical severity among those with opioid use disorder. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Ageing opioid users' increased risk of methadone-specific death in the UK.

PubMed

Pierce, Matthias; Millar, Tim; Robertson, J Roy; Bird, Sheila M

2018-05-01

The first evidence that the hazard ratio (HR) for methadone-specific death rises more steeply with age-group than for all drug-related deaths (DRDs) came from Scotland's cohort of 33,000 methadone-prescription clients. We aim to examine, for England, whether illicit opioid users' risk of methadone-specific death increases with age; and to pool age-related HRs for methadone-specific deaths with those for Scotland's methadone-prescription clients. The setting is all services in England that provide publicly-funded, structured treatment for illicit opioid users, the methodology linkage of the English National Drug Treatment Monitoring System and mortality database, and key measurements are DRDs, methadone-specific DRDs, or heroin-specific DRDs, by age-group and gender, with proportional hazards adjustment for substances used, injecting status and periods in/out of treatment. Linkage was achieved for 129,979 adults receiving prescribing treatment modalities for opioid dependence during April 2005 to March 2009 and followed-up for 378,009 person-years (pys). There were 1,266 DRDs: 271 methadone-specific (7 per 10,000 pys: irrespective of gender) and 473 heroin-specific (15 per 10,000 pys for males, 7 for females). Methadone-specific DRD-rate per 10,000 person-years was 3.5 (95% CI: 2.7-4.4) at 18-34 years, 8.9 (CI: 7.3-10.5) at 35-44 years and 18 (CI: 13.8-21.2) at 45+ years; heroin-specific DRD-rate was unchanged with age. Relative to 25-34 years, pooled HRs for UK clients' methadone-specific deaths were: 0.87 at <25 years (95% CI: 0.56-1.35); 2.14 at 35-44 years (95% CI: 1.76-2.60); 3.75 at 45+ years (95% CI: 2.99-4.70). International testing and explanation are needed of UK's sharp age-related increase in the risk of methadone-specific death. Clients should be alerted that their risk of methadone-specific death increases as they age. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Intraoperative use of remifentanil and opioid induced hyperalgesia/acute opioid tolerance: systematic review.

PubMed

Kim, Sang Hun; Stoicea, Nicoleta; Soghomonyan, Suren; Bergese, Sergio D

2014-01-01

The use of opioids has been increasing in operating room and intensive care unit to provide perioperative analgesia as well as stable hemodynamics. However, many authors have suggested that the use of opioids is associated with the expression of acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) in experimental studies and clinical observations in dose and/or time dependent exposure even when used within the clinically accepted doses. Recently, remifentanil has been used for pain management during anesthesia as well as in the intensive care units because of its rapid onset and offset. Search of the available literature to assess remifentanil AOT and OIH based on available published data. We reviewed articles analyzing remifentanil AOT and OIH, and focused our literature search on evidence based information. Experimental and clinical studies were identified using electronic searches of Medline (PubMed, Ovid, Springer, and Elsevier, ClinicalKey). Our results showed that the development of remifentanil AOT and OIH is a clinically significant phenomenon requiring further research. AOT - defined as an increase in the required opioid dose to maintain adequate analgesia, and OIH - defined as decreased pain threshold after chronic opioid treatment, should be suspected with any unexplained pain report unassociated with the disease progression. The clinical significance of these findings was evaluated taking into account multiple methodological issues including the dose and duration of opioids administration, the different infusion mode, the co-administrated anesthetic drug's effect, method assessing pain sensitivity, and the repetitive and potentially tissue damaging nature of the stimuli used to determine the threshold during opioid infusion. Future studies need to investigate the contribution of remifentanil induced hyperalgesia to chronic pain and the role of pharmacological modulation to reverse this process.

ALIENATION, SENSATION SEEKING AND MULTIPHASIC PERSONALITY QUESTIONNAIRE PROFILE IN MEN BEING TREATED FOR ALCOHOL AND/OR OPIOID DEPENDENCE

PubMed Central

Mattoo, Surendra K.; Varma, Vijoy K.; Singh, Ram Avatar; Khurana, Hitesh; Kaur, Rajinder; Sharma, Suresh K.

2001-01-01

Two hundred and thirty men, being treated for ICD-10 diagnosed dependence on alcohol, opioids or both, were studied 2-4 weeks after the last use of alcohol or opioids. Alienation Scale, Sensation Seeking Scale and Muliphasic Personality Questionnaire (MPQ), and selected sociodemographic and family history data were studied. All three groups showed high alienation (more in opioid cases), high sensation seeking (more in alcohol cases, more for boredom susceptibility), and a disturbed MPQ profile. The dual dependence group was similar to opioid group for age, but closer to alcohol group in terms of personality profile. Only alcohol cases showed a significantly positive correlation between alienation and sensation seeking- in terms of total scale, and boredom susceptibility and disinhibition subscales only. Thus, substance specificity was not reflected prominently in the inter-relationships between alienation, sensation seeking and MPQ scores, and sociodemographic variables. PMID:21407879

Current Research on Opioid Receptor Function

PubMed Central

Feng, Yuan; He, Xiaozhou; Yang, Yilin; Chao, Dongman; Lazarus, Lawrence H.; Xia, Ying

2012-01-01

The use of opioid analgesics has a long history in clinical settings, although the comprehensive action of opioid receptors is still less understood. Nonetheless, recent studies have generated fresh insights into opioid receptor-mediated functions and their underlying mechanisms. Three major opioid receptors (μ-opioid receptor, MOR; δ-opioid receptor, DOR; and κ-opioid receptor, KOR) have been cloned in many species. Each opioid receptor is functionally sub-classified into several pharmacological subtypes, although, specific gene corresponding each of these receptor subtypes is still unidentified as only a single gene has been isolated for each opioid receptor. In addition to pain modulation and addiction, opioid receptors are widely involved in various physiological and pathophysiological activities, including the regulation of membrane ionic homeostasis, cell proliferation, emotional response, epileptic seizures, immune function, feeding, obesity, respiratory and cardiovascular control as well as some neurodegenerative disorders. In some species, they play an essential role in hibernation. One of the most exciting findings of the past decade is the opioid-receptor, especially DOR, mediated neuroprotection and cardioprotection. The up-regulation of DOR expression and DOR activation increase the neuronal tolerance to hypoxic/ischemic stress. The DOR signal triggers (depending on stress duration and severity) different mechanisms at multiple levels to preserve neuronal survival, including the stabilization of homeostasis and increased pro-survival signaling (e.g., PKC-ERK-Bcl 2) and anti-oxidative capacity. In the heart, PKC and KATP channels are involved in the opioid receptor-mediated cardioprotection. The DOR-mediated neuroprotection and cardioprotection have the potential to significantly alter the clinical pharmacology in terms of prevention and treatment of life-threatening conditions like stroke and myocardial infarction. The main purpose of this article

Buprenorphine Implants for Treatment of Opioid Dependence: Randomized Comparison to Placebo and Sublingual Buprenorphine/Naloxone

PubMed Central

Rosenthal, Richard N.; Ling, Walter; Casadonte, Paul; Vocci, Frank; Bailey, Genie L.; Kampman, Kyle; Patkar, Ashwin; Chavoustie, Steven; Blasey, Christine; Sigmon, Stacey; Beebe, Katherine L.

2015-01-01

Aims To evaluate safety and efficacy of buprenorphine implants (BI) versus placebo implants (PI) for the treatment of opioid dependence. A secondary aim compared BI to open-label sublingual buprenorphine/naloxone tablets (BNX). Design Randomized, double-blind, placebo-controlled trial. Subjects received either 4 buprenorphine implants (80 mg/implant) (n=114), 4 placebo implants (n=54), or open-label BNX (12–16 mg/d) (n=119). Setting 20 addiction treatment centers. Participants Adult outpatients (ages 18 to 65) with DSM-IV-TR opioid dependence. Measurements The primary efficacy endpoint was the percent of urine samples negative for opioids collected from weeks 1 to 24, examined as a cumulative distribution function (CDF). Findings The BI CDF was significantly different from placebo (P<.0001). Mean (95% CI) proportions of urines negative for opioids were: BI: 31.2% (25.3, 37.1) and PI: 13.4% (8.3, 18.6). BI subjects had a higher study completion rate relative to placebo (64% vs. 26%, P<.0001), lower clinician-rated (P<.0001) and patient-rated (P<.0001) withdrawal, lower patient-ratings of craving (P<.0001), and better subjects’ (P=.031) and clinicians’ (P=.022) global ratings of improvement. BI also resulted in significantly lower cocaine use (P=.0016). Minor implant-site reactions were comparable in the buprenorphine (27.2% [31/114]) and placebo groups (25.9% [14/54]). BI were non-inferior to BNX on percent urines negative for opioids [mean (95% CI): 33.5 (27.3, 39.6); CI for the difference of proportions, (−10.7, 6.2)]. Conclusions Compared with placebo, buprenorphine implants result in significantly less frequent opioid use, and are non-inferior to sublingual buprenorphine/naloxone tablets. PMID:23919595

Buprenorphine implants for treatment of opioid dependence: randomized comparison to placebo and sublingual buprenorphine/naloxone.

PubMed

Rosenthal, Richard N; Ling, Walter; Casadonte, Paul; Vocci, Frank; Bailey, Genie L; Kampman, Kyle; Patkar, Ashwin; Chavoustie, Steven; Blasey, Christine; Sigmon, Stacey; Beebe, Katherine L

2013-12-01

To evaluate the safety and efficacy of buprenorphine implants (BI) versus placebo implants (PI) for the treatment of opioid dependence. A secondary aim compared BI to open-label sublingual buprenorphine/naloxone tablets (BNX). Randomized, double-blind, placebo-controlled trial. Subjects received either four buprenorphine implants (80 mg/implant) (n = 114), four placebo implants (n = 54) or open-label BNX (12-16 mg/day) (n = 119). Twenty addiction treatment centers. Adult out-patients (ages 18-65) with DSM-IV-TR opioid dependence. The primary efficacy end-point was the percentage of urine samples negative for opioids collected from weeks 1 to 24, examined as a cumulative distribution function (CDF). The BI CDF was significantly different from placebo (P < 0.0001). Mean [95% confidence interval (CI)] proportions of urines negative for opioids were: BI = 31.2% (25.3, 37.1) and PI = 13.4% (8.3, 18.6). BI subjects had a higher study completion rate relative to placebo (64 versus 26%, P < 0.0001), lower clinician-rated (P < 0.0001) and patient-rated (P < 0.0001) withdrawal, lower patient-ratings of craving (P < 0.0001) and better subjects' (P = 0.031) and clinicians' (P = 0.022) global ratings of improvement. BI also resulted in significantly lower cocaine use (P = 0.0016). Minor implant-site reactions were comparable in the buprenorphine [27.2% (31 of 114)] and placebo groups [25.9% (14 of 54)]. BI were non-inferior to BNX on percentage of urines negative for opioids [mean (95% CI) = 33.5 (27.3, 39.6); 95% CI for the difference of proportions = (-10.7, 6.2)]. Compared with placebo, buprenorphine implants result in significantly less frequent opioid use and are non-inferior to sublingual buprenorphine/naloxone tablets. © 2013 Society for the Study of Addiction.

Methadone induction in primary care for opioid dependence: a pragmatic randomized trial (ANRS Methaville).

PubMed

Carrieri, Patrizia Maria; Michel, Laurent; Lions, Caroline; Cohen, Julien; Vray, Muriel; Mora, Marion; Marcellin, Fabienne; Spire, Bruno; Morel, Alain; Roux, Perrine

2014-01-01

Methadone coverage is poor in many countries due in part to methadone induction being possible only in specialized care (SC). This multicenter pragmatic trial compared the effectiveness of methadone treatment between two induction models: primary care (PC) and SC. In this study, registered at ClinicalTrials.Gov (NCT00657397), opioid-dependent individuals not on methadone treatment for at least one month or receiving buprenorphine but needing to switch were randomly assigned to start methadone in PC (N = 155) or in SC (N = 66) in 10 sites in France. Visits were scheduled at months M0, M3, M6 and M12. The primary outcome was self-reported abstinence from street-opioids at 12 months (M12) (with an underlying 15% non-inferiority hypothesis for PC). Secondary outcomes were abstinence during follow-up, engagement in treatment (i.e. completing the induction period), retention and satisfaction with the explanations provided by the physician. Primary analysis used intention to treat (ITT). Mixed models and the log-rank test were used to assess the arm effect (PC vs. SC) on the course of abstinence and retention, respectively. In the ITT analysis (n = 155 in PC, 66 in SC), which compared the proportions of street-opioid abstinent participants, 85/155 (55%) and 22/66 (33%) of the participants were classified as street-opioid abstinent at M12 in PC and SC, respectively. This ITT analysis showed the non-inferiority of PC (21.5 [7.7; 35.3]). Engagement in treatment and satisfaction with the explanations provided by the physician were significantly higher in PC than SC. Retention in methadone and abstinence during follow-up were comparable in both arms (p = 0.47, p = 0.39, respectively). Under appropriate conditions, methadone induction in primary care is feasible and acceptable to both physicians and patients. It is as effective as induction in specialized care in reducing street-opioid use and ensuring engagement and retention in treatment for opioid dependence. Number Eudract

Growth In Buprenorphine Waivers For Physicians Increased Potential Access To Opioid Agonist Treatment, 2002-11.

PubMed

Dick, Andrew W; Pacula, Rosalie L; Gordon, Adam J; Sorbero, Mark; Burns, Rachel M; Leslie, Douglas; Stein, Bradley D

2015-06-01

Opioid use disorders are a significant public health problem, affecting two million people in the United States. Treatment with buprenorphine, methadone, or both is predominantly offered in methadone clinics, yet many people do not receive the treatment they need. In 2002 the Food and Drug Administration approved buprenorphine for prescription by physicians who completed a course and received a waiver from the Drug Enforcement Administration, exempting them from requirements in the Controlled Substances Act. To determine the waiver program's impact on the availability of opioid agonist treatment, we analyzed data for the period 2002-11 to identify counties with opioid treatment shortages. We found that the percentage of counties with a shortage of waivered physicians fell sharply, from 98.9 percent in 2002 to 46.8 percent in 2011. As a result, the percentage of the US population residing in what we classified as opioid treatment shortage counties declined from 48.6 percent in 2002 to 10.4 percent in 2011. These findings suggest that the increase in waivered physicians has dramatically increased potential access to opioid agonist treatment. Policy makers should focus their efforts on further increasing the number and geographical distribution of physicians, particularly in more rural counties, where prescription opioid misuse is rapidly growing. Project HOPE—The People-to-People Health Foundation, Inc.

Moderate to high use of opioid analgesics are associated with an increased risk of Clostridium difficile infection.

PubMed

Mora, Andrea L; Salazar, Miguel; Pablo-Caeiro, Juan; Frost, Craig P; Yadav, Yashoo; DuPont, Herbert L; Garey, Kevin W

2012-04-01

Risk factors for Clostridium difficile infection (CDI) include use of broad-spectrum antibiotics, advanced age and lack of an appropriate immune response. Whether antiperistaltics such as opioid analgesics also increase the risk of CDI is uncertain. The purpose of this preliminary study was to determine whether opioid analgesics increase the risk of developing CDI in hospitalized patients receiving broad-spectrum antibiotics. Hospitalized patients were assessed for incidence of CDI in relation to usage of opioid analgesics controlling for other known risk factors for CDI. During the study period, a total of 32,775 patients were identified of whom 192 had CDI. In univariate analysis, incidence of CDI increased significantly with moderate or high usage of opioids (P < 0.0001). One hundred of 21,396 (0.47%) patients who did not receive opioids developed CDI. Twenty-two of 6955 patients (0.32%) with mild usage of opioids developed CDI [odds ratio (OR): 0.68; 95% confidence interval (CI): 0.43-1.1; P = 0.10]. Thirty of 33,203 (0.93%) with moderate usage developed CDI (OR: 2.0; 95% CI: 1.3-3.0; P = 0.0009). Forty of 1029 (3.7%) patients with high usage of opioids developed CDI (OR: 8.3; 95% CI: 5.7-12.1; P < 0.0001). Similar results were observed using a multivariate Cox proportional hazard model. Moderate to high use of opioid analgesics were associated with an increased risk of CDI.

Sex-dependent effects of periadolescent exposure to the cannabinoid agonist CP-55,940 on morphine self-administration behaviour and the endogenous opioid system.

PubMed

Biscaia, Miguel; Fernández, Beatriz; Higuera-Matas, Alejandro; Miguéns, Miguel; Viveros, Maria-Paz; García-Lecumberri, Carmen; Ambrosio, Emilio

2008-04-01

Early cannabinoid consumption may predispose individuals to the misuse of addictive drugs later in life. However, there is a lack of experimental evidence as to whether cannabinoid exposure during adolescence might differently affect opiate reinforcing efficacy and the opioid system in adults of both sexes. Our aim was to examine whether periadolescent chronic exposure to the cannabinoid agonist CP-55,940 could exert sex-dependent effects on morphine reinforcing and the opioid system in adulthood. Morphine reinforcing was studied under a progressive ratio (PR) reinforcement schedule in adult male and female rats that previously acquired morphine self-administration under a fixed ratio 1 (FR1) schedule. Binding levels and functionality of mu-opioid receptors were also evaluated. Periadolescent cannabinoid exposure altered morphine self-administration and the opioid system in adult rats in a sex-dependent manner. CP-55,940-exposed males exhibited higher self-administration rates under a FR1, but not under a PR schedule. In females, CP-55,940 did not modify morphine self-administration under either schedule. Moreover, CP-55,940 also increased mu-opioid receptor levels in the subcallosal streak of pre-treated animals and decreased mu-opioid receptor functionality in the nucleus accumbens shell but again, only in males. Our data indicate that adult male rats exposed to the cannabinoid in adolescence self-administer more morphine than females, but only when the demands required by the schedule of reinforcement are low, which might be related to the decrease in mu-opioid receptor functionality in the NAcc-shell observed in these animals.

Laboratory-Induced Cue Reactivity among Individuals with Prescription Opioid Dependence

PubMed Central

Back, Sudie E.; Gros, Daniel F.; McCauley, Jenna; Flanagan, Julianne; Cox, Elizabeth; Barth, Kelly; Brady, Kathleen T.

2014-01-01

Prescription opioid (PO) dependence is a critical health problem. Although examination of drug cue reactivity paradigms has advanced the understanding of risk factors for relapse for a variety of substances (e.g., cocaine, alcohol, nicotine), no PO specific drug cue paradigm has been developed. The current study addressed this gap in the literature and evaluated the ability of a newly developed PO drug cue paradigm to elicit subjective, physiological, and neuroendocrine changes among PO-dependent participants (n = 20) as compared to controls (n = 17). The drug cue paradigm included an induction script, viewing and handling paraphernalia (e.g., bottle of oxycontin pills, pill crusher) and watching a video depicting people using POs as well as places related to POs (e.g., pharmacies). Consistent with hypotheses, the PO group demonstrated significant pre- to post-cue increases on subjective ratings of craving, difficulty resisting POs, stress, and anger. The control group did not demonstrate significant changes on any of the subjective measures. Both the PO group and the control group evidenced significant pre- to post-cue increases in physiological responses (e.g., blood pressure, skin conductance), as expected given the arousing nature of the drug cue stimuli. The PO group, but not the control group, evidenced a significant pre- to post-cue increase in heart rate and salivary cortisol levels. The development and validation of a drug cue paradigm for POs may help inform future research and treatment development efforts for patients with PO dependence. PMID:24813546

Increased serum IL-6 level time-dependently regulates hyperalgesia and spinal mu opioid receptor expression during CFA-induced arthritis

PubMed Central

Tekieh, E.; Zaringhalam, Jalal; Manaheji, H.; Maghsoudi, N.; Alani, B.; Zardooz, H.

2011-01-01

Interleukin (IL)-6 is known to cause pro- and anti-inflammatory effects during different stages of inflammation. Recent therapeutic investigations have focused on treatment of various inflammatory disorders with anti-cytokine substances. As a result, the aim of this study was to further elucidate the influence of IL-6 in hyperalgesia and edema during different stages of Complete Freund's Adjuvant (CFA)-induced arthritis (AA) in male Wistar rats. AA was induced by a single subcutaneous injection of CFA into the rats' hindpaw. Anti-IL-6 was administered either daily or weekly during the 21 days of study. Spinal mu opioid receptor (mOR) expression was detected by Western blotting. Daily and weekly treatment with an anti-IL-6 antibody significantly decreased paw edema in the AA group compared to the AA control group. Additionally, daily and weekly anti-IL-6 administration significantly reduced hyperalgesia on day 7 in the AA group compared to the AA control group; however, there were significant increases in hyperalgesia in the antibody-treated group on days 14 and 21 compared to the AA control group. IL-6 antibody-induced increases in hyperalgesia on the 14th and 21st days after CFA injection correlated with a time-dependent, significant reduction in spinal mOR expression during anti-IL-6 treatment. Our study confirmed the important time-dependent relationship between serum IL-6 levels and hyperalgesia during AA. These results suggest that the stages of inflammation in AA must be considered for anti-hyperalgesic and anti-inflammatory interventions via anti-IL-6 antibody treatment. PMID:27857662

Increased serum IL-6 level time-dependently regulates hyperalgesia and spinal mu opioid receptor expression during CFA-induced arthritis.

PubMed

Tekieh, E; Zaringhalam, Jalal; Manaheji, H; Maghsoudi, N; Alani, B; Zardooz, H

2011-01-01

Interleukin (IL)-6 is known to cause pro- and anti-inflammatory effects during different stages of inflammation. Recent therapeutic investigations have focused on treatment of various inflammatory disorders with anti-cytokine substances. As a result, the aim of this study was to further elucidate the influence of IL-6 in hyperalgesia and edema during different stages of Complete Freund's Adjuvant (CFA)-induced arthritis (AA) in male Wistar rats. AA was induced by a single subcutaneous injection of CFA into the rats' hindpaw. Anti-IL-6 was administered either daily or weekly during the 21 days of study. Spinal mu opioid receptor (mOR) expression was detected by Western blotting. Daily and weekly treatment with an anti-IL-6 antibody significantly decreased paw edema in the AA group compared to the AA control group. Additionally, daily and weekly anti-IL-6 administration significantly reduced hyperalgesia on day 7 in the AA group compared to the AA control group; however, there were significant increases in hyperalgesia in the antibody-treated group on days 14 and 21 compared to the AA control group. IL-6 antibody-induced increases in hyperalgesia on the 14 th and 21 st days after CFA injection correlated with a time-dependent, significant reduction in spinal mOR expression during anti-IL-6 treatment. Our study confirmed the important time-dependent relationship between serum IL-6 levels and hyperalgesia during AA. These results suggest that the stages of inflammation in AA must be considered for anti-hyperalgesic and anti-inflammatory interventions via anti-IL-6 antibody treatment.

Predictors of Abstinence: National Institute of Drug Abuse Multisite Buprenorphine/Naloxone Treatment Trial in Opioid-Dependent Youth

ERIC Educational Resources Information Center

Subramaniam, Geetha A.; Warden, Diane; Minhajuddin, Abu; Fishman, Marc J.; Stitzer, Maxine L.; Adinoff, Bryon; Trivedi, Madhukar; Weiss, Roger; Potter, Jennifer; Poole, Sabrina A.; Woody, George E.

2011-01-01

Objective: To examine predictors of opioid abstinence in buprenorphine/naloxone (Bup/Nal)-assisted psychosocial treatment for opioid-dependent youth. Method: Secondary analyses were performed of data from 152 youth (15-21 years old) randomly assigned to 12 weeks of extended Bup/Nal therapy or up to 2 weeks of Bup/Nal detoxification with weekly…

Methadone for the treatment of Prescription Opioids Dependence. A retrospective chart review.

PubMed

Barrio, Pablo; Ezzeldin, Mohamed; Bruguera, Pol; Pérez, Ana; Mansilla, Sara; Fàbrega, Marina; Lligoña, Anna; Mondón, Sílvia; Balcells, Mercè

2016-06-14

Prescription opioids (PO) addiction is increasing to an epidemic level. Few studies exist regarding its treatment. Although buprenorphine has been the mainstay so far, other treatment options might be considered, such as methadone. We conducted a retrospective assessment of all patients admitted to a psychiatry ward for PO detoxification using methadone between 2010 and 2013. The assessment and description was carried out during a 3-month follow-up period after their discharge. Although this is a retrospective chart review, our exploration included sociodemographic and treatment variables in addition to the abstinence rates for the whole sample. Eleven patients were included, mostly women (81.8%), with a median age of 50 years. The median duration of dependence was 8 years. Dependence on other substances and psychiatric comorbidities were high. Eight patients were monitored during three months. Of these, 7 (87.5%) were abstinent after that period. The results suggest that methadone deserves further exploration as a potentially efficacious treatment option for PO dependence.

A Retrospective Cohort Study of Obstetric Outcomes in Opioid-Dependent Women Treated with Implant Naltrexone, Oral Methadone or Sublingual Buprenorphine, and Non-Dependent Controls.

PubMed

Kelty, Erin; Hulse, Gary

2017-07-01

Opioid pharmacotherapies play an important role in the treatment of opioid-dependent women; however, very little is known about the safety of naltrexone in pregnant patients. This study examined the obstetric health of opioid-dependent women who were treated with implant naltrexone during pregnancy, and compared them with women treated with methadone and/or buprenorphine and a cohort of non-opioid-dependent controls. Women treated with implant naltrexone, oral methadone or sublingual buprenorphine between 2001 and 2010, along with a cohort of age-matched controls, were linked with records from midwives, hospital and emergency departments (EDs) and the death registry to identify pregnancy and health events that occurred during pregnancy and in the post-partum period. Overall rates of pregnancy loss (requiring hospital or ED attendance) were significantly elevated in naltrexone-treated women compared with buprenorphine-treated women (p = 0.018) and controls (p < 0.001); however, they were not statistically different to methadone-treated women (p = 0.210). Birth rates in women on naltrexone implant treatment were significantly higher than in all three comparison groups (p < 0.001). Rates of hospital and ED attendance during pregnancy in the naltrexone-treated women were not statistically different to those of either the methadone or buprenorphine groups, and neither were overall complications during pregnancy and labour. Overall rates of complications during pregnancy were significantly higher in the naltrexone-treated women than in the controls. Opioid-dependent women treated with naltrexone implant had higher rates of birth than the other three groups (methadone- or buprenorphine-treated women, or age-matched controls). Overall rates of complications during pregnancy were elevated in naltrexone-treated women when compared with the control group, but were generally not significantly different to rates in methadone- or buprenorphine-treated women.

Trends in heroin and pharmaceutical opioid overdose deaths in Australia.

PubMed

Roxburgh, Amanda; Hall, Wayne D; Dobbins, Timothy; Gisev, Natasa; Burns, Lucinda; Pearson, Sallie; Degenhardt, Louisa

2017-10-01

There has been international concern over the rise in fatal pharmaceutical opioid overdose rates, driven by increased opioid analgesic prescribing. The current study aimed to examine trends in opioid overdose deaths by: 1) opioid type (heroin and pharmaceutical opioids); and 2) age, gender, and intent of the death assigned by the coroner. Analysis of data from the National Coronial Information System (NCIS) of opioid overdose deaths occurring between 2001 and 2012. Deaths occurred predominantly (98%) among Australians aged 15-74 years. Approximately two-thirds of the decedents (68%) were male. The heroin overdose death rate remains unchanged over the period; these were more likely to occur among males. Pharmaceutical opioid overdose deaths increased during the study period (from 21.9 per million population in 2001-36.2), and in 2012 they occurred at 2.5 times the incident rate of heroin overdose deaths. Increases in pharmaceutical opioid deaths were largely driven by accidental overdoses. They were more likely to occur among males than females, and highest among Australians aged 45-54 years. Rates of fentanyl deaths in particular showed an increase over the study period (from a very small number at the beginning of the period) but in 2012 rates of morphine deaths were higher than those for oxycodone, fentanyl and tramadol. Given the increase in rates of pharmaceutical opioid overdose deaths, it is imperative to implement strategies to reduce pharmaceutical opioid-related mortality, including more restrictive prescribing practices and increasing access to treatment for opioid dependence. Copyright © 2017 Elsevier B.V. All rights reserved.

Determinants of Willingness to Enroll in Opioid Agonist Treatment among Opioid Dependent People Who Inject Drugs in Ukraine

PubMed Central

Makarenko, Iuliia; Mazhnaya, Alyona; Polonsky, Maxim; Marcus, Ruthanne; Bojko, Martha J.; Filippovich, Sergii; Springer, Sandra; Dvoriak, Sergii; Altice, Frederick L.

2016-01-01

Background Coverage with opioid agonist treatments (OAT) is low (N=8,400, 2.7%) for the 310,000 people who inject drugs (PWID) in Ukraine. In the context of widespread negative attitudes toward OAT in the region, patient-level interventions targeting the barriers and willingness to initiate OAT are urgently needed. Methods A sample of 1,179 opioid dependent PWID not currently on OAT from five regions in Ukraine was assessed using multivariable logistic regression for independent factors related to willingness to initiate OAT, stratified by their past OAT experience. Results Overall, 421 (36%) PWID were willing to initiate OAT. Significant adjusted odds ratios (aOR) for covariates associated with the willingness to initiate OAT common for both groups included: higher injection frequency (previously on OAT: aOR=2.7; never on OAT: aOR=1.8), social and family support (previously on OAT: aOR=2.0; never on OAT: aOR=2.0), positive attitude towards OAT (previously on OAT: aOR=1.3; never on OAT: aOR=1.4). Among participants previously on OAT, significant correlates also included: HIV-negative status (aOR=2.6) and depression (aOR=2.7). Among participants never on OAT, however, living in Kyiv (aOR=4.8) or Lviv (aOR=2.7), previous imprisonment (aOR=1.5), registration at a Narcology service (aOR=1.5) and recent overdose (aOR=2.6) were significantly correlated with willingness to initiate OAT. Conclusions These findings emphasize the need for developing interventions aimed to eliminate existing negative preconceptions regarding OAT among opioid dependent PWID in Ukraine, which should be tailored to the needs of specific characteristics of PWID in geographically distinct setting, higher injection frequency, prior incarceration, and psychiatric and HIV status. PMID:27370527

GIRK Channels Modulate Opioid-Induced Motor Activity in a Cell Type- and Subunit-Dependent Manner

PubMed Central

Kotecki, Lydia; Hearing, Matthew; McCall, Nora M.; Marron Fernandez de Velasco, Ezequiel; Pravetoni, Marco; Arora, Devinder; Victoria, Nicole C.; Munoz, Michaelanne B.; Xia, Zhilian; Slesinger, Paul A.; Weaver, C. David

2015-01-01

G-protein-gated inwardly rectifying K+ (GIRK/Kir3) channel activation underlies key physiological effects of opioids, including analgesia and dependence. GIRK channel activation has also been implicated in the opioid-induced inhibition of midbrain GABA neurons and consequent disinhibition of dopamine (DA) neurons in the ventral tegmental area (VTA). Drug-induced disinhibition of VTA DA neurons has been linked to reward-related behaviors and underlies opioid-induced motor activation. Here, we demonstrate that mouse VTA GABA neurons express a GIRK channel formed by GIRK1 and GIRK2 subunits. Nevertheless, neither constitutive genetic ablation of Girk1 or Girk2, nor the selective ablation of GIRK channels in GABA neurons, diminished morphine-induced motor activity in mice. Moreover, direct activation of GIRK channels in midbrain GABA neurons did not enhance motor activity. In contrast, genetic manipulations that selectively enhanced or suppressed GIRK channel function in midbrain DA neurons correlated with decreased and increased sensitivity, respectively, to the motor-stimulatory effect of systemic morphine. Collectively, these data support the contention that the unique GIRK channel subtype in VTA DA neurons, the GIRK2/GIRK3 heteromer, regulates the sensitivity of the mouse mesolimbic DA system to drugs with addictive potential. PMID:25948263

Employment-based abstinence reinforcement following inpatient detoxification in HIV-positive opioid and/or cocaine-dependent patients.

PubMed

Dunn, Kelly E; Fingerhood, Michael; Wong, Conrad J; Svikis, Dace S; Nuzzo, Paul; Silverman, Kenneth

2014-02-01

Employment-based reinforcement interventions have been used to promote abstinence from drugs among chronically unemployed injection drug users. The current study used an employment-based reinforcement intervention to promote opioid and cocaine abstinence among opioid and/or cocaine-dependent, HIV-positive participants who had recently completed a brief inpatient detoxification. Participants (n = 46) were randomly assigned to an abstinence and work group that was required to provide negative urine samples in order to enter the workplace and to earn incentives for work (n = 16), a work-only group that was permitted to enter the workplace and to earn incentives independent of drug use (n = 15), and a no-voucher control group that did not receive any incentives for working (n = 15) over a 26-week period. The primary outcome was urinalysis-confirmed opioid, cocaine, and combined opioid/cocaine abstinence. Participants were 78% male and 89% African American. Results showed no significant between-groups differences in urinalysis-verified drug abstinence or HIV risk behaviors during the 6-month intervention. The work-only group had significantly greater workplace attendance, and worked more minutes per day when compared to the no-voucher group. Several features of the study design, including the lack of an induction period, setting the threshold for entering the workplace too high by requiring immediate abstinence from several drugs, and increasing the risk of relapse by providing a brief detoxification that was not supported by any continued pharmacological intervention, likely prevented the workplace from becoming established as a reinforcer that could be used to promote drug abstinence. However, increases in workplace attendance have important implications for adult training programs.

Increasing Trends in Schedule II Opioid Use and Doctor Shopping during 1999–2007 in California

PubMed Central

Han, Huijun; Kass, Philip H.; Wilsey, Barth L.; Li, Chin-Shang

2013-01-01

Purpose To examine the age and gender-specific trends of schedule II opioid use among California residents, with special reference to multiple provider users (“doctor shoppers”). Methods Utilizing data from the California Prescription Drug Monitoring Program, we examined age and gender-specific trends of Schedule II opioid use during calendar years 1999–2007. Specifically, we analyzed: 1) the prevalence of Schedule II opioid users among California’s population, and 2) the proportion of these opioid users who were doctor shoppers (defined as an individual who used more than five different prescribers for all schedule II opioids he/she obtained in a calendar year). Results Among all age and gender groups, the prevalence of Schedule II opioid users in California increased by 150%–280% and the prevalence of doctor shoppers among users increased by 111%–213% over nine years. The prevalence of opioid users was lowest among 18–44 year-old males (1.25%) and highest among 65 years and older females (5.31%) by 2007. The prevalence of doctor shoppers was approximately 1.4% among those up to age 64 and 0.5% among those 65 years and older. The gender difference in doctor shoppers among all age groups was negligible. On average, the cumulative morphine-equivalent amount of Schedule II opioid per individual obtained per year was three- to six-fold higher for doctor shoppers than for the general population across different age and gender groups. Conclusions Age and gender differences in opioid use were relatively small, while the trends for use of opioids and multiple providers grew at a disquieting rate. PMID:23956137

Drug interactions: volatile anesthetics and opioids.

PubMed

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.

Combining stepped-care approaches with behavioral reinforcement to motivate employment in opioid-dependent outpatients.

PubMed

Kidorf, Michael; Neufeld, Karin; Brooner, Robert K

2004-01-01

Employment is associated with improved treatment outcome for opioid-dependent outpatients receiving methadone (e.g., Platt, 1995). Opioid-dependent individuals typically enter treatment unemployed and many remain unemployed despite reductions in heroin use. Additional interventions are needed to motivate employment seeking behaviors and outcome. This article reports on a promising approach to reduce the chronic unemployment commonplace in treatment-seeking, opioid-dependent patients--a "stepped care" service delivery intervention that incorporates multiple behavioral reinforcements to motivate patient participation in and adherence to the treatment plan. This therapeutic approach (Motivated Stepped Care--MSC; Brooner and Kidorf (2002) was refined and modified to motivate and support a range of positive treatment behaviors and outcomes in patients with opioid-dependence (Kidorf et al. 1999), including job-seeking and acquisition. Patients who are unemployed after one year of treatment are systematically advanced to more intensive steps of weekly counseling and remain there until employment is attained. Those who remain unemployed despite exposure to at least 4 weeks of counseling at the highest step of care (Step 3, which is 9 h weekly of counseling) are started on a methadone taper in preparation for discharge, which is reversible upon attaining a job. This article describes the MSC approach and presents rates of employment for patients who were judged capable of working (n = 228). A review of medical and billing records during August--September 2002 revealed that the great majority of these patients were employed (93%), usually in full-time positions. Employment was associated with less frequent advancement to higher intensities of weekly counseling because of drug use. Further, multiple indices of improved employment stability and functioning, including months of work, hours of work, and annualized salary, were associated with better drug use outcomes. These data

Comparing Mindfulness-Based Group Therapy With Treatment as Usual for Opioid Dependents: A Pilot Randomized Clinical Trial Study Protocol.

PubMed

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

2015-03-01

In response to high burden of opioid abuse in Iran, Ministry of Health has launched a large-scale opioid maintenance treatment program, delivered through a network of certified drug treatment centers. To promote opioid pharmacotherapies, there is an urgent need to develop and introduce evidence-based psychosocial interventions into the network. This is a randomized clinical trial (RCT) to investigate feasibility and effectiveness of adding mindfulness-based group therapy to opioid pharmacotherapies as compared to opioid pharmacotherapies alone. The primary outcomes were treatment retention and percentage of weekly morphine, methamphetamine, and benzodiazepine negative tests. This is the first RCT that explores the effectiveness of mindfulness-based relapse prevention group therapy among opioid dependent clients in Iran. The feasibility of group therapy and comparison of outcomes in intervention and control groups should be discussed in the outcome article.

Using iPSC-derived human DA neurons from opioid-dependent subjects to study dopamine dynamics.

PubMed

Sheng, Yang; Filichia, Emily; Shick, Elizabeth; Preston, Kenzie L; Phillips, Karran A; Cooperman, Leslie; Lin, Zhicheng; Tesar, Paul; Hoffer, Barry; Luo, Yu

2016-08-01

The dopaminergic (DA) system plays important roles in addiction. However, human DA neurons from drug-dependent subjects were not available for study until recent development in inducible pluripotent stem cells (iPSCs) technology. In this study, we produced DA neurons differentiated using iPSCs derived from opioid-dependent and control subjects carrying different 3' VNTR (variable number tandem repeat) polymorphism in the human dopamine transporter (DAT or SLC6A3). In addition, the effects of valproic acid (VPA) exposures on iPSC-derived human DA neurons are also examined. We present the first evidence suggesting that the 3' VNTR polymorphism in the hDAT gene affects DAT expression level in iPSC-derived human DA neurons. In human DA neurons, which provide an appropriate cellular milieu, VPA treatment alters the expression of several genes important for dopaminergic neuron function including DAT, Nurr1, and TH; this might partly explain its action in regulating addictive behaviors. VPA treatment also significantly increased DA D2 receptor (Drd2) expression, especially in the opioid-dependent iPSC cell lines. Our data suggest that human iPSC-derived DA neurons may be useful in in vitro experimental model to examine the effects of genetic variation in gene regulation, to examine the underlying mechanisms in neurological disorders including drug addiction, and to serve as a platform for therapeutic development.

Safety of Oral Dronabinol During Opioid Withdrawal in Humans

PubMed Central

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

2015-01-01

Background 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. Methods 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 30mg qid. Double-blind placebo substitutions occurred for 21 hours 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 60mg, dronabinol 5, 10, 20, and 30mg [decreased from 40mg]). Heart rate, blood pressure, respiratory outcomes and pupil diameter were assessed repeatedly. Results Dronabinol 40mg produced sustained sinus tachycardia accompanied by anxiety and panic necessitating dose reduction to 30mg. Sinus tachycardia and anxiety also occurred in one volunteer after dronabinol 20mg. Compared to placebo, dronabinol 20 and 30mg produced significant increases in heart rate beginning 1 hour after drug administration that lasted approximately two hours (p<0.05). Dronabinol 5 and 10mg produced placebo-like effects. Oxycodone produced prototypic mu-opioid agonist effects (e.g., miosis). Conclusion 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. PMID:26483357

Characteristics and treatment patterns of US commercially insured and Medicaid patients with opioid dependence or abuse.

PubMed

Wollschlaeger, Bernd A; Willson, Tina M; Montejano, Leslie B; Ronquest, Naoko A; Nadipelli, Vijay R

To identify the demographic and clinical characteristics of commercially insured and Medicaid patients with a diagnosis of opioid dependence or abuse and to describe the pharmacological and nonpharmacological treatments received by these patients. This was a retrospective observational study using de-identified administrative claims data. The analysis included commercially insured and Medicaid patient data extracted from the Truven Health MarketScan® Commercial and Medicaid Databases. Patients with a diagnosis of opioid dependence or abuse from 2008 to 2014 (earliest diagnosis = index date) and a minimum of 6 months of pre-index and postindex continuous enrollment in the database. Baseline demographic and clinical characteristics, medication-assisted treatment (MAT), and treatment other than MAT received following diagnosis, and the clinical practice setting in which patients received any opioid dependence-related care were reported. Data from commercially insured (N = 103,768) and Medicaid (N = 50,552) patients were analyzed. Common comorbid conditions included chronic pain (48.6 percent Commercial, 56.8 percent Medicaid), depressive disorder (24.0 percent Commercial, 32.8 percent Medicaid), and other substance abuse disorders (13.3 percent Commercial, 23.7 percent Medicaid). Nearly one third of both Commercial (31.6 percent) and Medicaid (33.6 percent) patients did not have any claims for psychosocial therapy or MAT during the follow-up period. Only 24.3 percent of Commercial patients and 20.4 percent of Medicaid patients had evidence of claims for both MAT and psychosocial treatment anytime following diagnosis. The results suggest that there are opportunities to improve care through comprehensive and coordinated treatment for opioid dependence/abuse. Policies aimed at improving treatment access may be warranted.

A cost-effectiveness analysis of opioid substitution therapy upon prison release in reducing mortality among people with a history of opioid dependence.

PubMed

Gisev, Natasa; Shanahan, Marian; Weatherburn, Don J; Mattick, Richard P; Larney, Sarah; Burns, Lucy; Degenhardt, Louisa

2015-12-01

Although opioid substitution therapy (OST) immediately after prison release reduces mortality, the cost-effectiveness of treatment has not been examined. Therefore, we undertook a cost-effectiveness analysis of OST treatment upon prison release and the prevention of death in the first 6 months post-release. Population-based, retrospective data linkage study using records of OST entrants (1985-2010), charges and court appearances (1993-2011), prison episodes (2000-11) and death notifications (1985-2011). New South Wales, Australia. A cohort of 16,073 people with a history of opioid dependence released from prison for the first time between 1 January 2000 and 30 June 2011. OST treatment compared to no OST treatment at prison release. Mortality and costs (treatment, criminal justice system-court, penalties, prison-and the social costs of crime) were evaluated at 6 months post-release. Analyses included propensity score matching, bootstrapping and regression. A total of 13,468 individuals were matched (6734 in each group). Twenty (0.3%) people released onto OST died, compared with 46 people (0.7%) not released onto OST. The final average costs were lower for the group that received OST post-release ($7206 versus $14,356). The incremental cost-effectiveness ratio showed that OST post-release was dominant, incurring lower costs and saving more lives. The probability that OST post-release is cost-effective per life-year saved is 96.7% at a willingness to pay of $500. Opioid substitution treatment (compared with no such treatment), given on release from prison to people with a history of opioid dependence, is cost-effective in reducing mortality in the first 6 months of release. © 2015 Society for the Study of Addiction.

Opioid Challenge Evaluation of Blockade by Extended-Release Naltrexone in Opioid-Abusing Adults: Dose-Effects and Time-Course

PubMed Central

Bigelow, George E.; Preston, Kenzie L.; Schmittner, John; Dong, Qunming; Gastfriend, David R.

2013-01-01

Background Oral naltrexone's effectiveness as an opioid antagonist has been limited due to poor patient adherence. A long-acting naltrexone formulation may be beneficial. This study evaluated the effects of extended-release injectable naltrexone (XR-NTX), targeted for a one-month duration of action, in blocking opioid agonist challenge effects in humans. Methods Outpatient non-dependent opioid abusers (N=27) were randomly assigned to a single double-blind IM administration of 75, 150, or 300 mg XR-NTX. To assess the extent of opioid blockade, hydromorphone challenges (0, 3, 4.5, 6 mg IM in ascending order at 1-hr intervals [up to 13.5 mg total]) were given at pretreatment baseline and on days 7, 14, 21, 28, 42, and 56. Opioid blockade was assessed via (1) tolerability of the ascending hydromorphone doses; (2) Visual Analog Scale (VAS) ratings of subjective opioid effects and (3) pupil diameter. Effects on the VAS and pupils were assessed via the slope of the time-action function over ascending hydromorphone doses, with zero slope indicating complete blockade. Results Blockade of the VAS “any drug effect” response to 3 mg hydromorphone was complete for 14, 21, and 28 days, respectively, for the XR-NTX doses of 75, 150 and 300 mg. Subjective effects were more readily blocked than was pupil constriction. Higher hydromorphone doses produced only modest increases in agonist effects. With the 300 mg XR-NTX dose the slope of VAS responses remained at or near zero for one month even with maximal cumulative hydromorphone dosing. Conclusions These data quantify the month-long opioid blockade underlying XR-NTX's efficacy in opioid dependence treatment. PMID:22079773

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

PubMed

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.

Cell death sensitization of leukemia cells by opioid receptor activation

PubMed Central

Friesen, Claudia; Roscher, Mareike; Hormann, Inis; Fichtner, Iduna; Alt, Andreas; Hilger, Ralf A.; Debatin, Klaus-Michael; Miltner, Erich

2013-01-01

Cyclic AMP (cAMP) regulates a number of cellular processes and modulates cell death induction. cAMP levels are altered upon stimulation of specific G-protein-coupled receptors inhibiting or activating adenylyl cyclases. Opioid receptor stimulation can activate inhibitory Gi-proteins which in turn block adenylyl cyclase activity reducing cAMP. Opioids such as D,L-methadone induce cell death in leukemia cells. However, the mechanism how opioids trigger apoptosis and activate caspases in leukemia cells is not understood. In this study, we demonstrate that downregulation of cAMP induced by opioid receptor activation using the opioid D,L-methadone kills and sensitizes leukemia cells for doxorubicin treatment. Enhancing cAMP levels by blocking opioid-receptor signaling strongly reduced D,L-methadone-induced apoptosis, caspase activation and doxorubicin-sensitivity. Induction of cell death in leukemia cells by activation of opioid receptors using the opioid D,L-methadone depends on critical levels of opioid receptor expression on the cell surface. Doxorubicin increased opioid receptor expression in leukemia cells. In addition, the opioid D,L-methadone increased doxorubicin uptake and decreased doxorubicin efflux in leukemia cells, suggesting that the opioid D,L-methadone as well as doxorubicin mutually increase their cytotoxic potential. Furthermore, we found that opioid receptor activation using D,L-methadone alone or in addition to doxorubicin inhibits tumor growth significantly in vivo. These results demonstrate that opioid receptor activation via triggering the downregulation of cAMP induces apoptosis, activates caspases and sensitizes leukemia cells for doxorubicin treatment. Hence, opioid receptor activation seems to be a promising strategy to improve anticancer therapies. PMID:23633472

Use of Emergency Department Data to Monitor and Respond to an Increase in Opioid Overdoses in New Hampshire, 2011-2015.

PubMed

Daly, Elizabeth R; Dufault, Kenneth; Swenson, David J; Lakevicius, Paul; Metcalf, Erin; Chan, Benjamin P

Opioid-related overdoses and deaths in New Hampshire have increased substantially in recent years, similar to increases observed across the United States. We queried emergency department (ED) data in New Hampshire to monitor opioid-related ED encounters as part of the public health response to this health problem. We obtained data on opioid-related ED encounters for the period January 1, 2011, through December 31, 2015, from New Hampshire's syndromic surveillance ED data system by querying for (1) chief complaint text related to the words "fentanyl," "heroin," "opiate," and "opioid" and (2) opioid-related International Classification of Diseases ( ICD) codes. We then analyzed the data to calculate frequencies of opioid-related ED encounters by age, sex, residence, chief complaint text values, and ICD codes. Opioid-related ED encounters increased by 70% during the study period, from 3300 in 2011 to 5603 in 2015; the largest increases occurred in adults aged 18-29 and in males. Of 20 994 total opioid-related ED visits, we identified 18 554 (88%) using ICD code alone, 690 (3%) using chief complaint text alone, and 1750 (8%) using both chief complaint text and ICD code. For those encounters identified by ICD code only, the corresponding chief complaint text included varied and nonspecific words, with the most common being "pain" (n = 3335, 18%), "overdose" (n = 1555, 8%), "suicidal" (n = 816, 4%), "drug" (n = 803, 4%), and "detox" (n = 750, 4%). Heroin-specific encounters increased by 827%, from 4% of opioid-related encounters in 2011 to 24% of encounters in 2015. Opioid-related ED encounters in New Hampshire increased substantially from 2011 to 2015. Data from New Hampshire's ED syndromic surveillance system provided timely situational awareness to public health partners to support the overall response to the opioid epidemic.

Faculty Development in Small-Group Teaching Skills Associated with a Training Course on Office-Based Treatment of Opioid Dependence

ERIC Educational Resources Information Center

Wong, Jeffrey G.; Holmboe, Eric S.; Becker, William C.; Fiellin, David A.; Jara, Gail B.; Martin, Judith

2005-01-01

The Drug Addiction Treatment Act of 2000 (DATA-2000) allows qualified physicians to treat opioid-dependent patients with schedule III-V medications, such as buprenorphine, in practices separate from licensed, accredited opioid treatment programs. Physicians may attain this qualification by completing 8-hours of training in treating opioid…

Sex differences in daily life stress and craving in opioid-dependent patients.

PubMed

Moran, Landhing M; Kowalczyk, William J; Phillips, Karran A; Vahabzadeh, Massoud; Lin, Jia-Ling; Mezghanni, Mustapha; Epstein, David H; Preston, Kenzie L

2018-04-11

Responses to stress and drug craving differ between men and women. Differences in the momentary experience of stress in relation to craving are less well-understood. Using ecological momentary assessment (EMA), we examined sex differences in real-time in two areas: (1) causes and contexts associated with stress, and (2) the extent to which stress and drug cues are associated with craving. Outpatients on opioid-agonist treatment (135 males, 47 females) reported stress, craving, and behavior on smartphones for 16 weeks. They initiated an entry each time they felt more stressed than usual (stress event) and made randomly prompted entries 3 times/day. In stress-event entries, they identified the causes and context (location, activity, companions), and rated stress and craving severity. The causes reported for stress events did not differ significantly by sex. Women reported arguing and being in a store more often during stress events, and men reported working more often during stress events, compared to base rates (assessed via random prompts). Women showed a greater increase in opioid craving as a function of stress (p < 0.0001) and had higher stress ratings in the presence of both stress and drug cues relative to men (p < 0.01). Similar effects were found for cocaine craving in men (p < 0.0001). EMA methods provide evidence based on real-time activities and moods that opioid-dependent men and women experience similar contexts and causes for stress but differ in stress- and cue-induced craving. These findings support sex-based tailoring of treatment, but because not all participants conformed to the overall pattern of sex differences, any such tailoring should also consider person-level differences.

Long-Term Opioid Therapy Reconsidered

PubMed Central

Von Korff, Michael; Kolodny, Andrew; Deyo, Richard A.; Chou, Roger

2012-01-01

In the past 20 years, primary care physicians have greatly increased prescribing of long-term opioid therapy. However, the rise in opioid prescribing has outpaced the evidence regarding this practice. Increased opioid availability has been accompanied by an epidemic of opioid abuse and overdose. The rate of opioid addiction among patients receiving long-term opioid therapy remains unclear, but research suggests that opioid misuse is not rare. Recent studies report increased risks for serious adverse events, including fractures, cardiovascular events, and bowel obstruction, although further research on medical risks is needed. New data indicate that opioid-related risks may increase with dose. From a societal perspective, higher-dose regimens account for the majority of opioids dispensed, so cautious dosing may reduce both diversion potential and patient risks for adverse effects. Limiting long-term opioid therapy to patients for whom it provides decisive benefits could also reduce risks. Given the warning signs and knowledge gaps, greater caution and selectivity are needed in prescribing long-term opioid therapy. Until stronger evidence becomes available, clinicians should err on the side of caution when considering this treatment. PMID:21893626

Rate of progression from first use to dependence on cocaine or opioids: a cross-substance examination of associated demographic, psychiatric, and childhood risk factors.

PubMed

Sartor, Carolyn E; Kranzler, Henry R; Gelernter, Joel

2014-02-01

A number of demographic factors, psychiatric disorders, and childhood risk factors have been associated with cocaine dependence (CD) and opioid dependence (OD), but little is known about their relevance to the rate at which dependence develops. Identification of the subpopulations at elevated risk for rapid development of dependence and the risk factors that accelerate the course of dependence is an important public health goal. Data were derived from cocaine dependent (n=6333) and opioid dependent (n=3513) participants in a multi-site study of substance dependence. Mean age was approximately 40 and 40% of participants were women; 51.9% of cocaine dependent participants and 29.5% of opioid dependent participants self-identified as Black/African-American. The time from first use to dependence was calculated for each substance and a range of demographic, psychiatric, and childhood risk factors were entered into ordinal logistic regression models to predict the (categorical) transition time to CD and OD. In both the cocaine and opioid models, conduct disorder and childhood physical abuse predicted rapid development of dependence and alcohol and nicotine dependence diagnoses were associated with slower progression to CD or OD. Blacks/African Americans were at greater risk than European Americans to progress rapidly to OD. Only a subset of factors known to be associated with CD and OD predicted the rate at which dependence developed. Nearly all were common to cocaine and opioids, suggesting that sources of influence on the timing of transitions to dependence are shared across the two substances. © 2013.

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

PubMed Central

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.

2009-01-01

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 3-to-5-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, whilst improving analgesia. PMID:18938237

Increasing availability of illicit and prescription opioids among people who inject drugs in a Canadian setting, 2010-2014.

PubMed

Ho, Joel; DeBeck, Kora; Milloy, M-J; Dong, Huiru; Wood, Evan; Kerr, Thomas; Hayashi, Kanna

2018-01-01

Nonmedical use of prescription opioid and illicit opioid has been increasing at an alarming rate in North America over the past decade. We sought to examine the temporal trends and correlates of the availability of illicit and prescription opioids among people who inject drugs (PWID) in Vancouver, Canada. Data were derived from three prospective cohort studies of PWID in Vancouver between 2010 and 2014. In semiannual interviews, participants reported the availability of five sets of illicit and prescription opioids: (1) heroin; (2) Percocet (oxycodone/acetaminophen), Vicodin (hydrocodone/acetaminophen), or Demerol (meperidine); (3) Dilaudid (hydromorphone); (4) Morphine; (5) oxycontin/OxyNEO (controlled-release oxycodone). We defined perceived availability as immediate (e.g., available within 10 minutes) versus no availability/available after 10 minutes. The trend and correlation of immediate availability were identified by multivariable generalized estimating equations logistic regression. Among 1584 participants, of which 564 (35.6%) were female, the immediate availability of all illicit and prescribed opioids (except for oxycontin/OxyNEO) increased over time, independent of potential confounders. The Adjusted Odds Ratios of immediate availability associated with every calendar year increase were between 1.09 (95% confidence interval 1.05-1.12) (morphine and Dilaudid) and 1.13 (95% confidence interval 1.09-1.17) (Percocet/Vicodin/Demerol) (all p-values <0.05). The availability of most prescription opioids had continued to increase in recent years among our sample of PWID in Vancouver. Concurrent increases in the availability of heroin were also observed, raising concerns regarding combination of both illicit and prescription opioid use among PWID that could potentially increase the risk of overdose.

Peptidases prevent mu-opioid receptor internalization in dorsal horn neurons by endogenously released opioids.

PubMed

Song, Bingbing; Marvizón, Juan Carlos G

2003-03-01

To evaluate the effect of peptidases on mu-opioid receptor (MOR) activation by endogenous opioids, we measured MOR-1 internalization in rat spinal cord slices. A mixture of inhibitors of aminopeptidases (amastatin), dipeptidyl carboxypeptidase (captopril), and neutral endopeptidase (phosphoramidon) dramatically increased the potencies of Leu-enkephalin and dynorphin A to produce MOR-1 internalization, and also enhanced the effects of Met-enkephalin and alpha-neoendorphin, but not endomorphins or beta-endorphin. The omission of any one inhibitor abolished Leu-enkephalin-induced internalization, indicating that all three peptidases degraded enkephalins. Amastatin preserved dynorphin A-induced internalization, and phosphoramidon, but not captopril, increased this effect, indicating that the effect of dynorphin A was prevented by aminopeptidases and neutral endopeptidase. Veratridine (30 microm) or 50 mm KCl produced MOR-1 internalization in the presence of peptidase inhibitors, but little or no internalization in their absence. These effects were attributed to opioid release, because they were abolished by the selective MOR antagonist CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2)) and were Ca(2+) dependent. The effect of veratridine was protected by phosphoramidon plus amastatin or captopril, but not by amastatin plus captopril or by phosphoramidon alone, indicating that released opioids are primarily cleaved by neutral endopeptidase, with a lesser involvement of aminopeptidases and dipeptidyl carboxypeptidase. Therefore, because the potencies of endomorphin-1 and endomorphin-2 to elicit internalization were unaffected by peptidase inhibitors, the opioids released by veratridine were not endomorphins. Confocal microscopy revealed that MOR-1-expressing neurons were in close proximity to terminals containing opioids with enkephalin-like sequences. These findings indicate that peptidases prevent the activation of extrasynaptic MOR-1 in dorsal horn neurons.

Peptidases prevent μ-opioid receptor internalization in dorsal horn neurons by endogenously released opioids

PubMed Central

Song, Bingbing; Marvizón, Juan Carlos G.

2008-01-01

To evaluate the effect of peptidases on μ-opioid receptor (MOR) activation by endogenous opioids, we measured MOR-1 internalization in rat spinal cord slices. A mixture of inhibitors of aminopeptidases (amastatin), dipeptidyl carboxypeptidase (captopril), and neutral endopeptidase (phosphoramidon) dramatically increased the potencies of Leu-enkephalin and dynorphin A to produce MOR-1 internalization, and also enhanced the effects of Met-enkephalin and α-neoendorphin, but not endomorphins or β-endorphin. Omission of any one inhibitor abolished Leu-enkephalin-induced internalization, indicating that all three peptidases degraded enkephalins. Amastatin preserved dynorphin A-induced internalization, and phosphoramidon, but not captopril, increased this effect, indicating that the effect of dynorphin A was prevented by aminopeptidases and neutral endopeptidase. Veratridine (30 μM) or 50 mM KCl produced MOR-1 internalization in the presence of peptidase inhibitors, but little or no internalization in their absence. These effects were attributed to opioid release, because they were abolished by the selective MOR antagonist CTAP and were Ca2+-dependent. The effect of veratridine was protected by phosphoramidon plus amastatin or captopril, but not by amastatin plus captopril or by phosphoramidon alone, indicating that released opioids are mainly cleaved by neutral endopeptidase, with a lesser involvement of aminopeptidases and dipeptidyl carboxypeptidase. Therefore, since the potencies of endomorphin-1 and -2 to elicit internalization were unaffected by peptidase inhibitors, the opioids released by veratridine were not endomorphins. Confocal microscopy revealed that MOR-1-expressing neurons were in close proximity to terminals containing opioids with enkephalin-like sequences. These findings indicate that peptidases prevent the activation of extrasynaptic MOR-1 in dorsal horn neurons. PMID:12629189

Opioids and Opioid Maintenance Therapies: Their Impact on Monocyte-Mediated HIV Neuropathogenesis

PubMed Central

Jaureguiberry-Bravo, Matias; Wilson, Rebecca; Carvallo, Loreto; Berman, Joan W.

2017-01-01

Background HIV-1 enters the CNS within two weeks after peripheral infection and results in chronic neuroinflammation that leads to HIV associated neurocognitive disorders (HAND) in more than 50% of infected people. HIV enters the CNS by transmigration of infected monocytes across the blood brain barrier. Intravenous drug abuse is a major risk factor for HIV-1 infection, and opioids have been shown to alter the progression and severity of HAND. Methadone and buprenorphine are opioid derivates that are used as opioid maintenance therapies. They are commonly used to treat opioid dependency in HIV infected substance abusers, but their effects on monocyte migration relevant to the development of cognitive impairment are not well characterized. Conclusion Here, we will discuss the effects of opioids and opioid maintenance therapies on the inflammatory functions of monocytes and macrophages that are related to the development of neuroinflammation in the context of HIV infection. PMID:27009099

The challenge of perioperative pain management in opioid-tolerant patients

PubMed Central

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

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

PubMed Central

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

Dark chocolate receptors: epicatechin-induced cardiac protection is dependent on delta-opioid receptor stimulation.

PubMed

Panneerselvam, Mathivadhani; Tsutsumi, Yasuo M; Bonds, Jacqueline A; Horikawa, Yousuke T; Saldana, Michelle; Dalton, Nancy D; Head, Brian P; Patel, Piyush M; Roth, David M; Patel, Hemal H

2010-11-01

Epicatechin, a flavonoid, is a well-known antioxidant linked to a variety of protective effects in both humans and animals. In particular, its role in protection against cardiovascular disease has been demonstrated by epidemiologic studies. Low-dose epicatechin, which does not have significant antioxidant activity, is also protective; however, the mechanism by which low-dose epicatechin induces this effect is unknown. Our laboratory tested the hypothesis that low-dose epicatechin mediates cardiac protection via opioid receptor activation. C57BL/6 mice were randomly assigned to 1 of 10 groups: control, epicatechin, naloxone (nonselective opioid receptor antagonist), epicatechin + naloxone, naltrindole (δ-specific opioid receptor antagonist), epicatechin + naltrindole, norbinaltorphimine (nor-BNI, κ-specific opioid receptor antagonist), epicatechin + nor-BNI, 5-hydroxydecanoic acid [5-HD, ATP-sensitive potassium channel antagonist], and epicatechin + 5-HD. Epicatechin (1 mg/kg) or other inhibitors (5 mg/kg) were administered by oral gavage or intraperitoneal injection, respectively, daily for 10 days. Mice were subjected to 30 min coronary artery occlusion followed by 2 h of reperfusion, and infarct size was determined via planimetry. Whole heart homogenates were assayed for downstream opioid receptor signaling targets. Infarct size was significantly reduced in epicatechin- and epicatechin + nor-BNI-treated mice compared with control mice. This protection was blocked by naloxone, naltrindole, and 5-HD. Epicatechin and epicatechin + nor-BNI increased the phosphorylation of Src, Akt, and IκBα, while simultaneously decreasing the expression of c-Jun NH(2)-terminal kinase and caspase-activated DNase. All signaling effects are consistent with opioid receptor stimulation and subsequent cardiac protection. Naloxone, naltrindole, and 5-HD attenuated these effects. In conclusion, epicatechin acts via opioid receptors and more specifically through the δ-opioid receptor to

Postsurgical prescriptions for opioid naive patients and association with overdose and misuse: retrospective cohort study

PubMed Central

Agniel, Denis; Beam, Andrew; Yorkgitis, Brian; Bicket, Mark; Homer, Mark; Fox, Kathe P; Knecht, Daniel B; McMahill-Walraven, Cheryl N; Palmer, Nathan; Kohane, Isaac

2018-01-01

Abstract Objective To quantify the effects of varying opioid prescribing patterns after surgery on dependence, overdose, or abuse in an opioid naive population. Design Retrospective cohort study. Setting Surgical claims from a linked medical and pharmacy administrative database of 37 651 619 commercially insured patients between 2008 and 2016. Participants 1 015 116 opioid naive patients undergoing surgery. Main outcome measures Use of oral opioids after discharge as defined by refills and total dosage and duration of use. The primary outcome was a composite of misuse identified by a diagnostic code for opioid dependence, abuse, or overdose. Results 568 612 (56.0%) patients received postoperative opioids, and a code for abuse was identified for 5906 patients (0.6%, 183 per 100 000 person years). Total duration of opioid use was the strongest predictor of misuse, with each refill and additional week of opioid use associated with an adjusted increase in the rate of misuse of 44.0% (95% confidence interval 40.8% to 47.2%, P<0.001), and 19.9% increase in hazard (18.5% to 21.4%, P<0.001), respectively. Conclusions Each refill and week of opioid prescription is associated with a large increase in opioid misuse among opioid naive patients. The data from this study suggest that duration of the prescription rather than dosage is more strongly associated with ultimate misuse in the early postsurgical period. The analysis quantifies the association of prescribing choices on opioid misuse and identifies levers for possible impact. PMID:29343479

Traditional Chinese and Indian medicine in the treatment of opioid-dependence: a review

PubMed Central

Doosti, Fatemeh; Dashti, Saeedeh; Tabatabai, Seyed Meghdad; Hosseinzadeh, Hossein

2013-01-01

Objective: In this study, the current literatures on the use of herbs and herbal preparations of Traditional Chinese and Indian Medicine for the treatment of opioid addiction were reviewed. Matherials and Methods: Search was done in databases such as Pub Med, Science Direct, Scopus, Springer Link, and Google Scholar. Results: Among 18 retrieved studies, 3 studies were about asafetida extract, an approved preparation for ameliorating drug abstinence in China. Chinese preparations including Composite Dong Yuan Gao, Qingjunyin and TJ-97 (a water extract of dai-bofu-to) as well as Indian ones, Mentate and Shilajit, were reported to have positive effects against opioid withdrawal, dependence, and tolerance. Moreover, Levo-tetrahydropalmatine and L-Stepholidine, in addition to extracts of Caulis Sinomenii and Sinomenium acutum showed similar effects. Banxia Houpu Decoction, Fu-Yuan pellet, Jinniu capsules, Qingjunyin, Tai-Kang-Ning capsule, and Xuan Xia Qudu Jiaonang (WeiniCom) from Chinese preparations, showed anti-addiction effects in randomized, double-blind and, in some studies, multicenter clinical trials. Conclusion : Traditional herbal preparations of China and India have anti-addiction effects with less adverse effects than alpha2-adrenergic or opioid agonists. PMID:25050276

Traditional Chinese and Indian medicine in the treatment of opioid-dependence: a review.

PubMed

Doosti, Fatemeh; Dashti, Saeedeh; Tabatabai, Seyed Meghdad; Hosseinzadeh, Hossein

2013-01-01

In this study, the current literatures on the use of herbs and herbal preparations of Traditional Chinese and Indian Medicine for the treatment of opioid addiction were reviewed. Matherials and Methods: Search was done in databases such as Pub Med, Science Direct, Scopus, Springer Link, and Google Scholar. Among 18 retrieved studies, 3 studies were about asafetida extract, an approved preparation for ameliorating drug abstinence in China. Chinese preparations including Composite Dong Yuan Gao, Qingjunyin and TJ-97 (a water extract of dai-bofu-to) as well as Indian ones, Mentate and Shilajit, were reported to have positive effects against opioid withdrawal, dependence, and tolerance. Moreover, Levo-tetrahydropalmatine and L-Stepholidine, in addition to extracts of Caulis Sinomenii and Sinomenium acutum showed similar effects. Banxia Houpu Decoction, Fu-Yuan pellet, Jinniu capsules, Qingjunyin, Tai-Kang-Ning capsule, and Xuan Xia Qudu Jiaonang (WeiniCom) from Chinese preparations, showed anti-addiction effects in randomized, double-blind and, in some studies, multicenter clinical trials. Conclusion : Traditional herbal preparations of China and India have anti-addiction effects with less adverse effects than alpha2-adrenergic or opioid agonists.

Clinical interpretation of opioid tolerance versus opioid-induced hyperalgesia.

PubMed

Chen, Lucy; Sein, Michael; Vo, Trang; Amhmed, Shihab; Zhang, Yi; Hilaire, Kristin St; Houghton, Mary; Mao, Jianren

2014-01-01

Opioid analgesics are commonly used to manage moderate to severe pain. However, the long-term use of opioids could lead to opioid tolerance (OT) and opioid-induced hyperalgesia (OIH). Distinguishing OIH from OT would impact the practice of opioid therapy because opioid dose adjustment may differentially influence OT and OIH. Currently, there are no standard criteria of OT versus OIH causing considerable ambiguity in clinical interpretation and management of these conditions. The authors designed a practitioner-based survey consisting of 20 targeted questions. Answering these questions would require responders' actual clinical experiences with opioid therapy. The survey was conducted between 2011 and 2012 through direct mails or e-mails to 1,408 physicians who are currently practicing in the United States. The authors find that certain clinical characteristics (eg, increased pain despite opioid dose escalation) are often used by practitioners to make differential diagnosis of OT and OIH despite some overlap in their clinical presentation. A key difference in clinical outcome is that OT and OIH could be improved and exacerbated by opioid dose escalation, respectively. Our survey results revealed a significant knowledge gap in some responders regarding differential diagnosis and management of OT and OIH. The results also identified several issues, such as opioid dose adjustment and clinical comorbidities related to OT and OIH, which require future patient-based studies.

Investigating the Co-Occurrence of Self-Mutilation and Suicide Attempts among Opioid-Dependent Individuals

ERIC Educational Resources Information Center

Maloney, Elizabeth; Degenhardt, Louisa; Darke, Shane; Nelson, Elliot C.

2010-01-01

The prevalence and risk factors associated with self-mutilation among opioid dependent cases and controls were determined, and the co-occurrence of self-mutilation and attempted suicide was examined. The prevalence of self-mutilation among cases and controls did not differ significantly (25% vs. 23%, respectively), with gender differences…

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

PubMed

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.

The human mu opioid receptor: modulation of functional desensitization by calcium/calmodulin-dependent protein kinase and protein kinase C.

PubMed

Mestek, A; Hurley, J H; Bye, L S; Campbell, A D; Chen, Y; Tian, M; Liu, J; Schulman, H; Yu, L

1995-03-01

Opioids are some of the most efficacious analgesics used in humans. Prolonged administration of opioids, however, often causes the development of drug tolerance, thus limiting their effectiveness. To explore the molecular basis of those mechanisms that may contribute to opioid tolerance, we have isolated a cDNA for the human mu opioid receptor, the target of such opioid narcotics as morphine, codeine, methadone, and fentanyl. The receptor encoded by this cDNA is 400 amino acids long with 94% sequence similarity to the rat mu opioid receptor. Transient expression of this cDNA in COS-7 cells produced high-affinity binding sites to mu-selective agonists and antagonists. This receptor displays functional coupling to a recently cloned G-protein-activated K+ channel. When both proteins were expressed in Xenopus oocytes, functional desensitization developed upon repeated stimulation of the mu opioid receptor, as observed by a reduction in K+ current induced by the second mu receptor activation relative to that induced by the first. The extent of desensitization was potentiated by both the multifunctional calcium/calmodulin-dependent protein kinase and protein kinase C. These results demonstrate that kinase modulation is a molecular mechanism by which the desensitization of mu receptor signaling may be regulated at the cellular level, suggesting that this cellular mechanism may contribute to opioid tolerance in humans.

Effectiveness of Injectable Extended-Release Naltrexone vs Daily Buprenorphine-Naloxone for Opioid Dependence: A Randomized Clinical Noninferiority Trial.

PubMed

Tanum, Lars; Solli, Kristin Klemmetsby; Latif, Zill-E-Huma; Benth, Jurate Šaltyte; Opheim, Arild; Sharma-Haase, Kamni; Krajci, Peter; Kunøe, Nikolaj

2017-12-01

To date, extended-release naltrexone hydrochloride has not previously been compared directly with opioid medication treatment (OMT), currently the most commonly prescribed treatment for opioid dependence. To determine whether treatment with extended-release naltrexone will be as effective as daily buprenorphine hydrochloride with naloxone hydrochloride in maintaining abstinence from heroin and other illicit substances in newly detoxified individuals. A 12-week, multicenter, outpatient, open-label randomized clinical trial was conducted at 5 urban addiction clinics in Norway between November 1, 2012, and December 23, 2015; the last follow-up was performed on October 23, 2015. A total of 232 adult opioid-dependent (per DSM-IV criteria) individuals were recruited from outpatient addiction clinics and detoxification units and assessed for eligibility. Intention-to-treat analyses of efficacy end points were performed with all randomized participants. Randomization to either daily oral flexible dose buprenorphine-naloxone, 4 to 24 mg/d, or extended-release naltrexone hydrochloride, 380 mg, administered intramuscularly every fourth week for 12 weeks. Primary end points (protocol) were the randomized clinical trial completion rate, the proportion of opioid-negative urine drug tests, and number of days of use of heroin and other illicit opioids. Secondary end points included number of days of use of other illicit substances. Safety was assessed by adverse event reporting. Of 159 participants, mean (SD) age was 36 (8.6) years and 44 (27.7%) were women. Eighty individuals were randomized to extended-release naltrexone and 79 to buprenorphine-naloxone; 105 (66.0%) completed the trial. Retention in the extended-release naltrexone group was noninferior to the buprenorphine-naloxone group (difference, -0.1; with 95% CI, -0.2 to 0.1; P = .04), with mean (SD) time of 69.3 (25.9) and 63.7 (29.9) days, correspondingly (P = .33, log-rank test). Treatment with extended

State-Targeted Funding and Technical Assistance to Increase Access to Medication Treatment for Opioid Use Disorder.

PubMed

Abraham, Amanda J; Andrews, Christina M; Grogan, Colleen M; Pollack, Harold A; D'Aunno, Thomas; Humphreys, Keith; Friedmann, Peter D

2018-04-01

As the United States grapples with an opioid epidemic, expanding access to effective treatment for opioid use disorder is a major public health priority. Identifying effective policy tools that can be used to expand access to care is critically important. This article examines the relationship between state-targeted funding and technical assistance and adoption of three medications for treating opioid use disorder: oral naltrexone, injectable naltrexone, and buprenorphine. This study draws from the 2013-2014 wave of the National Drug Abuse Treatment System Survey, a nationally representative, longitudinal study of substance use disorder treatment programs. The sample includes data from 695 treatment programs (85.5% response rate) and representatives from single-state agencies in 49 states and Washington, D.C. (98% response rate). Logistic regression was used to examine the relationships of single-state agency targeted funding and technical assistance to availability of opioid use disorder medications among treatment programs. State-targeted funding was associated with increased program-level adoption of oral naltrexone (adjusted odds ratio [AOR]=3.14, 95% confidence interval [CI]=1.49-6.60, p=.004) and buprenorphine (AOR=2.47, 95% CI=1.31-4.67, p=.006). Buprenorphine adoption was also correlated with state technical assistance to support medication provision (AOR=1.18, 95% CI=1.00-1.39, p=.049). State-targeted funding for medications may be a viable policy lever for increasing access to opioid use disorder medications. Given the historically low rates of opioid use disorder medication adoption in treatment programs, single-state agency targeted funding is a potentially important tool to reduce mortality and morbidity associated with opioid disorders and misuse.

Opioids in Preclinical and Clinical Trials

NASA Astrophysics Data System (ADS)

Nagase, Hiroshi; Fujii, Hideaki

Since 1952, when Gates determined the stereo structure of morphine, numerous groups have focused on discovering a nonnarcotic opioid drug [1]. Although several natural, semisynthetic, and synthetic opioid ligands (alkaloids and peptides) have been developed in clinical studies, very few were nonnarcotic opioid drugs [2]. One of the most important studies in the opioid field appeared in 1976, when Martin and colleagues [3] established types of opioid receptors (these are now classified into μ, δ, and κ types). Later, Portoghese discovered a highly selective μ type opioid receptor antagonist, β-funaltrexamine [4]. This led to the finding that the μ type opioid receptor was correlated to drug dependence [5]. Consequently, δ, and particularly κ, opioid agonists were expected to lead to ideal opioid drugs. Moreover, opioid antagonists were evaluated for the treatment of symptoms related to undesirable opioid system activation. In this chapter, we provide a short survey of opioid ligands in development and describe the discovery of the two most promising drugs, TRK-851 [6] and TRK-820 (nalfurafine hydrochloride) [7].

Massage Impact on Pain in Opioid-dependent Patients in Substance Use Treatment

PubMed Central

Wiest, Katharina L.; Asphaug, Victoria J.; Carr, Kathryn E.; Gowen, Emily A.; Hartnett, Timothy T.

2015-01-01

Background: Chronic pain is a common cause of health care utilization and high levels of pain are pronounced in individuals engaged in methadone maintenance treatment. Although massage has been demonstrated to alleviate chronic pain symptoms, its use as an adjunctive therapy to modify pain during opioid-replacement treatment is absent from the literature. Purpose: To consider the efficacy of Swedish massage in reducing pain in opioid-dependent patients with chronic pain receiving methadone treatment. Setting: Trial was conducted at a nonprofit methadone treatment center serving low-income patients. Research Design: A randomized clinical trial with randomized to either 1) massage plus treatment-as-usual (TAU) (n = 27) or 2) TAU (n = 24). Durability of treatment effect was evaluated at Week 12. Intervention: Eight weekly 50-minute Swedish massage sessions plus TAU or TAU alone. Main Outcome Measures: Pain, anxiety, depression, physical functioning, decreased substance use, and improvement in treatment engagement. Results: Randomized participants were comparable at Baseline for demographic, pain, physical, and emotional variables. Massage group reported improved pain scores; worst pain had a clinically significant 2-point improvement while the other pain scores did not. Overall improvements were not observed in treatment engagement or levels of anxiety, depression, or physical functioning. A subgroup of the participants, who felt they could be pain-free, consistently reported improvements in pain from Baseline to Week 8, and this was most pronounced and clinically significant in the massage group. Conclusions: These preliminary findings do not support an overall clinically significant positive effect of Swedish massage on reduction in pain ratings or improvement in anxiety, depression, or treatment engagement in a substance-using, opioid-dependent population with chronic pain. Future nonpharmacologic pain research in marginalized substance-using populations may wish

Opioid Rotation in Cancer Pain Treatment.

PubMed

Schuster, Michael; Bayer, Oliver; Heid, Florian; Laufenberg-Feldmann, Rita

2018-03-02

Rotating several different WHO level III opioid drugs is a therapeutic option for patients with chronic cancer-related pain who suffer from inadequate analgesia and/or intolerable side effects. The evidence favoring opioid rotation is controversial, and the current guidelines in Germany and other countries contain only weak recommendations for it. This review is based on pertinent publications retrieved by a systematic review of the literature on opioid rotation for adult patients with chronic cancerrelated pain who are regularly taking WHO level III opioids by the oral or trans - dermal route. 9 individual studies involving a total of 725 patients were included in the analysis, and 3 previous systematic reviews of studies involving a total of 2296 patients were also analyzed. Morphine, oxycodone, fentanyl, hydromorphone, and buprenorphine were used as first-line opioid drugs, and hydromorphone, bupre - norphine, tapentadol, fentanyl, morphine, oxymorphone, and methadone were used as second-line opioid drugs. In all of the studies, pain control was achieved for 14 days after each rotation. In most of them, the dose of the new drug introduced in each rotation needed to be increased above the dose initially calculated from a rotation ratio, with the exception of rotations to methadone. The frequency of side effects was only rarely lessened, but patients largely considered the result of opioid rotation to be positive. No particular opioid drug was found to be best. Opioid rotation can improve analgesia and patient satisfaction. The success of opioid rotation appears to depend on the magnitude of the initial dose, among other factors. Tables of equianalgesic doses should be considered no more than a rough guide for determining the dose of the new drug. Rotations to methadone should be carried out under clinical supervision in experienced hands.

Cost-effectiveness of long-term outpatient buprenorphine-naloxone treatment for opioid dependence in primary care.

PubMed

Schackman, Bruce R; Leff, Jared A; Polsky, Daniel; Moore, Brent A; Fiellin, David A

2012-06-01

Primary care physicians with appropriate training may prescribe buprenorphine-naloxone (bup/nx) to treat opioid dependence in US office-based settings, where many patients prefer to be treated. Bup/nx is off patent but not available as a generic. We evaluated the cost-effectiveness of long-term office-based bup/nx treatment for clinically stable opioid-dependent patients compared to no treatment. A decision analytic model simulated a hypothetical cohort of clinically stable opioid-dependent individuals who have already completed 6 months of office-based bup/nx treatment. Data were from a published cohort study that collected treatment retention, opioid use, and costs for this population, and published quality-of-life weights. Uncertainties in estimated monthly costs and quality-of-life weights were evaluated in probabilistic sensitivity analyses, and the economic value of additional research to reduce these uncertainties was also evaluated. Bup/nx, provider, and patient costs in 2010 US dollars, quality-adjusted life years (QALYs), and incremental cost-effectiveness (CE) ratios ($/QALY); costs and QALYs are discounted at 3% annually. In the base case, office-based bup/nx for clinically stable patients has a CE ratio of $35,100/QALY compared to no treatment after 24 months, with 64% probability of being < $100,000/QALY in probabilistic sensitivity analysis. With a 50% bup/nx price reduction the CE ratio is $23,000/QALY with 69% probability of being < $100,000/QALY. Alternative quality-of-life weights result in CE ratios of $138,000/QALY and $90,600/QALY. The value of research to reduce quality-of-life uncertainties for 24-month results is $6,400 per person eligible for treatment at the current bup/nx price and $5,100 per person with a 50% bup/nx price reduction. Office-based bup/nx for clinically stable patients may be a cost-effective alternative to no treatment at a threshold of $100,000/QALY depending on assumptions about quality-of-life weights. Additional

Opioid Analgesics for Chronic Non-Cancer Pain: A Guideline on Opioid Prescribing.

PubMed

Van Demark, Robert; Chang, Peter; Heinemann, Daniel

2016-01-01

Over the past decade, the use of opioid analgesics has risen dramatically both in the U.S. and South Dakota. Opioids have been increasingly used to treat chronic non-cancer pain; however, the utilization of opioids for this role has limited and questionable utility. The U.S. has also seen a rise of opioid abuse, addiction, misuse, and overdose. The various pharmacological and non-pharmacological strategies to help physicians manage chronic non-cancer pain and a guideline on appropriate opioid prescribing are presented. Before the decision is made to begin opioid therapy for chronic non-cancer pain, other pharmacological and non-pharmacological therapeutic strategies should be explored. The schema for responsible opioid prescribing can be dived into the following: the initial assessment, initiating opioid therapy, maintenance therapy, and the discontinuation of opioid treatment. These categories are explored, and a general approach to prescribing opioids for chronic non-cancer pain is presented. The Centers for Disease Control and Prevention (CDC) has declared opioid prescription abuse an "epidemic." There are a variety of methods clinicians can utilize to relieve chronic non-cancer pain. If opioid therapy is sought, clinicians should be mindful of the current state of opioid abuse and misuse. This guideline may aid clinicians in appropriate opioid prescribing.

Macroeconomic conditions and opioid abuse.

PubMed

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.

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

PubMed

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.

Effects of injectable extended-release naltrexone (XR-NTX) for opioid dependence on residential rehabilitation outcomes and early follow-up.

PubMed

Leslie, Douglas L; Milchak, William; Gastfriend, David R; Herschman, Philip L; Bixler, Edward O; Velott, Diana L; Meyer, Roger E

2015-04-01

Little is known about the use of extended-release naltrexone (XR-NTX) during residential rehabilitation, and its effects on early outcomes and rates of follow-up treatment. This study examined patient characteristics and rates of treatment completion and engagement in post-residential care of opioid dependent patients who received XR-NTX during residential rehabilitation, compared with patients who did not receive this medication. Electronic records for opioid dependent patients from three Pennsylvania residential detoxification and treatment facilities (N = 7,687) were retrospectively analyzed. We determined the proportion of patients who received XR-NTX (INJ), and compared rates of treatment completion and engagement in follow-up care relative to a naturalistic control group of patients recommended for, but not administered, XR-NTX (Non-INJ). Data on whether the patient initiated follow-up care were available from one site (N = 3,724). Overall, 598 (7.8%) patients were recommended for XR-NTX and of these, 168 (28.1%) received injections. Compared to non-INJ patients, INJ patients were less likely to leave against medical advice (4.8% vs. 30.2%, p < .001) and more likely to initiate follow-up care (37.7% vs. 19.7%, p < .001). These differences remained significant after controlling for demographic covariates using regression analysis. XR-NTX was associated with higher rates of residential and early post-residential care engagement in patients with opioid dependence. XR-NTX may be an effective adjunct in the residential treatment and aftercare of patients with opioid dependence. © American Academy of Addiction Psychiatry.

Ghrelin interacts with neuropeptide Y Y1 and opioid receptors to increase food reward.

PubMed

Skibicka, Karolina P; Shirazi, Rozita H; Hansson, Caroline; Dickson, Suzanne L

2012-03-01

Ghrelin, a stomach-derived hormone, is an orexigenic peptide that was recently shown to potently increase food reward behavior. The neurochemical circuitry that links ghrelin to the mesolimbic system and food reward behavior remains unclear. Here we examined the contribution of neuropeptide Y (NPY) and opioids to ghrelin's effects on food motivation and intake. Both systems have well-established links to the mesolimbic ventral tegmental area (VTA) and reward/motivation control. NPY mediates the effect of ghrelin on food intake via activation of NPY-Y1 receptor (NPY-Y1R); their connection with respect to motivated behavior is unexplored. The role of opioids in any aspect of ghrelin's action on food-oriented behaviors is unknown. Rats were trained in a progressive ratio sucrose-induced operant schedule to measure food reward/motivation behavior. Chow intake was measured immediately after the operant test. In separate experiments, we explored the suppressive effects of a selective NPY-Y1R antagonist or opioid receptor antagonist naltrexone, injected either intracerebroventricularly or intra-VTA, on ghrelin-induced food reward behavior. The ventricular ghrelin-induced increase in sucrose-motivated behavior and chow intake were completely blocked by intracerebroventricular pretreatment with either an NPY-Y1R antagonist or naltrexone. The intra-VTA ghrelin-induced sucrose-motivated behavior was blocked only by intra-VTA naltrexone. In contrast, the intra-VTA ghrelin-stimulated chow intake was attenuated only by intra-VTA NPY-Y1 blockade. Finally, ghrelin infusion was associated with an elevated VTA μ-opioid receptor expression. Thus, we identify central NPY and opioid signaling as the necessary mediators of food intake and reward effects of ghrelin and localize these interactions to the mesolimbic VTA.

Opioids in Pregnancy and Neonatal Abstinence Syndrome

PubMed Central

Stover, Megan W.; Davis, Jonathan M.

2015-01-01

Opiate use in pregnancy has increased dramatically over the past decade and now represents a major public health problem. More women are using prescription opioids, illegal opioids, and opioid substitution therapy. These drugs are associated with numerous obstetrical complications including intrauterine growth restriction, placental abruption, preterm delivery, oligohydramnios, stillbirth, and maternal death. Neonatal complications are also significant, such as an increased risk of mortality as well as neonatal abstinence syndrome (NAS). NAS is a serious and highly variable condition characterized by central nervous system hyperirritability and autonomic nervous system dysfunction. The present review seeks to define current practices regarding the management of opiate dependence in pregnancy and care of the neonate with prenatal opiate exposure. Since genetic factors appear to be associated with the incidence and severity of NAS, opportunities for “personalized genomic medicine” and unique therapeutic interventions could be developed in the future. PMID:26452318

Safe and competent opioid prescribing education: Increasing dissemination with a train-the-trainer program.

PubMed

Zisblatt, Lara; Hayes, Sean M; Lazure, Patrice; Hardesty, Ilana; White, Julie L; Alford, Daniel P

2017-01-01

Due to the high prevalence of prescription opioid misuse, the US Food and Drug Administration (FDA) mandated a Risk Evaluation and Mitigation Strategy (REMS) requiring manufacturers of extended-release/long-acting (ER/LA) opioids to fund continuing education based on an FDA curricular Blueprint. This paper describes the Safe and Competent Opioid Prescribing Education (SCOPE of Pain) train-the-trainer program and its impact on (1) disseminating the SCOPE of Pain curriculum and (2) knowledge, confidence, attitudes, and performance of the participants of trainer-led compared with expert-led meetings. SCOPE of Pain is a 3-hour ER/LA opioid REMS education. In addition to expert-led live statewide meetings, a 2-hour train-the-trainer (TTT) workshop was developed to increase dissemination nationally. The trainers were expected to conduct SCOPE of Pain meetings at their institutions. Participants of both the trainer-led and expert-led SCOPE of Pain programs were surveyed immediately post and 2 months post meetings to assess improvements in knowledge, confidence, attitudes, and self-reported safe opioid prescribing practices. During 9 months (May 2013 to February 2014), 89 trainers were trained during 9 TTT workshops in 9 states. Over 24 months (May 2013 to April 2015), 33% of the trainers conducted at least 1 SCOPE of Pain training, with a total of 79 meetings that educated 1419 participants. The average number of meetings of those who conducted at least 1 meeting was 2.8 (range: 1-19). The participants of the trainer-led programs were significantly more likely to be practicing in rural settings than those who participated in the expert-led meetings (39% vs. 26%, P < .001). At 2 months post training, there were no significant differences in improvements in participant knowledge, confidence, attitudes, and performance between expert-led and trainer-led meetings. The SCOPE of Pain TTT program holds promise as an effective dissemination strategy to increase guideline

Molecular Pharmacology of δ-Opioid Receptors

PubMed Central

Gendron, Louis; Cahill, Catherine M.; von Zastrow, Mark; Schiller, Peter W.

2016-01-01

Opioids are among the most effective analgesics available and are the first choice in the treatment of acute severe pain. However, partial efficacy, a tendency to produce tolerance, and a host of ill-tolerated side effects make clinically available opioids less effective in the management of chronic pain syndromes. Given that most therapeutic opioids produce their actions via µ-opioid receptors (MOPrs), other targets are constantly being explored, among which δ-opioid receptors (DOPrs) are being increasingly considered as promising alternatives. This review addresses DOPrs from the perspective of cellular and molecular determinants of their pharmacological diversity. Thus, DOPr ligands are examined in terms of structural and functional variety, DOPrs’ capacity to engage a multiplicity of canonical and noncanonical G protein–dependent responses is surveyed, and evidence supporting ligand-specific signaling and regulation is analyzed. Pharmacological DOPr subtypes are examined in light of the ability of DOPr to organize into multimeric arrays and to adopt multiple active conformations as well as differences in ligand kinetics. Current knowledge on DOPr targeting to the membrane is examined as a means of understanding how these receptors are especially active in chronic pain management. Insight into cellular and molecular mechanisms of pharmacological diversity should guide the rational design of more effective, longer-lasting, and better-tolerated opioid analgesics for chronic pain management. PMID:27343248

Willingness to pay for opioid agonist treatment among opioid dependent people who inject drugs in Ukraine.

PubMed

Makarenko, Iuliia; Mazhnaya, Alyona; Marcus, Ruthanne; Bojko, Martha J; Madden, Lynn; Filippovich, Sergii; Dvoriak, Sergii; Altice, Frederick L

2017-07-01

In the context of decreasing external and limited Ukrainian governmental funding for opioid agonist treatments (OAT) for opioid dependent people who inject drugs in Ukraine, information on sustainable financial models is needed. Data on 855 opioid dependent people who inject drugs (PWID) were drawn from a cross-sectional nationwide survey of 1613 PWID. They comprised 434 participants who were receiving OAT and 421 who were on OAT in the past or have never been on OAT and were interested in receiving the treatment. Multivariate logistic regression was used to examine factors associated with willingness-to-pay (WTP) for OAT, stratified by OAT experience. Variation in the price which respondents were willing to pay for OAT and its effect on their monthly income among PWID with different OAT experience were assessed as a continuous variable using one-way ANOVA and Kruskal-Wallis test. Overall, 378 (44%) expressed WTP for OAT. Factors independently associated with WTP differed by OAT experience. Among those using OAT, independent predictors of WTP included: city (Dnipro - aOR=1.9; 95%CI=1.1-4.8 and Lviv - (aOR=2.2; 95%CI=1.1-4.8) compared to those elsewhere in Ukraine), higher income (aOR=1.8; 95%CI=1.2-2.7) and receiving psychosocial counseling (aOR=1.8; 95%CI=1.2-2.7). Among those who had previously been on OAT, positive attitude towards OAT (aOR=1.3; 95%CI=1.1-1.6) and family support of OAT (aOR=2.5; 95%CI=1.1-5.7) were independently associated with WTP. Among PWID who had never been on OAT, being male (aOR=2.2; 95%CI=1.1-4.2), younger age (aOR=1.9; 95%CI=1.2-3.2), higher income (aOR=2.0; 95%CI=1.2-3.4) and previous unsuccessful attempts to enter OAT (aOR=2.3; 95%CI=1.1-4.7) were independently associated with WTP. PWID were willing to commit a large percentage of their monthly income for OAT, which, however, varied significantly based on OAT experience: current OAT: 37% of monthly income, previous OAT: 53%, and never OAT: 60% (p-value=0.0009). WTP for OAT was

Do drug treatment variables predict cognitive performance in multidrug-treated opioid-dependent patients? A regression analysis study

PubMed Central

2012-01-01

Background Cognitive deficits and multiple psychoactive drug regimens are both common in patients treated for opioid-dependence. Therefore, we examined whether the cognitive performance of patients in opioid-substitution treatment (OST) is associated with their drug treatment variables. Methods Opioid-dependent patients (N = 104) who were treated either with buprenorphine or methadone (n = 52 in both groups) were given attention, working memory, verbal, and visual memory tests after they had been a minimum of six months in treatment. Group-wise results were analysed by analysis of variance. Predictors of cognitive performance were examined by hierarchical regression analysis. Results Buprenorphine-treated patients performed statistically significantly better in a simple reaction time test than methadone-treated ones. No other significant differences between groups in cognitive performance were found. In each OST drug group, approximately 10% of the attention performance could be predicted by drug treatment variables. Use of benzodiazepine medication predicted about 10% of performance variance in working memory. Treatment with more than one other psychoactive drug (than opioid or BZD) and frequent substance abuse during the past month predicted about 20% of verbal memory performance. Conclusions Although this study does not prove a causal relationship between multiple prescription drug use and poor cognitive functioning, the results are relevant for psychosocial recovery, vocational rehabilitation, and psychological treatment of OST patients. Especially for patients with BZD treatment, other treatment options should be actively sought. PMID:23121989

Mu opioid receptor stimulation activates c-Jun N-terminal kinase 2 by distinct arrestin-dependent and independent mechanisms.

PubMed

Kuhar, Jamie Rose; Bedini, Andrea; Melief, Erica J; Chiu, Yen-Chen; Striegel, Heather N; Chavkin, Charles

2015-09-01

G protein-coupled receptor desensitization is typically mediated by receptor phosphorylation by G protein-coupled receptor kinase (GRK) and subsequent arrestin binding; morphine, however, was previously found to activate a c-Jun N-terminal kinase (JNK)-dependent, GRK/arrestin-independent pathway to produce mu opioid receptor (MOR) inactivation in spinally-mediated, acute anti-nociceptive responses [Melief et al.] [1]. In the current study, we determined that JNK2 was also required for centrally-mediated analgesic tolerance to morphine using the hotplate assay. We compared JNK activation by morphine and fentanyl in JNK1(-/-), JNK2(-/-), JNK3(-/-), and GRK3(-/-) mice and found that both compounds specifically activate JNK2 in vivo; however, fentanyl activation of JNK2 was GRK3-dependent, whereas morphine activation of JNK2 was GRK3-independent. In MOR-GFP expressing HEK293 cells, treatment with either arrestin siRNA, the Src family kinase inhibitor PP2, or the protein kinase C (PKC) inhibitor Gö6976 indicated that morphine activated JNK2 through an arrestin-independent Src- and PKC-dependent mechanism, whereas fentanyl activated JNK2 through a Src-GRK3/arrestin-2-dependent and PKC-independent mechanism. This study resolves distinct ligand-directed mechanisms of JNK activation by mu opioid agonists and understanding ligand-directed signaling at MOR may improve opioid therapeutics. Copyright © 2015 Elsevier Inc. All rights reserved.

Opioid Attentional Bias and Cue-Elicited Craving Predict Future Risk of Prescription Opioid Misuse Among Chronic Pain Patients*

PubMed Central

Garland, Eric L.; Howard, Matthew O.

2014-01-01

Background Some chronic pain patients receiving long-term opioid analgesic pharmacotherapy are at risk for misusing opioids. Like other addictive behaviors, risk of opioid misuse may be signaled by an attentional bias (AB) towards drug-related cues. The purpose of this study was to examine opioid AB as a potential predictor of opioid misuse among chronic pain patients following behavioral treatment. Methods Chronic pain patients taking long-term opioid analgesics (N = 47) completed a dot probe task designed to assess opioid AB, as well as self-report measures of opioid misuse and pain severity, and then participated in behavioral treatment. Regression analyses examined opioid AB and cue-elicited craving as predictors of opioid misuse at 3-months posttreatment follow-up. Results Patients who scored high on a measure of opioid misuse risk following treatment exhibited significantly greater opioid AB scores than patients at low risk for opioid misuse. Opioid AB for 200 ms cues and cue-elicited craving significantly predicted opioid misuse risk 20 weeks later, even after controlling for pre-treatment opioid dependence diagnosis, opioid misuse, and pain severity (Model R2 = .50). Conclusion Biased initial attentional orienting to prescription opioid cues and cue-elicited craving may reliably signal future opioid misuse risk following treatment. These measures may therefore provide potential prognostic indicators of treatment outcome. PMID:25282309

Millon Clinical Multiaxial Inventory-III Subtypes of Opioid Dependence: Validity and Matching to Behavioral Therapies

ERIC Educational Resources Information Center

Ball, Samuel A.; Nich, Charla; Rounsaville, Bruce J.; Eagan, Dorothy; Carroll, Kathleen M.

2004-01-01

The concurrent and predictive validity of 2 different methods of Millon Clinical Multiaxial Inventory-III subtyping (protocol sorting, cluster analysis) was evaluated in 125 recently detoxified opioid-dependent outpatients in a 12-week randomized clinical trial. Participants received naltrexone and relapse prevention group counseling and were…

How Does Cognitive Behaviour Therapy Work with Opioid-Dependent Clients? Results of the UKCBTMM Study

ERIC Educational Resources Information Center

Kouimtsidis, Christos; Reynolds, Martina; Coulton, Simon; Drummond, Colin

2012-01-01

Introduction: Process research in psychotherapy is important to understand how treatment works. The National Institute of Clinical Excellence guidelines suggest that in methadone maintenance treatment (MMT) for opioid dependence, drug key-working should be based on cognitive behavioural therapy (CBT) principles. This article reports the findings…

The prescription opioid epidemic: an overview for anesthesiologists.

PubMed

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

Healthy Adult Male Facial Skin Surface Lipid Pheromone p.o. to Treat Opioid Addiction

ClinicalTrials.gov

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

Opioid agonist efficacy predicts the magnitude of tolerance and the regulation of mu-opioid receptors and dynamin-2.

PubMed

Pawar, Mohit; Kumar, Priyank; Sunkaraneni, Soujanya; Sirohi, Sunil; Walker, Ellen A; Yoburn, Byron C

2007-06-01

It has been proposed that opioid agonist efficacy may play a role in tolerance and the regulation of opioid receptor density. To address this issue, the present studies estimated the in vivo efficacy of three opioid agonists and then examined changes in spinal mu-opioid receptor density following chronic treatment in the mouse. In addition, tolerance and regulation of the trafficking protein dynamin-2 were determined. To evaluate efficacy, the method of irreversible receptor alkylation was employed and the efficacy parameter tau estimated. Mice were injected with the irreversible mu-opioid receptor antagonist clocinnamox (0.32-25.6 mg/kg, i.p), and 24 h later, the analgesic potency of s.c. morphine, oxycodone and etorphine were determined. Clocinnamox dose-dependently antagonized the analgesic effects of morphine, etorphine and oxycodone. The shift to the right of the dose-response curves was greater for morphine and oxycodone compared to etorphine and the highest dose of clocinnamox reduced the maximal effect of morphine and oxycodone, but not etorphine. The order of efficacy calculated from these results was etorphine>morphine>oxycodone. Other mice were infused for 7 days with oxycodone (10-150 mg/kg/day, s.c.) or etorphine (50-250 microg/kg/day, s.c.) and the analgesic potency of s.c. morphine determined. The low efficacy agonist (oxycodone) produced more tolerance than the high efficacy agonist (etorphine) at equi-effective infusion doses. In saturation binding experiments, the low efficacy opioid agonists (morphine, oxycodone) did not regulate the density of spinal mu-opioid receptors, while etorphine produced approximately 40% reduction in mu-opioid receptor density. Furthermore, etorphine increased spinal dynamin-2 abundance, while oxycodone did not produce any significant change in dynamin-2 abundance. Overall, these data indicate that high efficacy agonists produce less tolerance at equi-effective doses. Furthermore, increased efficacy was associated with

Initiation into Prescription Opioid Misuse among Young Injection Drug Users

PubMed Central

Lankenau, Stephen E.; Teti, Michelle; Silva, Karol; Bloom, Jennifer Jackson; Harocopos, Alex; Treese, Meghan

2011-01-01

Background Prescription opioids are the most frequently misused class of prescription drugs among young adults. Initiation into prescription opioid misuse is an important public health concern since opioids are increasingly associated with drug dependence and fatal overdose. Descriptive data about initiation into prescription opioid misuse among young injection drug users (IDUs) are scarce. Methods An exploratory qualitative study was undertaken to describe patterns of initiation into prescription opioid misuse among IDUs aged 16 to 25 years. Those young IDUs who had misused a prescription drug at least three times in the past three months were recruited during 2008 and 2009 in Los Angeles (n=25) and New York (n=25). Informed by an ethno-epidemiological approach, descriptive data from a semi-structured interview guide were analysed both quantitatively and qualitatively. Results Initiation into prescription opioid misuse was facilitated by easy access to opioids via participant’s own prescription, family, or friends, and occurred earlier than misuse of other illicit drugs, such as heroin. Nearly all transitioned into sniffing opioids, most injected opioids, and many initiated injection drug use with an opioid. Motives for transitions to sniffing and injecting opioids included obtaining a more potent high and/or substituting for heroin; access to multiple sources of opioids was common among those who progressed to sniffing and injecting opioids. Conclusion Prescription opioid misuse was a key feature of trajectories into injection drug use and/or heroin use among this sample of young IDUs. A new pattern of drug use may be emerging whereby IDUs initiate prescription opioid misuse before using heroin. PMID:21689917

Prescription opioid misusing chronic pain patients exhibit dysregulated context-dependent associations: Investigating associative learning in addiction with the cue-primed reactivity task.

PubMed

Garland, Eric L; Bryan, Craig J; Kreighbaum, Lydia; Nakamura, Yoshio; Howard, Matthew O; Froeliger, Brett

2018-06-01

Associative learning undergirds the development of addiction, such that drug-related cues serve as conditioned stimuli to elicit drug-seeking responses. Plausibly, among opioid misusing chronic pain patients, pain-related information may serve as a conditioned stimulus to magnify opioid cue-elicited autonomic and craving responses through a process of second-order conditioning. We utilized a novel psychophysiological probe of pain-opioid conditioned associations, the Cue-Primed Reactivity (CPR) task. In this task, participants were presented with images as primes (200 ms) and cues (6000 ms) in pairs organized in four task blocks: "control-opioid," "pain-opioid," "control-pain," and "opioid-pain." Opioid-treated chronic pain patients (N = 30) recruited from an Army base in the Western United States were classified as opioid misusers (n = 17) or non-misusers (n = 13) via a validated cutpoint on the Prescription Drug Use Questionnaire (PDUQ; Compton et al., 2008). Opioid misuse status was examined as a predictor of HRV, craving, and mood responses on the CPR task. HRV increased to a greater extent during the pain-opioid block compared to the control-opioid block for non-misusers compared to misusers (p = .003, η 2 partial  = 0.27). In contrast, craving increased to a greater extent from baseline to the pain-opioid block for misusers than for non-misusers (p = .03, η 2 partial  = .16). Findings suggest that opioid-treated chronic pain patients exhibit Pavlovian conditioned responses to opioid cues strengthened by an associative learning process of second-order conditioning when primed by pain-related images. This pain-opioid contingency appears to become disrupted among individuals who engage in opioid misuse, such that opioid-related stimuli elicit motivational responses irrespective of pain-related contextual stimuli. Copyright © 2018 Elsevier B.V. All rights reserved.

Pain Volatility and Prescription Opioid Addiction Treatment Outcomes in Patients with Chronic Pain

PubMed Central

Worley, Matthew J.; Heinzerling, Keith G.; Shoptaw, Steven; Ling, Walter

2015-01-01

The combination of prescription opioid dependence and chronic pain is increasingly prevalent and hazardous to public health. Variability in pain may explain poor prescription opioid addiction treatment outcomes in persons with chronic pain. This study examined pain trajectories and pain volatility in patients with chronic pain receiving treatment for prescription opioid addiction. We conducted secondary analyses of adults with chronic pain (N = 149) who received buprenorphine-naloxone (BUP-NLX) and counseling for 12 weeks in an outpatient, multi-site clinical trial. Good treatment outcome was defined as urine-verified abstinence from opioids at treatment endpoint (Week 12) and during at least two of the previous three weeks. Pain severity significantly declined over time during treatment (b = − 0.36, p < .001). Patients with greater pain volatility were less likely to have a good treatment outcome (OR = 0.55, p < .05), controlling for baseline pain severity and rate of change in pain over time. A one standard deviation increase in pain volatility was associated with a 44% reduction in the probability of endpoint abstinence. The significant reduction in subjective pain during treatment provides observational support for the analgesic effects of BUP-NLX in patients with chronic pain and opioid dependence. Patients with greater volatility in subjective pain during treatment have increased risk for returning to opioid use by the conclusion of an intensive treatment with BUP-NLX and counseling. Future research should examine underlying mechanisms of pain volatility and identify related therapeutic targets to optimize interventions for prescription opioid addiction and co-occurring chronic pain. PMID:26302337

Pain volatility and prescription opioid addiction treatment outcomes in patients with chronic pain.

PubMed

Worley, Matthew J; Heinzerling, Keith G; Shoptaw, Steven; Ling, Walter

2015-12-01

The combination of prescription opioid dependence and chronic pain is increasingly prevalent and hazardous to public health. Variability in pain may explain poor prescription opioid addiction treatment outcomes in persons with chronic pain. This study examined pain trajectories and pain volatility in patients with chronic pain receiving treatment for prescription opioid addiction. We conducted secondary analyses of adults with chronic pain (n = 149) who received buprenorphine/naloxone (BUP/NLX) and counseling for 12 weeks in an outpatient, multisite clinical trial. Good treatment outcome was defined as urine-verified abstinence from opioids at treatment endpoint (Week 12) and during at least 2 of the previous 3 weeks. Pain severity significantly declined over time during treatment (b = -0.36, p < .001). Patients with greater pain volatility were less likely to have a good treatment outcome (odds ratio = 0.55, p < .05), controlling for baseline pain severity and rate of change in pain over time. A 1 standard deviation increase in pain volatility was associated with a 44% reduction in the probability of endpoint abstinence. The significant reduction in subjective pain during treatment provides observational support for the analgesic effects of BUP/NLX in patients with chronic pain and opioid dependence. Patients with greater volatility in subjective pain during treatment have increased risk of returning to opioid use by the conclusion of an intensive treatment with BUP/NLX and counseling. Future research should examine underlying mechanisms of pain volatility and identify related therapeutic targets to optimize interventions for prescription opioid addiction and co-occurring chronic pain. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Cohort Study of the Impact of High-Dose Opioid Analgesics on Overdose Mortality.

PubMed

Dasgupta, Nabarun; Funk, Michele Jonsson; Proescholdbell, Scott; Hirsch, Annie; Ribisl, Kurt M; Marshall, Steve

2016-01-01

Previous studies examining opioid dose and overdose risk provide limited granularity by milligram strength and instead rely on thresholds. We quantify dose-dependent overdose mortality over a large spectrum of clinically common doses. We also examine the contributions of benzodiazepines and extended release opioid formulations to mortality. Prospective observational cohort with one year follow-up. One year in one state (NC) using a controlled substances prescription monitoring program, with name-linked mortality data. Residential population of North Carolina (n = 9,560,234), with 2,182,374 opioid analgesic patients. Exposure was dispensed prescriptions of solid oral and transdermal opioid analgesics; person-years calculated using intent-to-treat principles. Outcome was overdose deaths involving opioid analgesics in a primary or additive role. Poisson models were created, implemented using generalized estimating equations. Opioid analgesics were dispensed to 22.8% of residents. Among licensed clinicians, 89.6% prescribed opioid analgesics, and 40.0% prescribed ER formulations. There were 629 overdose deaths, half of which had an opioid analgesic prescription active on the day of death. Of 2,182,374 patients prescribed opioids, 478 overdose deaths were reported (0.022% per year). Mortality rates increased gradually across the range of average daily milligrams of morphine equivalents. 80.0% of opioid analgesic patients also received benzodiazepines. Rates of overdose death among those co-dispensed benzodiazepines and opioid analgesics were ten times higher (7.0 per 10,000 person-years, 95 percent CI: 6.3, 7.8) than opioid analgesics alone (0.7 per 10,000 person years, 95 percent CI: 0.6, 0.9). Dose-dependent opioid overdose risk among patients increased gradually and did not show evidence of a distinct risk threshold. There is urgent need for guidance about combined classes of medicines to facilitate a better balance between pain relief and overdose risk. Published by

Prevalence of Prescription Opioid Misuse/Abuse as Determined by International Classification of Diseases Codes: A Systematic Review.

PubMed

Roland, Carl L; Lake, Joanita; Oderda, Gary M

2016-12-01

We conducted a systematic review to evaluate worldwide human English published literature from 2009 to 2014 on prevalence of opioid misuse/abuse in retrospective databases where International Classification of Diseases (ICD) codes were used. Inclusion criteria for the studies were use of a retrospective database, measured abuse, dependence, and/or poisoning using ICD codes, stated prevalence or it could be derived, and documented time frame. A meta-analysis was not performed. A qualitative narrative synthesis was used, and 16 studies were included for data abstraction. ICD code use varies; 10 studies used ICD codes that encompassed all three terms: abuse, dependence, or poisoning. Eight studies limited determination of misuse/abuse to an opioid user population. Abuse prevalence among opioid users in commercial databases using all three terms of ICD codes varied depending on the opioid; 21 per 1000 persons (reformulated extended-release oxymorphone; 2011-2012) to 113 per 1000 persons (immediate-release opioids; 2010-2011). Abuse prevalence in general populations using all three ICD code terms ranged from 1.15 per 1000 persons (commercial; 6 months 2010) to 8.7 per 1000 persons (Medicaid; 2002-2003). Prevalence increased over time. When similar ICD codes are used, the highest prevalence is in US government-insured populations. Limiting population to continuous opioid users increases prevalence. Prevalence varies depending on ICD codes used, population, time frame, and years studied. Researchers using ICD codes to determine opioid abuse prevalence need to be aware of cautions and limitations.

Investigating expectation and reward in human opioid addiction with [(11) C]raclopride PET.

PubMed

Watson, Ben J; Taylor, Lindsay G; Reid, Alastair G; Wilson, Sue J; Stokes, Paul R; Brooks, David J; Myers, James F; Turkheimer, Federico E; Nutt, David J; Lingford-Hughes, Anne R

2014-11-01

The rewarding properties of some abused drugs are thought to reside in their ability to increase striatal dopamine levels. Similar increases have been shown in response to expectation of a positive drug effect. The actions of opioid drugs on striatal dopamine release are less well characterized. We examined whether heroin and the expectation of heroin reward increases striatal dopamine levels in human opioid addiction. Ten opioid-dependent participants maintained on either methadone or buprenorphine underwent [(11) C]raclopride positron emission tomography imaging. Opioid-dependent participants were scanned three times, receiving reward from 50-mg intravenous heroin (diamorphine; pharmaceutical heroin) during the first scan to generate expectation of the same reward at the second scan, during which they only received 0.1-mg intravenous heroin. There was no heroin injection during the third scan. Intravenous 50-mg heroin during the first scan induced pronounced effects leading to high levels of expectation at the second scan. There was no detectable increase in striatal dopamine levels to either heroin reward or expectation of reward. We believe this is the first human study to examine whether expectation of heroin reward increases striatal dopamine levels in opioid addiction. The absence of detectable increased dopamine levels to both the expectation and delivery of a heroin-related reward may have been due to the impact of substitute medication. It does however contrast with the changes seen in abstinent stimulant users, suggesting that striatal dopamine release alone may not play such a pivotal role in opioid-maintained individuals. © 2013 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Opioids and Chronic Pain | NIH MedlinePlus the Magazine

MedlinePlus

... term daily use of opioids leads to physical dependence, which is not to be confused with addiction ... screened and closely monitored. When people have physical dependence and the opioid use is stopped, withdrawal symptoms ...

Characteristics of methadone maintenance treatment patients prescribed opioid analgesics.

PubMed

Glenn, Matthew C; Sohler, Nancy L; Starrels, Joanna L; Maradiaga, Jeronimo; Jost, John J; Arnsten, Julia H; Cunningham, Chinazo O

2016-01-01

Opioid analgesic use and disorders have dramatically increased among the general American population and those receiving methadone maintenance treatment (MMT). Most research among MMT patients focuses on opioid analgesics misuse or disorders; few studies focus on MMT patients prescribed opioid analgesics. We describe demographic, clinical, and substance use characteristics of MMT patients prescribed opioid analgesics and compare them with MMT patients not prescribed opioid analgesics. We conducted a cross-sectional secondary data analysis using screening interviews from a parent study. From 2012 to 2015, we recruited adults from 3 MMT Bronx clinics. Questionnaire data included patterns of opioid analgesic use, substance use, comorbid illnesses, and demographic characteristics. Our main dependent variable was patients' report of currently taking prescribed opioid analgesics. To compare characteristics between MMT patients prescribed and not prescribed opioid analgesics, we conducted chi-square tests, t tests, and Mann-Whitney U tests. Of 611 MMT patients, most reported chronic pain (62.0%), hepatitis C virus (HCV) infection (52.1%), and current use of illicit substances (64.2%). Of the 29.8% who reported currently taking prescribed opioid analgesics, most misused their opioid analgesics (57.5%). Patients prescribed (versus not prescribed) opioid analgesics were more likely to report human immunodeficiency virus (HIV) infection (adjusted odds ratio [aOR] = 1.6, 95% confidence interval [CI]: 1.1-2.3) and chronic pain (aOR = 7.6, 95% CI: 4.6-12.6). Among MMT patients primarily in 3 Bronx clinics, nearly one third reported taking prescribed opioid analgesics. Compared with patients not prescribed opioid analgesics, those prescribed opioid analgesics were more likely to report chronic pain and HIV infection. However, between these patients, there was no difference in illicit substance use. These findings highlight the complexity of addressing chronic pain in MMT patients.

Characteristics of methadone maintenance treatment patients prescribed opioid analgesics

PubMed Central

Glenn, Matthew C.; Sohler, Nancy L.; Starrels, Joanna L.; Maradiaga, Jeronimo; Jost, John J.; Arnsten, Julia H.; Cunningham, Chinazo O.

2016-01-01

Background Opioid analgesic use and disorders have dramatically increased among the general American population and those receiving methadone maintenance treatment (MMT). Most research among MMT patients focuses on opioid analgesics misuse or disorders; few studies focus on MMT patients prescribed opioid analgesics. We describe demographic, clinical, and substance use characteristics of MMT patients prescribed opioid analgesics and compare them to MMT patients not prescribed opioid analgesics. Methods We conducted a cross-sectional secondary data analysis using screening interviews from a parent study. From 2012–2015, we recruited adults from 3 MMT Bronx clinics. Questionnaire data included: patterns of opioid analgesic use, substance use, comorbid illnesses, and demographic characteristics. Our main dependent variable was patients’ report of currently taking prescribed opioid analgesics. To compare characteristics between MMT patients prescribed and not prescribed opioid analgesics, we conducted chi-squared tests, t-tests, and Mann-Whitney U tests. Results Of 611 MMT patients, most reported chronic pain (62.0%), HCV infection (52.1%), and currently using illicit substances (64.2%). Of the 29.8% who reported currently taking prescribed opioid analgesics, most misused their opioid analgesics (57.5%). Patients prescribed (versus not prescribed) opioid analgesics were more likely to report HIV infection (aOR=1.6, 95% CI: 1.1–2.3) and chronic pain (aOR=7.6, 95% CI: 4.6–12.6). Conclusion Among MMT patients primarily in three Bronx clinics, nearly one-third reported taking prescribed opioid analgesics. Compared to patients not prescribed opioid analgesics, those prescribed opioid analgesics were more likely to report chronic pain and HIV infection. However, between these patients, there was no difference in illicit substance use. These findings highlight the complexity of addressing chronic pain in MMT patients. PMID:26731299

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

PubMed

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.

Effectiveness, safety and feasibility of extended-release naltrexone for opioid dependence: a 9-month follow-up to a 3-month randomized trial.

PubMed

Solli, Kristin Klemmetsby; Latif, Zill-E-Huma; Opheim, Arild; Krajci, Peter; Sharma-Haase, Kamni; Benth, Jūratė Šaltytė; Tanum, Lars; Kunoe, Nikolaj

2018-05-28

This is a follow-up study of a previously published randomized clinical trial conducted in Norway that compared extended-release naltrexone (XR-NTX) to buprenorphine-naloxone (BP-NLX) over 3 months. At the conclusion of the trial, participants were offered their choice of study medication for an additional 9 months. While BP-NLX was available at no cost through opioid maintenance treatment programmes, XR-NTX was available only through study participation, accounting for why almost all participants chose XR-NTX in the follow-up. The aim of this follow-up study was to compare differences in outcome between adults with opioid dependence continuing XR-NTX and those inducted on XR-NTX for a 9-month period, on measures of effectiveness, safety and feasibility. In this prospective cohort study, participants were either continuing XR-NTX, changed from BP-NLX to XR-NTX or re-included into the study and inducted on XR-NTX treatment. Five urban, out-patient addiction clinics in Norway. Opioid-dependent adults continuing (n = 54) or inducted on (n = 63) XR-NTX. XR-NTX administrated as intramuscular injections (380 mg) every fourth week. Data on retention, use of heroin and other illicit substances, opioid craving, treatment satisfaction, addiction-related problems and adverse events were reported every fourth week. Nine-month follow-up completion rates were 51.9% among participants continuing XR-NTX in the follow-up and 47.6% among those inducted on XR-NTX. Opioid abstinence rates were, respectively, 53.7 and 44.4%. No significant group differences were found in use of heroin and other opioids. Opioid-dependent individuals who elect to switch from buprenorphine-naltrexone treatment after 3 months to extended-release naltrexone treatment for 9 months appear to experience similar treatment completion and abstinence rates and similar adverse event profiles to individuals who had been on extended-release naltrexone from the start of treatment. © 2018 Society for the

Impulsivity and opioid drugs: differential effects of heroin, methadone and prescribed analgesic medication.

PubMed

Baldacchino, A; Balfour, D J K; Matthews, K

2015-04-01

Previous studies have provided inconsistent evidence that chronic exposure to opioid drugs, including heroin and methadone, may be associated with impairments in executive neuropsychological functioning, specifically cognitive impulsivity. Further, it remains unclear how such impairments may relate of the nature, level and extent of opioid exposure, the presence and severity of opioid dependence, and hazardous behaviours such as injecting. Participants with histories of illicit heroin use (n = 24), former heroin users stabilized on prescribed methadone (methadone maintenance treatment; MMT) (n = 29), licit opioid prescriptions for chronic pain without history of abuse or dependence (n = 28) and healthy controls (n = 28) were recruited and tested on a task battery that included measures of cognitive impulsivity (Cambridge Gambling Task, CGT), motor impulsivity (Affective Go/NoGo, AGN) and non-planning impulsivity (Stockings of Cambridge, SOC). Illicit heroin users showed increased motor impulsivity and impaired strategic planning. Additionally, they placed higher bets earlier and risked more on the CGT. Stable MMT participants deliberated longer and placed higher bets earlier on the CGT, but did not risk more. Chronic opioid exposed pain participants did not differ from healthy controls on any measures on any tasks. The identified impairments did not appear to be associated specifically with histories of intravenous drug use, nor with estimates of total opioid exposure. These data support the hypothesis that different aspects of neuropsychological measures of impulsivity appear to be associated with exposure to different opioids. This could reflect either a neurobehavioural consequence of opioid exposure, or may represent an underlying trait vulnerability to opioid dependence.

Pharmacogenetic analysis of opioid dependence treatment dose and dropout rate.

PubMed

Crist, Richard C; Li, James; Doyle, Glenn A; Gilbert, Alex; Dechairo, Bryan M; Berrettini, Wade H

2018-01-01

Currently, no pharmacogenetic tests for selecting an opioid-dependence pharmacotherapy have been approved by the US Food and Drug Administration. Determine the effects of variants in 11 genes on dropout rate and dose in patients receiving methadone or buprenorphine/naloxone (ClinicalTrials.gov Identifier: NCT00315341). Variants in six pharmacokinetic genes (CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4) and five pharmacodynamic genes (HTR2A, OPRM1, ADRA2A, COMT, SLC6A4) were genotyped in samples from a 24-week, randomized, open-label trial of methadone and buprenorphine/naloxone for the treatment of opioid dependence (n = 764; 68.7% male). Genotypes were then used to determine the metabolism phenotype for each pharmacokinetic gene. Phenotypes or genotypes for each gene were analyzed for association with dropout rate and mean dose. Genotype for 5-HTTLPR in the SLC6A4 gene was nominally associated with dropout rate when the methadone and buprenorphine/naloxone groups were combined. When the most significant variants associated with dropout rate were analyzed using pairwise analyses, SLC6A4 (5-HTTLPR) and COMT (Val158Met; rs4860) had nominally significant associations with dropout rate in methadone patients. None of the genes analyzed in the study was associated with mean dose of methadone or buprenorphine/naloxone. This study suggests that functional polymorphisms related to synaptic dopamine or serotonin levels may predict dropout rates during methadone treatment. Patients with the S/S genotype at 5-HTTLPR in SLC6A4 or the Val/Val genotype at Val158Met in COMT may require additional treatment to improve their chances of completing addiction treatment. Replication in other methadone patient populations will be necessary to ensure the validity of these findings.

Review of Factors, Methods, and Outcome Definition in Designing Opioid Abuse Predictive Models.

PubMed

Alzeer, Abdullah H; Jones, Josette; Bair, Matthew J

2018-05-01

Several opioid risk assessment tools are available to prescribers to evaluate opioid analgesic abuse among chronic patients. The objectives of this study are to 1) identify variables available in the literature to predict opioid abuse; 2) explore and compare methods (population, database, and analysis) used to develop statistical models that predict opioid abuse; and 3) understand how outcomes were defined in each statistical model predicting opioid abuse. The OVID database was searched for this study. The search was limited to articles written in English and published from January 1990 to April 2016. This search generated 1,409 articles. Only seven studies and nine models met our inclusion-exclusion criteria. We found nine models and identified 75 distinct variables. Three studies used administrative claims data, and four studies used electronic health record data. The majority, four out of seven articles (six out of nine models), were primarily dependent on the presence or absence of opioid abuse or dependence (ICD-9 diagnosis code) to define opioid abuse. However, two articles used a predefined list of opioid-related aberrant behaviors. We identified variables used to predict opioid abuse from electronic health records and administrative data. Medication variables are the recurrent variables in the articles reviewed (33 variables). Age and gender are the most consistent demographic variables in predicting opioid abuse. Overall, there is similarity in the sampling method and inclusion/exclusion criteria (age, number of prescriptions, follow-up period, and data analysis methods). Intuitive research to utilize unstructured data may increase opioid abuse models' accuracy.

[Maintenance treatment in opioid-dependent patients with migration background].

PubMed

Bald, L K; Schouler-Ocak, M; Penka, S; Schoofs, N; Häbel, T; Bermpohl, F; Gutwinski, S

2016-05-01

No regional analyses regarding opioid-dependent patients in maintenance treatment with a migration background have so far been performed in German-speaking countries. This study examined patients with and without a migration background regarding socioeconomic parameters, characteristics of dependency and attitude towards opiate maintenance treatment (OMT). From May to October 2011 patients in OMT from all of the 20 psychiatry clinics and 110 physician practices in Berlin with a licence to provide OMT were included in this analysis. Out of the 986 participating patients, 956 gave information on migration background and of these, 204 (21.3 %) originated from a country other than Germany. Compared to patients without a migration background, their participation in a maintenance program was significantly shorter and they more often expressed a desire to end OMT and wanted a limited duration of OMT. The differences regarding duration of OMT and the wish to end OMT can reflect a stronger desire for abstinence and a different attitude towards maintenance treatment of patients with a migration background.

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

PubMed Central

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

2017-01-01

Summary Background 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. Methods 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). Findings 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

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

PubMed Central

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

Dextromethorphan differentially affects opioid antinociception in rats

PubMed Central

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

Clinically Employed Opioid Analgesics Produce Antinociception via μ-δ Opioid Receptor Heteromers in Rhesus Monkeys

PubMed Central

2012-01-01

Morphine and related drugs are widely employed as analgesics despite the side effects associated with their use. Although morphine is thought to mediate analgesia through mu opioid receptors, delta opioid receptors have been implicated in mediating some side effects such as tolerance and dependence. Here we present evidence in rhesus monkeys that morphine, fentanyl, and possibly methadone selectively activate mu-delta heteromers to produce antinociception that is potently antagonized by the delta opioid receptor antagonist, naltrindole (NTI). Studies with HEK293 cells expressing mu-delta heteromeric opioid receptors exhibit a similar antagonism profile of receptor activation in the presence of NTI. In mice, morphine was potently inhibited by naltrindole when administered intrathecally, but not intracerebroventricularly, suggesting the possible involvement of mu-delta heteromers in the spinal cord of rodents. Taken together, these results strongly suggest that, in primates, mu-delta heteromers are allosterically coupled and mediate the antinociceptive effects of three clinically employed opioid analgesics that have been traditionally viewed as mu-selective. Given the known involvement of delta receptors in morphine tolerance and dependence, our results implicate mu-delta heteromers in mediating both antinociception and these side effects in primates. These results open the door for further investigation in humans. PMID:23019498

Clinically employed opioid analgesics produce antinociception via μ-δ opioid receptor heteromers in Rhesus monkeys.

PubMed

Yekkirala, Ajay S; Banks, Matthew L; Lunzer, Mary M; Negus, Stevens S; Rice, Kenner C; Portoghese, Philip S

2012-09-19

Morphine and related drugs are widely employed as analgesics despite the side effects associated with their use. Although morphine is thought to mediate analgesia through mu opioid receptors, delta opioid receptors have been implicated in mediating some side effects such as tolerance and dependence. Here we present evidence in rhesus monkeys that morphine, fentanyl, and possibly methadone selectively activate mu-delta heteromers to produce antinociception that is potently antagonized by the delta opioid receptor antagonist, naltrindole (NTI). Studies with HEK293 cells expressing mu-delta heteromeric opioid receptors exhibit a similar antagonism profile of receptor activation in the presence of NTI. In mice, morphine was potently inhibited by naltrindole when administered intrathecally, but not intracerebroventricularly, suggesting the possible involvement of mu-delta heteromers in the spinal cord of rodents. Taken together, these results strongly suggest that, in primates, mu-delta heteromers are allosterically coupled and mediate the antinociceptive effects of three clinically employed opioid analgesics that have been traditionally viewed as mu-selective. Given the known involvement of delta receptors in morphine tolerance and dependence, our results implicate mu-delta heteromers in mediating both antinociception and these side effects in primates. These results open the door for further investigation in humans.

Opioid Addiction and Implications for Employers.

PubMed

Kuhn, Sandra

2017-01-01

Although the prevalence and destruction of opioid addiction have touched individuals and families across all social groups and geographies, until recently, federal and state-level efforts to confront this growing problem have lacked focus and rigor. With several legislative actions already underway and the recent enactment of the Comprehensive Addiction and Recovery Act (CARA), we will continue to see a focus on program development and treatment strategies. Employers can contribute toward curbing the opioid addiction epidemic in a number of ways and should play an instrumental role in facilitating increased awareness of and access to needed programming. These efforts will improve quality of life for employees and their dependents, as well as have a positive impact on productivity (including reduced absenteeism and decreased presenteeism). This article will explore the size and prevalence of the opioid epidemic, reflect on its implications for employers-including public policy initiatives-and suggest specific strategies for employer interventions.

The availability of web sites offering to sell opioid medications without prescriptions.

PubMed

Forman, Robert F; Woody, George E; McLellan, Thomas; Lynch, Kevin G

2006-07-01

This study was designed to determine the availability of web sites offering to sell opioid medications without prescriptions. Forty-seven Internet searches were conducted with a variety of opioid medication terms, including "codeine," "no prescription Vicodin," and "OxyContin." Two independent raters examined the links generated in each search and resolved any coding disagreements. The resulting links were coded as "no prescription web sites" (NPWs) if they offered to sell opioid medications without prescriptions. In searches with terms such as "no prescription codeine" and "Vicodin," over 50% of the links obtained were coded as "NPWs." The proportion of links yielding NPWs was greater when the phrase "no prescription" was added to the opioid term. More than 300 opioid NPWs were identified and entered into a database. Three national drug-use monitoring studies have cited significant increases in prescription opioid use over the past 5 years, particularly among young people. The emergence of NPWs introduces a new vector for unregulated access to opioids. Research is needed to determine the effect of NPWs on prescription opioid use initiation, misuse, and dependence.

Laboratory-Induced Stress and Craving among Individuals with Prescription Opioid Dependence

PubMed Central

Back, Sudie E.; Gros, Daniel F.; Price, Matthew; LaRowe, Steve; Flanagan, Julianne; Brady, Kathleen T.; Davis, Charles; Jaconis, Maryanne; McCauley, Jenna L.

2015-01-01

Background Stress and conditioned drug cues have been implicated in the initiation, maintenance and relapse to substances of abuse. Although stress and drug cues are often encountered together, little research exists on whether stress potentiates the response to drug cues. Method Participants (N = 75) were 39 community recruited individuals with current prescription opioid (PO) dependence and 36 healthy controls. Participants stayed overnight in the hospital for one night and then completed laboratory testing the following morning. During laboratory testing, participants were randomly assigned to a stress task (Trier Social Stress Task; TSST) or a no-stress condition. Following the stress manipulation, all participants completed a PO cue paradigm. Immediately before and after the stress and cue tasks, the following were assessed: subjective (stress, craving, anger, sadness, happiness), physiological (heart rate, blood pressure, galvanic skin response), and neuroendocrine responses (cortisol and dehydroepiandrosterone). Results Internal validity of the stress task was demonstrated, as evidenced by significantly higher subjective stress, as well as cortisol, heart rate and blood pressure in the TSST compared to the no-stress group. Individuals with PO dependence evidenced significantly greater reactivity to the stress task than controls. Craving increased significantly in response to the drug cue task among PO participants. No stress × cue interaction was observed. Conclusions In this study, heightened stress reactivity was observed among individuals with PO dependence. Exposure to acute stress, however, did not potentiate craving in response to conditioned drug cues. PMID:26342626

Alcohol Screening among Opioid Agonist Patients in a Primary Care Clinic and an Opioid Treatment Program.

PubMed

Klimas, Jan; Muench, John; Wiest, Katharina; Croff, Raina; Rieckman, Traci; McCarty, Dennis

2015-01-01

Problem alcohol use is associated with adverse health and economic outcomes, especially among people in opioid agonist treatment. Screening, brief intervention, and referral to treatment (SBIRT) are effective in reducing alcohol use; however, issues involved in SBIRT implementation among opioid agonist patients are unknown. To assess identification and treatment of alcohol use disorders, we reviewed clinical records of opioid agonist patients screened for an alcohol use disorder in a primary care clinic (n = 208) and in an opioid treatment program (n = 204) over a two-year period. In the primary care clinic, 193 (93%) buprenorphine patients completed an annual alcohol screening and six (3%) had elevated AUDIT scores. In the opioid treatment program, an alcohol abuse or dependence diagnosis was recorded for 54 (27%) methadone patients. Practitioner focus groups were completed in the primary care (n = 4 physicians) and the opioid treatment program (n = 11 counselors) to assess experience with and attitudes towards screening opioid agonist patients for alcohol use disorders. Focus groups suggested that organizational, structural, provider, patient, and community variables hindered or fostered alcohol screening. Alcohol screening is feasible among opioid agonist patients. Effective implementation, however, requires physician training and systematic changes in workflow.

Demographic Trends of Adults in New York City Opioid Treatment Programs--An Aging Population.

PubMed

Han, Benjamin; Polydorou, Soteri; Ferris, Rosie; Blaum, Caroline S; Ross, Stephen; McNeely, Jennifer

2015-01-01

The population of adults accessing opioid treatment is growing older, but exact estimates vary widely, and little is known about the characteristics of the aging treatment population. Further, there has been little research regarding the epidemiology, healt h status, and functional impairments in this population. To determine the utilization of opioid treatment services by older adults in New York City. This study used administrative data from New York State licensed drug treatment programs to examine overall age trends and characteristics of older adults in opioid treatment programs in New York City from 1996 to 2012. We found significant increases in utilization of opioid treatment programs by older adults in New York City. By 2012, those aged 50-59 made up the largest age group in opioid treatment programs. Among older adults there were notable shifts in demographic background including gender and ethnicity, and an increase in self-reported impairments. More research is needed to fully understand the specific characteristics and needs of older adults with opioid dependence.

Opioid management of pain: the impact of the prescription opioid abuse epidemic.

PubMed

Rauenzahn, Sherri; Del Fabbro, Egidio

2014-09-01

The greater emphasis on pain control over the last decade has been accompanied by increased opioid prescriptions and an epidemic of opioid abuse. This review examines the financial, regulatory, and clinical practice impact of the epidemic, the factors contributing to its growth, and strategies that may counter this public health crisis. Despite the call for urgent practice change and the introduction of new initiatives such as electronic prescription monitoring and additional education programs for providers and patients, the evidence for improved outcomes are limited. There are also concerns that some patients may suffer from underprescribing as an unintended consequence of more stringent state and federal regulations. There is consensus that some form of universal precautions should be adopted for all patients, including those being treated for cancer-related pain, in order to better identify and manage those at risk of opioid abuse. The opioid prescription abuse epidemic has precipitated calls for increased regulation. Clinicians can improve patient care and diminish opioid abuse by identifying patient risk factors, increasing vigilance and structure for those at risk, and providing interdisciplinary care for any patients coping in a maladaptive manner.

A critical period in the supraspinal control of pain: opioid-dependent changes in brainstem rostroventral medulla function in preadolescence

PubMed Central

Hathway, Gareth J.; Vega-Avelaira, David; Fitzgerald, Maria

2012-01-01

We have previously shown that the balance of electrically evoked descending brainstem control of spinal nociceptive reflexes undergoes a switch from excitation to inhibition in preadolescent rats. Here we show that the same developmental switch occurs when μ-opioid receptor agonists are microinjected into the rostroventral medulla (RVM). Microinjections of the μ-opioid receptor agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) into the RVM of lightly anaesthetised adult rats produced a dose-dependent decrease in mechanical nociceptive hindlimb reflex electromyographic activity. However, in preadolescent (postnatal day 21 [P21]) rats, the same doses of DAMGO produced reflex facilitation. RVM microinjection of δ-opioid receptor or GABAA receptor agonists, on the other hand, caused reflex depression at both ages. The μ-opioid receptor-mediated descending facilitation is tonically active in naive preadolescent rats, as microinjection of the μ-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) into the RVM at this age decreases spinal nociceptive reflexes while having no effect in adults. To test whether tonic opioid central activity is required for the preadolescent switch in RVM descending control, naloxone hydrochloride was delivered continuously from subcutaneous osmotic mini-pumps for 7-day periods, at various postnatal stages. Blockade of tonic opioidergic activity from P21 to P28, but not at earlier or later ages, prevented the normal development of descending RVM inhibitory control of spinal nociceptive reflexes. Enhancing opioidergic activity with chronic morphine over P7 to P14 accelerated this development. These results show that descending facilitation of spinal nociception in young animals is mediated by μ-opioid receptor pathways in the RVM. Furthermore, the developmental transition from RVM descending facilitation to inhibition of pain is determined by activity in central opioid networks at a critical period of

Imaging opioid analgesia in the human brain and its potential relevance for understanding opioid use in chronic pain

PubMed Central

Lee, Michael C.; Wanigasekera, Vishvarani; Tracey, Irene

2014-01-01

Opioids play an important role for the management of acute pain and in palliative care. The role of long-term opioid therapy in chronic non-malignant pain remains unclear and is the focus of much clinical research. There are concerns regarding analgesic tolerance, paradoxical pain and issues with dependence that can occur with chronic opioid use in the susceptible patient. In this review, we discuss how far human neuroimaging research has come in providing a mechanistic understanding of pain relief provided by opioids, and suggest avenues for further studies that are relevant to the management of chronic pain with opioids. This article is part of the Special Issue Section entitled ‘Neuroimaging in Neuropharmacology’. PMID:23891639

Study of Serum Malondialdehyde Level in Opioid and Methamphetamine Dependent Patients.

PubMed

Najafi, Khadije; Ahmadi, Sajad; Rahpeyma, Mahdi; Khazaie, Habibolah; Vaisi-Raygani, Asad; Moini, Ali; Kiani, Amir

2017-10-01

Opioid compound and methamphetamine are commonly used in drug abuse; these can disrupt the normal function of cellular and molecular systems, leading to several events such as oxidative stress, aging, apoptosis, and necrosis. Malondialdehyde (MDA) is the most important biomarker for evaluation of oxidative stress and determination of lipid peroxidation. In this study, 42 drug abusers and 22 healthy persons participated as case and control groups, respectively. MDA in volunteer sera was determined by high-performance liquid chromatography (HPLC) with fluorescence detection after pre-column derivatization using thiobarbituric acid. The analysis was performed on a ODS column by spectrofluorometer detection, operated at excitation of 515 nm and emission of 535 nm. A mixture of phosphate buffer (0.05 M, pH 6.8), containing potassium monobasic phosphate and methanol (60:40, v/v) at a flow rate of 1 ml/min, was used as the mobile phase. The retention time of MDA-TBA was 3.2 min. Our findings showed that the MDA level increased in the opioid and methamphetamine abusers when compared to the control group (P<0.05); however, no significant difference was observed between the opioid and methamphetamine groups. A state of oxidative stress during biological processes leads to lipid peroxidation, DNA damage, biomolecule dysfunctions, and many other diseases. Since it is impossible to eradicate the drug addiction, we should reduce the side effects of drug abuse, such as oxidative stress, by intake of proper nutrition and antioxidants.

Combination of intrathecal opioids with bupivacaine attenuates opioid dose escalation in chronic noncancer pain patients.

PubMed

Veizi, I Elias; Hayek, Salim M; Narouze, Samer; Pope, Jason E; Mekhail, Nagy

2011-10-01

The purpose of this study was to examine the effect of intrathecal (IT) coadministration of bupivacaine with opioids during the initial phase of opioid titration and up to 1 year after implantation of an IT drug delivery system (IDDS). The study was designed as a retrospective study. OUTCOMES ANALYZED: The outcomes analyzed for this study were pain relief, oral opioid consumption, IT opioid, and bupivacaine dosage. METHODS AND PATIENT POPULATION: The patient population for this study were consecutively implanted patients over a period of 6 years in a tertiary single center with multiple practitioners. In this retrospective study, 126 consecutive noncancer intractable pain patients were implanted with IDDS and initiated with an IT opioid (O) as a single medication or an IT opioid and bupivacaine (O + B). Pain intensity, amount of oral opioids, dose, rate, and concentration of IT opioids and bupivacaine, and number and type of IT medication used were recorded at preimplant, implant, and at 3, 6, and 12 months postimplant. The intervention used for the study was the IT delivery device implant. Significant reduction in pain intensity was observed in both groups at 12 months postimplant (O group: baseline 7.42 ± 2.1 to 5.85 ± 2.8 [n = 72, P < 0.001]; O + B group 7.35 ± 2 to 5.03 ± 2.4 (n = 54; P < 0.001]). The combination of opioids with bupivacaine from the start of IT infusion treatment resulted in a reduced progression of opioid dose escalation in comparison to patients started with opioids (O group). The rate of increase of IT opioids in the O group at 12 months was 535 ± 180%, whereas in the O + B, the dose increase was significantly lower at 185 ± 85% (P < 0.004). In both groups, there was a statistically significant decrease in oral opioid consumption compared with preimplant doses. Concomitant initial coadministration of IT bupivacaine with opioids blunts the rate of IT opioid dose escalation during the first year after implant of an IDDS. More studies are

Risk of Prolonged Opioid Use Among Opioid-Naïve Patients Following Common Hand Surgery Procedures.

PubMed

Johnson, Shepard P; Chung, Kevin C; Zhong, Lin; Shauver, Melissa J; Engelsbe, Michael J; Brummett, Chad; Waljee, Jennifer F

2016-10-01

To evaluate prolonged opioid use in opioid-naïve patients after common hand surgery procedures in the United States. We studied insurance claims from the Truven MarketScan databases to identify opioid-naïve adult patients (no opioid exposure 11 months before the perioperative period) who underwent an elective (carpal tunnel release, carpometacarpal arthroplasty/arthrodesis, cubital tunnel release, or trigger finger release) or trauma-related (closed distal radius fracture fixation, flexor tendon repair, metacarpal fracture fixation, or phalangeal fracture fixation) hand surgery procedure between 2010 and 2012 (N = 77,573 patients). Patients were observed for 6 months to determine the number, timing, duration, and oral morphine equivalent dosage of postoperative opioid prescriptions. We assessed prolonged postoperative opioid use, defined as patients who filled a perioperative opioid prescription followed by a prescription between 90 and 180 days after surgery, and evaluated associated risk factors using multivariable logistic regression. In this cohort, 59,725 opioid-naïve patients (77%) filled a perioperative opioid prescription. Of these, 13% of patients continued to fill prescriptions between 90 and 180 days after surgery. Elective surgery patients were more likely to continue to fill opioid prescriptions after 90 days compared with trauma patients (13.5% vs 10.5%). Younger age, female gender, lower income, comprehensive insurance, higher Elixhauser comorbidity index, mental health disorders, and tobacco dependence or abuse were associated with prolonged opioid use. Approximately 13% of opioid-naïve patients continue to fill opioid prescriptions after hand surgery procedures 90 days after surgery. Preoperative interventions centered on opioid alternatives and early cessation, particularly among patients at risk for long-term use, is critical to addressing the prescription opioid crisis in the United States. The current national opioid use epidemic requires

Compulsive-like responding for opioid analgesics in rats with extended access.

PubMed

Wade, Carrie L; Vendruscolo, Leandro F; Schlosburg, Joel E; Hernandez, Daniel O; Koob, George F

2015-01-01

The abuse of prescription opioids that are used for the treatment of chronic pain is a major public health concern, costing ∼$53.4 billion annually in lost wages, health-care costs, and criminal costs. Although opioids remain a first-line therapy for the treatment of severe chronic pain, practitioners remain cautious because of the potential for abuse and addiction. Opioids such as heroin are considered very rewarding and reinforcing, but direct and systematic comparisons of compulsive intake between commonly prescribed opioids and heroin in animal models have not yet been performed. In the present study, we evaluated the potential for compulsive-like drug seeking and taking, using intravenous self-administration of oxycodone, fentanyl, and buprenorphine in rats allowed long access sessions (12 h). We measured compulsive-like intake using an established escalation model and responding on a progressive ratio schedule of reinforcement. We compared the potential for compulsive-like self-administration of these prescription opioids and heroin, which has been previously established to induce increasing intake that models the transition to addiction in humans. We found that animals that self-administered oxycodone, fentanyl, or heroin, but not buprenorphine had similar profiles of escalation and increases in breakpoints. The use of extended access models of prescription opioid intake will help better understand the biological factors that underlie opioid dependence.

Social Stress Engages Opioid Regulation of Locus Coeruleus Norepinephrine Neurons and Induces a State of Cellular and Physical Opiate Dependence

PubMed Central

Chaijale, Nayla N; Curtis, Andre L; Wood, Susan K; Zhang, Xiao-Yan; Bhatnagar, Seema; Reyes, Beverly AS; Van Bockstaele, Elisabeth J; Valentino, Rita J

2013-01-01

Stress is implicated in diverse psychiatric disorders including substance abuse. The locus coeruleus–norepinephrine (LC–NE) system is a major stress response system that is also a point of intersection between stress neuromediators and endogenous opioids and so may be a site at which stress can influence drug-taking behaviors. As social stress is a common stressor for humans, this study characterized the enduring impact of repeated social stress on LC neuronal activity. Rats were exposed to five daily consecutive sessions of social stress using the resident-intruder model or control manipulation. LC discharge rate recorded 2 days after the last manipulation was decreased in stressed rats compared with controls. By 10 days after the last manipulation, LC rates were comparable between groups. Systemic administration of the opiate antagonist, naloxone, robustly increased LC discharge rate in a manner suggestive of opiate withdrawal, selectively in stressed rats when administered 2 or 10 days after the last manipulation. This was accompanied by behavioral signs of mild opiate withdrawal. Western blot and electron microscopic studies indicated that repeated social stress decreased corticotropin-releasing factor type 1 receptor and increased μ-opioid receptor levels in the LC. Together, the results suggest that repeated social stress engages endogenous opioid modulation of LC activity and induces signs of cellular and physical opiate dependence that endure after the stress. These cellular effects may predispose individuals with a history of repeated social stress to substance abuse behaviors. PMID:23660707

Social stress engages opioid regulation of locus coeruleus norepinephrine neurons and induces a state of cellular and physical opiate dependence.

PubMed

Chaijale, Nayla N; Curtis, Andre L; Wood, Susan K; Zhang, Xiao-Yan; Bhatnagar, Seema; Reyes, Beverly As; Van Bockstaele, Elisabeth J; Valentino, Rita J

2013-09-01

Stress is implicated in diverse psychiatric disorders including substance abuse. The locus coeruleus-norepinephrine (LC-NE) system is a major stress response system that is also a point of intersection between stress neuromediators and endogenous opioids and so may be a site at which stress can influence drug-taking behaviors. As social stress is a common stressor for humans, this study characterized the enduring impact of repeated social stress on LC neuronal activity. Rats were exposed to five daily consecutive sessions of social stress using the resident-intruder model or control manipulation. LC discharge rate recorded 2 days after the last manipulation was decreased in stressed rats compared with controls. By 10 days after the last manipulation, LC rates were comparable between groups. Systemic administration of the opiate antagonist, naloxone, robustly increased LC discharge rate in a manner suggestive of opiate withdrawal, selectively in stressed rats when administered 2 or 10 days after the last manipulation. This was accompanied by behavioral signs of mild opiate withdrawal. Western blot and electron microscopic studies indicated that repeated social stress decreased corticotropin-releasing factor type 1 receptor and increased μ-opioid receptor levels in the LC. Together, the results suggest that repeated social stress engages endogenous opioid modulation of LC activity and induces signs of cellular and physical opiate dependence that endure after the stress. These cellular effects may predispose individuals with a history of repeated social stress to substance abuse behaviors.

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.

PubMed

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

Novel opioid cyclic tetrapeptides: Trp isomers of CJ-15,208 exhibit distinct opioid receptor agonism and short-acting κ opioid receptor antagonism.

PubMed

Ross, Nicolette C; Reilley, Kate J; Murray, Thomas F; Aldrich, Jane V; McLaughlin, Jay P

2012-02-01

The κ opioid receptor antagonists demonstrate potential for maintaining abstinence from psychostimulant abuse, but existing non-peptide κ-receptor selective antagonists show exceptionally long activity. We hypothesized that the L- and D-Trp isomers of CJ-15,208, a natural cyclic tetrapeptide reported to be a κ-receptor antagonist in vitro, would demonstrate short-acting, dose-dependent antagonism in vivo, preventing reinstatement of cocaine-seeking behaviour. Affinity, selectivity and efficacy of the L-Trp and D-Trp isomers for opioid receptors were assessed in vitro in radioligand and GTPγS binding assays. Opioid receptor agonist and antagonist activities were characterized in vivo following i.c.v. administration with the 55°C warm water tail-withdrawal assay. The D-Trp isomer, which demonstrated primarily κ-receptor selective antagonist activity, was further evaluated for its prevention of stress- and drug-induced reinstatement of extinguished cocaine conditioned place preference (CPP). The two isomers showed similar affinity and selectivity for κ receptors (K(i)  30-35 nM) as well as κ receptor antagonism in vitro. As expected, the D-Trp cyclic tetrapeptide exhibited minimal agonist activity and induced dose-dependent κ-receptor selective antagonism lasting less than 18 h in vivo. Pretreatment with this peptide prevented stress-, but not cocaine-induced, reinstatement of extinguished cocaine CPP. In contrast, the L-Trp cyclic tetrapeptide unexpectedly demonstrated mixed opioid agonist/antagonist activity. The L-Trp and the D-Trp isomers of CJ-15,208 demonstrate stereospecific opioid activity in vivo. The relatively brief κ opioid receptor antagonism, coupled with the prevention of stress-induced reinstatement of extinguished cocaine-seeking behaviour, suggests the D-Trp isomer could be used therapeutically to maintain abstinence from psychostimulant abuse. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological

National and State Treatment Need and Capacity for Opioid Agonist Medication-Assisted Treatment

PubMed Central

Campopiano, Melinda; Baldwin, Grant; McCance-Katz, Elinore

2015-01-01

Objectives. We estimated national and state trends in opioid agonist medication-assisted treatment (OA-MAT) need and capacity to identify gaps and inform policy decisions. Methods. We generated national and state rates of past-year opioid abuse or dependence, maximum potential buprenorphine treatment capacity, number of patients receiving methadone from opioid treatment programs (OTPs), and the percentage of OTPs operating at 80% capacity or more using Substance Abuse and Mental Health Services Administration data. Results. Nationally, in 2012, the rate of opioid abuse or dependence was 891.8 per 100 000 people aged 12 years or older compared with national rates of maximum potential buprenorphine treatment capacity and patients receiving methadone in OTPs of, respectively, 420.3 and 119.9. Among states and the District of Columbia, 96% had opioid abuse or dependence rates higher than their buprenorphine treatment capacity rates; 37% had a gap of at least 5 per 1000 people. Thirty-eight states (77.6%) reported at least 75% of their OTPs were operating at 80% capacity or more. Conclusions. Significant gaps between treatment need and capacity exist at the state and national levels. Strategies to increase the number of OA-MAT providers are needed. PMID:26066931

Discharge prescribing of enteral opioids after initiation as a weaning strategy from continuous opioid infusions in the Intensive Care Unit.

PubMed

Kram, Bridgette; Weigel, Kylie M; Kuhrt, Michelle; Gilstrap, Daniel L

To evaluate the proportion of patients receiving a hospital discharge prescription for a scheduled enteral opioid following initiation as a weaning strategy from a continuous opioid infusion in the Intensive Care Unit (ICU). Retrospective, observational study. Five adult ICUs at a large, quaternary care academic medical center. Endotracheally intubated, opioid-naive adults receiving a continuous opioid infusion with a concomitant scheduled enteral opioid initiated. Exclusion criteria were receipt of fewer than two enteral opioid doses, documentation of a long-acting opioid as a home medication, the indication for the enteral opioid was not a weaning strategy, death during hospital admission or discharge to hospice. None. The proportion of ICU and hospital survivors who received a discharge prescription for a scheduled enteral opioid, total duration of continuous opioid infusion, duration of continuous opioid infusion after initiation of an enteral opioid therapy, total duration of enteral therapy, ICU and hospital length of stay. Of 62 included patients, 19 patients (30.6 percent) received a new prescription for a scheduled enteral opioid at hospital discharge. The median duration of enteral opioid therapy was longer for patients who received a discharge prescription compared to those who did not (20.09 vs 8.89 days, p = 0.02), though the remaining endpoints were not different. Utilizing scheduled enteral opioids as a weaning strategy from continuous opioid infusions may place patients at risk of ICU-acquired physical dependence on opioids.

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

PubMed

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.

CXCL10 Controls Inflammatory Pain via Opioid Peptide-Containing Macrophages in Electroacupuncture

PubMed Central

Wang, Ying; Gehringer, Rebekka; Mousa, Shaaban A.; Hackel, Dagmar; Brack, Alexander; Rittner, Heike L.

2014-01-01

Acupuncture is widely used for pain treatment in patients with osteoarthritis or low back pain, but molecular mechanisms remain largely enigmatic. In the early phase of inflammation neutrophilic chemokines direct opioid-containing neutrophils in the inflamed tissue and stimulate opioid peptide release and antinociception. In this study the molecular pathway and neuroimmune connections in complete Freund's adjuvant (CFA)-induced hind paw inflammation and electroacupuncture for peripheral pain control were analyzed. Free moving Wistar rats with hind paw inflammation were treated twice with electroacupuncture at GB30 (Huan Tiao - gall bladder meridian) (day 0 and 1) and analyzed for mechanical and thermal nociceptive thresholds. The cytokine profiles as well as the expression of opioid peptides were quantified in the inflamed paw. Electroacupuncture elicited long-term antinociception blocked by local injection of anti-opioid peptide antibodies (beta-endorphin, met-enkephalin, dynorphin A). The treatment altered the cytokine profile towards an anti-inflammatory pattern but augmented interferon (IFN)-gamma and the chemokine CXCL10 (IP-10: interferon gamma-inducible protein) protein and mRNA expression with concomitant increased numbers of opioid peptide-containing CXCR3+ macrophages. In rats with CFA hind paw inflammation without acupuncture repeated injection of CXCL10 triggered opioid-mediated antinociception and increase opioid-containing macrophages. Conversely, neutralization of CXCL10 time-dependently decreased electroacupuncture-induced antinociception and the number of infiltrating opioid peptide-expressing CXCR3+ macrophages. In summary, we describe a novel function of the chemokine CXCL10 - as a regulator for an increase of opioid-containing macrophages and antinociceptive mediator in inflammatory pain and as a key chemokine regulated by electroacupuncture. PMID:24732949

Informed consent to opioid agonist maintenance treatment: recommended ethical guidelines.

PubMed

Carter, Adrian; Hall, Wayne

2008-02-01

Some bioethicists have questioned whether opioid addicted individuals are able to provide free and informed consent to opioid agonist maintenance treatment. Conflicting motives for providing such treatment (e.g. improving the personal health of addicts and protecting public health and order) can also influence what individuals are required to consent to, and how that consent is obtained. We discuss both issues and attempt to specify the conditions for obtaining informed consent to agonist maintenance treatment for opioid addiction. We briefly review the neuroscientific literature on the effects of addiction on the autonomy and decision-making capacity of opioid dependent individuals, and ascertain how informed consent to the treatment of opioid addiction should be obtained. We also provide an ethical analysis of the competing social and medical forces that influence the consent process and make some recommendations on how to ensure that individuals enter maintenance treatment that is provided in an effective and ethical way. Our analysis shows that whilst the autonomy of opioid dependent individuals is impaired by their addiction, they do retain the ability to consent to treatment provided they are not in acute withdrawal or intoxication. These symptoms should have abated, either by supervised withdrawal or stabilisation on agonist maintenance, before they are asked to consent to a detailed treatment contract. Once stabilised, individuals should be provided with detailed information about the risks and benefits of all treatments, and restrictions and regulations under which they are provided. Informed consent is an important part of the treatment process that should be obtained in ways that increase the autonomy and decision-making capacity in opioid addicts.

Employment-based reinforcement of adherence to an FDA approved extended release formulation of naltrexone in opioid-dependent adults: a randomized controlled trial.

PubMed

DeFulio, Anthony; Everly, Jeffrey J; Leoutsakos, Jeannie-Marie S; Umbricht, Annie; Fingerhood, Michael; Bigelow, George E; Silverman, Kenneth

2012-01-01

Naltrexone provides excellent opioid blockade, but its clinical utility is limited because opioid-dependent patients typically refuse it. An injectable suspension of naltrexone for extended release (XR-NTX) was recently approved by the FDA for treatment of opioid dependence. XR-NTX treatment may require concurrent behavioral intervention to maximize adherence and effectiveness, thus we sought to evaluate employment-based reinforcement as a method of improving adherence to XR-NTX in opiate dependent adults. Opioid-dependent adults (n=38) were detoxified and inducted onto oral naltrexone, then randomly assigned to contingency or prescription conditions. Participants received up to six doses of XR-NTX at four-week intervals. All participants could earn vouchers for attendance and performance at a therapeutic workplace. Contingency participants were required to accept XR-NTX injections to access the workplace and earn vouchers. Prescription participants could earn vouchers independent of their acceptance of XR-NTX injections. Contingency participants accepted significantly more naltrexone injections than prescription participants (87% versus 52%, p=.002), and were more likely to accept all injections (74% versus 26%, p=.004). Participants in the two conditions provided similar percentages of samples negative for opiates (72% versus 65%) and for cocaine (58% versus 54%). Opiate positivity was significantly more likely when samples were also cocaine positive, independent of naltrexone blockade (p=.002). Long-term adherence to XR-NTX in unemployed opiate dependent adults is low under usual care conditions. Employment-based reinforcement can maintain adherence to XR-NTX. Ongoing cocaine use appears to interfere with the clinical effectiveness of XR-NTX on opiate use. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

More pain, more gain: Blocking the opioid system boosts adaptive cognitive control.

PubMed

van Steenbergen, Henk; Weissman, Daniel H; Stein, Dan J; Malcolm-Smith, Susan; van Honk, Jack

2017-06-01

The ability to adaptively increase cognitive control in response to cognitive challenges is crucial for goal-directed behavior. Recent findings suggest that aversive arousal triggers adaptive increases of control, but the neurochemical mechanisms underlying these effects remain unclear. Given the known contributions of the opioid system to hedonic states, we investigated whether blocking this system increases adaptive control modulations. To do so, we conducted a double-blind, placebo-controlled psychopharmacological study (n=52 females) involving a Stroop-like task. Specifically, we assessed the effect of naltrexone, an opioid blocker most selective to the mu-opioid system, on two measures of adaptive control that are thought to depend differentially on aversive arousal: post-error slowing and conflict adaptation. Consistent with our hypothesis, relative to placebo, naltrexone increased post-error slowing without influencing conflict adaptation. This finding not only supports the view that aversive arousal triggers adaptive control but also reveals a novel role for the opioid system in modulating such effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Opioid adjuvant strategy: improving opioid effectiveness.

PubMed

Bihel, Frédéric

2016-01-01

Opioid analgesics continue to be the mainstay of pharmacologic treatment of moderate to severe pain. Many patients, particularly those suffering from chronic pain, require chronic high-dose analgesic therapy. Achieving clinical efficacy and tolerability of such treatment regimens is hampered by the appearance of opioid-induced side effects such as tolerance, hyperalgesia and withdrawal syndrome. Among the therapeutic options to improve the opioid effectiveness, this current review focuses on strategies combining opioids to other drugs that can modulate opioid-mediated effects. We will discuss about experimental evidences reported for several potential opioid adjuvants, including N-methyl-D-aspartate receptor antagonists, 5-HT7 agonists, sigma-1 antagonists, I2-R ligands, cholecystokinin antagonists, neuropeptide FF-R antagonists and toll-like receptor 4 antagonists.

A Randomized, Controlled Trial of the Efficacy of an Interoceptive Exposure-Based CBT for Treatment-Refractory Outpatients with Opioid Dependence

PubMed Central

Otto, Michael W.; Hearon, Bridget A.; McHugh, R. Kathryn; Calkins, Amanda W.; Pratt, Elizabeth; Murray, Heather W.; Safren, Steven A.; Pollack, Mark H.

2018-01-01

Many patients diagnosed with opioid dependence do not adequately respond to pharmacologic, psychosocial, or combination treatment, highlighting the importance of novel treatment strategies for this population. The current study examined the efficacy of a novel behavioral treatment focusing on internal cues for drug use (Cognitive Behavioral Therapy for Interoceptive Cues; CBT-IC) relative to an active comparison condition, Individual Drug Counseling (IDC), when added to methadone maintenance treatment (MMT) among those who had not responded to MMT. Participants (N=78) were randomly assigned to receive 15 sessions of CBT-IC or IDC as an adjunct to ongoing MMT and counseling. Oral toxicology screens were the primary outcome. Results indicated no treatment differences between CBT-IC and IDC and a small, significant reduction of self-reported drug use, but no change on toxicology screens. Tests of potential moderators, including sex, anxiety sensitivity, and coping motives for drug use, did not yield significant interactions. Among opioid-dependent out-patients who have not responded to MMT and counseling, the addition of IDC or CBT-IC did not result in additive outcome benefits. These results highlight the need for more potent treatment strategies for opioid dependence, particularly among those who do not fully respond to frontline treatment. PMID:25364993

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

PubMed Central

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

2017-01-01

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% 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. Conclusion Nurses in both countries employ analytical and affective mental

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

PubMed

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

Imaging Sex Differences in Regional Brain Metabolism during Acute Opioid Withdrawal

PubMed Central

Santoro, Giovanni C; Carrion, Joseph; Dewey, Stephen L

2017-01-01

The rate of opioid overdose continues to rise, necessitating improved treatment options. Current therapeutic approaches rely on administration of either a blocking agent, such as naloxone, or chronic treatment with replacement drugs, including methadone and/or buprenorphine. Recent findings suggest that males and females respond to these treatments uniquely. In an effort to better understand this sex-specific variation in treatment efficacy, we investigated the effects of acute opioid withdrawal in male and female rats using 18FDG and microPET. These data demonstrate that acute opioid withdrawal produces metabolic alterations in brain regions associated with reward and drug dependence, namely corpus striatum, thalamic nuclei, septum, and frontal cortex. Furthermore, certain changes are unique to males. Specifically, males demonstrated increased metabolism in the anterior cingulate cortex and the ventral hippocampus (CA3) following acute opioid withdrawal. If males and females exhibit sex-specific changes in regional brain metabolism following acute opioid withdrawal, then perhaps it is not surprising that they respond to treatment differently. PMID:29046888

Maintenance treatment for opioid dependence with slow-release oral morphine: a randomized cross-over, non-inferiority study versus methadone

PubMed Central

Beck, Thilo; Haasen, Christian; Verthein, Uwe; Walcher, Stephan; Schuler, Christoph; Backmund, Markus; Ruckes, Christian; Reimer, Jens

2014-01-01

Aims To compare the efficacy of slow-release oral morphine (SROM) and methadone as maintenance medication for opioid dependence in patients previously treated with methadone. Design Prospective, multiple-dose, open label, randomized, non-inferiority, cross-over study over two 11-week periods. Methadone treatment was switched to SROM with flexible dosing and vice versa according to period and sequence of treatment. Setting Fourteen out-patient addiction treatment centres in Switzerland and Germany. Participants Adults with opioid dependence in methadone maintenance programmes (dose ≥50 mg/day) for ≥26 weeks. Measurements The efficacy end-point was the proportion of heroin-positive urine samples per patient and period of treatment. Each week, two urine samples were collected, randomly selected and analysed for 6-monoacetyl-morphine and 6-acetylcodeine. Non-inferiority was concluded if the two-sided 95% confidence interval (CI) in the difference of proportions of positive urine samples was below the predefined boundary of 10%. Findings One hundred and fifty-seven patients fulfilled criteria to form the per protocol population. The proportion of heroin-positive urine samples under SROM treatment (0.20) was non-inferior to the proportion under methadone treatment (0.15) (least-squares mean difference 0.05; 95% CI = 0.02, 0.08; P > 0.01). The 95% CI fell within the 10% non-inferiority margin, confirming the non-inferiority of SROM to methadone. A dose-dependent effect was shown for SROM (i.e. decreasing proportions of heroin-positive urine samples with increasing SROM doses). Retention in treatment showed no significant differences between treatments (period 1/period 2: SROM: 88.7%/82.1%, methadone: 91.1%/88.0%; period 1: P = 0.50, period 2: P = 0.19). Overall, safety outcomes were similar between the two groups. Conclusions Slow-release oral morphine appears to be at least as effective as methadone in treating people with opioid use disorder. PMID:24304412

Use of electroanalgesia and laser therapies as alternatives to opioids for acute and chronic pain management

PubMed Central

White, Paul F.; Elvir Lazo, Ofelia Loani; Galeas, Lidia; Cao, Xuezhao

2017-01-01

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 neuropathic pain

Opioid receptor trafficking and interaction in nociceptors

PubMed Central

Zhang, X; Bao, L; Li, S

2015-01-01

Opiate analgesics such as morphine are often used for pain therapy. However, antinociceptive tolerance and dependence may develop with long-term use of these drugs. It was found that μ-opioid receptors can interact with δ-opioid receptors, and morphine antinociceptive tolerance can be reduced by blocking δ-opioid receptors. Recent studies have shown that μ- and δ-opioid receptors are co-expressed in a considerable number of small neurons in the dorsal root ganglion. The interaction of μ-opioid receptors with δ-opioid receptors in the nociceptive afferents is facilitated by the stimulus-induced cell-surface expression of δ-opioid receptors, and contributes to morphine tolerance. Further analysis of the molecular, cellular and neural circuit mechanisms that regulate the trafficking and interaction of opioid receptors and related signalling molecules in the pain pathway would help to elucidate the mechanism of opiate analgesia and improve pain therapy. LINKED ARTICLES 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 PMID:24611685

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

PubMed

Fernandes, Kimberly; Martins, Diana; Juurlink, David; Mamdani, Muhammad; Paterson, J Michael; Spooner, Luke; Singh, Samantha; Gomes, Tara

2016-01-01

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-cancer pain led

Intravenous flurbiprofen axetil enhances analgesic effect of opioids in patients with refractory cancer pain by increasing plasma β-endorphin.

PubMed

Wu, Ting-Ting; Wang, Zhi-Gang; Ou, Wu-Ling; Wang, Jun; Yao, Guo-Qing; Yang, Bo; Rao, Zhi-Guo; Gao, Jian-Fei; Zhang, Bi-Cheng

2014-01-01

The study aimed to investigate the analgesic effect of a combination of intravenous flurbiprofen axetil and opioids, and evaluate the relationship between refractory pain relief and plasma β-endorphin levels in cancer patients. A total of 120 cancer patients was randomly divided into two groups, 60 patients took orally morphine sulfate sustained-release tablets in group A, and another 60 patients receiving the combination treatment of intravenous flurbiprofen axetil and opioid drugs in group B. After 7 days, pain relief, quality of life improvement and side effects were evaluated. Furthermore, plasma β-endorphin levels were measured by radioimmunoassay. With the combination treatment of intravenous intravenous flurbiprofen axetil and opioids, the total effective rate of pain relief rose to 91.4%, as compared to 82.1% when morphine sulfate sustained-release tablet was used alone. Compared with that of group A, the analgesic effect increased in group B (p=0.031). Moreover, satisfactory pain relief was associated with a significant increase in plasma β-endorphin levels. After the treatment, plasma β-endorphin level in group B was 62.4±13.5 pg/ml, which was higher than that in group A (45.8±11.2 pg/ml) (p<0.05). Our results suggest the combination of intravenous flurbiprofen axetil and opioids can enhance the analgesic effect of opioid drugs by increasing plasma β-endorphin levels, which would offer a selected and reliable strategy for refractory cancer pain treatment.

Opioid and amphetamine dependence is associated with methicillin-resistant Staphylococcus aureus (MRSA): An epidemiological register study with 73,201 Swedish in- and outpatients 1997-2013.

PubMed

Dahlman, Disa; Berge, Jonas; Nilsson, Anna C; Kral, Alex H; Bjorkman, Per; Hakansson, Anders C

2017-02-01

While methicillin-resistant Staphylococcus aureus (MRSA) is increasing in prevalence globally, Sweden is still a low-prevalence country enabling studies on the natural MRSA spread in subpopulations unaffected by a surrounding highly infected population. Substance dependence and injection drug use have been risk factors for MRSA carriage and infection in other countries. In this retrospective, longitudinal register study, we investigated MRSA epidemiology 1997-2013 in opioid and amphetamine-dependent individuals, in comparison with alcohol-dependent subjects. Data from the national Swedish in- and outpatients registers included 73,201 individuals from 1997, 1999, 2004, 2009 and 2013. We analyzed substance use disorder and demographic predictors for MRSA using generalized estimating equations. The main finding was that both opioid (adjusted odds ratio [AOR] = 2.82; 95% confidence interval [CI] = 2.16, 3.67) and amphetamine dependence (AOR = 2.71; 95% CI = 1.70, 4.16) were significantly associated with MRSA diagnosis compared with alcohol dependence, when adjusting for age, sex and year. These findings are of value to understand the dynamics of MRSA epidemiology among substance dependent persons with presumably low socioeconomic status and potential injection drug use, and implicate repeated surveillance of MRSA among these patients.

Remifentanil-acute opioid tolerance and opioid-induced hyperalgesia: a systematic review.

PubMed

Kim, Sang Hun; Stoicea, Nicoleta; Soghomonyan, Suren; Bergese, Sergio D

2015-01-01

The use of opioids may seem to be a double-edged sword; they provide straight analgesic and antihyperalgesic effects initially, but subsequently are associated with the expression of acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) that have been reported in experimental studies and clinical observations. It has been suggested that opioids can induce an acute tolerance and hyperalgesia in dose- and/or time-dependent manners even when used within the clinically accepted doses. Recently, remifentanil has been used for pain management in clinical anesthesia and in the intensive care units because of its rapid onset and offset. We reviewed articles analyzing AOT and/or OIH by remifentanil and focused on the following issues: (1) evidence of remifentanil inducing AOT and/or OIH and (2) importance of AOT and/or OIH in considering the reduction of remifentanil dosage or adopting preventive modulations. Twenty-four experimental and clinical studies were identified using electronic searches of MEDLINE (PubMed, Ovid, Springer, and Elsevier). However, the development of AOT and OIH by remifentanil administration remains controversial. There is no sufficient evidence to support or refute the existence of OIH in humans.

Extended-release naltrexone opioid treatment at jail reentry (XOR)

PubMed Central

McDonald, Ryan D.; Tofighi, Babak; Laska, Eugene; Goldfeld, Keith; Bonilla, Wanda; Flannery, Mara; Santana-Correa, Nadina; Johnson, Christopher W.; Leibowitz, Neil; Rotrosen, John; Gourevitch, Marc N.; Lee, Joshua D.

2017-01-01

Background Extended-release naltrexone (XR-NTX) is an injectable monthly sustained-release mu opioid receptor antagonist, which blocks the typical effects of heroin and other opioid agonists. Use of XR-NTX among opioid dependent persons leaving jails and prisons is increasing despite scant high-quality evidence regarding XR-NTX’s effectiveness at re-entry. Methods This 24-week, open-label randomized controlled trial examines the effectiveness of XR-NTX as opioid relapse prevention at release from jail (N = 85) compared to enhanced treatment as usual (ETAU, N = 85). A third, non-randomized, quasi-experimental naturalistic arm of participants who have newly initiated a jail-to-community methadone treatment program (MTP, N = 85) allows for comparisons to a methadone standard-of-care. Results We describe the rationale, design, and primary and secondary outcomes of the study. The primary outcome is an opioid relapse event; the primary contrast is a time-to-relapse comparison of XR-NTX and ETAU over a 24-week treatment phase. Secondary outcomes are rates of: (a) post-release opioid treatment participation, (b) opioid, alcohol, and cocaine use, (c) injection drug use and HIV sexual risk behaviors, (d) overdose (fatal and non-fatal) and all-cause mortality, and, (e) re-incarceration. Conclusions XR-NTX is a potentially important, effective treatment and relapse prevention option for a large US population of persons with opioid use disorders leaving jails. This study will estimate XR-NTX’s effectiveness relative to existing standards of care, including counseling-only treatment-as-usual and methadone maintenance. PMID:27178765

Is systematic training in opioid overdose prevention effective?

PubMed

Espelt, Albert; Bosque-Prous, Marina; Folch, Cinta; Sarasa-Renedo, Ana; Majó, Xavier; Casabona, Jordi; Brugal, M Teresa

2017-01-01

The objectives were to analyze the knowledge about overdose prevention, the use of naloxone, and the number of fatal overdoses after the implementation of Systematic Training in Overdose Prevention (STOOP) program. We conducted a quasi-experimental study, and held face-to-face interviews before (n = 725) and after (n = 722) implementation of systematic training in two different samples of people who injected opioids attending harm reduction centers. We asked participants to list the main causes of overdose and the main actions that should be taken when witnessing an overdose. We created two dependent variables, the number of (a) correct and (b) incorrect answers. The main independent variable was Study Group: Intervention Group (IG), Comparison Group (CG), Pre-Intervention Group With Sporadic Training in Overdose Prevention (PREIGS), or Pre-Intervention Group Without Training in Overdose Prevention (PREIGW). The relationship between the dependent and independent variables was assessed using a multivariate Poisson regression analysis. Finally, we conducted an interrupted time series analysis of monthly fatal overdoses before and after the implementation of systematic program during the period 2006-2015. Knowledge of overdose prevention increased after implementing systematic training program. Compared to the PREIGW, the IG gave more correct answers (IRR = 1.40;95%CI:1.33-1.47), and fewer incorrect answers (IRR = 0.33;95%CI:0.25-0.44). Forty percent of people who injected opioids who received a naloxone kit had used the kit in response to an overdose they witnessed. These courses increase knowledge of overdose prevention in people who use opioids, give them the necessary skills to use naloxone, and slightly diminish the number of fatal opioid overdoses in the city of Barcelona.

mu-Opioid receptor-independent fashion of the suppression of sodium currents by mu-opioid analgesics in thalamic neurons.

PubMed

Hashimoto, Keisuke; Amano, Taku; Kasakura, Akiko; Uhl, George R; Sora, Ichiro; Sakai, Norio; Kuzumaki, Naoko; Suzuki, Tsutomu; Narita, Minoru

2009-03-27

Most reports in the literature have shown that the effects of opioid analgesics are primarily mediated by mu-opioid receptor (MOR), whereas other potential targets of opioid analgesics have not been thoroughly characterized. In this study, we found that extracellular application of morphine, fentanyl or oxycodone, which are all considered to be MOR agonists, at relatively high concentrations, but not endogenous mu-opioid peptides, produced a concentration-dependent suppression of sodium currents in cultured thalamic neurons. These effects of opioids were not affected by either a MOR antagonist naloxone or a deletion of MOR gene. Among these opioids, fentanyl strongly suppressed sodium currents to the same degree as lidocaine, and both morphine and oxycodone slightly but significantly reduced sodium currents when they were present extracellularly. In contrast, the intracellular application of morphine, but not oxycodone, fentanyl or lidocaine, reduced sodium currents. These results suggest that morphine, fentanyl and oxycodone each produce the MOR-independent suppression of sodium currents by distinct mechanisms in thalamic neurons.

Targeting Dynorphin/Kappa Opioid Receptor Systems to Treat Alcohol Abuse and Dependence

PubMed Central

Walker, Brendan M.; Valdez, Glenn R.; McLaughlin, Jay P.; Bakalkin, Georgy

2012-01-01

This review represents the focus of a symposium that was presented at the “Alcoholism and Stress: A Framework for Future Treatment Strategies” conference in Volterra, Italy on May 3–6, 2011 and organized / chaired by Dr. Brendan M. Walker. The primary goal of the symposium was to evaluate and disseminate contemporary findings regarding the emerging role of kappa-opioid receptors (KORs) and their endogenous ligands dynorphins (DYNs) in the regulation of escalated alcohol consumption, negative affect and cognitive dysfunction associated with alcohol dependence, as well as DYN / KOR mediation of the effects of chronic stress on alcohol reward and seeking behaviors. Dr. Glenn Valdez described a role for KORs in the anxiogenic effects of alcohol withdrawal. Dr. Jay McLaughlin focused on the role of KORs in repeated stress-induced potentiation of alcohol reward and increased alcohol consumption. Dr. Brendan Walker presented data characterizing the effects of KOR antagonism within the extended amygdala on withdrawal-induced escalation of alcohol self-administration in dependent animals. Dr. Georgy Bakalkin concluded with data indicative of altered DYNs and KORs in the prefrontal cortex of alcohol dependent humans that could underlie diminished cognitive performance. Collectively, the data presented within this symposium identified the multifaceted contribution of KORs to the characteristics of acute and chronic alcohol-induced behavioral dysregulation and provided a foundation for the development of pharmacotherapeutic strategies to treat certain aspects of alcohol use disorders. PMID:22459870

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

PubMed

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.

Escitalopram is Associated with Reductions in Pain Severity and Pain Interference in Opioid Dependent Patients with Depressive Symptoms

PubMed Central

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

2011-01-01

Pain is common among opioid dependent patients, yet pharmacologic strategies are limited. The aim of this study was to explore whether escitalopram, a selective serotonin reuptake inhibitor, was associated with reductions in pain. The study used longitudinal data from a randomized, controlled trial that evaluated the effects of escitalopram on treatment retention in patients with depressive symptoms who were initiating buprenorphine/naloxone for treatment of opioid dependence. Participants were randomized to take escitalopram 10mg or placebo daily. Changes in pain severity, pain interference and depression were assessed at 1, 2 and 3 months visits using the Visual Analog Scale, Brief Pain Inventory and the Beck Depression Inventory II, respectively. Fixed-effects estimator for panel regression models were used to assess the effects of intervention on changes in outcomes over time. Additional models were estimated to explore whether the intervention effect was mediated by within-person changes in depression. In this sample of 147 adults, we found that participants randomized to escitalopram had significantly larger reductions on both pain severity (b = −14.34, t = −2.66, p < .01) and pain interference (b = −1.20, t = −2.23, p < .05) between baseline and follow-up. After adjusting for within-subject changes in depression, the estimated effects of escitalopram on pain severity and pain interference were virtually identical to the unadjusted effects. In summary, this study of opioid-dependent patients with depressive symptoms found that treatment with escitalopram was associated with clinically meaningful reductions in pain severity and pain interference during the first three months of therapy. PMID:21924552

Child Maltreatment as a Risk Factor for Opioid Dependence: Comparison of Family Characteristics and Type and Severity of Child Maltreatment with a Matched Control Group

ERIC Educational Resources Information Center

Conroy, Elizabeth; Degenhardt, Louisa; Mattick, Richard P.; Nelson, Elliot C.

2009-01-01

Objective: To examine the prevalence, characteristics and risk factors for child maltreatment among opioid-dependent persons compared to a community sample of similar social disadvantage. Method: The study employed a case-control design. Cases had a history of opioid pharmacotherapy. Controls were frequency matched to cases with regard to age, sex…

New Opioid Analgesic Approvals and Outpatient Utilization of Opioid Analgesics in the United States, 1997 through 2015.

PubMed

Chai, Grace; Xu, Jing; Osterhout, James; Liberatore, Mark A; Miller, Kathleen L; Wolff, Carolyn; Cruz, Marisa; Lurie, Peter; Dal Pan, Gerald

2018-05-01

The opioid epidemic, driven in part by increased prescribing, is a public health emergency. This study examines dispensed prescription patterns and approvals of new opioid analgesic products to investigate whether the introduction of these new drugs increases prescribing. Prescribing patterns based on dispensed prescription claims from the U.S. retail setting were assessed with new brand and generic opioid analgesic products approved in the United States from 1997 through 2015. From 1997 through 2015, the U.S. Food and Drug Administration (Silver Spring, Maryland) approved 263 opioid analgesic products, including 33 brand products. Dispensed prescriptions initially increased 80% from 145 million prescriptions in 1997 to a peak of 260 million prescriptions in 2012 before decreasing by 12% to 228 million prescriptions in 2015. Morphine milligram equivalents dispensed per prescription increased from 486 in 1997 to a peak of 950 in 2010, before decreasing to 905 in 2015. In 2015, generic products accounted for 96% (218/228 million prescriptions) of all opioid analgesic prescriptions dispensed. The remaining prescriptions were dispensed for brand products, of which nearly half were dispensed for one brand product (OxyContin, Purdue, USA). There has been a dramatic increase in prescriptions dispensed for opioid analgesics since 1997 and an increasing number of opioid analgesic approvals; however, the number of prescriptions dispensed has declined since 2012 despite an increasing number of approvals. Examination of dispensed prescriptions shows a shifting and complex market where multiple factors likely influence prescribing; the approval of new products alone may not be sufficient to be a primary driver of increased prescribing. An online visual overview is available for this article at http://links.lww.com/ALN/B705.

Secular trends in opioid prescribing in the USA.

PubMed

Pezalla, Edmund J; Rosen, David; Erensen, Jennifer G; Haddox, J David; Mayne, Tracy J

2017-01-01

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.

Mindfulness Is Associated with Increased Hedonic Capacity Among Chronic Pain Patients Receiving Extended Opioid Pharmacotherapy

PubMed Central

Thomas, Elizabeth A.; Garland, Eric L.

2016-01-01

Objectives Chronic pain and long-term opioid use may lead to a persistent deficit in hedonic capacity, characterized by increased sensitivity to aversive states and insensitivity to natural rewards. Dispositional mindfulness has been linked with improved emotion regulation and pain coping. The aim of the current study was to examine associations between dispositional mindfulness, hedonic capacity, and pain-related interference in an opioid-using chronic pain sample. Methods Data were obtained from a sample of 115 chronic pain patients on long-term opioid therapy (68% females, M age=48.3, SD=13.6) who completed the Five Facet Mindfulness Questionnaire (FFMQ), the Snaith Hamilton Anhedonia and Pleasure Scale (SHAPS), the Brief Pain Inventory (BPI), and a psychiatric assessment of major depression. Bivariate correlations, hierarchical multiple regression, and path analysis were used to determine if dispositional mindfulness scores (FFMQ) predicted variance in hedonic capacity (SHAPS), and if hedonic capacity mediated the association between mindfulness and pain interference. Results We observed a significant positive correlation between dispositional mindfulness and hedonic capacity scores, r=.33, p<.001. Hierarchical regression indicated that after controlling for pain interference and major depressive disorder diagnosis, dispositional mindfulness explained a significant portion of variance in hedonic capacity (Beta = .30, p< .01). The association between dispositional mindfulness and pain interference was mediated by hedonic capacity (b = −.011, SE=.005, 95% C.I. = −.004 to −.024, full model R2=.39). Discussion Findings indicate that dispositional mindfulness was associated with hedonic capacity among this chronic pain sample. In light of this association, it is plausible that interventions that increase mindfulness may reduce pain-related impairment among opioid-using patients by enhancing hedonic capacity. PMID:28060783

Opioid Utilization and Opioid-Related Adverse Events in Non-Surgical Patients in U.S. Hospitals

PubMed Central

Herzig, Shoshana J.; Rothberg, Michael B.; Cheung, Michael; Ngo, Long H.; Marcantonio, Edward R.

2014-01-01

Background Recent studies in the outpatient setting have demonstrated high rates of opioid prescribing and overdose-related deaths. Prescribing practices in hospitalized patients are unexamined. Objective To investigate patterns and predictors of opioid utilization in non-surgical admissions to U.S. hospitals, variation in use, and the association between hospital-level use and rates of severe opioid-related adverse events. Design, Setting, and Patients Adult non-surgical admissions to 286 U.S. hospitals. Measurements Opioid exposure and severe opioid-related adverse events during hospitalization, defined using hospital charges and ICD-9-CM codes. Results Of 1.14 million admissions, opioids were used in 51%. The mean ± s.d. daily dose received in oral morphine equivalents (OME) was 68 ± 185 mg; 23% of exposed received a total daily dose of ≥ 100 mg OME. Opioid prescribing rates ranged from 5% in the lowest to 72% in the highest prescribing hospital (mean 51% ± 10%). After adjusting for patient characteristics, the adjusted opioid prescribing rates ranged from 33–64% (mean 50% ± s.d. 4%). Among exposed, 0.97% experienced severe opioid-related adverse events. Hospitals with higher opioid prescribing rates had higher adjusted relative risk of a severe opioid-related adverse event per patient exposed (RR 1.23 [1.14–1.33] for highest compared to lowest prescribing quartile). Conclusions The majority of hospitalized non-surgical patients were exposed to opioids, often at high doses. Hospitals that used opioids most frequently had increased adjusted risk of a severe opioid-related adverse event per patient exposed. Interventions to standardize and enhance the safety of opioid prescribing in hospitalized patients should be investigated. PMID:24227700

Opioids Increase Sexual Dysfunction in Patients With Non-Cancer Pain.

PubMed

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 < .05), although they reported having a regular partner (84% vs 70%, P = .03) and a 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

A comparison of independent depression and substance-induced depression in cannabis-, cocaine-, and opioid-dependent treatment seekers.

PubMed

Dakwar, Elias; Nunes, Edward V; Bisaga, Adam; Carpenter, Kenneth C; Mariani, John P; Sullivan, Maria A; Raby, Wilfrid N; Levin, Frances R

2011-01-01

Depressive symptoms often coexist with substance use disorders (SUDs). The DSM-IV has identified two distinct categories for depression coexisting with SUDs-independent depression and substance-induced depression. While this distinction has important therapeutic and prognostic implications, it remains difficult to make in clinical practice; the differentiation is often guided by chronological and symptom severity criteria that patients may be unable to precisely provide. Furthermore, it is unclear whether the various substances commonly abused-cannabis, cocaine, and opioids-are equally associated with the two types of depression. Predictors, associations, and other markers may be helpful in guiding the diagnostic process. We, therefore, examined the differences between cannabis-, cocaine-, and opioid-dependent individuals contending with independent depression and those contending with substance-induced depression in regard to several variables, hypothesizing that independent depression is more commonly found in females, and that it is associated with higher symptom severity and psychiatric comorbidity. Cocaine-, cannabis-, and/or opioid-dependent, treatment-seeking individuals underwent a structured clinical interview for DSM-IV-TR disorders after providing consent at our clinical research site; those with co-existing primary depression or substance-induced depression diagnoses were provided with further questionnaires and were entered into this analysis (n= 242). Pair-wise comparisons were conducted between the groups classified as independent versus substance-induced depression with 2-by-2 tables and chi-square tests for dichotomous independent variables, and t-tests for continuous variables. Binomial logistic regression was performed in order to ascertain which of the variables were significant predictors. Women were more likely than men to have independent depression (p< .005). Cannabis dependence was highly associated with independent depression (p< .001

Long-term Use of Opioids for Complex Chronic Pain

PubMed Central

Von Korff, Michael R.

2014-01-01

Increased opioid prescribing for back pain and other chronic musculoskeletal pain conditions has been accompanied by dramatic increases in prescription opioid addiction and fatal overdose. Opioid-related risks appear to increase with dose. While short-term randomized trials of opioids for chronic pain have found modest analgesic benefits (a one-third reduction in pain intensity on average), the long-term safety and effectiveness of opioids for chronic musculoskeletal pain is unknown. Given the lack of large, long-term randomized trials, recent epidemiologic data suggests the need for caution when considering long-term use of opioids to manage chronic musculoskeletal pain, particularly at higher dosage levels. Principles for achieving more selective and cautious use of opioids for chronic musculoskeletal pain are proposed. PMID:24315147

Activation of kappa opioid receptors in the dorsal raphe have sex dependent effects on social behavior in California mice.

PubMed

Wright, Emily C; Parks, Tiffany V; Alexander, Jonathon O; Supra, Rajesh; Trainor, Brian C

2018-06-06

Kappa opioid receptor activation has been linked to stress and anxiety behavior, thus leading to kappa antagonists being popularized in research as potential anxiolytics. However, while these findings may hold true in standard models, the neuromodulatory effects of social defeat may change the behavioral outcome of kappa opioid receptor activation. Previous research has shown that social defeat can lead to hyperactivity of serotonergic neurons in the dorsal raphe nucleus, and that inhibition of this increase blocks the social deficits caused by defeat. Kappa opioid receptor activation in the dorsal raphe nucleus works to decrease serotonergic activity. We injected the kappa opioid receptor U50,488 directly into the dorsal raphe nucleus of male and female, defeat and control adult California mice. Here we show evidence that U50,488 induces anxiety behavior in control male California mice, but helps relieve it in defeated males. Consistent with previous literature, we find little effect in females adding evidence that there are marked and important sex differences in the kappa opioid system. Copyright © 2018 Elsevier B.V. All rights reserved.

Brief versus extended counseling along with buprenorphine/naloxone for HIV-infected opioid dependent patients.

PubMed

Tetrault, Jeanette M; Moore, Brent A; Barry, Declan T; O'Connor, Patrick G; Schottenfeld, Richard; Fiellin, David A; Fiellin, Lynn E

2012-12-01

Untreated opioid dependence adversely affects HIV outcomes. Integrating buprenorphine/naloxone into HIV treatment settings is feasible; however, the optimal level of counseling has not been established. We conducted a 12-week randomized clinical trial of physician management (PM) versus PM plus enhanced medical management (EMM) in 47 subjects. At 12 weeks, there were no differences between the two groups in percentage of opioid negative urines (63.6% PM vs. 69.0% PM+EMM, p=.5), maximum duration of continuous abstinence (4.9 weeks PM vs. 5.2 weeks PM+EMM, p=.8) or retention (80% PM vs. 59% PM+EMM, p=.1). The percentage of subjects with detectable HIV viral loads decreased from 58% at baseline to 40% at 12 weeks across both groups (p=.02 for time) with no between group differences (p=.84 and p=.27 for the interaction). Providing more extensive counseling beyond PM is feasible in an HIV clinic, but we are unable to detect an improvement in outcomes associated with these services. Copyright © 2012 Elsevier Inc. All rights reserved.

Something for pain: Responsible opioid use in emergency medicine.

PubMed

Strayer, Reuben J; Motov, Sergey M; Nelson, Lewis S

2017-02-01

The United States is currently experiencing a public health crisis of opioid addiction, which has its genesis in an industry marketing effort that successfully encouraged clinicians to prescribe opioids liberally, and asserted the safety of prescribing opioids for chronic non-cancer pain, despite a preponderance of evidence demonstrating the risks of dependence and misuse. The resulting rise in opioid use has pushed drug overdose deaths in front of motor vehicle collisions to become the leading cause of accidental death in the country. Emergency providers frequently treat patients for complications of opioid abuse, and also manage patients with acute and chronic pain, for which opioids are routinely prescribed. Emergency providers are therefore well positioned to both prevent new cases of opioid misuse and initiate appropriate treatment of existing opioid addicts. In opioid-naive patients, this is accomplished by a careful consideration of the likelihood of benefit and harm of an opioid prescription for acute pain. If opioids are prescribed, the chance of harm is reduced by matching the number of pills prescribed to the expected duration of pain and selecting an opioid preparation with low abuse liability. Patients who present to acute care with exacerbations of chronic pain or painful conditions associated with opioid misuse are best managed by treating symptoms with opioid alternatives and encouraging treatment for opioid addiction. Copyright © 2016 Elsevier Inc. All rights reserved.

Psychophysiology of pain and opioid use: implications for managing pain in patients with an opioid use disorder.

PubMed

Wachholtz, Amy; Foster, Simmie; Cheatle, Martin

2015-01-01

Opioid therapy is one component of an effective pain management regimen for patients with chronic pain and the majority of these patients use their medications responsibly. However, there are a growing number of these patients who develop an opioid use disorder and in some cases require opioid replacement therapy. Managing these patients is complex and the underlying mechanisms of pain and addiction are not well understood. Developing an effective interdisciplinary treatment program for the individual with pain and an opioid use disorder will depend on enhancing our knowledge of the psychophysiology of pain and addiction. Authors gathered key empirical and theoretical papers examining the psychophysiology of comorbid pain and opioid misuse disorders. This article reviews the current theory of the effect of pain on patients with pain and concomitant addiction, the psychophysiology of pain, opioid use and addiction, and future research in this area. Individuals with a history of opioid misuse have greater levels of hyperalgesia which may be due to alterations in psychophysiological pathways. More research is needed into the psychophysiological biomarkers among individuals with comorbid pain and addiction in order to develop better treatment approaches and improve outcomes among this difficult to treat population. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chronic Nicotine Treatment Impacts the Regulation of Opioid and Non-opioid Peptides in the Rat Dorsal Striatum*

PubMed Central

Petruzziello, Filomena; Falasca, Sara; Andren, Per E.; Rainer, Gregor; Zhang, Xiaozhe

2013-01-01

The chronic use of nicotine, the main psychoactive ingredient of tobacco smoking, alters diverse physiological processes and consequently generates physical dependence. To understand the impact of chronic nicotine on neuropeptides, which are potential molecules associated with dependence, we conducted qualitative and quantitative neuropeptidomics on the rat dorsal striatum, an important brain region implicated in the preoccupation/craving phase of drug dependence. We used extensive LC-FT-MS/MS analyses for neuropeptide identification and LC-FT-MS in conjunction with stable isotope addition for relative quantification. The treatment with chronic nicotine for 3 months led to moderate changes in the levels of endogenous dorsal striatum peptides. Five enkephalin opioid peptides were up-regulated, although no change was observed for dynorphin peptides. Specially, nicotine altered levels of nine non-opioid peptides derived from precursors, including somatostatin and cerebellin, which potentially modulate neurotransmitter release and energy metabolism. This broad but selective impact on the multiple peptidergic systems suggests that apart from the opioid peptides, several other peptidergic systems are involved in the preoccupation/craving phase of drug dependence. Our finding permits future evaluation of the neurochemical circuits modulated by chronic nicotine exposure and provides a number of novel molecules that could serve as potential therapeutic targets for treating drug dependence. PMID:23436905

Loaded: Gun involvement among opioid users.

PubMed

Stein, Michael D; Kenney, Shannon R; Anderson, Bradley J; Bailey, Genie L

2018-06-01

Despite ample research examining how alcohol use relates to gun involvement, little is known about the relationship between opioids and gun involvement. In the current study, we examined correlates of gun possession, accessibility, and related behaviors in an opioid dependent sample. Between October 2016 and April 2017, we surveyed persons entering a brief, inpatient opioid detoxification (n = 386) and 51 contemporaneous persons seeking alcohol detoxification at the same facility in Massachusetts and recorded their lifetime experiences with gun involvement. Participants averaged 33 years of age, 74% were male, 83% were White, and 64% had a history of incarceration. Opioid users had significantly higher rates of gun involvement than persons in alcohol detoxification; for example, 31.3% (vs. 3.9%) had carried a gun for protection, 45.1% (vs. 25.5%) had been threatened with a gun, and 13.8% (vs. 2.0%) had shot at another person. Among persons misusing opioids, male and non-White respondents, and those with a history of incarceration or poorer self-control reported greater gun involvement. Opioid users, both men and women, lead gun-involved lives. Copyright © 2018 Elsevier B.V. All rights reserved.

Is systematic training in opioid overdose prevention effective?

PubMed Central

Bosque-Prous, Marina; Folch, Cinta; Sarasa-Renedo, Ana; Majó, Xavier; Casabona, Jordi; Brugal, M. Teresa

2017-01-01

The objectives were to analyze the knowledge about overdose prevention, the use of naloxone, and the number of fatal overdoses after the implementation of Systematic Training in Overdose Prevention (STOOP) program. We conducted a quasi-experimental study, and held face-to-face interviews before (n = 725) and after (n = 722) implementation of systematic training in two different samples of people who injected opioids attending harm reduction centers. We asked participants to list the main causes of overdose and the main actions that should be taken when witnessing an overdose. We created two dependent variables, the number of (a) correct and (b) incorrect answers. The main independent variable was Study Group: Intervention Group (IG), Comparison Group (CG), Pre-Intervention Group With Sporadic Training in Overdose Prevention (PREIGS), or Pre-Intervention Group Without Training in Overdose Prevention (PREIGW). The relationship between the dependent and independent variables was assessed using a multivariate Poisson regression analysis. Finally, we conducted an interrupted time series analysis of monthly fatal overdoses before and after the implementation of systematic program during the period 2006–2015. Knowledge of overdose prevention increased after implementing systematic training program. Compared to the PREIGW, the IG gave more correct answers (IRR = 1.40;95%CI:1.33–1.47), and fewer incorrect answers (IRR = 0.33;95%CI:0.25–0.44). Forty percent of people who injected opioids who received a naloxone kit had used the kit in response to an overdose they witnessed. These courses increase knowledge of overdose prevention in people who use opioids, give them the necessary skills to use naloxone, and slightly diminish the number of fatal opioid overdoses in the city of Barcelona. PMID:29088247

Prescription of Opioid and Non-opioid Analgesics for Dental Care in Emergency Departments: Findings from the National Hospital Ambulatory Medical Care Survey

PubMed Central

Okunseri, Christopher; Okunseri, Elaye; Xiang, Qun; Thorpe, Joshua M.; Szabo, Aniko

2014-01-01

Objective The aim of this study was to examine trends and associated factors in the prescription of opioid analgesics, non-opioid analgesics, opioid and non-opioid analgesic combinations and no analgesics by emergency physicians for nontraumatic dental condition (NTDC)-related visits. Our secondary aim was to investigate whether race/ethnicity is a possible predictor of receiving a prescription for either type of medication for NTDC visits in emergency departments (EDs) after adjustment for potential covariates. Methods We analyzed data from the National Hospital Ambulatory Medical Care Survey for 1997–2000 and 2003–2007, and used multinomial multivariate logistic regression to estimate the probability of receiving a prescription for opioid analgesics, non-opioid analgesics, or a combination of both compared to receiving no analgesics for NTDC-related visits. Results During 1997–2000 and 2003–2007, prescription of opioid analgesics and combinations of opioid and non-opioid analgesics increased and that of no analgesics decreased over time. The prescription rates for opioid analgesics, non-opioid analgesics, opioid and non-opioid analgesic combinations and no analgesics for NTDC-related visits in EDs were 43%, 20%, 12% and 25% respectively. Majority of patients categorized as having severe pain received prescriptions for opioids for NTDC-related visits in EDs. After adjusting for covariates, patients with self-reported dental reasons for visit and severe pain had a significantly higher probability of receiving prescriptions for opioid analgesics and opioid and non-opioid analgesic combinations. Conclusion Prescription of opioid analgesics increased over time. ED physicians were more likely to prescribe opioid analgesics and opioid and non-opioid analgesic combinations for NTDC-related visits with reported severe pain. PMID:24863407

Brief Opioid Overdose Knowledge (BOOK): A Questionnaire to Assess Overdose Knowledge in Individuals Who Use Illicit or Prescribed Opioids.

PubMed

Dunn, Kelly E; Barrett, Frederick S; Yepez-Laubach, Claudia; Meyer, Andrew C; Hruska, Bryce J; Sigmon, Stacey C; Fingerhood, Michael; Bigelow, George E

2016-01-01

Opioid overdose is a public health crisis. This study describes efforts to develop and validate the Brief Opioid Overdose Knowledge (BOOK) questionnaire to assess patient knowledge gaps related to opioid overdose risks. Two samples of illicit opioid users and a third sample of patients receiving an opioid for the treatment of chronic pain (total N = 848) completed self-report items pertaining to opioid overdose risks. A 3-factor scale was established, representing Opioid Knowledge (4 items), Opioid Overdose Knowledge (4 items), and Opioid Overdose Response Knowledge (4 items). The scale had strong internal and face validity. Patients with chronic pain performed worse than illicit drug users in almost all items assessed, highlighting the need to increase knowledge of opioid overdose risk to this population. This study sought to develop a brief, internally valid method for quickly assessing deficits in opioid overdose risk areas within users of illicit and prescribed opioids, to provide an efficient metric for assessing and comparing educational interventions, facilitate conversations between physicians and patients about overdose risks, and help formally identify knowledge deficits in other patient populations.

Opioid Analgesics and Nicotine: More Than Blowing Smoke.

PubMed

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.

Methadone, Buprenorphine and Preferences for Opioid Agonist Treatment: A Qualitative Analysis

PubMed Central

Yarborough, Bobbi Jo H.; Stumbo, Scott P.; McCarty, Dennis; Mertens, Jennifer; Weisner, Constance; Green, Carla A.

2016-01-01

Background Patients and clinicians have begun to recognize the advantages and disadvantages of buprenorphine relative to methadone, but factors that influence choices between these two medications remain unclear. For example, we know little about how patients’ preferences and previous experiences influence treatment decisions. Understanding these issues may enhance treatment engagement and retention. Methods Adults with opioid dependence (n = 283) were recruited from two integrated health systems to participate in interviews focused on prior experiences with treatment for opioid dependence, knowledge of medication options, preferences for treatment, and experiences with treatment for chronic pain in the context of problems with opioids. Interviews were audio-recorded, transcribed verbatim, and coded using Atlas.ti. Results Our analysis revealed seven areas of consideration for opioid agonist treatment decision-making: 1) awareness of treatment options; 2) expectations and goals for duration of treatment and abstinence; 3) prior experience with buprenorphine or methadone; 4) need for accountability and structured support; 5) preference to avoid methadone clinics or associated stigma; 6) fear of continued addiction and perceived difficulty of withdrawal; and 7) pain control. Conclusion The availability of medication options increases the need for clear communication between clinicians and patients, for additional patient education about these medications, and for collaboration and patient influence over choices in treatment decision-making. Our results suggest that access to both methadone and buprenorphine will increase treatment options and patient choice and may enhance treatment adherence and outcomes. PMID:26796596

Opioid analgesia in mechanically ventilated children: results from the multicenter Measuring Opioid Tolerance Induced by Fentanyl study.

PubMed

Anand, Kanwaljeet J S; Clark, Amy E; Willson, Douglas F; Berger, John; Meert, Kathleen L; Zimmerman, Jerry J; Harrison, Rick; Carcillo, Joseph A; Newth, Christopher J L; Bisping, Stephanie; Holubkov, Richard; Dean, J Michael; Nicholson, Carol E

2013-01-01

To examine the clinical factors associated with increased opioid dose among mechanically ventilated children in the pediatric intensive care unit. Prospective, observational study with 100% accrual of eligible patients. Seven pediatric intensive care units from tertiary-care children's hospitals in the Collaborative Pediatric Critical Care Research Network. Four hundred nineteen children treated with morphine or fentanyl infusions. None. Data on opioid use, concomitant therapy, demographic and explanatory variables were collected. Significant variability occurred in clinical practices, with up to 100-fold differences in baseline opioid doses, average daily or total doses, or peak infusion rates. Opioid exposure for 7 or 14 days required doubling of the daily opioid dose in 16% patients (95% confidence interval 12%-19%) and 20% patients (95% confidence interval 16%-24%), respectively. Among patients receiving opioids for longer than 3 days (n = 225), this occurred in 28% (95% confidence interval 22%-33%) and 35% (95% confidence interval 29%-41%) by 7 or 14 days, respectively. Doubling of the opioid dose was more likely to occur following opioid infusions for 7 days or longer (odds ratio 7.9, 95% confidence interval 4.3-14.3; p < 0.001) or co-therapy with midazolam (odds ratio 5.6, 95% confidence interval 2.4-12.9; p < 0.001), and it was less likely to occur if morphine was used as the primary opioid (vs. fentanyl) (odds ratio 0.48, 95% confidence interval 0.25-0.92; p = 0.03), for patients receiving higher initial doses (odds ratio 0.96, 95% confidence interval 0.95-0.98; p < 0.001), or if patients had prior pediatric intensive care unit admissions (odds ratio 0.37, 95% confidence interval 0.15-0.89; p = 0.03). Mechanically ventilated children require increasing opioid doses, often associated with prolonged opioid exposure or the need for additional sedation. Efforts to reduce prolonged opioid exposure and clinical practice variation may prevent the complications of

Extended release naltrexone injection is performed in the majority of opioid dependent patients receiving outpatient induction: a very low dose naltrexone and buprenorphine open label trial.

PubMed

Mannelli, Paolo; Wu, Li-Tzy; Peindl, Kathleen S; Swartz, Marvin S; Woody, George E

2014-05-01

The approval of extended release injectable naltrexone (XR-NTX; Vivitrol(®)) has introduced a new option for treating opioid addiction, but studies are needed to identify its place within the spectrum of available therapies. The absence of physiological opioid dependence is a necessary and challenging first step for starting XR-NTX. Outpatient detoxification gives poor results and inpatient detoxification is either unavailable or too brief for the physiological effects of opioids to resolve. Here we present findings from an open label study that tested whether the transition from opioid addiction to XR-NTX can be safely and effectively performed in an outpatient setting using very low dose naltrexone and buprenorphine. Twenty treatment seeking opioid addicted individuals were given increasing doses of naltrexone starting at 0.25mg with decreasing doses of buprenorphine starting at 4 mg during a 7-day outpatient XR-NTX induction procedure. Withdrawal discomfort, craving, drug use, and adverse events were assessed daily until the XR-NTX injection, then weekly over the next month. Fourteen of the 20 participants received XR-NTX and 13 completed weekly assessments. Withdrawal, craving, and opioid or other drug use were significantly lower during induction and after XR-NTX administration compared with baseline, and no serious adverse events were recorded. Outpatient transition to XR-NTX combining upward titration of very low dose naltrexone with downward titration of low dose buprenorphine was safe, well tolerated, and completed by most participants. Further studies with larger numbers of subjects are needed to see if this approach is useful for naltrexone induction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Opioid intake prior to admission is not increased in elderly patients with low-energy fractures: a case control study in a German hospital population.

PubMed

Schwarzer, A; Kaisler, M; Kipping, K; Seybold, D; Rausch, V; Maier, C; Vollert, J

2018-05-14

Recent studies revealed an increased prescription rate of opioids for elderly patients suffering bone fractures. To gain further insight, we conducted face-to-face interviews in the present study to compare the opioid intake between patients with low energy fractures and patients suffering from internal diseases. In this case-control study, 992 patients, aged 60 years and older, were enrolled between March 2014 and February 2015. The interview comprised a fall and medication history, comorbidities, mobility and other risk factors for fractures. Odds ratios (OR) and a multiple logistic regression model were calculated. The number of patients with pre-admission opioid intake in the last 12 months was comparable in the fracture (n=399, 13.3%) and the control group (n=593, 14.7% OR: 0.89, CI: 0.62-1.29). The number of patients with current opioid intake of short duration (<3 months) was similar in both groups (14% vs. 20%; OR: 0.66, CI: 0.23-1.93). Patients with opioid intake in the fracture group reported more frequently fatigue as an adverse event of opioid medication (58% vs. 30%; OR: 3.32, CI: 1.48-7.45). Patients with opioid intake showed more severe comorbidities and significantly decreased mobility compared to those without opioids. Elderly patients internalized due to low-energy fractures did not take opioids more frequently than patients with internal admission, for both short (<3 months) and longer duration intake. Patients with opioid intake were generally in poorer physical condition. The risk of fracture might increase in patients suffering from fatigue as a side effect of opioid medication. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

PubMed

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.

Sex-specific Linkage Scans in Opioid Dependence

PubMed Central

Yang, Bao-Zhu; Han, Shizhong; Kranzler, Henry R.; Palmer, Abraham A.; Gelernter, Joel

2017-01-01

Sex influences risk for opioid dependence (OD). We hypothesized that sex might interact with genetic loci that influence the risk for OD. Therefore we performed an analysis to identify sex-specific genomic susceptibility regions for OD using linkage. Over 6000 single nucleotide polymorphism (SNP) markers were genotyped for 1758 African- and European-American (AA and EA) individuals from 739 families, ascertained via affected sib-pairs with OD and/or cocaine dependence. Autosomewide non-parametric linkage scans, stratified by sex and population, were performed. We identified one significant linkage region, segregating with OD in EA men, at 71.1 cM on chromosome 4 (LOD=3.29; point-wise p=0.00005; empirical autosome-wide p=0.042), which significantly differed from the linkage signal at the same location in EA women (empirical p=0.002). Three suggestive linkage signals were identified at 181.3 cM on chromosome 7 (LOD=2.18), 104 cM on chromosome 11 (LOD=1.85), and 60.9 cM on chromosome 16 (LOD=1.93) in EA women. In AA men, four suggestive linkage signals were detected at 201.1 cM on chromosome 3 (LOD=2.32), 152.9 cM on chromosome 6 (LOD=1.86), 16.8 cM on chromosome 7 (LOD=1.95), and 36.1 cM on chromosome 17 (LOD=1.99). The significant region, mapping to 4q12-4q13.1, harbors several OD candidate genes with interconnected functionality, including VEGFR, CLOCK, PDCL2, NMU, NRSF, and IGFBP7. In conclusion, these results provide an evidence for the existence of sex-specific and population-specific differences in OD. Furthermore, these results provide positional information that will facilitate the use of targeted next-generation sequencing to search for genes that contribute to sex-specific differences in OD. PMID:27762075

Sex Differences in Regional Brain Glucose Metabolism Following Opioid Withdrawal and Replacement.

PubMed

Santoro, Giovanni C; Carrion, Joseph; Patel, Krishna; Vilchez, Crystal; Veith, Jennifer; Brodie, Jonathan D; Dewey, Stephen L

2017-08-01

Methadone and buprenorphine are currently the most common pharmacological treatments for opioid dependence. Interestingly, the clinical response to these drugs appears to be sex specific. That is, females exhibit superior therapeutic efficacy, defined as extended periods of abstinence and longer time to relapse, compared with males. However, the underlying metabolic effects of opioid withdrawal and replacement have not been examined. Therefore, using 18 FDG and microPET, we measured differences in regional brain glucose metabolism in males and females following morphine withdrawal and subsequent methadone or buprenorphine replacement. In both males and females, spontaneous opioid withdrawal altered glucose metabolism in regions associated with reward and drug dependence. Specifically, metabolic increases in the thalamus, as well as metabolic decreases in insular cortex and the periaqueductal gray, were noted. However, compared with males, females exhibited increased metabolism in the preoptic area, primary motor cortex, and the amygdala, and decreased metabolism in the caudate/putamen and medial geniculate nucleus. Methadone and buprenorphine initially abolished these changes uniformly, but subsequently produced their own regional metabolic alterations that varied by treatment and sex. Compared with sex-matched control animals undergoing spontaneous opioid withdrawal, male animals treated with methadone exhibited increased caudate/putamen metabolism, whereas buprenorphine produced increased ventral striatum and motor cortex metabolism in females, and increased ventral striatum and somatosensory cortex metabolism in males. Notably, when treatment effects were compared between sexes, methadone-treated females showed increased cingulate cortex metabolism, whereas buprenorphine-treated females showed decreased metabolism in cingulate cortex and increased metabolism in the globus pallidus. Perhaps the initial similarities in males and females underlie early therapeutic

The impact of opioids on the endocrine system.

PubMed

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.

Opioid activation of Toll-Like receptor 4 contributes to drug reinforcement

PubMed Central

Hutchinson, M.R.; Northcutt, A.L.; Hiranita, T.; Wang, X.; Lewis, S.; Thomas, J.; van Steeg, K.; Kopajtic, T.A.; Loram, L.; Sfregola, C.; Galer, E.; Miles, N.E.; Bland, S.T.; Amat, J.; Rozeske, R.R.; Maslanik, T.; Chapman, T.; Strand, K.; Fleshner, M.; Bachtell, R.K.; Somogyi, A.A.; Yin, H.; Katz, J.L.; Rice, K.C.; Maier, S.F.; Watkins, L.R.

2012-01-01

Opioid action was thought to exert reinforcing effects solely via the initial agonism of opioid receptors. Here we present evidence for an additional novel contributor to opioid reward: the innate immune pattern-recognition receptor, Toll-like receptor 4 (TLR4), and its MyD88-dependent signaling. Blockade of TLR4/MD2 by administration of the non-opioid, unnatural isomer of naloxone, (+)-naloxone (rats), or two independent genetic knockouts of MyD88-TLR4-dependent signaling (mice), suppressed opioid-induced conditioned place preference. (+)-Naloxone also reduced opioid (remifentanil) self-administration (rats), another commonly used behavioral measure of drug reward. Moreover, pharmacological blockade of morphine-TLR4/MD2 activity potently reduced morphine-induced elevations of extracellular dopamine in rat nucleus accumbens, a region critical for opioid reinforcement. Importantly, opioid-TLR4 actions are not a unidirectional influence on opioid pharmacodynamics, since TLR4 −/− mice had reduced oxycodone-induced p38 and JNK phosphorylation, whilst displaying potentiated analgesia. Similar to our recent reports of morphine-TLR4/MD2 binding, here we provide a combination of in silico and biophysical data to support (+)-naloxone and remifentanil binding to TLR4/MD2. Collectively, these data indicate that the actions of opioids at classical opioid receptors, together with their newly identified TLR4/MD2 actions, affect the mesolimbic dopamine system which amplifies opioid-induced elevations in extracellular dopamine levels and therefore possibly explaining altered opioid reward behaviors. Thus, the discovery of TLR4/MD2 recognition of opioids as foreign xenobiotic substances adds to the existing hypothesized neuronal reinforcement mechanisms, identifies a new drug target in TLR4/MD2 for the treatment of addictions, and provides further evidence supporting a role for central proinflammatory immune signaling in drug reward. PMID:22895704

Proinflammatory cytokines oppose opioid induced acute and chronic analgesia

PubMed Central

Hutchinson, Mark R.; Coats, Benjamen D.; Lewis, Susannah S.; Zhang, Yingning; Sprunger, David B.; Rezvani, Niloofar; Baker, Eric M.; Jekich, Brian M.; Wieseler, Julie L.; Somogyi, Andrew A.; Martin, David; Poole, Stephen; Judd, Charles M.; Maier, Steven F.; Watkins, Linda R.

2008-01-01

Spinal proinflammatory cytokines are powerful pain-enhancing signals that contribute to pain following peripheral nerve injury (neuropathic pain). Recently, one proinflammatory cytokine, interleukin-1, was also implicated in the loss of analgesia upon repeated morphine exposure (tolerance). In contrast to prior literature, we demonstrate that the action of several spinal proinflammatory cytokines oppose systemic and intrathecal opioid analgesia, causing reduced pain suppression. In vitro morphine exposure of lumbar dorsal spinal cord caused significant increases in proinflammatory cytokine and chemokine release. Opposition of analgesia by proinflammatory cytokines is rapid, occurring ≤5 minutes after intrathecal (perispinal) opioid administration. We document that opposition of analgesia by proinflammatory cytokines cannot be accounted for by an alteration in spinal morphine concentrations. The acute anti-analgesic effects of proinflammatory cytokines occur in a p38 mitogen-activated protein kinase and nitric oxide dependent fashion. Chronic intrathecal morphine or methadone significantly increased spinal glial activation (toll-like receptor 4 mRNA and protein) and the expression of multiple chemokines and cytokines, combined with development of analgesic tolerance and pain enhancement (hyperalgesia, allodynia). Statistical analysis demonstrated that a cluster of cytokines and chemokines was linked with pain-related behavioral changes. Moreover, blockade of spinal proinflammatory cytokines during a stringent morphine regimen previously associated with altered neuronal function also attenuated enhanced pain, supportive that proinflammatory cytokines are importantly involved in tolerance induced by such regimens. These data implicate multiple opioid-induced spinal proinflammatory cytokines in opposing both acute and chronic opioid analgesia, and provide a novel mechanism for the opposition of acute opioid analgesia. PMID:18599265

Dextromethorphan attenuated inflammation and combined opioid use in humans undergoing methadone maintenance treatment.

PubMed

Chen, Shiou-Lan; Lee, Sheng-Yu; Tao, Pao-Luh; Chang, Yun-Hsuan; Chen, Shih-Heng; Chu, Chun-Hsien; Chen, Po See; Lee, I Hui; Yeh, Tzung Lieh; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band

2012-12-01

Recent studies show that proinflammatory cytokines might be related to the development of opioid dependence (physiological, psychological, or both). In a double-blind, randomly stratified clinical trial investigating whether add-on dextromethorphan (60-120 mg/day) attenuated inflammation and the combined use of opioids in heroin-dependent patients undergoing methadone maintenance treatment, we evaluated whether inflammation is related to the progression of opioid dependence. All participants (107 heroin-dependent patients and 84 nondependent healthy controls) were recruited from National Cheng Kung University Hospital. Their plasma cytokine levels were measured to evaluate the effect of add-on dextromethorphan. Plasma TNF-α and IL-8 levels were significantly higher in long-term heroin-dependent patients than in healthy controls (p < 0.001). Chronic heroin-use-induced TNF-α and IL-8 levels were significantly (p < 0.05) attenuated in patients treated for 12 weeks with add-on dextromethorphan. Moreover, both tolerance to methadone and the combined use of opioids were significantly (p < 0.05) attenuated in patients taking dextromethorphan. We conclude that dextromethorphan might be a feasible adjuvant therapeutic for attenuating inflammation and inhibiting methadone tolerance and combined opioid use in heroin-dependent patients.

Opioid-use disorder among patients on long-term opioid therapy: impact of final DSM-5 diagnostic criteria on prevalence and correlates.

PubMed

Boscarino, Joseph A; Hoffman, Stuart N; Han, John J

2015-01-01

Previously, we estimated the prevalence and risk factors for prescription opioid-use disorder among outpatients on opioid therapy using the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 and DSM-4 criteria. However, at the time, the DSM-5 criteria were not finalized. In the current study, we analyzed these data using the final DSM-5 criteria and compared these results. Using electronic records from a large US health care system, we identified outpatients receiving five or more prescription orders for opioid therapy in the past 12 months for noncancer pain (mean prescription orders =10.72; standard deviation =4.96). In 2008, we completed diagnostic interviews with 705 of these patients using the DSM-4 criteria. In the current study, we reassessed these results using the final DSM-5 criteria. The lifetime prevalence of DSM-5 opioid-use disorders using the final DSM-5 criteria was 58.7% for no or few symptoms (<2), 28.1% for mild symptoms (2-3), 9.7% for moderate symptoms (4-5), and 3.5% for severe symptoms (six or more). Thus, the lifetime prevalence of "any" prescription opioid-use disorder in this cohort was 41.3% (95% confidence interval [CI] =37.6-45.0). A comparison to the DSM-4 criteria indicated that the majority of patients with lifetime DSM-4 opioid dependence were now classified as having mild opioid-use disorder, based on the DSM-5 criteria (53.6%; 95% CI =44.1-62.8). In ordinal logistic regression predicting no/few, mild, moderate, and severe opioid-use disorder, the best predictors were age <65 years, current pain impairment, trouble sleeping, suicidal thoughts, anxiety disorders, illicit drug use, and history of substance abuse treatment. Given the final DSM-5 criteria, including the elimination of tolerance and withdrawal, inclusion of craving and abuse symptoms, and introduction of a new graded severity classification, the prevalence of opioid-use disorders has changed, while many of the DSM-4 risk factors for opioid dependence were

Opioid-use disorder among patients on long-term opioid therapy: impact of final DSM-5 diagnostic criteria on prevalence and correlates

PubMed Central

Boscarino, Joseph A; Hoffman, Stuart N; Han, John J

2015-01-01

Aims Previously, we estimated the prevalence and risk factors for prescription opioid-use disorder among outpatients on opioid therapy using the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 and DSM-4 criteria. However, at the time, the DSM-5 criteria were not finalized. In the current study, we analyzed these data using the final DSM-5 criteria and compared these results. Methods Using electronic records from a large US health care system, we identified outpatients receiving five or more prescription orders for opioid therapy in the past 12 months for noncancer pain (mean prescription orders =10.72; standard deviation =4.96). In 2008, we completed diagnostic interviews with 705 of these patients using the DSM-4 criteria. In the current study, we reassessed these results using the final DSM-5 criteria. Results The lifetime prevalence of DSM-5 opioid-use disorders using the final DSM-5 criteria was 58.7% for no or few symptoms (<2), 28.1% for mild symptoms (2–3), 9.7% for moderate symptoms (4–5), and 3.5% for severe symptoms (six or more). Thus, the lifetime prevalence of “any” prescription opioid-use disorder in this cohort was 41.3% (95% confidence interval [CI] =37.6–45.0). A comparison to the DSM-4 criteria indicated that the majority of patients with lifetime DSM-4 opioid dependence were now classified as having mild opioid-use disorder, based on the DSM-5 criteria (53.6%; 95% CI =44.1–62.8). In ordinal logistic regression predicting no/few, mild, moderate, and severe opioid-use disorder, the best predictors were age <65 years, current pain impairment, trouble sleeping, suicidal thoughts, anxiety disorders, illicit drug use, and history of substance abuse treatment. Conclusion Given the final DSM-5 criteria, including the elimination of tolerance and withdrawal, inclusion of craving and abuse symptoms, and introduction of a new graded severity classification, the prevalence of opioid-use disorders has changed, while many of the DSM-4

Involvement of opioid peptides in the regulation of reproduction in the prawn Penaeus indicus

NASA Astrophysics Data System (ADS)

Sreenivasula Reddy, P.

The possible involvement of an endogenous opioid system in the regulation of ovarian development in the prawn Penaeus indicus was investigated. Injection of leucine-enkephalin significantly increased the ovarian index and oocyte diameter in a dose-dependent manner. In contrast, injection of methionine-enkephalin significantly decreased the ovarian index and oocyte diameters. These results provide evidence to support the hypothesis that an opioid system is involved in the regulation of reproduction in crustaceans.

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

PubMed

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, p<.05). Engagement in agonist therapy was associated with a greater likelihood of illicit-opioid 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.

Population Genetic-Based Pharmacokinetic Modeling of Methadone and its Relationship with the QTc Interval in Opioid-Dependent Patients.