Assessment of Probable Opioid Use Disorder Using Electronic Health Record Documentation.

Importance: Electronic health records are a potentially valuable source of information for identifying patients with opioid use disorder (OUD). Objective: To evaluate whether proxy measures from electronic health record data can be used reliably to identify patients with probable OUD based on Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) criteria. Design, Setting, and Participants: This retrospective cross-sectional study analyzed individuals within the Geisinger health system who were prescribed opioids between December 31, 2000, and May 31, 2017, using a mixed-methods approach. The cohort was identified from 16 253 patients enrolled in a contract-based, Geisinger-specific medication monitoring program (GMMP) for opioid use, including patients who maintained or violated contract terms, as well as a demographically matched control group of 16 253 patients who were prescribed opioids but not enrolled in the GMMP. Substance use diagnoses and psychiatric comorbidities were assessed using automated electronic health record summaries. A manual medical record review procedure using DSM-5 criteria for OUD was completed for a subset of patients. The analysis was conducted beginning from June 5, 2017, until May 29, 2020. Main Outcomes and Measures: The primary outcome was the prevalence of OUD as defined by proxy measures for DSM-5 criteria for OUD as well as the prevalence of comorbidities among patients prescribed opioids within an integrated health system. Results: Among the 16 253 patients enrolled in the GMMP (9309 women [57%]; mean [SD] age, 52 [14] years), OUD diagnoses as defined by diagnostic codes were present at a much lower rate than expected (291 [2%]), indicating the necessity for alternative diagnostic strategies. The DSM-5 criteria for OUD can be assessed using manual medical record review; a manual review of 200 patients in the GMMP and 200 control patients identifed a larger percentage of patients with probable moderate to severe OUD (GMMP, 145 of 200 [73%]; and control, 27 of 200 [14%]) compared with the prevalence of OUD assessed using diagnostic codes. Conclusions and Relevance: These results suggest that patients with OUD may be identified using information available in the electronic health record, even when diagnostic codes do not reflect this diagnosis. Furthermore, the study demonstrates the utility of coding for DSM-5 criteria from medical records to generate a quantitative DSM-5 score that is associated with OUD severity.

Treating Opioid Dependence: Pain Medicine Physiology of Tolerance and Addiction.

Inappropriate and excessive opioid prescribing practices for treatment of chronic nonmalignant pain contributed to rising rates of opioid related mortality. Effective and widely available opioid addiction treatment resources are needed to ensure successful resolution of the "opioid epidemic". This chapter outlines the basic pathophysiology of addiction as well as principles of opioid addiction management focusing on the pharmacological and nonpharmacological aspects of care. Pharmacological treatment focuses on opioid substitution therapy, with aim at prevention of opioid cravings and opioid withdrawal symptoms. Nonpharmacological treatment involves psychological and supportive approaches to addiction such as group meetings, psychological counseling, and mindfulness training.

Autonomic and affective mediators of the relationship between mindfulness and opioid craving among chronic pain patients.

Prescription opioid misuse among chronic pain patients is undergirded by self-regulatory deficits, affective distress, and opioid-cue reactivity. Dispositional mindfulness has been associated with enhanced self-regulation, lower distress, and adaptive autonomic responses following drug-cue exposure. We hypothesized that dispositional mindfulness might serve as a protective factor among opioid-treated chronic pain patients. We examined heart-rate variability (HRV) during exposure to opioid cues and depressed mood as mediators of the association between dispositional mindfulness and opioid craving. Data were obtained from a sample of chronic pain patients (N = 115) receiving long-term opioid pharmacotherapy. Participants self-reported opioid craving and depression, and HRV was measured during an opioid-cue dot-probe task. Dispositional mindfulness was significantly positively correlated with HRV, and HRV was significantly inversely associated with opioid craving. Dispositional mindfulness was significantly negatively correlated with depression, and depression was significantly positively correlated with opioid craving. Path analysis revealed significant indirect effects of dispositional mindfulness on craving through both HRV and depression. Dispositional mindfulness may buffer against opioid craving among chronic pain patients prescribed opioids; this buffering effect may be a function of improved autonomic and affective responses. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Mindfulness-based interventions modulate structural network strength in patients with opioid dependence.

Mindfulness-based interventions (MBI) are increasingly used in the treatment of patients with mental disorders, in particular in individuals presenting with affective disorders or in patients exhibiting abnormal levels of impulsive behavior. MBI have been also offered to patients with substance use disorders, where such treatment options may yield considerable clinical effects. Neural effects associated with MBI have been increasingly acknowledged, but is unknown whether MBI exert specific effects on brain structure in patients with substance use disorders. In this study, we investigated 19 inpatients with opioid dependence receiving treatment-as-usual (TAU, n = 9) or additional MBI (n = 10). Structural magnetic resonance imaging data were acquired before and after four weeks of treatment. Source-based morphometry was used to investigate modulation of structural networks after treatment. Both treatment modalities led to significant clinical improvement. Patients receiving MBI showed a significant change in distress tolerance levels. An increase in bilateral striatal/insular and prefrontal/cingulate network strength was found in patients receiving MBI compared to individuals receiving TAU. Prefrontal/cingulate cortical network strength was associated with impulsivity levels. These findings suggest that MBI can have a recognizable role in treatment of substance use disorders and that neural effects of MBI may be captured in terms of frontostriatal structural network change.

Heightened sympathetic arousal is demonstrated by skin conductance responsivity to auditory stimuli in a small cohort of neonates with opiate withdrawal.

To determine the effects of auditory stimulus on skin conductance (SC) in infants with severe neonatal abstinence syndrome (NAS) that required morphine treatment (MT) compared with NAS infants that did not require morphine treatment (non-MT). We prospectively enrolled opiate-exposed term infants without polysubstance exposure. Skin conductance responses to an auditory stimulus (ringing a bell for 3s) near the time of discharge were obtained. Skin conductance was measured before, during, and after the stimulus. Non-parametric tests were used to determine between group and within phase differences. Infants were off MT at the time of SC measurement in response to an auditory stimulus. In a 2-group comparison of MT vs. non-MT infants, there was significantly higher SC responsivity to an auditory stimulus (p <0.05) in the MT group as compared with the non-MT group near discharge. The mean +SE peak morphine dose was 0.85+0.20mg/kg/day in the MT group. The mean Length of Stay (LOS) was 32 vs. 7 (p <0.05) days respectively, for the MT vs. the non-MT group. Our preliminary data suggest that in infants with severe NAS symptoms, higher sympathetic arousal in response to an auditory stimulus persists at discharge, underscoring the need for ongoing evaluation and specialized care at home.

Cannabidiol: Swinging the Marijuana Pendulum From 'Weed' to Medication to Treat the Opioid Epidemic.

Epidemics require a paradigm shift in thinking about all possible solutions. The rapidly changing sociopolitical marijuana landscape provides a foundation for the therapeutic development of medicinal cannabidiol to address the current opioid abuse crisis.

Special indications for Opioid Free Anaesthesia and Analgesia, patient and procedure related: Including obesity, sleep apnoea, chronic obstructive pulmonary disease, complex regional pain syndromes, opioid addiction and cancer surgery.

Opioid-free anaesthesia (OFA) is a technique where no intraoperative systemic, neuraxial or intracavitary opioid is administered with the anaesthetic. Opioid-free analgesia similarly avoids opioids in the perioperative period. There are many compelling reasons to avoid opioids in the surgical population. A number of case reports and, increasingly, prospective studies from all over the world support its benefits, especially in the morbidly obese population with or without sleep apnoea. A derivative technique is opioid sparing, where the same techniques are used but some opioid use is allowed. This chapter is a review of the current knowledge regarding opioid-free or low-dose opioid anaesthetic and analgesic techniques for the following special populations: obesity, sleep apnoea, chronic obstructive pulmonary disease, complex regional pain syndromes, acute/chronic opioid addiction and cancer surgery. Practical aspects include sympatholysis, analgesia and Minimum Alveolar Concentration (MAC) reduction with dexmedetomidine; analgesia with low-dose ketamine and co-anaesthesia; and sympatholysis with intravenous lignocaine. Non-opioid adjuvants such as NSAIDS, paracetamol, magnesium, local anaesthetic infiltration and high-dose steroids are added in the perioperative period to further achieve co-analgesia. Loco-regional anaesthesia and analgesia are also maximised. It remains to be seen whether OFA and early postoperative analgesia, which similarly avoids opioids, can prevent the development of hyperalgesia and persistent postoperative pain syndromes.

Lifetime methamphetamine dependence is associated with cerebral microgliosis in HIV-1-infected adults.

Methamphetamine (Meth) use is common among HIV-infected persons. It remains unclear whether Meth dependence is associated with long-lasting degenerative changes in the brain parenchyma and microvasculature of HIV-infected individuals. We examined the postmortem brains of 78 HIV-infected adults, twenty of whom were diagnosed with lifetime Meth dependence (18 past and two current at the final follow-up visit). Using logistic regression models, we analyzed associations of Meth with cerebral gliosis (immunohistochemistry for ionized calcium-binding adapter molecule-1 (Iba1) and glial fibrillary acidic protein (GFAP) in frontal, temporo-parietal, and putamen-internal capsule regions), synaptodendritic loss (confocal microscopy for synaptophysin (SYP) and microtubule-associated protein-2 (MAP2) in frontal cortex), ß-amyloid plaque deposition (immunohistochemistry in frontal and temporo-parietal cortex and putamen), and arteriolosclerosis (histopathology in forebrain white matter). We found that Meth was associated with marked Iba1 gliosis in the temporo-parietal region (odds ratio, 4.42 (95 % confidence interval, 1.36, 14.39), p = 0.014, n = 62), which remained statistically significant after adjusting for HIV encephalitis, white matter lesions, and opportunistic diseases (n = 61); hepatitis C virus seropositivity (n = 54); and lifetime dependence on alcohol, opiates, and cannabis (n = 62). There was no significant association of Meth with GFAP gliosis, SYP or MAP2 loss, ß-amyloid plaque deposition, or arteriolosclerosis. In conclusion, we found lifetime Meth dependence to be associated with focal cerebral microgliosis among HIV-infected adults, but not with other brain degenerative changes examined. Some of the changes in select brain regions might be reversible following extended Meth abstinence or, alternatively, might have not been induced by Meth initially.

A thalamic input to the nucleus accumbens mediates opiate dependence.

Chronic opiate use induces opiate dependence, which is characterized by extremely unpleasant physical and emotional feelings after drug use is terminated. Both the rewarding effects of a drug and the desire to avoid withdrawal symptoms motivate continued drug use, and the nucleus accumbens is important for orchestrating both processes. While multiple inputs to the nucleus accumbens regulate reward, little is known about the nucleus accumbens circuitry underlying withdrawal. Here we identify the paraventricular nucleus of the thalamus as a prominent input to the nucleus accumbens mediating the expression of opiate-withdrawal-induced physical signs and aversive memory. Activity in the paraventricular nucleus of the thalamus to nucleus accumbens pathway is necessary and sufficient to mediate behavioural aversion. Selectively silencing this pathway abolishes aversive symptoms in two different mouse models of opiate withdrawal. Chronic morphine exposure selectively potentiates excitatory transmission between the paraventricular nucleus of the thalamus and D2-receptor-expressing medium spiny neurons via synaptic insertion of GluA2-lacking AMPA receptors. Notably, in vivo optogenetic depotentiation restores normal transmission at these synapses and robustly suppresses morphine withdrawal symptoms. This links morphine-evoked pathway- and cell-type-specific plasticity in the paraventricular nucleus of the thalamus to nucleus accumbens circuit to opiate dependence, and suggests that reprogramming this circuit holds promise for treating opiate addiction.

Zinc involvement in opioid addiction and analgesia--should zinc supplementation be recommended for opioid-treated persons?

INTRODUCTION: Zinc chelators were shown to facilitate some opioid-withdrawal signs in animals. Zinc deficiency, which affects more than 15% the world's population, is also common among opioid consumers and opioid-treated animals exhibit misbalances of zinc distribution. AIM: The present study focuses on how zinc ions interfere with opioid dependence/addiction and analgesia, trying to preliminary discuss if zinc supplementation in opioid-users should be recommended in order to reduce the risk of addiction. METHODS: All relevant literature was searched up to April 2015. The search was performed using the term "zinc" plus combinations of following terms: "opioid receptors", "opioid" or representatives of this class, "addiction", "dependence", "analgesia", and "pain". Human, animal, in vitro studies and reviews were including. RESULTS: Both human and animal studies revealed decreased serum zinc under opioid-administration conditions, attributed mainly to increased urinary elimination (humans) or redistribution (animals). Moreover, animal studies revealed decreased brain zinc levels in morphine-treated animals, with increased zinc hepatic levels, but also an enhancement of endogenous opioid system activity and a possible reduction of morphine withdrawal by zinc. In vitro studies revealed reduction of opioid ligands binding to receptors by zinc. However, the very few in vivo animal studies on opioid analgesia revealed controversial results, as zinc demonstrated clear analgesic effect, but zinc associated to opioids doesn't result in a potentiation of the analgesic effect. CONCLUSION: Zinc dietary supplementation in patients treated with opioids for cancer-related chronic pain should be considered, due to the high incidence of zinc deficiency, also well-documented in opioid consumers. The low toxicity of orally-administered zinc also pleads for this idea. The main contra-argument to zinc administration in opioid-treated persons is related to the way zinc influences opioid-induced analgesia.

Neurophysiological evidence for remediation of reward processing deficits in chronic pain and opioid misuse following treatment with Mindfulness-Oriented Recovery Enhancement: exploratory ERP findings from a pilot RCT.

Dysregulated processing of natural rewards may be a central pathogenic process in the etiology and maintenance of prescription opioid misuse and addiction among chronic pain patients. This study examined whether a Mindfulness-Oriented Recovery Enhancement (MORE) intervention could augment natural reward processing through training in savoring as indicated by event-related brain potentials (ERPs). Participants were chronic pain patients at risk for opioid misuse who were randomized to 8 weeks of MORE (n = 11) or a support group control condition (n = 18). ERPs to images representing naturally rewarding stimuli (e.g., beautiful landscapes, intimate couples) and neutral images were measured before and after 8 weeks of treatment. Analyses focused on the late positive potential (LPP)--an ERP response in the 400-1,000 ms time window thought to index allocation of attention to emotional information. Treatment with MORE was associated with significant increases in LPP response to natural reward stimuli relative to neutral stimuli which were correlated with enhanced positive affective cue-responses and reductions in opioid craving from pre- to post-treatment. Findings suggest that cognitive training regimens centered on strengthening attention to natural rewards may remediate reward processing deficits underpinning addictive behavior.

A Preliminary Study Examining Nutritional Risk Factors, Body Mass Index, and Treatment Retention in Opioid-Dependent Patients.

Poor nutritional health among opioid-dependent individuals is well established, yet no nutritional screening tool exists for this specific population. The utility of "Determine Your Nutritional Health" developed by the Nutrition Screening Initiative is considered. The study examines the questionnaire's relevance in patients beginning opioid dependence treatment at a methadone-assisted treatment program (N = 140) by examining nutritional risk factor prevalence, body mass index, and association between nutritional risk level and treatment retention. The majority of patients reported at least one nutritional risk factor (89 %) and 59 % were at high nutritional risk. Body mass index was not related to nutritional risk; however, a trend was identified between increasing nutritional risk and decreased retention in treatment. These preliminary findings suggest the need for incorporation of nutritional screening at intake in opioid treatment programs, consideration of the effect of dietary risk on treatment retention, and the potential utility of this screening tool.

Opium addiction increases interleukin 1 receptor antagonist (IL-1Ra) in the coronary artery disease patients.

BACKGROUND: There is evidence that opium addiction has immunosuppressant effects. Coronary artery disease (CAD) is a condition resulted from atherosclerosis which is dependent on the immune response. PURPOSE: To evaluate plasma levels of interleukin-6 and interleukin-1Ra in 30 patients with three-vessel coronary artery disease, ejection fraction of more than 35% and to evaluate their changes after prognostic treadmill test in 15 opium addicted and 15 non-addicted patients. METHODS: The participants underwent prognostic treadmill test and plasma levels of interleukin-6 (IL-6) and interleukin-1Ra (IL-1Ra) were evaluated with ELISA method before, just after and 4 hours after the test. RESULTS: IL-1Ra (2183 pg/ml) tended to decrease over time in the opium addicted group (1372 pg/ml after prognostic treadmill test and 1034 pg/ml 4 hours after that), although such decrease did not reach the statistical significance. IL-1Ra levels were significantly higher in opium addicted than in non addicted patients. Opium addiction had no significant effect on IL-6 changes. CONCLUSION: Consumption of opium in CAD patients is associated with higher IL-1Ra levels.

Effects of a Rhodiola rosea L. extract on the acquisition, expression, extinction, and reinstatement of morphine-induced conditioned place preference in mice.

RATIONALE: Opioid addiction is a chronic, recurrent brain disease that is characterised by compulsive drug seeking and a high rate of relapse even after long periods of abstinence. Prevention of relapse is the primary goal of addiction treatment and is still the major limitation in drug therapy. OBJECTIVES: The present study investigated the effects of a Rhodiola rosea L. hydroalcoholic extract (RHO), a well-known traditional oriental medicine, on establishment and reinstatement of morphine-induced conditioned place preference (CPP) in mice. METHODS: CPP was induced by intraperitoneal injection of morphine (10 mg/kg) as an 8-day conditioning schedule. The effects of RHO on the rewarding properties of morphine were tested in mice receiving oral administration of RHO (10, 15, and 20 mg/kg) 60 min prior to each morphine injection (acquisition) or prior to the CPP test on day 9 (expression). Once established, CPP was extinguished by repeated testing, during which conditioned mice were injected daily with different doses of RHO. Finally, the efficacy of RHO in blocking reinstatement of CPP provoked by priming injections and physical stress was also evaluated. RESULTS: RHO administration showed dose dependency for prevention of establishment of CPP and was effective in facilitating extinction of morphine-induced CPP. RHO suppressed both priming- and stress-induced reinstatement of CPP in a dose-dependent manner. CONCLUSIONS: In conclusion, as RHO was effective for reducing craving and vulnerability to relapse, it might be a very effective natural remedy for the treatment of opioid addiction.

Some determinants of morphine effects on intracranial self-stimulation in rats: dose, pretreatment time, repeated treatment, and rate dependence.

Intracranial self-stimulation (ICSS) is a procedure used to evaluate the abuse liability of drugs. The µ opioid receptor agonist morphine is an acknowledged drug of abuse, and this study examined factors that may influence expression of abuse-related morphine effects on ICSS in rats. Adult male rats were equipped with intracranial electrodes targeting the medial forebrain bundle, and 10 stimulus frequencies (56-158 Hz in 0.05 log increments) were available during each daily session under a continuous reinforcement schedule. The primary dependent variable was the ICSS rate at each frequency. Under baseline conditions, the ICSS rate increased with frequency. After acute morphine (1-10 mg/kg), rate-decreasing effects predominated at early pretreatment times (10-30 min) and rate-increasing effects predominated at later pretreatment times (100-180 min). Acute morphine effects dissipated after 300 min. Repeated morphine (3.2-18 mg/kg/day×7 days at each dose) produced tolerance to rate-decreasing effects, enhanced expression of rate-increasing effects, and enhanced rate dependency of morphine effects. Withdrawal from repeated morphine produced small but significant dose-dependent decreases in ICSS. These results show that the magnitude and valence of morphine effects on rates of ICSS in rats are strongly influenced by morphine dose and pretreatment time, history of morphine exposure, and baseline ICSS rate.

Protective effect of Nigella sativa oil against tramadol-induced tolerance and dependence in mice: role of nitric oxide and oxidative stress.

Nigella sativa seed extracts and its oil have been exploited for their various health benefits. In this study, the effects of N. sativa oil on tramadol-induced tolerance and dependence and possible mechanism(s) of these effects were investigated, for the first time, in mice. Repeated administration of N. sativa oil (4 ml/kg, p.o.) along with tramadol (50mg/kg, s.c.) inhibited the development of tramadol tolerance, as measured by the hot plate test, and dependence as assessed by naloxone (5mg/kg, i.p.)-precipitated withdrawal manifestations. Concomitantly, nitric oxide overproduction and increase in brain malondialdehyde level induced by repeated administration of tramadol to mice or by administration of naloxone to tramadol-dependent mice were inhibited by co-administration of the oil. Also, the decrease in brain intracellular reduced glutathione level and glutathione peroxidase activity induced by both treatments was inhibited by co-administration of the oil. The increase in brain glutamate level induced by both treatments was not inhibited by concurrent administration of the oil. The inhibitory effect of N. sativa oil on tramadol-induced tolerance and dependence was enhanced by concurrent i.p. administration of the NMDA receptor antagonist, dizocilpine (0.25mg/kg). Also, the inhibitory effect of the oil on naloxone-induced biochemical alterations in tramadol-dependent mice was enhanced by concurrent administration of dizocilpine. Similarly, concurrent i.p. administration of the NO synthase inhibitor, L-N(G)-nitroarginine methyl ester (10mg/kg) or the antioxidant, N-acetylcysteine (50mg/kg) enhanced these inhibitory effects of N. sativa oil. On the other hand, these effects were antagonized by concurrent i.p. administration of the NO precursor, L-arginine (300 mg/kg). These results provide evidence that N. sativa oil appears to have a therapeutic potential in tramadol tolerance and dependence through blockade of NO overproduction and oxidative stress induced by the drug.

Acupuncture-related techniques for the treatment of opiate addiction: a case of translational medicine.

Drug addiction is a chronic brain disorder characterized by withdrawal symptoms that occur during drug abstinence and a high tendency of relapse. Compared with the currently available pharmacological interventions, acupuncture therapy has the potential to help drug addicts stay away from drugs without major adverse side effects. It has taken decades of research to optimize the parameters of electrical acupoint stimulation for detoxification and for relapse prevention, as well as to establish a safe and easy procedure by which drug addicts can use it on themselves. The discovery that acupuncture can trigger the release of opioid substances from the brain in the 1970s provided the inspiration. Following this, basic research on animals made it possible to understand the mechanisms of action and establish the procedure for treating drug addictions. This article reviews the past, present, and foreseeable future regarding the use of acupuncture-related technique for the treatment of opiate addiction from the perspective of translational medicine.

Reported lifetime aberrant drug-taking behaviors are predictive of current substance use and mental health problems in primary care patients.

BACKGROUND: The aim of this report is to determine the frequency of aberrant drug behaviors and their relationship to substance abuse disorders in a large primary sample of patients receiving opioids for chronic pain. METHODS: The data utilized for this report was obtained from 904 chronic pain patients receiving opioid therapy from their primary care physician. A questionnaire was developed based on 12 aberrant drug behaviors reported in the clinical literature. The diagnosis of a current substance use disorder was determined using Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition(DSM-IV) criteria. RESULTS: The average duration of chronic pain in the sample was 16 years and for opioid therapy, 6.4 years. Of the patients, 80.5% reported one or more lifetime aberrant drug behaviors. The most frequent behaviors reported included early refills (41.7%), increase dose without physician consent (35.7%), and felt intoxicated from opioids (32.2%). Only 1.1% of subjects with 1-3 aberrant behaviors (N = 464, 51.2%) met DSM-IV criteria for current opioid dependence compared with 9.9% of patients with four or more behaviors (N = 264, 29.3%). Persons with positive urine toxicology tests for cocaine were 14 times more likely to report four or more behaviors than no behaviors (14.1% vs 1.1%). A logistic model found that subjects who reported four or more aberrant behaviors were more likely to have a current substance use disorder (odds ratio [OR] 10.14; 3.72, 27.64), a positive test for cocaine (odds ratio [OR] 3.01; 1.74, 15.4), an Addiction Severity Index (ASI) psychiatric composite score >0.5 (OR 2.38; 1.65, 3.44), male gender (OR 2.08: 1.48, 2.92), and older age (OR 0.69; 0.59, 0.81) compared with subjects with three or fewer behaviors. Pain levels, employment status, and morphine equivalent dose do not enter the model. CONCLUSIONS: Patients who report four or more aberrant drug behaviors are associated with a current substance use disorder and illicit drug use, whereas subjects with up to three aberrant behaviors have a very low probability of a current substance abuse disorder. Four behaviors--oversedated oneself, felt intoxicated, early refills, increase dose on own--appear useful as screening questions to predict patients at greatest risk for a current substance use disorders.