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Opioid Abuse [keywords]
- Eight principles for safer opioid prescribing and cautions with benzodiazepines. [JOURNAL ARTICLE]
- Postgrad Med 2014 Dec 15.:1-6.
Abstract The provision of long-term opioid analgesic therapy for chronic pain requires a careful risk/benefit analysis followed by clinical safety measures to identify and reduce misuse, abuse, and addiction and their associated morbidity and mortality. Multiple data sources show that benzodiazepines, prescribed for comorbid insomnia, anxiety, and mood disorders, heighten the risk of respiratory depression and other adverse outcomes when combined with opioid therapy. Evidence is presented for hazards associated with coadministration of opioids and benzodiazepines and the need for caution when initiating opioid therapy for chronic pain. Clinical recommendations follow, as drawn from 2 previously published literature reviews, one of which proffers 8 principles for safer opioid prescribing; the other review presents risks associated with benzodiazepines, suggests alternatives for co-prescribing benzodiazepines and opioids, and outlines recommendations regarding co-prescribing if alternative therapies are ineffective.
- Efficacy and safety of once-daily, extended-release hydrocodone in individuals previously receiving hydrocodone/acetaminophen combination therapy for chronic pain. [JOURNAL ARTICLE]
- Postgrad Med 2014 Dec 16.:1-8.
Abstract Background: Hydrocodone/acetaminophen combination analgesics are frequently prescribed for chronic pain management; however, acetaminophen presents potential hepatotoxicity to patients and thus dose limitations. These opioid medications are also widely abused. Once-daily, single-entity hydrocodone (Hysingla™ ER tablets [HYD]) is a novel formulation with abuse-deterrent properties for the management of chronic pain and represents a suitable option for those patients receiving analgesics containing the same opioid analgesic, hydrocodone. This post-hoc analysis evaluated the efficacy and safety of HYD in patients whose primary pre-study analgesic was hydrocodone/acetaminophen analgesics (23-31% of the study populations). Methods: Data were analyzed from two Phase III trials, a 12-week randomized, placebo-controlled trial (RCT) and an open-label, 52-week trial. In both trials, a dose-titration period with HYD was followed by respective periods of fixed-dose double-blind (randomized controlled trial [RCT]) or open-label, flexible-dose maintenance treatment. Pain intensity was assessed using a numerical rating scale (0-10, 0 = no pain). For the RCT, primary and sensitivity analyses of pain scores used different approaches to handle missing data. Safety data for both studies were summarized. Results: In the RCT, the mean baseline pain score was 7.3. Pain relief was greater with HYD than placebo during double-blind treatment. In the open-label, flexible-dose trial, the majority of patients were maintained on their titrated dose. Mean baseline pain score was 6.3, about 57% of patients completed the 1-year maintenance period, and mean pain scores were between 3.6 and 4.1 during the maintenance period. Use of supplemental pain medication decreased or was maintained during the maintenance treatment with HYD. Adverse events in both trials were typical of those associated with opioid analgesics. Conclusion: In patients whose primary pretrial analgesic was hydrocodone/acetaminophen combination tablets, single-entity HYD was effective in reducing pain intensity and in maintaining analgesia over time without need for continued dose increase. HYD's safety and tolerability profiles were similar to other opioid analgesics.
- [Human Single Drug Exposures to Non-opioid Analgesics Reported to the Poisons Information Centre Erfurt from 2003 to 2012.] [JOURNAL ARTICLE]
- Gesundheitswesen 2014 Dec 19.
Aim of the Study: Because of their frequency, non-opioid analgesics (NOA) single drug exposures registered by Poisons Information Centre (PIC) Erfurt have been studied over a decade. Methods: A retrospective analysis of frequencies, circumstances of exposure, symptom severity, and age groups in NOA single drug exposures received by the PIC Erfurt from the beginning of 2003 to the end of 2012 was undertaken. Results: Of all 4749 NOA single drug exposures, the 10 most frequent were caused by paracetamol (n=1 686), ibuprofen (n=1 439), acetylsalicylic acid (n=456), dipyrone (n=274), diclofenac (n=267), flupirtine (n=138), naproxen (n=41), etoricoxib (n=36), indomethacin (n=24), and dexketoprofen (n=19). Paracetamol single drug exposures increased from 158 in 2003 to 216 in 2007 and fell afterwards to 133 in 2012. Ibuprofen single drug exposures continously rose from 57 in 2003 to 258 in 2012. Adults were more often involved in NOA (53.8%) and all single drug exposures (54.1%) than children (45.9% and 45.6%, respectively). Suicidal attempts were more frequent in NOA (43.1%) than in all single drug exposures (34.2%), whereas accidental exposures or exposures in abuse were less often (33.4 and 0.2%, 46.0 and 0.9% respectively). NOA single drug exposures resulted mostly in none to minor symptoms (77.0%) and rarely in moderate (2.1%) or severe symptoms (1.0%). One adult was found dead after probable ingestion of 32 g of acetylsalicylic acid in suicidal intention. Conclusions: Because many NOA are over-the-counter drugs, it is difficult to obtain data on their use. PIC data could provide information on the NOA use in the population.
- The Prescription of Addiction Medications After Implementation of Chronic Care Management for Substance Dependence in Primary Care. [JOURNAL ARTICLE]
- J Subst Abuse Treat 2014 Dec 2.
People with addictive disorders commonly do not receive efficacious medications. Chronic care management (CCM) is designed to facilitate delivery of effective therapies. Using data from the CCM group in a trial testing its effectiveness for addiction (N=282), we examined factors associated with the prescription of addiction medications. Among participants with alcohol dependence, 17% (95% CI 12.0-22.1%) were prescribed alcohol dependence medications. Among those with drug dependence, 9% (95% CI 5.5-12.6%) were prescribed drug dependence medications. Among those with opioids as a substance of choice, 15% (95% CI 9.3-20.9%) were prescribed opioid agonist therapy. In contrast, psychiatric medications were prescribed to 64% (95% CI 58.2-69.4%). Absence of co-morbid drug dependence was associated with prescription of alcohol dependence medications. Lower alcohol addiction severity and recent opioid use were associated with prescription of drug dependence medications. Better understanding of infrequent prescription of addiction medications, despite a supportive clinical setting, might inform optimal approaches to delivering addiction medications.
- The A6V polymorphism of the human μ-opioid receptor negatively impacts signalling of morphine and endogenous opioids in vitro. [JOURNAL ARTICLE]
- Br J Pharmacol 2014 Dec 17.
Polymorphisms of the μ-opioid receptor (MOPr) may contribute to the variation in responses to opioid drugs in clinical and unregulated situations. The A6V variant of MOPr (MOPr-A6V) is present in up to 20% of individuals in some populations, and may be associated with heightened susceptibility to drug abuse. There are no functional studies examining the acute signalling of MOPr-A6V in vitro, so we investigated potential functional differences between MOPr and MOPr-A6V at several signalling pathways using structurally distinct opioid ligands.CHO and AtT-20 cells stably expressing MOPr and MOPr-A6V used. Adenylyl cyclase (AC) inhibition and ERK1/2 phosphorylation assays were conducted in CHO cells, assays of K channel activation in AtT-20 cells.Buprenorphine did not inhibit AC or stimulate ERK1/2 phosphorylation in CHO cells expressing MOPr-A6V, but buprenorphine activation of K channels in AtT-20 cells was preserved. DAMGO, morphine and β-endorphin inhibition of AC was significantly reduced via MOPr-A6V, as was signalling of all opioids to ERK1/2. However, there was little effect of the A6V variant on K channel activation.This study shows that signalling to AC and ERK via MOPr-A6V is reduced for many opioids, including the clinically significant drugs morphine, buprenorphine and fentanyl, as well endogenous opioids. The MOPr-A6V variant can be common and this compromised signalling may affect individual responses to opioid therapy, while the possible disruption of the endogenous opioid system may contribute to susceptibility to substance abuse.
- Evaluation of Opioid Modulation in Major Depressive Disorder. [JOURNAL ARTICLE]
- Neuropsychopharmacology 2014 Dec 18.
Although opioids have known antidepressant activity, their use in major depressive disorder (MDD) has been greatly limited by risk of abuse and addiction. Our aim was to determine whether opioid modulation achieved through a combination of a μ opioid partial agonist, buprenorphine (BUP), and a potent μ opioid antagonist, samidorphan (SAM), would demonstrate antidepressant activity without addictive potential. A placebo-controlled crossover study assessed the opioid pharmacodynamic profile following escalating doses of SAM co-administered with BUP in opioid-experienced adults. A subsequent one-week, placebo-controlled, parallel-group study was conducted in subjects with MDD and an inadequate response to standard antidepressant therapy. This second study evaluated safety and efficacy of ratios of BUP/SAM that were associated with partial and with maximal blockade of opioid responses in the initial study. Pupillometry, visual analog scale assessments and self-report questionnaires demonstrated that increasing amounts of SAM added to a fixed dose of BUP resulted in dose-dependent reductions in objective and subjective opioid effects, including euphoria and drug liking, in opioid-experienced adults. Following 7 days of treatment in subjects with MDD, a 1 : 1 ratio of BUP and SAM, the ratio associated with maximal antagonism of opioid effects, exhibited statistically significant improvement vs. placebo in HAM-D17 total score (p=0.032) and nearly significant improvement in MADRS total score (p=0.054). Overall, BUP/SAM therapy was well tolerated. A combination of BUP and SAM showed antidepressant activity in subjects with MDD. Balanced agonist-antagonist opioid modulation represents a novel and potentially clinically important approach to the treatment of MDD and other psychiatric disorders.Neuropsychopharmacology accepted article preview online, 18 December 2014. doi:10.1038/npp.2014.330.
- Anticipated and unanticipated consequences of abuse deterrent formulations of opioid analgesics. [JOURNAL ARTICLE]
- Pharmacoepidemiol Drug Saf 2014 Dec 16.
- Preventing Opioid Misuse and Potential Abuse: The Nurse's Role in Patient Education. [JOURNAL ARTICLE]
- Pain Manag Nurs 2014 Dec 8.
Nurses play a vital role in providing patient education for proper use of opioids. This descriptive study was designed to explore nurses' knowledge of opioids. Nurses in two large urban East Coast medical centers in the United States were invited to participate in the study, and 133 nurses completed the survey in its entirety. Registered nurses' knowledge of and attitudes about opioid use were assessed using a 48-item web-based questionnaire sent via e-mail. Frequencies were computed for all items on the questionnaire. Chi-squared testing was used to analyze data for all questions that fewer than 50% of participants answered correctly. The results of this study revealed a pain management knowledge gap among nurses caring for patients who are receiving opioid analgesics. This gap includes patient assessment; pharmacologic management; use of adjuvant medications; risks of addiction; risks of respiratory depression; and disposal and storage of opioid analgesics. Only 25% of the nurses answered 50% of the survey questions correctly. Demographic variables such as experience working as a nurse and length of time as a nurse did not influence how nurses performed on the questionnaire, nor did educational level. However, nurses who received education on opioids as a separate class of medication answered a higher percentage of questions correctly than those who did not receive education on opioids. The results of this study reveal a knowledge gap and nurses' lack of sufficient information about opioids that may affect their ability to provide effective medication instructions to their patients.