Opioid Regimen Research Articles

Patterns of Symptom Reporting During Pregnancy Comparing Opioid Maintained and Control Women

To characterize the range of symptoms experienced by pregnant methadone-maintained (MM) and buprenorphine-maintained (BM) women to determine whether these differ from those experienced by a control group of nonopioid exposed pregnant women. Opioid-maintained (OM) patients report high rates of symptoms related to direct opioid effects and withdrawal. Pregnancy is associated with a range of symptoms, some overlapping with opioid effects and withdrawal. Prospective, nonrandomized, open-label comparison study undertaken in a large teaching maternity hospital in South Australia. Pregnant BM (n = 25), MM (n = 25) and nonopioid exposed controls (n = 25) were recruited and matched for age, parity, gravidity, alcohol consumption, and smoking status. Symptom report patterns, maternal withdrawal, and additional substance use were assessed. MM women reported 10 and BM women reported 2 symptoms throughout pregnancy at rates greater than controls. Methadone-maintained women reported significantly (P < 0.05) more symptoms than BM women compared to controls throughout pregnancy. Methadone-maintained women reported 8 and BM women reported 3 symptoms in the third trimester at rates greater than controls. Methadone-maintained women reported greater opioid withdrawal than controls; this did not occur in BM women. Additional substance use was comparable between BM and MM women but greater than controls. Patterns of symptom reports may have clinical implications for maternal and fetal health during pregnancy for OM women including optimization of opioid dosing regimens, education regarding maternal nutritional intake and preventing postnatal depression, thereby ensuring maternal health and fetal development during pregnancy and enhancing mother-infant bonding and healthy child development postnatally.

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Introduction: Critically ill children in the pediatric intensive care unit (PICU) often receive multiple classes of sedatives and analgesics for comfort and safety. Dexmedetomidine is frequently added when a child proves challenging to sedate with traditional opioid and benzodiazepine regimens. Discontinuation of prolonged infusions of high dose dexmedetomidine may result in a clinical withdrawal syndrome similar to opioid withdrawal, and clonidine is utilized to treat children experiencing withdrawal. Hypothesis: We hypothesize that longer duration and higher dose of dexmedetomidine is associated with clinical withdrawal syndrome and discharge home on transdermal or oral clonidine. Methods: We performed a retrospective chart review from June 2011 to June 2012 of all children who received dexmedetomidine for sedation in the pediatric intensive care unit. Dosing variables for dexmedetomidine, concurrent administration of other sedatives, and documentation of withdrawal with the Withdrawal Assessment Tool (WAT-1) were collected. Results: 37 children received dexmedetomidine during the 12-month period studied. The average daily dose of dexmedetomidine was 1.1 mcg/kg/hour and the mean duration of administration was 12.2 days. 10 children (27%) were discharged home on clonidine. The presence of greater than two concurrent sedatives at the time of dexmedetomidine initiation was predictive of longer dexmedetomidine duration and higher average daily dose. Longer duration of dexmedetomidine was associated with increased WAT scores within 24 hours of discontinuation and higher doses of clonidine upon discharge to home. After adjustment for age, sex and duration of intubation, dexmedetomidine dose and duration were not associated with survival to discharge. Conclusions: These data support the role of dexmedetomidine as a cause of physiologic withdrawal in critically ill children receiving sedatives. As dexmedetomidine use becomes more widespread in the critically ill pediatric population, further research is necessary to determine the physiologic effects of discontinuation of this drug after prolonged duration of therapy, and long-term outcomes in children discharged home on clonidine.

Evaluation of inpatient cancer pain management at an academic medical center.

128 Background: The National Comprehensive Cancer Network (NCCN) guidelines on cancer pain management were developed to direct pain assessment and management. The purpose of this study was to assess whether adherence to guidelines was associated with improved outcomes. Methods: One-hundred and nine patients admitted to the inpatient hematology oncology service that received at least one dose of morphine, oxycodone, or hydromorphone were evaluated and allocated into groups based on adherence to the NCCN guidelines. Safety and achievement of analgesia (pain score ≤ 4) at 24-hours after opioid initiation were compared between the two groups. A multivariate analysis was performed to identify predictors of opioid regimens non-adherent to guidelines. Results: Sixty-four percent of patients were initiated on regimens adherent to the NCCN guidelines. 63% of patients initiated on regimens adherent to NCCN guidelines reached the endpoint of analgesia at 24 hours compared to 41% of those who were not (p = 0.028). Adverse events were infrequent (p &gt; 0.5). Opioid tolerance was the variable most predictive of being initiated on regimens non-adherent to guideline recommendations (OR 3.1, 95% confidence interval 1.24-7.82). Conclusions: A significant number of patients presenting with cancer pain are initiated on regimens non-adherent to NCCN guidelines, leading to reduced attainment of adequate analgesia. Opioid tolerant patients are at an increased risk of inadequate analgesia, and should be identified and initiated on proper pain regimens taking home opioid usage into consideration.

Management of cancer pain: ESMO Clinical Practice Guidelines

Management of cancer pain: ESMO Clinical Practice Guidelines

Prescribed opioid difficulties, depression and opioid dose among chronic opioid therapy patients

BackgroundChronic opioid therapy has increased dramatically, as have complications related to prescription opioids. Little is known about the problems and concerns attributed to opioids by patients receiving different opioid doses. MethodsWe surveyed 1883 patients who were receiving chronic opioid therapy for chronic noncancer pain. Opioid regimen characteristics were ascertained from electronic pharmacy records. Patient-reported opioid-related problems and concerns were measured using the Prescription Opioid Difficulties Scale. Depression was assessed with the Patient Health Questionnaire. ResultsPatients prescribed higher opioid doses reported modestly higher pain intensity and pain impact. After adjustment, patients on higher doses attributed higher levels of psychosocial problems and control concerns to prescribed opioids (P<.0001). They also had higher levels of depression and were more likely to meet criteria for clinical depression. Over 60% of patients receiving 120+ mg daily (morphine equivalent) were clinically depressed, a 2.6-fold higher risk (95% confidence interval: 1.5–4.4) than patients on low-dose regimens (<20 mg daily). ConclusionsHigher opioid doses were associated with somewhat higher pain severity and higher levels of patient-reported opioid-related psychosocial problems, control concerns and depression. These findings may result from patient selection for high-dose therapy or problems caused by higher-dose opioids.

Morphine and Hydromorphone-Induced Hyperalgesia in a Hospice Patient

Opioids including morphine and hydromorphone are widely used for control of moderate to severe pain and dyspnea in hospice and palliative care patients. Accumulation of the active morphine-3-glucuronide (M3G) and hydromorphone-3-glucuronide (H3G) metabolites is one proposed mechanism for the development of neuroexcitatory effects including allodynia and opioid-induced hyperalgesia (OIH). We report the case of a 43-year-old female hospice patient with metastatic non-small cell lung cancer who initially developed allodynia following morphine administration and again following administration of hydromorphone. The allodynia resolved both times following the discontinuation of the opioid and rotation to a different opioid regimen. Potential opioid-induced neuroexcitatory treatment options include opioid rotation to an agent with inactive metabolites, use of adjuvant pain medications for opioid-sparing effects, management of undesired symptoms (e.g., myoclonus), or increasing opioid clearance with intravenous (IV) fluids. Although the incidence is not well defined in the literature, hospice and palliative care clinicians should suspect OIH in patients with allodynia and/or hyperalgesia, especially when repeated dose escalations do not improve analgesia or pain escalates following opioid dose titration.

Fentanyl transmucosal tablets: current status in the management of cancer-related breakthrough pain

Breakthrough pain is a newly recognized pain category that was first described by Portenoy and Hagen in 1990. The term describes pain that increases in intensity to “break through” chronic pain that is being controlled by a scheduled opioid regimen. The development of fluctuations in pain intensity is challenging due to their unpredictable nature, rapid onset, and need for rapid treatment intervention. Breakthrough pain has been treated by using an extra opioid dose in addition to the scheduled opioid being used for pain. Recommendations for dose and frequency are based on expert opinion only, and have included dosing based on a percentage of the total opioid dose. Other recommendations include increasing the regularly scheduled opioid dose. Clinical trials have now focused on delivery of opioids that have both potency and a rapid onset of action. Lipophilic opioids have received a substantial amount of study due to their quick absorption and rapid onset of analgesia. Lipophilic opioids that have been studied to date include transmucosal fentanyl, sublingual fentanyl, intranasal sufentanil, and oral and sublingual methadone. Initial clinical trials have established the superiority of transmucosal fentanyl as a breakthrough analgesic when compared with immediate-release oral opioid formulations. Problems with bioavailability have led to a search for newer formulations of transmucosal delivery. Newer formulations, such as fentanyl transmucosal tablets, have been developed to ensure superior delivery for the patient suffering from breakthrough pain. The purpose of this paper is to discuss the current status of transmucosal tablet formulations for cancer breakthrough pain.

Dosing fentanyl buccal tablet for breakthrough cancer pain: dose titration versus proportional doses

Objectives:The aim of this study was to compare the efficacy and safety of doses of fentanyl buccal tablet (FBT) proportional to doses of opioids used for background analgesia versus dose titration starting with the minimal dose for the management of breakthrough cancer pain (BTcP).Methods:A total of 82 cancer patients with BTcP who were receiving strong opioids in doses of at least 60 mg of oral morphine equivalents and having acceptable background analgesia, were selected for a multicenter unblinded study. Forty-one patients were randomized to receive FBT in doses proportional to the daily opioid doses for four consecutive episodes of BTcP (group P). Forty-one patients underwent dose titration of FBT, with an initial dose of 100 µg, for four consecutive episodes (group T). Pain intensity and symptoms associated with opioid therapy were measured before administering any dose of FBT (T0) and 15 minutes after (T15).Results:In all, 80 patients were considered for analysis (39 and 41 patients in group P and T, respectively). Patients were receiving a mean of 126 ± 100 mg of oral morphine equivalents (range 60–480 mg) for background analgesia. A total of 293 episodes of BTcP (144 and 149 in group P and T, respectively) were treated and considered for analysis. No differences were found in the decrease of pain intensity between the two groups. However, in patients receiving doses of oral morphine equivalents of >120 mg/day, a significant number of patients obtained a decrease in pain intensity >50% in group P in comparison with group T (p = 0.040). Also, the need for rescue medication was significantly more frequently reported in group T for the first episode of BTcP (p < 0.0005). No differences in the level of adverse effects were observed between the two groups. No differences in patients’ satisfaction were reported.Conclusion:According to the data obtained in this study, there is no evidence for the use of dose titration in the management of BTcP in opioid-tolerant patients. Indeed, doses proportional to basal opioid regimen for background pain seem to be effective and safe in the majority of patients. Further studies should confirm this data in patients receiving higher doses of opioids, with other rapid-onset opioids, and in other settings.

Breakthrough Pain-Novel Analgesics

Breakthrough pain (BTP) is a transitory exacerbation of pain that occurs on a background of otherwise controlled pain. It is associated in conjunction with severe chronic pain and may result in impaired physical and psychological functioning, reduced effectiveness to opioids and also, increased financial burden. It manifests commonly in malignant pain, as manifested by well managed round the clock regular opioid medication but associated with intermittent sharp pain symptoms that are not controlled by the regular medication. It is a significant clinical problem and should be independently assessed and treated. The most common approach being used is 'rescue' medication--a short acting opioid in combination with the fixed-schedule opioid regimen. The lag time between peak pain intensity during an episode of BPT and onset of analgesia of most short-acting opioids is approximately 30-60 minutes. This suggests that the effectiveness of supplemental medications for BTP might be improved with analgesic agents that have a more rapid onset of action. Traditionally the rapid onset analgesia for breakthrough pain has been achieved by administering potent opioids through sublingual route bypassing the first pass metabolism. However with recent advances in drug delivery systems, transmucosal and buccal routes have gained popularity. Pharmacokinetic studies have demonstrated a high early systemic exposure to opioids well over their therapeutic dose range resulting in management of the breakthrough pain. This article proposes to review the evidence base on the effectiveness of these novel opioid delivery systems in managing the breakthrough pain.

Methadone Induced Hyperalgesia: Is It Possible? (775)

1.Recognition of opioid induced hyperalgesia (OIH) as a possible complication of pain management with opioids.Review of opioids that can induce OIH.2.Review of treatment options available for OIH. Opioid induced hyperalgesia (OIH) is characterized by paradoxical worsening of pain despite escalating doses of opioids. It can pose a significant challenge to pain management. The management of OIH usually requires decreasing the dose of opiates, opiate rotation and the use of non-opioids. Although OIH has been generally recognized in patients with chronic use of morphine or hydromorphone, we present a case of OIH most likely induced by methadone. The patient is a 64 year-old male with severe COPD and a remote history of polysubstance abuse, hospitalized for pneumonia and chronic low back pain secondary to osteoarthritis. His past medical history was significant for type 2 diabetes mellitus, chronic kidney disease and hepatitis C. While in the hospital, he sustained a mechanical fall resulting in left tibial and fibular fractures, treated conservatively with a long cast and non-weight bearing status. Prior to admission he was taking acetaminophen/codeine for low back pain. After the fracture, he was tried on various opioid regimens to control a flare-up of the low back pain and his painful fractured leg. Due to uncontrolled back and leg pain, methadone and hydromorphone were initiated. While on methadone 5 mg orally three times a day and hydromorphone 1 mg orally every 4 hours for breakthrough pain for one week, he developed severe pain in the cervical spine, low back, hips and left lower leg. He also developed mild confusion and myoclonus which were thought to be secondary to opioids. The dose of methadone was decreased to 2.5 mg twice a day and within 48hrs he had a remarkable improvement in his pain, and his confusion and myoclonus resolved. The remarkable improvement in pain control following a reduction the in dose of methadone suggests the clinical scenario of OIH induced by methadone.

The Concurrent Use of Gabapentin and Opioid Analgesia in Burns Patients

Dear Editor, I read with interest the study by Rimaz et al. (1) which showed a statistically significant reduction in visual analogue pain scores and morphine consumption in a double blind randomised setting with 25 patients in each wing. This is not the first study to suggest that in tackling the complex mechanism of post-burn hypersensitivity, as yet not fully understood but thought to be similar to post-operative pain hypersensitivity; analgesics with different but synergistic effects may prove superior to opioid analgesia alone (2, 3). Although in common use for neuropathic pain worldwide gabapentin has only relatively recently been taken up by plastic surgeons for use in acute burn pain both pre and post-surgical debridement. Although the study undoubtedly shows promising results in terms of a significant decrease in both pain scores and morphine consumption, there are some difficulties which must be addressed prior to gabapentin potentially becoming an accepted adjunct to opioid analgesia in the treatment of acute burns pain. As is often the case with the introduction of adjuvant drug treatment studies are difficult to compare due to the inherent variability of drug dosage, regimen, and use of adjuvant drugs and length of treatment. A similar study looking at the effects of gabapentin on morphine consumption in burns patients by Cuignet et al. (2), although reaching the same overall conclusions as Rimaz et al. (1) used a very different dosing regimen; a single dose of 1200mg gabapentin pre-operatively (1) and 2400mg daily from burn day 3-24 and results recorded for 21 days pre and post-surgical debridement (2) respectively. Additionally, in a further case series using gabapentin for acute burn pain Gray et al. (3) used regimens as varied as 1000mg four times per day with concurrent oxycodone and 300mg three times per day are described. Therefore although several studies have now shown gabapentin to be a beneficial addition to an opioid analgesia regimen in burns patients (1-3) what is required is collaborative research effort in order to determine the lowest possible dose of gabapentin to achieve maximal pain relief but with minimal side effects. This will allow a future systematic review with significant power to change recommended practice should future research continue to produce positive results. Although Rimaz et al. (1) found no side effects with the 1200mg single pre-operative dose of gabapentin, it must not be forgotten that gabapentin is a drug which can cause significant side effects even if only used for a short period of time, especially at the relatively high doses recommended by Cuignet et al. (2) Multicentre studies of gabapentin in post-herpetic neuralgia and painful diabetic neuropathy have shown significant side effects reporting day-time somnolence of up to 27% (4) and dizziness at 24% (5) which must be balanced with the potential analgesic benefit of gabapentin in burns patients. In the interests of burns patients world-wide is it hoped that further collaborative research will follow promptly to advance a treatment which, although currently in its infancy, has the potential to alleviate the significant pain that many such patients currently suffer.

The impact of opioid analgesics on the gastrointestinal tract function and the current management possibilities.

Opioid-induced bowel dysfunction (OIBD) comprises gastrointestinal symptoms such as constipation, anorexia, nausea, vomiting, gastro-oesophageal reflux, delayed digestion, abdominal pain, bloating, hard stool and incomplete evacuation that significantly deteriorate patients’ quality of life and compliance. Approximately one third of patients treated with opioids do not adhere to the opioid regimen or simply quit the treatment due to OIBD. Several strategies are undertaken to prevent or treat OIBD. Traditional oral laxatives are used but their effectiveness is limited and they display adverse effects. Other possibilities comprise opioid switch or changing the administration route. New therapies target opioid receptors in the gut that seem to be the main source of OIBD. One is a combination of an opioid and opioid antagonist (oxycodone/naloxone) in prolonged-release tablets, and another is a purely peripherally acting opioid receptor antagonist (methylnaltrexone) available in subcutaneous injections. The aim of this article is to review the pathomechanism and possible treatment strategies of OIBD.

Pharmacist Documentation of Fentanyl Patch Orders in an Academic Medical Center

Purpose The fentanyl transdermal patch label carries a boxed warning indicating that it should only be used in opioid-tolerant patients. Both prescribers and pharmacists must adhere to these recommendations to ensure safe use of the patches. Our goal was to determine the fentanyl patch documentation rate at our institution and evaluate the quality of documentation, and to make recommendations for improvement if appropriate to ensure patient safety. Methods We conducted a retrospective data analysis to determine pharmacist adherence rate to medical center documentation practices for fentanyl patch orders at UC San Diego Medical Center between July 2009 and July 2010. Results A total of 296 adult fentanyl patch orders were prescribed during the study period. Sixty-four of these orders were new initiations and 232 orders were continued from outpatient regimens. Overall, pharmacist documentation rate, without regard to completeness of notation, was 97.0%, with no difference between new and continuing orders. Evaluation of the quality of documentation showed that the most important factor lacking in the majority of documentations was duration of previous opioid therapy. Conclusion Examination of fentanyl patch documentation data suggests that the existing pharmacy notation system can be improved. We believe that a revised documentation template that includes source of information, chronic pain indication, opioid regimen, duration, daily oral morphine equivalent, pain assessment, and final patch plan will help to ensure the safety of prescribed patches and completeness of documentation. These findings can be used to develop policies and procedures to achieve complete adherence to transdermal fentanyl's boxed warning at any institution.

Use of Opioids or Benzodiazepines and Risk of Pneumonia in Older Adults: A Population‐Based Case–Control Study

To examine whether use of opioids or benzodiazepines is associated with risk of community-acquired pneumonia in older adults. Population-based case-control study. An integrated healthcare delivery system. Community-dwelling, immunocompetent adults aged 65 to 94 from 2000 to 2003. Presumptive pneumonia cases were identified from health plan automated data and validated through medical record review. Two controls were selected for each case with pneumonia, matched on age, sex, and calendar year. Information about opioid and benzodiazepine use came from computerized pharmacy data. Information on covariates including comorbid illnesses and functional and cognitive status came from medical record review and electronic health data. One thousand thirty-nine validated cases of pneumonia and 2,022 matched controls were identified. One hundred forty-four (13.9%) cases and 161 (8.0%) controls used prescription opioids (adjusted odds ratio (OR)=1.38, 95% confidence interval (CI)=1.08-1.76 vs nonuse). Risk was highest for opioids categorized as immunosuppressive based on immunological studies (OR=1.88, 95% CI=1.26-1.79 vs nonuse), whereas for nonimmunosuppressive opioids the OR was 1.23 (95% CI=0.89-1.69). Risk was highest in the first 14days of use (OR=3.24, 95% CI=1.64-6.39 vs nonuse). For long-acting opioids, the OR was 3.43 (95% CI=1.44-8.21) versus nonuse, whereas for short-acting opioids, it was 1.27 (95% CI=0.98-1.64). No greater risk was seen for current benzodiazepine use compared to nonuse (OR=1.08, 95% CI=0.80-1.47). Use of opioids but not benzodiazepines was associated with pneumonia risk. The differences in risk seen for different opioid regimens warrant further study.

Opioid therapy for chronic pain: Physicians’ attitude and current practice patterns

Although opioid therapy is widely used for the treatment of chronic pain conditions, there is a lack of consensus on a number of practical issues related to the use of prescription opioids. The authors conducted a comprehensive practice-oriented survey to examine physicians' attitudes, knowledge, experience, and practice patterns regarding opioid therapy for chronic pain management. The survey was conducted during 2007 and 2008 through nationwide direct mails and e-mails to physicians who are currently practicing in the United States. The survey contained 23 questions divided into six categories: (1) physicians' overall view on opioid therapy for chronic pain management; (2) clinical indications for opioid therapy; (3) patient-related factors influencing the decision to begin opioid therapy; (4) effectiveness of opioid therapy; (5) choice of opioid regimen; and (6) opioid agreement and opioid abuse behavior. The survey results suggest that opioid therapy remains as an important treatment option for chronic malignant and nonmalignant pain. However, the survey results should be viewed in the context of a low response rate (18.2 percent). These results also suggest that by improving the clinical knowledge of physicians participating in opioid therapy through education and collaboration, including a team approach with consultation from pain specialists, psychologists, and others, a better outcome for opioid therapy in patients with chronic pain conditions could be achieved.

Computational Opioid Prescribing: A Novel Application of Clinical Pharmacokinetics

ABSTRACTWe implemented a pharmacokinetics-based mathematical modeling technique using algebra to assist prescribers with point-of-care opioid dosing. We call this technique computational opioid prescribing (COP). Because population pharmacokinetic parameter values are needed to estimate drug dosing regimen designs for individual patients using COP, and those values are not readily available to prescribers because they exist scattered in the vast pharmacology literature, we estimated the population pharmacokinetic parameter values for 12 commonly prescribed opioids from various sources using the bootstrap resampling technique. Our results show that opioid dosing regimen design, evaluation, and modification is feasible using COP. We conclude that COP is a new technique for the quantitative assessment of opioid dosing regimen design evaluation and adjustment, which may help prescribers to manage acute and chronic pain at the point-of-care. Potential benefits include opioid dose optimization and minimization of adverse opioid drug events, leading to potential improvement in patient treatment outcomes and safety.

Prescribed Opioids Adherence Among Taiwanese Oncology Outpatients

The purpose of this study was to evaluate adherence to prescribed opioids in Taiwanese oncology outpatients and to examine the associations between various demographic and medical characteristics and prescribed opioids adherence. Ninety-two outpatients who had taken prescribed opioid analgesics for cancer-related pain at least once in the past week participated in this study. Patients were asked to recall the dose of each opioid analgesic that they had taken in the past 24 hours. Mean adherence rates were calculated for analgesic adherence. For mean adherence rates, all opioid analgesics were converted to morphine equivalents. The results of this study reveal a priority issue of poor opioid analgesic adherence. The adherence rate of 63.6% for the around-the-clock opioid analgesics in this study is well below acceptable levels. Also, an adherence rate of 30.9% for the as-needed opioid analgesics is very low. This study identified that women tend to be less adherent to their prescribed opioid analgesic regimen than men. Findings of this study suggest that to improve pain control, efforts to promote patients’ opioid regimen adherence should be given high priority. Clinicians should be particularly aware that there may be some gender difference in adherence to prescribed opioid analgesics. There is a need for better programmatic efforts to improve analgesic adherence.

Association Between Opioid Prescribing Patterns and Opioid Overdose-Related Deaths

The rate of prescription opioid-related overdose death increased substantially in the United States over the past decade. Patterns of opioid prescribing may be related to risk of overdose mortality. To examine the association of maximum prescribed daily opioid dose and dosing schedule ("as needed," regularly scheduled, or both) with risk of opioid overdose death among patients with cancer, chronic pain, acute pain, and substance use disorders. Case-cohort study. Veterans Health Administration (VHA), 2004 through 2008. All unintentional prescription opioid overdose decedents (n = 750) and a random sample of patients (n = 154,684) among those individuals who used medical services in 2004 or 2005 and received opioid therapy for pain. Main Outcome Measure Associations of opioid regimens (dose and schedule) with death by unintentional prescription opioid overdose in subgroups defined by clinical diagnoses, adjusting for age group, sex, race, ethnicity, and comorbid conditions. The frequency of fatal overdose over the study period among individuals treated with opioids was estimated to be 0.04%.The risk of overdose death was directly related to the maximum prescribed daily dose of opioid medication. The adjusted hazard ratios (HRs) associated with a maximum prescribed dose of 100 mg/d or more, compared with the dose category 1 mg/d to less than 20 mg/d, were as follows: among those with substance use disorders, adjusted HR = 4.54 (95% confidence interval [CI], 2.46-8.37; absolute risk difference approximation [ARDA] = 0.14%); among those with chronic pain, adjusted HR = 7.18 (95% CI, 4.85-10.65; ARDA = 0.25%); among those with acute pain, adjusted HR = 6.64 (95% CI, 3.31-13.31; ARDA = 0.23%); and among those with cancer, adjusted HR = 11.99 (95% CI, 4.42-32.56; ARDA = 0.45%). Receiving both as-needed and regularly scheduled doses was not associated with overdose risk after adjustment. Among patients receiving opioid prescriptions for pain, higher opioid doses were associated with increased risk of opioid overdose death.

An evaluation of the impact of opioid use on the analgesic effects of REC1100 in chronic low back patients

Dexmedetomidine is a potent α2-agonist which has been observed to produce post-operative analgesic and opioid sparing effects upon intravenous administration. This study evaluated the safety, pharmacokinetics, and analgesic efficacy of REC1100 (sublingual dexmedetomidine) in chronic low back pain (CLBP) patients. Twenty-one CLBP patients with and without a history of opioid use for their back pain were enrolled at a single U.S. site. The study protocol and informed consent received IRB approval prior to enrollment. Patients were randomized to treatment with a 50 μg dose of REC1100 or matching placebo in a double-blind, crossover, followed by an open-label phase with a 50 μg repeated dose of REC1100. Opioids were not permitted prior to dosing in the crossover periods, while opioid regimens were maintained throughout the repeated dose phase. Analgesia was measured using a 100 mm Visual Analog Scale of Pain (VASPain). Overall, REC1100 treated patients showed a significant decrease in mean VASPain scores compared with placebo two hours after dosing (-19.7 vs. -8.4; p=0.0408). Mean predose VASPain scores were lower before each treatment in patients with a history of opioid use than those without; crossover REC1100 (46.33 vs. 61.92), crossover placebo (50.11 vs. 58.83), repeated dose REC1100 (40.33 vs. 55.58). During the placebo-controlled crossover phase, peak reductions in mean VASPain scores were numerically greater in non-opioid compared with opioid users (22.08 vs. 16.55). Upon repeated dosing in the unblinded phase of the study, peak mean VASPain reductions remained numerically greater in non-opioid users versus opioid users (20.42 vs. 16.22). Doses of REC1100 were well tolerated; no patients discontinued from the study and no SAEs were observed. Improvements in VASPain scores support the analgesic efficacy of REC1100 in CLBP patients alone and in combination with opioid medications. Further study is warranted to evaluate REC1100 in larger and more diverse pain populations.

Use of Prescription Opioid Medication among Community-Dwelling Older Adults with Noncancer Chronic Pain

Research exploring the use of prescription opioid medications among community-dwelling older adults is lacking within the current body of health related literature. Previous studies on prescription opioid use have focused on misuse among young and middle-aged adults. The purpose of this pilot study was to: (1) describe older adults' patterns of adherence to their prescription opioid medication regimens and their reasons for these medication use patterns; and (2) examine the associations between adherence of prescription opioids, pain intensity, and pain interference on daily activity. This study utilized a cross-sectional design. Twenty-one participants aged 65 years and older with non-cancer chronic pain were recruited for this study. Findings revealed that almost half of the study participants reported taking less prescription opioids than prescribed, with 2 participants taking more than the recommended dose. There was no significant association between prescription opioid medication adherence and pain ...