Long-term Opioid Therapy For Pain Research Articles

How Should the Use of Opioids Be Regulated to Motivate Better Clinical Practice?

This article describes historical and political reasons for-and devastating consequences of-US opioid prescribing policy since the 1990s, which has restricted opioid prescribing for pain less than for treating opioid use disorder (OUD) treatment. This article considers merits and drawbacks of a new diagnostic category and proposes a regulatory and clinical framework for prescribing long-term opioid therapy for pain and for prescribing opioids to treat OUD.

Discontinuation and tapering of prescribed opioids and risk of overdose among people on long-term opioid therapy for pain with and without opioid use disorder in British Columbia, Canada: A retrospective cohort study.

The overdose crisis in North America has prompted system-level efforts to restrict opioid prescribing for chronic pain. However, little is known about how discontinuing or tapering prescribed opioids for chronic pain shapes overdose risk, including possible differential effects among people with and without concurrent opioid use disorder (OUD). We examined associations between discontinuation and tapering of prescribed opioids and risk of overdose among people on long-term opioid therapy for pain, stratified by diagnosed OUD and prescribed opioid agonist therapy (OAT) status. For this retrospective cohort study, we used a 20% random sample of residents in the provincial health insurance client roster in British Columbia (BC), Canada, contained in the BC Provincial Overdose Cohort. The study sample included persons aged 14 to 74 years on long-term opioid therapy for pain (≥90 days with ≥90% of days on therapy) between October 2014 and June 2018 (n = 14,037). At baseline, 7,256 (51.7%) persons were female, the median age was 55 years (quartile 1-3: 47-63), 227 (1.6%) persons had been diagnosed with OUD (in the past 3 years) and recently (i.e., in the past 90 days) been prescribed OAT, and 483 (3.4%) had been diagnosed with OUD but not recently prescribed OAT. The median follow-up duration per person was 3.7 years (quartile 1-3: 2.6-4.0). Marginal structural Cox regression with inverse probability of treatment weighting (IPTW) was used to estimate the effect of prescribed opioid treatment for pain status (discontinuation versus tapered therapy versus continued therapy [reference]) on risk of overdose (fatal or nonfatal), stratified by the following groups: people without diagnosed OUD, people with diagnosed OUD receiving OAT, and people with diagnosed OUD not receiving OAT. In marginal structural models with IPTW adjusted for a range of demographic, prescription, comorbidity, and social-structural exposures, discontinuing opioids (i.e., ≥7-day gap[s] in therapy) was associated with increased overdose risk among people without OUD (adjusted hazard ratio [AHR] = 1.44; 95% confidence interval [CI] 1.12, 1.83; p = 0.004), people with OUD not receiving OAT (AHR = 3.18; 95% CI 1.87, 5.40; p < 0.001), and people with OUD receiving OAT (AHR = 2.52; 95% CI 1.68, 3.78; p < 0.001). Opioid tapering (i.e., ≥2 sequential decreases of ≥5% in average daily morphine milligram equivalents) was associated with decreased overdose risk among people with OUD not receiving OAT (AHR = 0.31; 95% CI 0.14, 0.67; p = 0.003). The main study limitations are that the outcome measure did not capture overdose events that did not result in a healthcare encounter or death, medication dispensation may not reflect medication adherence, residual confounding may have influenced findings, and findings may not be generalizable to persons on opioid therapy in other settings. Discontinuing prescribed opioids was associated with increased overdose risk, particularly among people with OUD. Prescribed opioid tapering was associated with reduced overdose risk among people with OUD not receiving OAT. These findings highlight the need to avoid abrupt discontinuation of opioids for pain. Enhanced guidance is needed to support prescribers in implementing opioid therapy tapering strategies with consideration of OUD and OAT status.

Patient outcomes following state-mandated opioid dose reductions.

Maine Public Law Chapter 488 required that all opioid doses be reduced to below 100 morphine milligram equivalent (MME) by July 1, 2017, and VA Maine Healthcare System implemented policies consistent with the state law. The purpose of this study was to assess self-reported pain scores over 2 years and overall utilization of alternative healthcare services for veterans who were using opioid doses in excess of 100 MME prior to the implementation of policies consistent with Maine PL Chapter 488 in the VA Maine Healthcare System. In this retrospective chart review, veterans were selected for inclusion if they were receiving chronic opioid therapy at the VA Maine Healthcare System of at least 100 MME daily in March 2016 according to the opioid therapy risk report (OTRR). Self-reported pain scores and use of alternative healthcare services were evaluated using VA Computerized Patient Record System (CPRS) data. Of the 147 patients evaluated per protocol, 75 patients (51%) did not have a clinically significant change in self-reported pain scores, and the self-reported pain scores of 29 patients (20%) improved from March 2016 to March 2018 (P = 0.054). We found that mandatory dose reductions of chronic opioid medications did not result in a clinically or statistically significant worsening of self-reported pain scores. Our study suggests that opioid dose reductions may not negatively impact a patient's functioning and pain intensity and calls into question the use of long-term opioid therapy for pain given the safety implications.

Impact of multidisciplinary chart reviews on opioid dose reduction and monitoring practices

IntroductionThe Veterans Affairs (VA) Eastern Colorado Health Care System implemented an Opioid Safety Initiative (OSI); this included multidisciplinary chart reviews of patients with chronic, non-malignant pain on high-dose opioid therapy to provide safety recommendations to prescribers through the electronic medical record. Our study objective was to evaluate the impact of these documented recommendations. Outcomes included change in total daily opioid dose, concurrent prescribing of opioids and benzodiazepines, adherence to local VA/Veterans Integrated Service Network (VISN) policy, and monitoring practices. MethodsThis retrospective chart review of patients prescribed ≥200 mg of morphine equivalent daily dose (MEDD) collected data from OSI chart reviews conducted between January 1, 2015 and March 31, 2015. Outcomes were assessed during the 12 months following initial review. Primary outcomes included: opioid dose reduction, discontinuation of concurrent benzodiazepines, and adherence to VA/VISN policy, including documentation of signed informed Consent for Long-Term Opioid Therapy for Pain, biannual urine drug screens (UDS), and follow-up every six months with primary opioid prescriber. ResultsOf 147 patients meeting inclusion criteria, 50 patients (34%) reduced opioid dose with the baseline median MEDD decreasing from 315 mg to 278 mg. Of the 48 patients prescribed benzodiazepines and opioids, 10 patients discontinued benzodiazepines (21%). Completion of informed consents increased from 31% to 48%, biannual UDS increased from 44% to 61%, and follow-up with opioid prescriber was unchanged. ConclusionAfter completion of OSI chart reviews, reduction in opioid dose and concurrent prescribing of benzodiazepines was observed. VA/VISN policy and monitoring adherence also showed improvement.

Group Visits for Overdose Education and Naloxone Distribution in Primary Care: A Pilot Quality Improvement Initiative.

Opioid prescribing for chronic pain significantly contributes to opioid overdose deaths in the United States. Naloxone as a take-home antidote to opioid overdose is underutilized and has not been evaluated in the high-risk chronic pain population. The objective was to increase overdose education and naloxone distribution (OEND) to high-risk patients on long-term opioid therapy for pain by utilizing group visits in primary care. Quality improvement intervention among two primary care clinics. A large, academic facility within the Veterans Health Administration. Patients prescribed ≥100 mg morphine-equivalent daily dose or coprescribed opioids and benzodiazepines. One clinic provided usual care with respect to OEND; another clinic encouraged attendance at an OEND group visit to all of its high-risk patients. We used attendance at group visits, prescriptions of naloxone issued, and patient satisfaction scores to evaluate this format of OEND. Group OEND visits resulted in significantly more naloxone prescriptions than usual care. At these group visits, patients were engaged, valued the experience, and all requested a prescription for the naloxone kit. This quality improvement pilot study suggests that OEND group visits are a promising model of care.

Improving Adherence to Long-term Opioid Therapy Guidelines to Reduce Opioid Misuse in Primary Care

Prescription opioid misuse is a national crisis. Few interventions have improved adherence to opioid-prescribing guidelines. To determine whether a multicomponent intervention, Transforming Opioid Prescribing in Primary Care (TOPCARE; http://mytopcare.org/), improves guideline adherence while decreasing opioid misuse risk. Cluster-randomized clinical trial among 53 primary care clinicians (PCCs) and their 985 patients receiving long-term opioid therapy for pain. The study was conducted from January 2014 to March 2016 in 4 safety-net primary care practices. Intervention PCCs received nurse care management, an electronic registry, 1-on-1 academic detailing, and electronic decision tools for safe opioid prescribing. Control PCCs received electronic decision tools only. Primary outcomes included documentation of guideline-concordant care (both a patient-PCC agreement in the electronic health record and at least 1 urine drug test [UDT]) over 12 months and 2 or more early opioid refills. Secondary outcomes included opioid dose reduction (ie, 10% decrease in morphine-equivalent daily dose [MEDD] at trial end) and opioid treatment discontinuation. Adjusted outcomes controlled for differing baseline patient characteristics: substance use diagnosis, mental health diagnoses, and language. Of the 985 participating patients, 519 were men, and 466 were women (mean [SD] patient age, 54.7 [11.5] years). Patients received a mean (SD) MEDD of 57.8 (78.5) mg. At 1 year, intervention patients were more likely than controls to receive guideline-concordant care (65.9% vs 37.8%; P < .001; adjusted odds ratio [AOR], 6.0; 95% CI, 3.6-10.2), to have a patient-PCC agreement (of the 376 without an agreement at baseline, 53.8% vs 6.0%; P < .001; AOR, 11.9; 95% CI, 4.4-32.2), and to undergo at least 1 UDT (74.6% vs 57.9%; P < .001; AOR, 3.0; 95% CI, 1.8-5.0). There was no difference in odds of early refill receipt between groups (20.7% vs 20.1%; AOR, 1.1; 95% CI, 0.7-1.8). Intervention patients were more likely than controls to have either a 10% dose reduction or opioid treatment discontinuation (AOR, 1.6; 95% CI, 1.3-2.1; P < .001). In adjusted analyses, intervention patients had a mean (SE) MEDD 6.8 (1.6) mg lower than controls (P < .001). A multicomponent intervention improved guideline-concordant care but did not decrease early opioid refills. clinicaltrials.gov Identifier: NCT01909076.

Capsule Commentary on Behar et al., Acceptability of Naloxone Co-Prescription Among Primary Care Providers Treating Patients on Long-Term Opioid Therapy for Pain.

Capsule Commentary on Behar et al., Acceptability of Naloxone Co-Prescription Among Primary Care Providers Treating Patients on Long-Term Opioid Therapy for Pain.

Nonrandomized Intervention Study of Naloxone Coprescription for Primary Care Patients Receiving Long-Term Opioid Therapy for Pain

Naloxone can be coprescribed to patients receiving prescriptions of opiates for pain and this may have ancillary benefits such as reducing opiate-related adverse events.

Acceptability of Naloxone Co-Prescription Among Primary Care Providers Treating Patients on Long-Term Opioid Therapy for Pain.

Naloxone co-prescription is recommended for patients on long-term opioids for pain, yet there are few data on the practice. To explore naloxone co-prescribing acceptability among primary care providers for patients on long-term opioids. We surveyed providers at six safety-net primary care clinics in San Francisco that had initiated naloxone co-prescribing. Providers were encouraged to offer naloxone to patients on long-term opioids or otherwise at risk of witnessing or experiencing an overdose. Surveys were administered electronically 4 to 11 months after co-prescribing began. One hundred eleven providers (69%) responded to the survey, among whom 41.4% were residents; 40.5% practiced internal medicine and 55.0% practiced family medicine. Most (79.3%) prescribed naloxone, to a mean of 7.7 patients; 99.1% were likely to prescribe naloxone in the future. Providers reported they were likely to prescribe naloxone to most patients, including those on low doses, defined as <20 morphine equivalent mg daily (59.8%), ≥65years old (83.9%), with no overdose history (80.7%), and with no substance use disorder (73.6%). Most providers felt that prescribing naloxone did not affect their opioid prescribing, 22.5% felt that they might prescribe fewer opioids, and 3.6% felt that they might prescribe more. Concerns about providing naloxone were largely administrative, relating to time and pharmacy or payer logistics. Internists (incidence rate ratio [IRR] = 0.49, 95 % CI = 0.26-0.93, p = 0.029), those licensed for 5-20 years (IRR = 2.10, 95 % CI = 1.35-3.25, p = 0.001), and those with more patients prescribed long-term opioids (IRR = 1.10, 95 % CI = 1.05-1.14, p <0.001) were independently more likely to prescribe a greater number of naloxone compared to participants without these exposures. Naloxone co-prescription is considered acceptable among primary care providers. Barriers such as time and dispensing logistics may be alleviated by novel naloxone formulations intended for laypersons recently approved by the U.S. Food and Drug Administration.

Mortality and guideline-concordant long-term opioid therapy for pain

Mortality and guideline-concordant long-term opioid therapy for pain

Electrocardiographic and cardiovascular diagnostic characteristics of patients receiving long-term opioid therapy for pain

To examine cardiovascular and electrocardiogram (ECG) abnormalities seen in patients with chronic pain receiving long-term opioid therapy and to compare them with findings in normal subjects. Clinical pharmaceutical drug trial in a phase I pharmacology unit (normal subjects) and multiple phase 2b study sites (pain patients). Four hundred sixty-one pain patients with constipation due to long-term opioid therapy who were screened for a clinical trial of an investigational treatment for opioid-induced constipation. None; all data used in this study were obtained prior to drug treatment. This is a retrospective analysis of ECG abnormalities and clinical cardiovascular abnormalities in study participants compared with those in a normal reference group of 36,999 subjects. Numerical ECG values were modestly but not clinically significantly different in the pain patients requiring opioids (mean heart rate +1.5 BPM, PR +5.2 milliseconds, QRS -4.7 milliseconds, and QT corrected for heart rate using the Fridericia formula +7.2 milliseconds). The largest difference in ECG diagnoses between the two groups was a fivefold greater incidence of previous myocardial infarction in the pain patient group (4.1 percent vs 0.8 percent). In addition, 50 percent of the pain patient group had a clinical cardiovascular diagnosis. Patients with significant chronic pain requiring opioids have underlying clinical disorders that may be associated with abnormal cardiovascular physiology and ECGs. Clinicians who manage patients with chronic pain should be aware of the higher incidence of cardiovascular disease in this group.

Managing Surgical Pain in Long-Term Opioid Patients

ABSTRACTThe number of patients taking long-term opioid therapy for pain is increasing, with opioid use no longer being confined to advanced cancer patients. Challenges to peri- and postoperative pain management in chronic pain patients include complex existing drug regimens and problems arising from tolerance to opioid analgesia. Postoperatively, individualized, multimodal pain therapy involving a round-the-clock regimen of nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) inhibitors, paracetamol, and regional blocks should be used. Other considerations may include patients receiving opioids by intrathecal drug delivery systems, spinal cord stimulator (SCS), and potential substance abusers.