Chronic Pain: Reducing Costs Through Early Implementation of Adherence Testing and Recognition of Opioid Misuse

Abstract

Objective: To review the literature on costs associated with chronic pain therapy and to identify key contributing factors. Also, to assess the potential cost-saving benefits of monitoring pain treatment adherence using urine drug tests (UDTs), emphasizing their use in opioid therapy. Results: Reduced productivity, compensation costs, and treatment of comorbid conditions related to chronic pain contribute to the substantial financial burden of chronic pain management in the United States. The growing use of opioids for chronic pain increases the risk for drug nonadherence and associated drug abuse, potential addiction, and aberrant drug-related behaviors (ADRBs). Treatment of drug abuse increases health care costs; opioid abusers are 25 times more likely to require hospitalization than nonopioid abusers. Early detection of patient nonadherence using UDTs could significantly reduce costs of chronic pain therapy by allowing the physician to identify and treat patients' ADRBs related to controlled substances and drug addiction and abuse problems. Adherence in chronic pain may be determined by point-of-care (POC) tests, and more sensitive laboratory urine tests employing gas chromatography/mass spectrometry with high-performance liquid chromatography tests (LUTs). Cost-benefit studies suggest that the cost of LUTs to optimize adherence may reduce costs associated with nonadherence, such as inpatient clinical care and patient self-release. Current estimates indicate that appropriate use of LUTs could produce decreases up to 14.8-fold in the cost of chronic pain therapy. Conclusions: The cost benefits of UDTs can only be fully realized if physicians know how to define and detect various types of drug abuse, addiction, and diversion. Physicians should be educated on the proper implementation of POC tests and LUTs, and interpretation of adherence data. Early monitoring of drug adherence using POC tests and follow-up LUTs may provide substantial cost savings associated with health care issues incurred in nonadherent chronic pain patients, especially those taking opioid therapy.     

Improving Family Medicine Residents’ Opioid Prescribing: A Nurse Practitioner-Led Model

Academic family medicine teaching centers face distinct challenges with opioid prescribing, including higher rates of opioid misuse in resident patient populations and lower levels of experience managing chronic noncancer pain. To improve opioid prescribing practices in an academic family practice, we introduced and evaluated a nurse practitioner-led collaborative care model. After implementation of the model, we found a reduction in the average dose of opioids prescribed, increased use of urine drug tests and opioid treatment agreements, and fewer prescribers per patient. The nurse practitioner-led model was successfully implemented in an academic family practice with improvements in opioid prescribing and monitoring practices.     

The Role of Urine Toxicology in Chronic Opioid Analgesic Therapy

The current trend of treating chronic nonmalignant pain with opioid therapy means that pain management nurses are increasingly involved in the care of patients who are prescribed and using potent opioid analgesics on a daily basis. Although demonstrated to be quite effective in certain patients, sanctioned access to these medications brings with it risks for abuse, addiction, and diversion. Urine toxicology analysis is a valuable, yet underutilized, tool to monitor patterns of medication use and potential use of illicit drugs to evaluate the effect of these on health outcomes. This review provides a guide for the use of urine toxicology in the nursing management of chronic pain patients on opioid therapy, detailing the information provided by urine toxicology analysis, the benefits and limitations of urine drug testing, principles of sample collection, and correct interpretation of findings. It is emphasized that the results of urine toxicology analysis should never be used in isolation to identify abuse, addiction, or diversion, and that patterns of medication and other drug use should always be evaluated with respect to evidence of improved functionality. Nurses involved in the care of patients with chronic pain are encouraged to consider urine toxicology analysis as an integral component in care plan for those on chronic opioid therapy, and to knowledgeably implement and interpret this powerful tool in the practice of pain care.     

Barriers to Guideline-Concordant Opioid Management in Primary Care—A Qualitative Study

Prior studies have demonstrated poor physician adherence to opioid management guidelines in primary care. The objectives of this qualitative study were to understand physicians' and patients' perspectives on recommended opioid management practices and to identify potential barriers to and facilitators of guideline-concordant opioid management in primary care. Individual semistructured interviews were conducted with 14 primary care physicians and 26 of their patients receiving long-term opioid therapy. Data were analyzed using a qualitative immersion/crystallization approach. We identified 3 major barriers to and 1 facilitator of use of recommended opioid management practices. Major barriers were inadequate time and resources available; relying on general impressions of risk for opioid misuse; and viewing opioid monitoring as a “law enforcement” activity. The third barrier was most apparent for physicians in the context of drug testing and for patients in the context of opioid agreements. Beliefs about the need to protect patients from opioid-related harm emerged as a major facilitator, especially among patients. We hypothesize that future interventions to improve opioid management in primary care will be more effective if they address identified barriers and use a patient-centered framework, in which prevention of opioid-related harm to patients is emphasized as the primary goal.PerspectiveThis article describes primary care perspectives on guideline-recommended opioid management practices. Barriers identified in this study may contribute to underuse of recommended opioid management practices. Consideration of barriers and facilitators to guideline-concordant care could improve effectiveness of future interventions aimed at improving opioid management in primary care.     

Oral Prolonged‐Release Oxycodone/Naloxone for Managing Pain and Opioid‐Induced Constipation: A Review of the Evidence

Background

Opioids provide effective relief from moderate‐to‐severe pain and should be prescribed as part of a multifaceted approach to pain management when other treatments have failed. Fixed‐dose oxycodone/naloxone prolonged‐release tablets (OXN PR) were designed to address the opioid class effect of opioid‐induced constipation (OIC) by combining the analgesic efficacy of oxycodone with the opioid receptor antagonist, naloxone, which has negligible systemic availability when administered orally. This formulation has abuse‐deterrent properties, since systemic exposure to naloxone by parenteral administration would antagonize the euphoric effects of oxycodone.

Methods

A literature search was conducted to assess the evidence base for OXN PR to treat moderate‐to‐severe pain and its impact on bowel function, based on published clinical trials and observational studies.

Results

Extensive data demonstrate that OXN PR provides effective analgesia and clinically relevant improvements in bowel function in patients with OIC and moderate‐to‐severe cancer‐related pain and noncancer pain types such as low back pain, neuropathic pain, and musculoskeletal pain. OXN PR has also been found to improve bowel function in patients with OIC refractory to multiple types of laxatives, and improve Parkinson's disease–related pain. No unanticipated safety concerns have been reported in elderly patients.

Conclusions

Evidence from clinical trials and observational studies confirms that for selected patients OXN PR significantly improves moderate‐to‐severe chronic pain and provides relief from OIC. Treatment should be tailored to individual patients to establish the lowest effective dose. An absence of analgesic ceiling effect was seen across the clinically relevant dose range investigated (≤ 160/80 mg/day).     

What is the Case for Prescribing Long‐Acting Opioids Over Short‐Acting Opioids for Patients with Chronic Pain? A Critical Review

Introduction:   Effective pain management requires appropriate patient assessment, ongoing reassessment, and an understanding of the options available for the treatment of patients with chronic pain. Opioids have long been an important option in the management of moderate to severe chronic pain, but optimal use requires understanding the variety of choices currently available.
Methods:   Literature search was carried out using PubMed. Search terms included "steady state,""pharmacokinetics,""pharmacodynamics,""chronic non-cancer pain,""sustained release opioid," "extended release opioid," "controlled release opioid,""morphine,""oxymorphone,""hydromorphone,""oxycodone," and "fentanyl."
Results:   This search found 12 chronic pain studies that compared short- and long-acting opioids head-to-head. These were supplemented with representative studies from the chronic pain literature.
Discussion:   The objective of this article is to review clinical data for the use of long-acting and short-acting opioids in a variety of chronic noncancer pain conditions. Although some patients with chronic pain appear to prefer short-acting opioids, many patients receiving long-acting opioid formulations show improved treatment responses and better perception of quality of life. In addition, the sustained reductions in pain seen with long-acting opioid formulations may promote patients' focus on daily activities rather than on their pain, thereby improving therapy adherence and reducing pain-related anxieties.
Conclusion:   Long-term clinical trials of these formulations are needed to allow clinicians to make informed decisions about which patient groups might benefit most from these formulations.     

Opioids Versus Physical Therapy for Management of Chronic Back Pain

Chronic low back pain (CLBP) is a common disabling disorder managed by a variety of interventions. The purpose of this article was to review the literature and critique the evidence to determine if opioid analgesics improved patient outcomes compared with physical therapy. No research was found that directly compared the efficacy of opioid analgesics with physical therapy. Although the evidence supports the use of physical therapy in chronic back pain, the study results are conflicting regarding the usefulness of opioid analgesics in CLBP management. More research involving the efficacy of opioid analgesic in treating CLBP is needed.     

Opioid Rotation in the Management of Chronic Pain: Where Is the Evidence?

The management of chronic pain remains a challenge because of its complexity and unpredictable response to pharmacological treatment. In addition, accurate pain management may be hindered by the prejudice of physicians and patients that strong opioids, classified as step 3 medications in the World Health Organization ladder for cancer pain management, are reserved for the end stage of life. Recent information indicates the potential value of strong opioids in the treatment of chronic nonmalignant pain. There are, up until now, insufficient data to provide indications about which opioid to use to initiate treatment or the dose to be used for any specific pain syndrome. The strong inter‐patient variability in opioid receptor response and in the pharmacokinetic and pharmacodynamic behavior of strong opioids justifies an individual selection of the appropriate opioid and stepwise dose titration. Clinical experience shows that switching from one opioid to another may optimize pain control while maintaining an acceptable side effect profile or even improving the side effects. This treatment strategy, described as opioid rotation or switch, requires a dose calculation for the newly started opioid. Currently, conversion tables and equianalgesic doses are available. However, those recommendations are often based on data derived from studies designed to evaluate acute pain relief, and sometimes on single dose studies, which reduces this information to the level of an indication. In daily practice, the clinician needs to titrate the optimal dose during the opioid rotation from a reduced calculated dose, based on the clinical response of the patient. Further research and studies are needed to optimize the equianalgesic dosing tables.     

Long‐term Safety and Tolerability of Tapentadol Extended Release for the Management of Chronic Low Back Pain or Osteoarthritis Pain

Background: Tapentadol is a novel, centrally acting analgesic with 2 mechanisms of action: µ‐opioid receptor agonism and norepinephrine reuptake inhibition. This randomized, open‐label phase 3 study (ClinicalTrials.gov Identifier: NCT00361504) assessed the long‐term safety and tolerability of tapentadol extended release (ER) in patients with chronic knee or hip osteoarthritis pain or low back pain. Methods: Patients were randomized 4:1 to receive controlled, adjustable, oral, twice‐daily doses of tapentadol ER (100 to 250 mg) or oxycodone HCl controlled release (CR; 20 to 50 mg) for up to 1 year. Efficacy evaluations included assessments at each study visit of average pain intensity (11‐point numerical rating scale) over the preceding 24 hours. Treatment‐emergent adverse events (TEAEs) and discontinuations were monitored throughout the study. Results: A total of 1,117 patients received at least 1 dose of study drug. Mean (standard error) pain intensity scores in the tapentadol ER and oxycodone CR groups, respectively, were 7.6 (0.05) and 7.6 (0.11) at baseline and decreased to 4.4 (0.09) and 4.5 (0.17) at endpoint. The overall incidence of TEAEs was 85.7% in the tapentadol ER group and 90.6% in the oxycodone CR group. In the tapentadol ER and oxycodone CR groups, respectively, TEAEs led to discontinuation in 22.1% and 36.8% of patients; gastrointestinal TEAEs led to discontinuation in 8.6% and 21.5% of patients. Conclusion: Tapentadol ER (100 to 250 mg bid) was associated with better gastrointestinal tolerability than oxycodone HCl CR (20 to 50 mg bid) and provided sustainable relief of moderate to severe chronic knee or hip osteoarthritis or low back pain for up to 1 year.     

Eight principles for safer opioid prescribing and cautions with benzodiazepines

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.     

Benefits of Extended-Release Opioid Analgesic Formulations in the Treatment of Chronic Pain

Chronic noncancer pain represents a major health problem that affects many patients, resulting in suffering, reduced productivity, and substantial health care costs. The patient with chronic noncancer pain is burdened by decreased quality of life, decreased sleep, interference with social relationships, diminished cognitive functions, interference with activities of daily living, decreased productivity, and increased anxiety and depression. A survey examining the burden of pain on health and productivity found decreases of 45% in physical health and 23% in mental health at a cost of $61.2 billion per year in productive work time. An American Pain Society survey of 800 patients with moderate to severe chronic pain reported that 47% felt their pain was not under control. The goal of pharmacological therapy for chronic noncancer pain is to provide sustained analgesia. Chronic pain management guidelines recommend the use of long-acting, extended-release (ER) analgesics because they provide prolonged, more consistent plasma concentrations of drug compared with short-acting agents, thus minimizing fluctuations that could contribute to end-of-dose breakthrough pain. ER analgesics offer more consistent and improved nighttime pain control, less need to awaken at night to take another dose of pain medication, and less clock-watching by patients in chronic noncancer pain. Among the available ER opioids, tramadol ER possesses a unique mechanism of action, making it a viable opioid of first choice for patients suffering from a variety of chronic noncancer pain conditions, such as osteoarthritis, low back pain, and neuropathic pain.     

Clinical Uses of Intrathecal Therapy and Its Placement in the Pain Care Algorithm

Intrathecal drug delivery is an effective treatment option for patients with severe chronic pain who have not obtained adequate analgesia from more conservative therapies (eg, physical therapy, systemic opioids, nonsteroidal anti‐inflammatory drugs, antidepressants, and anticonvulsants). This review focuses on, but is not limited to, the 2 agents currently approved by the U.S. Food and Drug Administration for intrathecal analgesia: preservative‐free morphine and ziconotide (a nonopioid, selective N‐type calcium channel blocker). We describe the appropriate use of intrathecal therapy in the management of severe chronic pain, based on current best practices. Topics addressed here include patient selection, trialing, dosing and titration, adverse event profiles, long‐term management, intrathecal therapy for cancer‐related pain, and the placement of intrathecal therapy in the pain care algorithm. In appropriately selected patients with chronic pain, intrathecal therapy can provide substantial pain relief with improved functioning and quality of life. Successful long‐term management requires ongoing patient monitoring for changes in efficacy and the occurrence of adverse events, with subsequent changes in intrathecal dosing and titration, the addition of adjuvant intrathecal agents, and the use of concomitant oral medications to address side effects, as needed. Based on an infrequent but clinically concerning risk of overdose, granuloma, and other opioid‐induced complications, nonopioid therapy with ziconotide may be preferred as a first‐line intrathecal therapy in patients without a history of psychosis or allergy.     

Time-scheduled vs. pain-contingent opioid dosing in chronic opioid therapy

Some expert guidelines recommend time-scheduled opioid dosing over pain-contingent dosing for patients receiving chronic opioid therapy (COT). The premise is that time-scheduled dosing results in more stable opioid blood levels and better pain relief, fewer adverse effects, less reinforcement of pain behaviors, and lower addiction risk. We report results of a survey of 1781 patients receiving COT for chronic noncancer pain, in which 967 reported time-scheduled opioid dosing only and 325 reported pain-contingent opioid dosing only. Opioid-related problems and concerns were assessed with the Prescribed Opioids Difficulties Scale. We hypothesized that respondents using time-scheduled opioid dosing would report significantly fewer problems and concerns than those using pain-contingent dosing. Patients receiving time-scheduled dosing received substantially higher average daily opioid doses than those using pain-contingent dosing (97.2 vs. 37.2 mg average daily dose morphine equivalents, P < .0001). Contrary to expectation, time-scheduled opioid dosing was associated with higher levels of patient opioid control concerns than pain-contingent dosing (6.2 vs. 4.8, P = .008), after adjusting for patient and drug regimen differences. Opioid-related psychosocial problems were somewhat greater among patients using time-scheduled dosing, but this difference was nonsignificant after controlling for patient and drug regimen differences (5.9 vs. 5.0, P = .14). Time-scheduled dosing typically involved higher dosage levels and was associated with higher levels of patient concerns about opioid use. Controlled comparative effectiveness research is needed to assess benefits and risks of time-scheduled opioid dosing relative to pain-contingent opioid dosing among COT patients in ambulatory care.     

Therapeutic Interactive Voice Response (TIVR) to Reduce Analgesic Medication Use for Chronic Pain Management

This paper examines whether a telephone-based, automated maintenance enhancement program can help to reduce opioid and nonsteroidal anti-inflamatory drugs (NSAID) analgesic use in patients with chronic pain. Following 11 weeks of group cognitive-behavioral therapy (CBT), 51 subjects with chronic musculoskeletal pain were randomized to 1 of 2 study groups. Twenty-six subjects participated in 4 months of a Therapeutic Interactive Voice Response (TIVR) program in addition to standard follow-up care, while a control group of 25 subjects received standard follow-up care only. TIVR is an automated, telephone-based tool developed for the maintenance and enhancement of CBT skills. Opioid analgesic use decreased in the experimental group in both follow-ups: 4 and 8 months postCBT. In addition, at 8-month follow-up, 21% of the TIVR subjects had discontinued the use of opioid analgesics, 23% had discontinued NSAIDS, and 10% had discontinued antidepressant medications. In contrast, the control group showed increases in opioid and NSAIDS use. Analysis of covariance (ANCOVA) revealed significant between-group differences in opioid analgesic use at 8-month follow up (P = .004). We have previously demonstrated the efficacy of TIVR to decrease pain and improve coping; this analysis demonstrates that the use of TIVR may also result in concurrent reductions in opioid analgesic and NSAID medications use.     

Variable Use of Opioid Pharmacotherapy for Chronic Noncancer Pain in Europe: Causes and Consequences

ABSTRACT.?

According to the 2005 Pain in Europe Survey, the use of opioids to treat patients with chronic noncancer pain varies considerably among different countries in Europe. Undertreatment of chronic pain is common. This review examines the possible causes and consequences of limiting opioid availability to these patients. The causes of inadequate opioid use include medical, ethical, and cultural factors that influence prescribing decisions; legislative and health care system controls that serve to restrict the use of opioids for long-term treatment of non–cancer-related pain conditions; and poor treatment acceptance by patients. The validity of these restrictions is discussed in relation to the need to protect patients and society from harm due to adverse events, and the potential for misuse and abuse with prescribed opioids. This is balanced against the therapeutic goal of providing the best available pain-relieving treatment and to avoid the consequences of unnecessary suffering in patients with chronic noncancer pain.