Treatment Of Chronic Nonmalignant Pain Research Articles

Specific Pharmacology of Long-Acting, Extended-Release, and Sustained-Release Opioids for the Treatment of Chronic Nonmalignant Pain

Opioid products, specifically long-acting (LA), extended-release (ER), and sustained-release (SR) formulations, are used for the treatment of a subset of patients with chronic noncancer pain (CNCP). This article will review the specific pharmacology and risks associated with specific LA, ER, and SR opioid formulations that have been used in the treatment of chronic pain. This article will not address the indications for, evidence for and against, or general controversy regarding the use of any form of long-term opioid therapy for the treatment of chronic nonmalignant pain (CNMP), as this has been presented in other published works.

Case studies of long-acting, extended-release, and sustained-release opioids for the treatment of chronic nonmalignant pain.

Chronic pain of nonmalignant nature (CNMP) is often treated with chronic opioid therapy (COT). Although many guidelines exist to help the clinician use COT in a safe and effective manner, many controversies surrounding the exact prescribing practicesremain. The purpose of these following brief case studies is to help the practicing clinician consider real patient scenarios and help further understanding of the principles outlined by the US FDA REMS document. The patient case scenarios presented in this article do not represent any one real patient. However, each case scenario is entirely plausible and has presented themselves in some likemanner to the author. These discussion and recommendations following each case scenario represent the opinion of the author alone, based on the author’s 30-year experience, a review of common published guidelines, review of the US FDA REMS paper, and a review of the literature concerning COT for CNMP. Some of the discussion points remain controversial and recommendations for therapy are based on a low level of evidence.

General pharmacology of long-acting, extended-release, and sustained-release opioids for the treatment of chronic nonmalignant pain.

Both short-acting (SA) opioids and long-acting (LA) opioids have been used for chronic pain (defined as pain lasting >3 months). SA opioids have a duration of action ranging between 2 and 4 hours, result in rapidly fluctuating drug levels and are suitable for acute, unstable, intermittent, breakthrough, and procedure-related pain.

Intentional Structured Opioid Monitoring Protocol: Responsible and Viable Opioid Deprescribing

INTRODUCTION Primary care providers are increasingly called to address the problem of treatment of non-malignant chronic pain with opioids, particularly in low resource areas. An Intentional Structured Opioid Management Protocol (ISOMP) is a primary care-based program shown to significantly decrease opioid burden. The development of sustainable programs that improve opioid-related outcomes is especially important in these low resource areas. METHODS A retrospective electronic health record review was conducted for financial data and billing practices for a cohort engaged in the ISOMP between 2011 and 2014. Data was analyzed for sustainability within macroscopic practice-wide and microscopic daily scopes. Further analysis was conducted on the implications of patients maintained on (Group A) and weaned from (Group B) opioids. Data was analyzed with STATA software. RESULTS ISOMP demonstrated decreased patient encounters numbers (-7.38%), increased total work relative value unit (RVU) (+7.73%), reduced no-show visits (-12.14%), and increased total reimbursement (+13.06%). Group A had fewer encounters (-6.41%) and increased work RVU (+42.95%). Group B had fewer encounters (-24.04%) but decreased work RVU (-17.56%). Significant decreases in encounters (-44.99%) and work RVUs (-47.39%) were seen after discontinuation of opioids. CONCLUSIONS Besides its previously documented opioid discontinuation rate, the ISOMP model was associated with fewer visits and better visit compli-ance. Sustainability was proven as neither global practice nor daily productivity was negatively impacted. Time-based coding for Group A offset losses seen in Group B productivity with savings directly related to speed of opioid wean

Non-Medical Factors Associated with the Outcome of Treatment of Chronic Non-Malignant Pain: A Cross-Sectional Study

Background: Chronic pain is a global public health issue with increasing prevalence. Chronic pain causes sleep disorder, reactive anxiety, and depression, impairs the quality of life; it burdens the individual and society as a whole. The aim of this study was to examine non-medical factors related to the outcome of the treatment of chronic non-malignant pain. Methods: A cross-sectional study with two groups of patients was conducted using a questionnaire with biological, psychological, and social characteristics of patients. Since this study was cross-sectional, it was not possible to determine whether some factors were the cause or the consequence of unsuccessful treatment outcome, which is at the same time one of the disadvantages of cross-sectional studies. Results: The poor outcome of the treatment of chronic non-malignant pain in a multivariate binary logistic regression model was statistically significantly associated with the lower quality of life (OR = 0.95 (95% CI: 0.91–0.99; p = 0.009), and higher depression level OR = 1.08 (95% CI: 1.02–1.14; p = 0.009). The outcome of the treatment was not directly related to social support measured by the multivariate binary logistic regression model (OR = 1.04, 95% CI: 0.95–1.15, p = 0.395), but solitary life (without partner) was (OR = 2.16 (95% CI: 1.03–4.53; p = 0.043). Conclusion: The typical patient with a poor pain management outcome is retired, presents depressive behavior; their pain disturbs general activity and sleeping. Moreover, they have a physically disturbed quality of life and require self-treatment due to the inaccessibility of doctors and therapies. The principle of treatment of patients with chronic, non-malignant pain should take into account a biopsychosocial approach with individually adjusted procedures.

PSY28 The Effect of Medicinal Cannabis on Quality of Life in the Management of NON-Cancer Chronic PAIN: A Systematic Review

Medicinal cannabis (MC) is an emerging therapeutic option for non-cancer chronic pain. However, its effects on a patient’s quality of life are still widely unknown, and its use still illegal in many countries. The aim of this systematic review was to examine the results of randomised controlled trials (RCTs) that study the effect of medicinal cannabis on quality of life in the treatment of non-cancer chronic pain. This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) protocol and was registered with PROSPERO. A search of Cochrane Library, MEDLINE, Embase and Web of Science was undertaken for literature published on the use of medicinal cannabis for the treatment of non-malignant chronic pain, and its effect on quality of life. Relevant data was extracted from studies and methodological quality assessed using the Cochrane Risk of Bias tool. The search identified 659 research articles. Six studies were selected following application of the inclusion and exclusion criteria. The qualitative review of these studies showed methodological quality was medium/high. The included studies show an overall improvement in quality of life with the use of medicinal cannabis using recognised assessment tools such as the EQ-5D and SF-36. This reached statistical significance in four studies. For the improvement of pain, five of the studies favoured medicinal cannabis over comparators, while one RCT favoured the use of dihydrocodeine. The low number of included studies highlights the lack of trials and research in the use of medicinal cannabis in non-cancer chronic pain for this purpose. This review suggests that medicinal cannabis has positive effects on patients’ quality of life in treating chronic pain. However, further research of its clinical effectiveness is required with consideration of longer term safety data.

Role of pharmacists in optimising opioid therapy for chronic non-malignant pain; A systematic review.

Opioid optimisation is a global issue in Chronic Non-malignant Pain (CNMP) management. This systematic review aims to assess the effectiveness of interventions delivered by pharmacists in outpatient clinical settings, community pharmacies and primary care services in optimising opioid therapy for people with CNMP and to explore stakeholders' opinions about role of pharmacists in optimising opioid therapy. We conducted searches in PubMed, CINAHL, Psych Info, EMBASE, ISI Web of Science and Conference Proceedings and International Pharmaceutical Abstracts. All studies where pharmacists in outpatient clinical settings, community pharmacies and patient care services helped in optimisation of opioids in the treatment of CNMP as individuals or part of a team were included. Authors followed the 27-item PRISMA guidelines and the review was registered in PROSPERO. All authors were involved in screening and selection of studies and included studies between January 1990-June 2020. Studies not published in English language and participants with cancer pain were excluded. All the included studies were descriptively synthesized. Fourteen studies were included in the final data synthesis of this review and the total number of participants in all studies was 1175. Interventions by pharmacists were successful in decreasing opioid dose in 4 studies and improved patient opioid safety in 5 studies. Stakeholders considered that the role of pharmacists in optimisation of opioid therapy for people with CNMP can be promising and should be further developed. This systematic review gives an overview of pharmacist intervention feasibility, stakeholders' opinions and possible benefits on opioid optimisation in people with CNMP in outpatient clinical settings, community pharmacies and primary care settings. However, further research is warranted, which can guide the development of new policies and guidelines for the utilisation of pharmacists to promote opioid safety in people using prescription opioids for CNMP management.

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.

Poster 114: An Ethical Framework for Mitigating Physician Bias in the Treatment of Chronic Non-Malignant Pain

Poster 114: An Ethical Framework for Mitigating Physician Bias in the Treatment of Chronic Non-Malignant Pain

Psychotherapeutic interventions for chronic pain: Evidence, rationale, and advantages.

Long-term use of opioids to treat chronic pain incurs serious risks for the individual-including misuse, abuse, addiction, overdose and death-as well as creating economic, social, and cultural impacts on society as a whole. Chronic pain and substance use disorders are often co-morbid with other medical problems and at the present time, primary care clinicians serve most of this population. Primary care clinicians would benefit from having alternatives to opioids to employ in treating such patients. We electronically searched different medical databases for studies evaluating the effect of nonpharmacological treatments for chronic pain. We describe alternative approaches for the treatment of chronic pain and cite studies that provide substantial evidence in favor of the use of these treatments. Cognitive behavioral therapy, acceptance and commitment therapy, and mindfulness-based programs have well-documented effectiveness for the treatment of chronic nonmalignant pain. Integration of such behavioral health therapies into primary care settings may optimize health resources and improve treatment outcomes. Evidence-based psychotherapy for chronic pain has established efficacy and safety and improves quality of life and physical and emotional functioning. Such interventions may be used as an alternative or adjunct to pharmacological management. Chronic opioid use should be reserved for individuals undergoing active cancer treatment, palliative care, or end-of-life care.

Pharmacological treatment of chronic non-malignant pain among elderly persons: an integrative review

Abstract Objective: The objective of the present study was to perform an integrative review of proposed pharmacological treatments for chronic non-malignant pain in elderly patients. Method: An integrative review was carried out. The search of literature included papers about the treatment of chronic pain among the elderly, published from 2007 to 2017 and available in Portuguese or English. Searches were conducted on the LILACS and MEDLINE electronic databases using the key words “chronic pain”, “treatment” and “elderly” combined with the Boolean operator “AND”. To analyse methodological quality, the adapted Critical Appraisal Skill Program (CASP) was used. Results: Of a total of 303 studies found, 32 were included. The articles selected included 20 reviews, five observational studies, five clinical trials, one case series and one retrospective study. A total of 75% of the articles were published in the last five years, of which one was in Portuguese and 31 in English. Conclusion :The results demonstrate a variety of treatments for chronic pain among the elderly population, highlighting the role of opioids which, according to more recent evidence, can be carefully used in treatment. Several drugs, however, have not been specifically tested for the elderly population. A number of factors are relevant in pain management of elderly patients, including comorbidities, polypharmacy and patient functionality. An individualized approach should be applied to elderly patients to improve outcomes and reduce side effects.

Intranasal abuse of prescription hydrocodone/acetaminophen results in oronasal fistula: A case report

Opioids are becoming more common in the treatment of chronic nonmalignant pain. With increased availability of opioids for chronic pain we may expect an increased misuse of these as analgesics as well. The authors describe the case report of a young woman with chronic back pain and intranasal abuse of prescribed hydrocodone/acetaminophen who was diagnosed after presenting for hypernasal speech and foreign body in the nose. This case report highlights the need for vigilance on the part of the physician for any aberrant drug-related behaviors. Any unusual symptoms or signs such as hypernasal speech, chronic nasal infection, or unexplained foreign body sensation in the nose should be thoroughly investigated.

The need for an ethics framework for the use of opioids in the treatment of chronic nonmalignant pain.

The need for an ethics framework for the use of opioids in the treatment of chronic nonmalignant pain.

Inhibition of α9α10 nicotinic acetylcholine receptors prevents chemotherapy-induced neuropathic pain

Opioids are first-line drugs for moderate to severe acute pain and cancer pain. However, these medications are associated with severe side effects, and whether they are efficacious in treatment of chronic nonmalignant pain remains controversial. Medications that act through alternative molecular mechanisms are critically needed. Antagonists of α9α10 nicotinic acetylcholine receptors (nAChRs) have been proposed as an important nonopioid mechanism based on studies demonstrating prevention of neuropathology after trauma-induced nerve injury. However, the key α9α10 ligands characterized to date are at least two orders of magnitude less potent on human vs. rodent nAChRs, limiting their translational application. Furthermore, an alternative proposal that these ligands achieve their beneficial effects by acting as agonists of GABAB receptors has caused confusion over whether blockade of α9α10 nAChRs is the fundamental underlying mechanism. To address these issues definitively, we developed RgIA4, a peptide that exhibits high potency for both human and rodent α9α10 nAChRs, and was at least 1,000-fold more selective for α9α10 nAChRs vs. all other molecular targets tested, including opioid and GABAB receptors. A daily s.c. dose of RgIA4 prevented chemotherapy-induced neuropathic pain in rats. In wild-type mice, oxaliplatin treatment produced cold allodynia that could be prevented by RgIA4. Additionally, in α9 KO mice, chemotherapy-induced development of cold allodynia was attenuated and the milder, temporary cold allodynia was not relieved by RgIA4. These findings establish blockade of α9-containing nAChRs as the basis for the efficacy of RgIA4, and that α9-containing nAChRs are a critical target for prevention of chronic cancer chemotherapy-induced neuropathic pain.

Les modalités de prescription d’analgésiques opiacés par les médecins de l’Hôtel-Dieu de France de Beyrouth

ObjectivesUse of chronic opioid therapy has increased substantially over the past few years, even though opioid therapy is associated with potentially serious harms, including opioid-related adverse effects and outcomes. Prescription of opioids for chronic pain, particularly nonmalignant chronic pain, remains controversial. In the midst of this controversy, patterns of actual prescription and influences on these patterns are not well understood. This study aims to describe the frequency of prescription of opioid analgesics in a university hospital, the attitudes of doctors towards this category of drugs, and the follow-up modalities of patients taking these drugs. The study also explores the association between the practitioners’ characteristics and the modalities of prescription. Design and methodsA survey was delivered to 112 doctors and surgeons in the hospital during the four months between August and December 2013 and it was returned by 55 (49.0%). The survey consists of three parts. The first part addresses the frequency and reluctance of doctors’ prescription of opioids and other analgesics for acute and chronic pain. The second part studies the doctors’ attitudes and concerns towards opioids. It explores the belief of the doctors in the efficacy of this category of drugs, their confidence in prescribing such medications and the eventual side effects they might worry about. The third part of the survey studies the modalities of evaluation prior to the prescription and the modalities of follow-up of the patients receiving a long-term opioid treatment. ResultsOverall, 76.4% of doctors reported they sometimes, frequently, or always, prescribe opioids, which, using the Wilcoxon test, proved to be a significantly lower frequency than for prescribing of minor analgesics or nonsteroidal anti-inflammatory drugs (NSAIDS). Similarly, 60.1% reported a reluctance to prescribe opioids for chronic nonmalignant pain, which was a significantly greater reluctance than for cancer pain. The age and sex of the participants were unrelated to prescribing, but those with specialty training and use of practice guidelines were more likely to prescribe opioids and were less reluctant to do so. A majority of practitioners felt that opioids are effective for the treatment of chronic nonmalignant pain and that they have the sufficient training to prescribe them adequately; however, they still worry about the long-term prescription of opioids, particularly fearing the psychological dependence this treatment might cause. Using a series of Spearman correlation tests, we found that practitioners who thought they were adequately trained and who believed in the efficacy of long-term opioid treatment were more likely to prescribe them but that the worries about side effects decreased the frequency of prescription. A significant proportion of practitioners do not evaluate addiction risk factors of patients before prescribing opioids. The results concerning the modalities of follow-up of prescription were very heterogeneous with 87% of practitioners not explaining and 65% not screening for adverse effects. We similarly found that the frequency of follow-up and the management of patients who were exhibiting signs of dependence were very diverse. ConclusionThe results of this study were compatible with those of other recent studies about opioid prescription. The doctors practicing in the university hospital Hôtel-Dieu de France de Beyrouth present comparable prescription patterns, independent of their personal or professional characteristics, and they are more confident in their prescription when professionally trained for it. However, they exhibit a notable heterogeneity in their attitudes towards opioids and in their modalities of evaluating patients receiving long-term treatment. These results suggest a need for additional training in the management of this category of drugs.

The relationship of salivary testosterone and male sexual dysfunction in opioid-associated androgen deficiency (OPIAD)

Background: Opioids are an effective treatment for chronic non-malignant pain (CNP). Long-term use risks and side effects such as opioid-induced androgen deficiency (OPIAD) exist. This could be measured by saliva testosterone (Sal-T).Objectives: To evaluate OPIAD in long-term opioid use in CNP patients.Methods: A cross-sectional study included CNP male outpatients under opioid treatment. Total-Testosterone (Total-T), Free-Testosterone (Free-T), Bio-Testosterone (Bio-T) and Sal-T were measured. Correlations were calculated by Spearman’s rho (SPSS 20).Results: From 2012 to 2014, 134 from 249 (54%) consecutive male outpatients reported erectile dysfunction (ED), 37% of them related to opioids and 19% evidenced OPIAD. A total of 120 subjects (94 cases and 26 matched-controls) were included. A significantly lower luteinizing hormone, Total-T and Free-T were found, as well as, a significant correlation between Sal-T and Total-T (r = 0.234, p = 0.039), Bio-T (r = 0.241, p = 0.039), IIEF (r = 0.363, p = 0.003) and HAD-anxiety (r = −0.414, p = 0.012) in OPIAD patients. Sal-T levels were significantly lower in patients with severe–moderate ED versus mild ED (p = 0.045) and in patients with severe ED versus moderate–mild ED (p = 0.036).Conclusions: These data demonstrate the high prevalence of ED in long-term use of opioids, part of this is associated to OPIAD, which can be tested by Sal-T as a non-invasive approach.

2.14 - Adherence To Pharmacological Treatment Of Chronic Non-Malignant Pain In Individuals Aged 65 and Older

2.14 - Adherence To Pharmacological Treatment Of Chronic Non-Malignant Pain In Individuals Aged 65 and Older

Predictive Value of Positive Drug Screening Results in an Urban Outpatient Population.

Urine drug testing (UDT) has become an essential component in the management of patients prescribed opioid analgesics for the treatment of chronic non-malignant pain. Several laboratory methods are available to monitor adherence with the pharmacological regimen and abstinence from illicit or unauthorized medications. Immunochemical screening methods are rapid and economical, but they have limitations, including lack of specificity, and confirmatory methods are often necessary to verify presumptive positive results. We analyzed the results of confirmatory assays in an outpatient setting to determine the predictive value of presumptive positive urine drug screen results using an automated immunoassay for eight common drugs or drug classes. Positive predictive values (PPVs), in descending order, were as follows: cannabinoids (100%), cocaine (100%), opiates (86.8%), benzodiazepines (74.6%), oxycodone (67.6%), methadone (44.1%) and amphetamines (9.3%). The number of positive barbiturate results was too small to be included in the statistical analysis.

The Clinical Applications of Extended-Release Abuse-Deterrent Opioids.

Opioids are the mainstay for treatment of acute pain and cancer pain, and also have a role in the treatment of chronic non-malignant pain. There has been, however, a growing public health problem stemming from the misuse of opioid analgesics leading to serious consequences. To deter abuse, new formulations of extended-release opioid analgesics and tamper-resistant opioids have recently been developed. The concept of abuse-deterrent extended-release opioids is relatively new and, although abuse may not be completely prevented, the utilization of such abuse-deterrent extended-release opioids could reduce this risk. Extended-release abuse-deterrent opioids have been found to have important clinical applications in cancer, acute pain, and chronic non-malignant pain for analgesia control with decreased incidence of tampering and abuse. In this review, different extended-release formulations of opioids available for clinical applications are presented with descriptions of the formulations, their physical properties, and the clinical studies performed to provide physicians with a better understanding of their uses.

Opioid prescriptions for pain and epidemic of overdose death: can the dramatic reduction in anesthesia mortality serve as an example?

The annual number of US deaths from prescription-opioid overdose quadrupled between 1999 and 2010 and in 2010 alone reached 16,651. Deaths from opioid overdose have now surpassed the historic death toll from another drug-related epidemic – anesthesia mortality. In 1954, Beecher and Todd published reliable data on anesthesia-related mortality in the US, estimating the annual number of deaths to be nearly 5,000. Presently anesthesia/anesthetics are reported as the underlying cause in approximately 34 deaths in the US annually. This spectacular decline in anesthesia-related mortality could serve as an example for attempts to curb the epidemic of opioid overdose death. The main reason that led to the dramatic decline in anesthesia-related mortality is the context in which anesthetics are used. It includes training of the anesthesia providers, the introduction of specific standards of patient safety, and anesthesia monitoring. I suggest that the introduction of a similar multifactorial proper context for the use of opioids in the treatment of chronic nonmalignant pain might be the same “game changer” it was for safety in anesthesia.