Suicidal thoughts and behaviors in patients with chronic pain, with and without co-occurring opioid use disorder.

BACKGROUND: Individuals with chronic pain and a co-occurring substance use disorder present higher risk of suicide, but the individual and joint impacts of chronic pain and substance use disorders on suicide risk are not well defined. The objective of this study was to exam the factors associated with suicidal thoughts and behaviors in a cohort of patients with chronic non-cancer pain (CNCP), with or without concomitant opioid use disorder (OUD). DESIGN: Cross sectional cohort design. SETTING: Primary care clinics, pain clinics, and substance abuse treatment facilities in Pennsylvania, Washington, and Utah. SUBJECTS: In total, 609 adults with CNCP treated with long-term opioid therapy (>/= 6 months) who either developed an OUD (cases, n = 175) or displayed no evidence of OUD (controls, n = 434). METHODS: The predicted outcome was elevated suicidal behavior in patients with CNCP as indicated by a Suicide Behavior Questionnaire-Revised (SBQ-R) score of 8 or above. The presence of CNCP and OUD were key predictors. Covariates included demographics, pain severity, psychiatric history, pain coping, social support, depression, pain catastrophizing and mental defeat. RESULTS: Participants with CNCP and co-occurring OUD had an increased odds ratio of 3.44 in reporting elevated suicide scores as compared to participants with chronic pain only. Multivariable modeling revealed that mental defeat, pain catastrophizing, depression, and having chronic pain, and co-occurring OUD significantly increased the odds of elevated suicide scores. CONCLUSIONS: Patients with CNCP and co-morbid OUD are associated with a 3-fold increase in risk of suicide.

Low Risk of Producing an Opioid Use Disorder in Primary Care by Prescribing Opioids to Prescreened Patients with Chronic Noncancer Pain.

Objective: To examine the risk of developing aberrant behaviors that might lead to a substance use disorder (addiction) when prescribing opioids for the relief of chronic noncancer pain in primary care settings. Design: Longitudinal, prospective, descriptive design with repeated measures. Setting: Private community-based internal medicine and family medicine clinics. Subjects: Patients with chronic musculoskeletal pain. Methods: Standardized measures of patient status (pain, functional impairment, psychiatric disorders, family history) and treatments provided, urine drug monitoring, and medical chart audits (presence of aberrant drug-related behaviors) were obtained in a cohort of 180 patients at the time of initiating opioids for chronic noncancer pain and at three, six, and 12 months thereafter. Results: Over the 12-month follow-up period, subjects demonstrated stable, mild to moderate levels of depression (PHQ-9 scores ranging from 9.43 to 10.92), mild anxiety (BAI scores ranging from 11.80 to 14.67), minimal aberrant drug-related behaviors as assessed by chart reviews, and a low percentage of illicit drug use as revealed by results of urine drug monitoring. Less than 5% of our study population revealed any evidence of substance use disorder. Conclusions: This prospective study suggests that patients without a recent or prior history of substance use disorder who were prescribed primarily short-acting opioids in low doses for chronic noncancer pain have a low risk for developing a substance use disorder. This finding supports the importance of prescreening patients being considered for opioid therapy and that prescription of opioids for noncancer pain may carry a lower risk of abuse in selected populations such as in private, community-based practices.

Scope and Nature of Pain- and Analgesia-Related Content of the United States Medical Licensing Examination (USMLE).

Background: "The ongoing opioid crisis lies at the intersection of two substantial public health challenges-reducing the burden of suffering from pain and containing the rising toll of the harms that can result from the use of opioid medications" [1]. Improved pain education for health care providers is an essential component of the multidimensional response to both still-unmet challenges [2,3]. Despite the importance of licensing examinations in assuring competency in health care providers, there has been no prior appraisal of pain and related content within the United States Medical Licensing Examination (USMLE). Methods: An expert panel developed a novel methodology for characterizing USMLE questions based on pain core competencies and topical and public health relevance. Results: Under secure conditions, raters used this methodology to score 1,506 questions, with 28.7% (432) identified as including the word "pain." Of these, 232 questions (15.4% of the 1,506 USMLE questions reviewed) were assessed as being fully or partially related to pain, rather than just mentioning pain but not testing knowledge of its mechanisms and their implications for treatment. The large majority of questions related to pain (88%) focused on assessment rather than safe and effective pain management, or the context of pain. Conclusions: This emphasis on assessment misses other important aspects of safe and effective pain management, including those specific to opioid safety. Our findings inform ways to improve the long-term education of our medical and other graduates, thereby improving the health care of the populations they serve.

Prescription Opioid Misuse, Abuse, Morbidity, and Mortality: Balancing Effective Pain Management and Safety.

OBJECTIVE: The burgeoning rate of prescription opioid misuse, abuse, addiction, and opioid related overdose deaths has gained substantial professional and national media attention. This manuscript provides a narrative review and critique of the literature on prescription opioid misuse, abuse, addiction and opioid-related mortality and discusses future research needs in this area. DESIGN: Current literature on misuse, abuse, addiction and opioid related fatalities was reviewed in patients with chronic noncancer pain receiving long-term prescription opioid therapy. RESULTS: There have been inconclusive results on the efficacy of long-term opioid therapy in patients with chronic pain but moderate level evidence of dose-dependent risk of harm. The estimated prevalence of prescription opioid abuse and opioid use disorders ranges from <1% to 40% due to the paucity of uniform definitions of what constitutes misuse, abuse, and addiction but several recent studies have developed unique methodology to more accurately assess these states in the pain population. The rate of opioid-related overdose deaths is not inconsequential and a number of patient related and medication specific risk factors have been identified that may provide a basis for risk mitigation strategies. CONCLUSIONS: Accurately assessing the prevalence of misuse, abuse, and addiction in the pain population has been challenging due to inconsistent definitions between studies. Additional high-quality research is needed in this area utilizing consistent definitions and in reducing the risk of opioid-related overdose fatalities.

Opioid Therapy and Sleep Disorders: Risks and Mitigation Strategies.

OBJECTIVE: Patients with chronic pain frequently experience concomitant sleep disorders. There has been controversy on whether opioids have a beneficial or deleterious effect on sleep quality, duration and efficiency. There is also concern regarding the association between chronic opioid therapy (COT) and sleep disordered breathing (SDB) and the increased risk for unintentional opioid related overdose. This article provides a narrative review of the literature on the effect of opioids on sleep disorders and discusses risk assessment and mitigation strategies. DESIGN: A narrative review of the current literature on the effect of prescription opioids on sleep quality and efficiency, the relationship between opioids and sleep disorders and potential risk factors in patients with chronic pain. RESULTS: There is conflicting evidence regarding the benefit of opioids in improving sleep quality, duration and efficiency with several studies and reviews suggesting a beneficial effect of opioids on sleep and other studies demonstrating the opioids can cause sleep disturbance leading to hyperalgesia. There was credible evidence of a strong relationship between opioids and SDB with noted risk factors including use of methadone, high opioid dosing (>200 mg MED) and combining opioids with benzodiazepines. CONCLUSIONS: Further research is required to elucidate the effect of prescription opioids on sleep quality and pain intensity and the risks associated with opioids and SDB. The risk of SDB should be routinely assessed in patients on COT.

The complexity model: a novel approach to improve chronic pain care.

OBJECTIVE: More than 25% of the US population experiences chronic pain; yet few physicians specialize in the field of pain medicine. This article will review a theoretical model of care that stratifies treatment and patients by level and type of complexity and promotes communication between specialist and primary care providers. DISCUSSION: The undertreatment of pain was recently brought to national attention to encourage both clinicians and patients to advocate for improved pain care. The specialty of pain medicine and models of care, challenges of managing pain in a primary care setting, and the reliance on an opioid-focused approach are reviewed. An evolved model of pain care based on the complexity of pain and emphasizing a dynamic collaboration between the primary care provider and the pain specialist is discussed. CONCLUSIONS: From the perspective of the busy clinician, the treatment of chronic pain can be overwhelming. The scarcity of trained pain practitioners and the burgeoning number of patients with chronic pain necessitate a new approach that values the complex nature of chronic pain and offers a practical blueprint to meet these challenges.

Trajectories and predictors of high-occurrence pain flares in ambulatory cancer patients on opioids.

BACKGROUND: Pain flares have a substantive impact on the quality of life and well-being of patients with cancer. We identified longitudinal trajectories (clusters) of cancer pain flares in ambulatory patients and sociodemographic and clinical predictors of these trajectories. METHODS: In a prospective cohort study using ecological momentary assessment (mEMA), we collected patient-reported daily pain flare ratings data over 5 months and identified predictors and correlates using validated measures. RESULTS: The mean age of the sample (N = 270) was 60.9 years (SD = 11.2), 64.8% were female, and 32.6% self-identified as African American. Four pain flare clusters were identified. The "high-occurrence" cluster (23% of patients) experienced 5.5 (SD = 5.47) daily flares, whereas low-moderate clusters (77%) reported 2.4 (SD = 2.74) daily flares (P < .000). Those in the high-occurrence cluster reported higher pain scores (P = .000), increased pain-related interference (P = .000), depressive symptoms (P = .023), lower quality of life (P = .001), and reduced pain self-efficacy (P = .006). Notably, 67.2% of those prescribed opioids as needed (PRN only) were in the high-occurrence pain flare cluster, compared with 27.9% with PRN and around-the-clock opioid prescriptions (P = .024). Individual predictors of high-occurrence pain flares were income below $30 000, unemployment, being African American, lower education level, Medicaid insurance, current opioid misuse (COMM), baseline inpatient hospital stay duration, and PRN-only opioid regimen. In the multiple predictor model, lower education level, unemployment, COMM score, extended inpatient duration, and PRN-only opioid regimen remained significant. CONCLUSION: In ambulatory patients with cancer, high occurrence of pain flares may be mitigated by attention to opioid prescription factors and addressing social determinants of health needs of underserved patients.

A multi-ancestry genetic study of pain intensity in 598,339 veterans.

Chronic pain is a common problem, with more than one-fifth of adult Americans reporting pain daily or on most days. It adversely affects the quality of life and imposes substantial personal and economic costs. Efforts to treat chronic pain using opioids had a central role in precipitating the opioid crisis. Despite an estimated heritability of 25-50%, the genetic architecture of chronic pain is not well-characterized, in part because studies have largely been limited to samples of European ancestry. To help address this knowledge gap, we conducted a cross-ancestry meta-analysis of pain intensity in 598,339 participants in the Million Veteran Program, which identified 126 independent genetic loci, 69 of which are new. Pain intensity was genetically correlated with other pain phenotypes, level of substance use and substance use disorders, other psychiatric traits, education level and cognitive traits. Integration of the genome-wide association studies findings with functional genomics data shows enrichment for putatively causal genes (n = 142) and proteins (n = 14) expressed in brain tissues, specifically in GABAergic neurons. Drug repurposing analysis identified anticonvulsants, ß-blockers and calcium-channel blockers, among other drug groups, as having potential analgesic effects. Our results provide insights into key molecular contributors to the experience of pain and highlight attractive drug targets.

Mental Defeat and Suicidality in Chronic Pain: A Prospective Analysis.

Living with chronic pain has been identified as a significant risk factor for suicide. Qualitative and cross-sectional studies have reported an association between mental defeat and suicidal thoughts and behavior in patients with chronic pain. In this prospective cohort study, we hypothesized that higher levels of mental defeat would be associated with increased suicide risk at a 6-month follow-up. A total of 524 patients with chronic pain completed online questionnaires measuring variables related to suicide risk, mental defeat, sociodemographic, psychological, pain, activity, and health variables. At 6 months, 70.8% (n = 371) of respondents completed the questionnaires again. Weighted univariate and multivariable regression models were run to predict suicide risk at 6 months. The clinical suicide risk cutoff was met by 38.55% of the participants at baseline and 36.66% at 6 months. Multivariable modeling revealed that mental defeat, depression, perceived stress, head pain, and active smoking status significantly increased the odds of reporting higher suicide risk, while older age reduced the odds. Receiver operating characteristic (ROC) analysis showed that assessment of mental defeat, perceived stress, and depression is effective in discriminating between 'low' and 'high' suicide risk. Awareness of the prospective links from mental defeat, depression, perceived stress, head pain, and active smoking status to increased suicide risk in patients with chronic pain may offer a novel avenue for assessment and preventative intervention. PERSPECTIVE: Results from this prospective cohort study suggest that mental defeat is a significant predictor of increased suicide risk among patients with chronic pain, along with depression, perceived stress, head pain, and active smoking status. These findings offer a novel avenue for assessment and preventative intervention before risk escalates.

The genetic architecture of pain intensity in a sample of 598,339 U.S. veterans.

Chronic pain is a common problem, with more than one-fifth of adult Americans reporting pain daily or on most days. It adversely affects quality of life and imposes substantial personal and economic costs. Efforts to treat chronic pain using opioids played a central role in precipitating the opioid crisis. Despite an estimated heritability of 25-50%, the genetic architecture of chronic pain is not well characterized, in part because studies have largely been limited to samples of European ancestry. To help address this knowledge gap, we conducted a cross-ancestry meta-analysis of pain intensity in 598,339 participants in the Million Veteran Program, which identified 125 independent genetic loci, 82 of which are novel. Pain intensity was genetically correlated with other pain phenotypes, level of substance use and substance use disorders, other psychiatric traits, education level, and cognitive traits. Integration of the GWAS findings with functional genomics data shows enrichment for putatively causal genes (n = 142) and proteins (n = 14) expressed in brain tissues, specifically in GABAergic neurons. Drug repurposing analysis identified anticonvulsants, beta-blockers, and calcium-channel blockers, among other drug groups, as having potential analgesic effects. Our results provide insights into key molecular contributors to the experience of pain and highlight attractive drug targets.

Recommendations for urine drug monitoring as a component of opioid therapy in the treatment of chronic pain.

OBJECTIVE: Several prominent guidelines recommend that patients on long-term opioid therapy have periodic urine drug monitoring (UDM) for appropriate use; however, none address the specific questions of which patients to test, which substances to test for, how often to test, and how to act on the results. DESIGN: In the absence of adequate scientific evidence in the literature, a panel of experts in the field of pain and addiction medicine was convened to develop consensus UDM recommendations. The panel met three times between March 2010 and April 2011, and reviewed several drafts of the recommendations document between meetings. RESULTS: The group was able to achieve consensus on a set of UDM recommendations addressing test selection, test frequency, interpretation of results, and how to handle discrepancies based on specific results. CONCLUSION: While the participating panel members recognize that there currently is a limited evidence base to support the expert panel's recommendations, primary care providers and pain specialists are largely acting today based on anecdote, intuition, and individual experience. The recommendations are meant to begin to provide a framework for standardizing practices for UDM in the treatment of chronic pain, and to serve as a catalyst to advance research that quantifies the effects of UDM on opioid therapy management and patient outcomes.

Depression, chronic pain, and suicide by overdose: on the edge.

Comorbid conditions that pose risks for suicide, especially depression, are prevalent in people living with chronic pain. The true numbers of failed attempts and successful suicides are unknown and may never be determined. Yet, risk factors for suicidal ideation are so high in this population that it must be assumed that some proportion of those who die of drug overdoses might have intended to end their lives, not just temporarily relieve their pain. The purpose of this manuscript is to highlight to clinicians the important association between chronic pain and intentional self-harm. Contemporary understanding of the epidemiology of depression and suicide and the relationship to chronic pain will be reviewed. Recommendations for the use of validated and practical screening tools as part of a comprehensive clinical assessment and for approaches to suicide prevention and interventions as crucial components of chronic pain management are outlined.

Opioid therapy in patients with chronic noncancer pain: diagnostic and clinical challenges.

Chronic opioid therapy for patients with chronic noncancer pain has become controversial, given the rising prevalence of opioid abuse. The prevailing literature suggests that the rate of addiction in chronic noncancer pain patients exposed to opioid therapy is relatively low, especially in those patients without significant concomitant psychiatric disorders and personal and family history of addiction. However, the escalating rate of misuse of prescription opioids has resulted in many clinicians caring for these patients to be more judicious in prescribing opioids. Accurately diagnos ing addiction in chronic pain patients receiving opioids is complex. Managing the patient with pain and co-occurring opioid abuse is equally challenging. Diagnostic issues, current guidelines for the appropriate use of opioids in the chronic pain population and risk stratification models are examined. Pharmacologic and nonpharmacologic treatment strategies for the patient with pain and opioid addiction are reviewed.

Perceived social support in patients with chronic pain with and without opioid use disorder and role of medication for opioid use disorder.

BACKGROUND: A significant predictor of treatment outcomes for patients with chronic non-cancer pain (CNCP) and opioid use disorder (OUD) is the degree and quality of social support they receive. Specifically, in patients with CNCP and on long-term opioid therapy, the development of OUD tends to be associated with losses in social support, while engagement in treatment for OUD improves support networks. Delivery of the evidence-based OUD treatment medications, methadone and buprenorphine, occurs in clinical environments which patently differ with respect to social support resources. The aims of this study were to describe perceived social support in patients with CNCP without OUD (no-OUD), with OUD and on buprenorphine (OUD-BP), and with OUD and on methadone (OUD-methadone). METHODS: Using the Duke Social Support Index (DSSI), perceived social support in a sample of Caucasian patients with CNCP and on opioid therapy was compared between no-OUDs (n = 834), OUD-methadone (n = 83) and OUD-BP (n = 99) therapy. Average DSSI scores were compared across groups and a linear regression model computed to describe association between group and perceived social support. RESULTS: No difference was observed in DSSI scores between no-OUDs and OUD-methadone, however scores were lower among OUD-BP participants than those receiving methadone (x = -5.2; 95% CI: -7.5, -2.9) and (x = -6.5, 95% CI: -8.2, -4.9). CONCLUSIONS: Patients with CNCP and OUD on methadone therapy endorse levels of social support comparable to those without OUD, however those on buprenorphine therapy report significantly less support, bringing implications for OUD treatment outcomes.

Impact of Cannabis Use on Least Pain Scores Among African American and White Patients with Cancer Pain: A Moderation Analysis.

INTRODUCTION: Based on many published reports, African American patients with cancer experience higher pain severity scores and lower pain relief than White patients. This disparity results from undertreatment of pain and is compounded by low adherence to prescribed non-opioid and opioid analgesics among African American patients with cancer. While nearly one in four patients use cannabis to manage cancer-related symptoms, less is known about how cannabis use influences pain relief in this patient population. METHODS: This study is based on preliminary data from an ongoing study of longitudinal outcomes of opioid therapy among African American and White patients with cancer. Linear mixed-effects models were utilized to assess the interaction of race and cannabis use on pain relief using "least pain" item scores from the Brief Pain Inventory (BPI) averaged across three time points. Models were adjusted for sociodemographic and clinical variables. RESULTS: This analysis included 136 patients (49 African American, 87 White). Overall, 30.1% of the sample reported cannabis use for cancer pain. The mean "least pain" score on BPI was 3.3 (SD=2.42) on a scale of 0-10. African American patients had a mean "least pain" score 1.32±0.48 units higher (indicating lower pain relief) than White patients (p=0.006). Cannabis use did not have a significant main effect (p=0.28). However, cannabis use was a significant moderator of the relationship between race and "least pain" (p=0.03). In the absence of cannabis use, African Americans reported higher "least pain" scores compared to Whites (mean difference=1.631±0.5, p=0.001). However, this disparity was no longer observed in African American patients reporting cannabis use (mean "least pain" difference=0.587±0.59, p=0.32). CONCLUSION: These findings point to the possible role of cannabis in cancer pain management and its potential to reduce racial disparities. These findings are preliminary and further research into the role of cannabis in cancer pain outcomes is needed.

Nonpharmacologic Treatments for Opioid Reduction in Patients With Advanced Chronic Kidney Disease.

Opioid analgesics carry risk for serious health-related harms in patients with advanced chronic kidney disease (CKD) and end-stage kidney disease. In the general population with chronic noncancer pain, there is some evidence that opioid reduction or discontinuation is associated with improved pain outcomes; however, tapering opioids abruptly or without providing supportive interventions can lead to physical and psychological harms and relapse of opioid use. There is emerging evidence that nonpharmacologic treatments such as psychosocial interventions, acupuncture, and interdisciplinary pain management programs are effective approaches to support opioid dose reduction in patients experiencing persistent pain, but research in this area still is relatively new. This review describes the current evidence for nonpharmacologic interventions to support opioid reduction in non-CKD patients with pain and discusses the application of the available evidence to patients with advanced CKD who are prescribed opioids to manage pain.