Christine Miaskowski

Pharmacologic management of neuropathic pain: evidence-based recommendations.

Abstract Patients with neuropathic pain (NP) are challenging to manage and evidence‐based clinical recommendations for pharmacologic management are needed. Systematic literature reviews, randomized clinical trials, and existing guidelines were evaluated at a consensus meeting. Medications were considered for recommendation if their efficacy was supported by at least one methodologically‐sound, randomized clinical trial (RCT) demonstrating superiority to placebo or a relevant comparison treatment. Recommendations were based on the amount and consistency of evidence, degree of efficacy, safety, and clinical experience of the authors. Available RCTs typically evaluated chronic NP of moderate to severe intensity. Recommended first‐line treatments include certain antidepressants (i.e., tricyclic antidepressants and dual reuptake inhibitors of both serotonin and norepinephrine), calcium channel α2‐δ ligands (i.e., gabapentin and pregabalin), and topical lidocaine. Opioid analgesics and tramadol are recommended as generally second‐line treatments that can be considered for first‐line use in select clinical circumstances. Other medications that would generally be used as third‐line treatments but that could also be used as second‐line treatments in some circumstances include certain antiepileptic and antidepressant medications, mexiletine, N‐methyl‐d‐aspartate receptor antagonists, and topical capsaicin. Medication selection should be individualized, considering side effects, potential beneficial or deleterious effects on comorbidities, and whether prompt onset of pain relief is necessary. To date, no medications have demonstrated efficacy in lumbosacral radiculopathy, which is probably the most common type of NP. Long‐term studies, head‐to‐head comparisons between medications, studies involving combinations of medications, and RCTs examining treatment of central NP are lacking and should be a priority for future research.

Recommendations for the Pharmacological Management of Neuropathic Pain: An Overview and Literature Update

The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain recently sponsored the development of evidence-based guidelines for the pharmacological treatment of neuropathic pain. Tricyclic antidepressants, dual reuptake inhibitors of serotonin and norepinephrine, calcium channel alpha(2)-delta ligands (ie, gabapentin and pregabalin), and topical lidocaine were recommended as first-line treatment options on the basis of the results of randomized clinical trials. Opioid analgesics and tramadol were recommended as second-line treatments that can be considered for first-line use in certain clinical circumstances. Results of several recent clinical trials have become available since the development of these guidelines. These studies have examined botulinum toxin, high-concentration capsaicin patch, lacosamide, selective serotonin reuptake inhibitors, and combination therapies in various neuropathic pain conditions. The increasing number of negative clinical trials of pharmacological treatments for neuropathic pain and ambiguities in the interpretation of these negative trials must also be considered in developing treatment guidelines. The objectives of the current article are to review the Neuropathic Pain Special Interest Group guidelines for the pharmacological management of neuropathic pain and to provide a brief overview of these recent studies.

Review of the literature on the effects of caring for a patient with cancer

Objective: To adequately help family caregivers (FCs) of cancer patients, clinicians need to understand the complexity of the problems and responsibilities associated with cancer patients illness that FCs experience.

The prevalence, severity, and impact of opioid-induced bowel dysfunction: results of a US and European Patient Survey (PROBE 1).

OBJECTIVE This multinational, Internet-based survey was designed to assess the prevalence, frequency, severity, and impact of opioid-induced bowel dysfunction (OBD) in patients receiving opioid therapy for chronic pain and taking laxatives. DESIGN In total, 322 patients taking daily oral opioids and laxatives completed the 45-item questionnaire. At the time of the survey, 45% of patients reported <3 bowel movements per week. The most prevalent opioid-induced side effects were constipation (81%) and straining to pass a bowel movement (58%). Those side effects considered most bothersome by patients were (in order of rank) constipation, straining, fatigue, small or hard bowel movements, and insomnia. RESULTS Most of the OBD symptoms specified in the questionnaire were experienced by the majority of patients >or=4 times a week. Constipation was the OBD symptom that was most often reported as severe. Most patients reported that their OBD symptoms had at least a moderate negative impact on their overall quality of life and activities of daily living. A third of patients had missed, decreased or stopped using opioids in order to make it easier to have a bowel movement. CONCLUSION The survey findings confirm that OBD occurs frequently, despite the use of laxatives, in individuals taking daily oral opioids for chronic pain. These gastrointestinal symptoms add to the burden already experienced by chronic pain patients, negatively impacting quality of life and, in some cases, affecting opioid treatment itself.

Pain, Fatigue, and Sleep Disturbances in Oncology Outpatients Receiving Radiation Therapy for Bone Metastasis: A Pilot Study

Pain and fatigue are two of the most common problems experienced by oncology patients. This study evaluated 24 oncology patients who were receiving radiation therapy for bone metastases to (1) describe the patterns of pain intensity and fatigue severity over a 48-hour period; (2) evaluate for sleep disturbances; (3) describe the relationships between these symptoms and various treatment characteristics; and (4) describe the self-care strategies used by patients to manage pain and fatigue. Patients reported moderate amounts of pain and fatigue. Average pain scores did not vary significantly over a 48-hour period. However, patients reported significantly lower fatigue scores in the morning compared to the evening. In addition, patients experienced significant sleep disturbances, with a mean sleep efficiency index of 70.7% (estimated using wrist actigraphy). Patients with lower Karnofsky Performance Status scores reported more sleep disturbances. In addition, patients who had received a higher percentage of their radiation treatment reported more sleep disturbances. Patients used a variety of self-care strategies to manage pain and fatigue. Additional research is warranted to describe more completely the patterns of pain, fatigue, and sleep disturbances in oncology outpatients receiving radiation therapy.

Opioids for Chronic Noncancer Pain: Prediction and Identification of Aberrant Drug-Related Behaviors: A Review of the Evidence for an American Pain Society and American Academy of Pain Medicine Clinical Practice Guideline

UNLABELLED Optimal methods to predict risk of aberrant drug-related behaviors before initiation of opioids for chronic noncancer pain and to identify aberrant behaviors after therapy is initiated are uncertain. We systematically reviewed published literature identified through searches of Ovid MEDLINE and the Cochrane databases through July 2008. Diagnostic test characteristics and accompanying confidence intervals were calculated with data extracted from the studies. Four prospective studies evaluated diagnostic accuracy of risk prediction instruments. Two higher-quality derivation studies found that high scores on the Screener and Opioid Assessment for Patients with Pain (SOAPP) Version 1 and the Revised SOAPP (SOAPP-R) instruments weakly increased the likelihood for future aberrant drug-related behaviors (positive likelihood ratios [PLR], 2.90 [95% CI, 1.91 to 4.39] and 2.50 [95% CI, 1.93 to 3.24], respectively). Low scores on the SOAPP Version 1 moderately decreased the likelihood for aberrant drug-related behaviors (negative likelihood ratio [NLR], 0.13 [95% CI, 0.05 to 0.34]) and low scores on the SOAPP-R weakly decreased the likelihood (NLR, 0.29 [95% CI, 0.18 to 0.46]), but estimates are too imprecise to determine if there is a difference between these instruments. One lower-quality study found that categorization as high risk using the Opioid Risk Tool strongly increased the likelihood for future aberrant drug-related behaviors (PLR, 14.3 [95% CI, 5.35 to 38.4]) and classification as low risk strongly decreased the likelihood (PLR, 0.08 [95% CI, 0.01 to 0.62]). Nine studies evaluated monitoring instruments for identification of aberrant drug-related behaviors in patients on opioid therapy. One higher-quality derivation study found higher scores on the Current Opioid Misuse Measure (COMM) weakly increased the likelihood of current aberrant drug-related behaviors (PLR, 2.77 [95% CI, 2.06 to 3.72]) and lower scores weakly decreased the likelihood (NLR, 0.35 [95% CI, 0.24 to 0.52]). In 8 studies of other monitoring instruments, diagnostic accuracy was poor, results were difficult to interpret due to methodological shortcomings, or standard diagnostic test characteristics were not reported. Definitions for aberrant drug-related behaviors were not standardized across studies and did not account for seriousness of identified behaviors. No reliable evidence exists on accuracy of urine drug screening, pill counts, or prescription drug monitoring programs; or clinical outcomes associated with different assessment or monitoring strategies. PERSPECTIVE Evidence on prediction and identification of aberrant drug-related behaviors is limited. Although several screening instruments may be useful, evidence is sparse and primarily based on derivation studies, and methodological shortcomings exist in all studies. Research that performs external validation, uses standardized definitions for clinically relevant aberrant drug-related behaviors, and evaluates clinical outcomes associated with different assessment and monitoring strategies is needed.

Research Gaps on Use of Opioids for Chronic Noncancer Pain: Findings From a Review of the Evidence for an American Pain Society and American Academy of Pain Medicine Clinical Practice Guideline

UNLABELLED Chronic noncancer pain is common and use of opioids is increasing. Previously published guidelines on use of opioids for chronic noncancer pain have been based primarily on expert consensus due to lack of strong evidence. We conducted searches on Ovid MEDLINE and the Cochrane databases through July 2008 to identify studies that addressed one or more of 37 Key Questions that a multidisciplinary expert panel identified as important to be answered to generate evidence-based recommendations on the use of opioids for chronic noncancer pain. A total of 14 systematic reviews, 38 randomized trials not included in a previously published systematic review, and 13 other studies met inclusion criteria. Almost all of the randomized trials of opioids for chronic noncancer pain were short-term efficacy studies. Critical research gaps on use of opioids for chronic noncancer pain include: lack of effectiveness studies on long-term benefits and harms of opioids (including drug abuse, addiction, and diversion); insufficient evidence to draw strong conclusions about optimal approaches to risk stratification, monitoring, or initiation and titration of opioid therapy; and lack of evidence on the utility of informed consent and opioid management plans, the utility of opioid rotation, the benefits and harms specific to methadone or higher doses of opioids, and treatment of patients with chronic noncancer pain at higher risk for drug abuse or misuse. PERSPECTIVE Currently, clinical decisions regarding the use of opioids for chronic noncancer pain need to be made based on weak evidence. Research funding priorities need to be set to address these critical research needs if the care of patients with chronic noncancer pain is to improve.

The kappa opioid nalbuphine produces gender- and dose-dependent analgesia and antianalgesia in patients with postoperative pain

Nalbuphine, pentazocine, and butorphanol, mixed agonist/antagonist opioids that induce analgesia by acting predominantly at kappa opioid receptors, have recently been shown in single-dose studies to have greater analgesic efficacy in women than in men. In the current experiments, the first placebo controlled dose response study of opioid analgesic efficacy that examines for gender differences, nalbuphine (5, 10, or 20 mg) and placebo were evaluated in 62 men and 69 women for the treatment of moderate to severe postoperative pain following extraction of impacted wisdom teeth. In a randomized, open injection, double blind experimental design, pain intensity was recorded on a 10 cm visual analog scale (VAS) immediately prior to drug administration (baseline) and at 20 min intervals thereafter. Although responses to placebo were similar in men and women, for all doses of nalbuphine women exhibited significantly greater analgesic response than men, compatible with our previous results. Unexpectedly, men receiving the 5 mg dose of nalbuphine experienced significantly greater pain than those receiving placebo; only the 20 mg dose of nalbuphine in men produced significant analgesia compared to placebo. While a similar antianalgesic effect was not observed in women, only the 10 mg dose of nalbuphine produced significant analgesia compared to placebo. These results suggest that the optimal analgesic dose of nalbuphine for women is lower than the highest dose that can be safely administered. In contrast, the antianalgesic effect of nalbuphine suggests avoidance of its routine use for postoperative analgesia in men until further studies clarify this issue. Because gender differences in other mixed kappa agonists/antagonists (i.e. pentazocine and butorphanol) have previously been shown, these results may generally apply to this class of opioid analgesics.

Assessment of patient satisfaction utilizing the American Pain Society's quality assurance standards on acute and cancer-related pain

An evaluation of patient satisfaction with pain management is one component of a total quality assurance program on pain management recommended by the American Pain Society. This study utilized the patient satisfaction survey recommended by the Quality Assurance Committee of the American Pain Society and was conducted in an acute care, municipal hospital. Seventy-two medical-surgical patients were interviewed about their pain management. Data from the survey suggest that while patients experienced moderate-to-severe pain and had to wait relatively long periods of time for pain medications, in most cases they were satisfied with their overall pain management. Recommendations for conducting patient satisfaction surveys of pain management in acute care settings are reviewed, and methods for interpreting data from these types of surveys are discussed.

Prevalence and characteristics of chronic pain in the general Norwegian population

Background. Population‐based studies suggest that prevalence of chronic pain is increasing. The purpose of this study was to determine the prevalence of chronic pain in a sample drawn from the general Norwegian population. In addition, the characteristics of chronic pain, as well as differences in demographic characteristics and health‐related variables between persons with and without chronic pain were evaluated.