Bill H. McCarberg

Long-acting opioids for chronic pain: pharmacotherapeutic opportunities to enhance compliance, quality of life, and analgesia.

Effective management of chronic pain has become an increasingly critical issue in health care. Opioid agonists are among the most effective analgesics available for reducing pain perception; however, their chronic use is controversial. This is primarily due to regulatory barriers, misunderstandings about pain management among primary caregivers, fear of adverse side effects, and misconceptions about the potential risks of addiction. Short-acting opioids provide effective analgesia for acute pain but should be avoided as primary analgesics for chronic pain management. Long-acting opioids have greater utility than short-acting opioids in treating chronic pain in patients with consistent pain levels. Results of studies show that improved quality of life is directly related to the use of long-acting opioids in patients with chronic pain of both cancer and noncancer etiology. Short-acting opioids may be used during the initial dose titration period of long-acting formulations and as rescue medication for episodes of breakthrough pain. Clinical experience reveals that selection of an effective pain regimen for the patient with chronic pain, combined with aggressive management of side effects, leads to improved overall functioning and quality of life.

Improving the Recognition and Diagnosis of Fibromyalgia

Fibromyalgia (FM) is a chronic widespread pain disorder often seen in primary care practices. Advances in the understanding of FM pathophysiology and clinical presentation have improved the recognition and diagnosis of FM in clinical practice. Fibromyalgia is a clinical diagnosis based on signs and symptoms and is appropriate for primary care practitioners to make. The hallmark symptoms used to identify FM are chronic widespread pain, fatigue, and sleep disturbances. Awareness of common mimics of FM and comorbid disorders will increase confidence in establishing a diagnosis of FM.

Consensus Guidelines: Treatment Planning and Options

Despite the number of patients affected by diabetic peripheral neuropathic pain (DPNP), little consensus exists about the pathophysiology, best diagnostic tools, and primary treatment choices. Theories about the causes of DPNP are inextricably linked with the causes of diabetic neuropathies, yet most patients with such neuropathies do not experience pain. The factors that differentiate patients with pain from those without remain unknown and are the subject of much research. When choosing treatment for patients with DPNP, physicians are confronted with a myriad of choices, none of which has been shown to be effective for all patients. This article reviews the evidence for these treatments and attempts to guide physicians in choosing those treatments based on evidence from well-designed clinical trials to support their use. Two agents, duloxetine and pregabalin, are formally approved by the Food and Drug Administration for the treatment of DPNP. In addition, several other agents, including the tricyclic class of antidepressants, have been effective in clinical trials. Ultimately, treatment choice must also include consideration of adverse effects, individual patient factors such as comorbidities, and often cost.

The impact of pain on quality of life and the unmet needs of pain management: results from pain sufferers and physicians participating in an Internet survey.

Pain is one of the most common medical complaints, but despite its prevalence, many individuals still suffer with unrelieved or undertreated pain. This marketing research survey was designed to determine the physical, psychological, and economic impact pain has on the lives of individuals suffering with pain and to identify the unmet needs of patients who have taken opioid medications to treat their pain. In addition, the survey sought to address the challenges physicians face when treating patients with pain.Pain sufferers were recruited through e-mail invitation to an Internet survey; 173,854 invitations were sent out, 22,018 people responded (12.7%), and 606 met the criteria for inclusion in the survey as pain sufferers. Of these, 359 people had moderate to moderately severe chronic pain and 247 people had moderate to moderately severe acute pain. Additionally, physicians currently treating pain were recruited through e-mail and postal mail invitations and 492 met eligibility criteria: 241 specialists (orthopedic or general surgeons, pain specialists or anesthesiologists), 125 primary care, and 126 emergency medicine physicians.Results of this survey supported what many physicians observe in their practice and hear from their patients, that pain has a negative impact on daily activities in the majority of pain sufferers. Many chronic pain sufferers reported that pain had deleterious effects on their mental health, employment status, sleep, and personal relationships.The impact of pain on patient quality of life and the unmet needs in pain management were recognized by the majority of physicians surveyed, with inadequate pain control, end-of-dose pain, and side effects associated with increased dosing reported as negative factors influencing their choice of pain medication.In conclusion, effective communication between physicians and patients is encouraged to not only improve overall pain management but also to establish shared treatment goals with functional outcomes.

The future of cannabinoids as analgesic agents: a pharmacologic, pharmacokinetic, and pharmacodynamic overview.

For thousands of years, physicians and their patients employed cannabis as a therapeutic agent. Despite this extensive historical usage, in the Western world, cannabis fell into disfavor among medical professionals because the technology available in the 1800s and early 1900s did not permit reliable, standardized preparations to be developed. However, since the discovery and cloning of cannabinoid receptors (CB1 and CB2) in the 1990s, scientific interest in the area has burgeoned, and the complexities of this fascinating receptor system, and its endogenous ligands, have been actively explored. Recent studies reveal that cannabinoids have a rich pharmacology and may interact with a number of other receptor systems-as well as with other cannabinoids-to produce potential synergies. Cannabinoids-endocannabinoids, phytocannabinoids, and synthetic cannabinoids-affect numerous bodily functions and have indicated efficacy of varying degrees in a number of serious medical conditions. Nevertheless, despite promising preclinical and early clinical data, particularly in the areas of inflammation and nociception, development challenges abound. Tetrahydrocannabinol (THC) and other CB1 receptor agonists can have an undesirable CNS impact, and, in many cases, dose optimization may not be realizable before onset of excessive side effects. In addition, complex botanically derived cannabinoid products must satisfy the demanding criteria of the U.S. Food and Drug Associations approval process. Recent agency guidance suggests that these obstacles are not insurmountable, although cannabis herbal material (“medical marijuana”) may present fatal uncertainties of quality control and dosage standardization. Therefore, formulation, composition, and delivery system issues will affect the extent to which a particular cannabinoid product may have a desirable risk-benefit profile and acceptable abuse liability potential. Cannabinoid receptor agonists and/or molecules that affect the modulation of endocannabinoid synthesis, metabolism, and transport may, in the future, offer extremely valuable tools for the treatment of a number of currently intractable disorders. Further research is warranted to explore the therapeutic potential of this area.

Long-term evaluation of opioid treatment in fibromyalgia

Objectives:In a 12-month observational study, we evaluated the effect of opioid use on the outcomes in 1700 adult patients with fibromyalgia. Methods:Data were evaluated using propensity score matching after patients were divided into cohorts based on their baseline medication use: (1) taking an opioid (concurrent use of tramadol was permitted); (2) taking tramadol (but no opioids); and (3) not taking opioids or tramadol. Changes in outcomes were assessed using the Brief Pain Inventory for severity and pain-related interference (BPI-S, BPI-I), Fibromyalgia Impact Questionnaire (FIQ), Patient Health Questionnaire for depression (PHQ-8), Insomnia Severity Index (ISI), Sheehan Disability Scale (SDS), 7-item Generalized Anxiety Disorder Scale (GAD-7), and economic factors. Time-to-opioid or tramadol discontinuation was analyzed using Kaplan-Meier survival analyses. Results:Compared with the opioid cohort, the nonopioid cohort demonstrated significantly greater reductions (P<0.05) in BPI-I, FIQ, PHQ-8, SDS, and ISI; the tramadol cohort compared with the opioid group showed greater reductions on FIQ and ISI. Reductions in BPI-S and GAD-7 did not differ significantly among cohorts. Compared with the opioid cohort, patients in the tramadol cohort had fewer outpatient visits to health care providers. Few significant differences were found between the tramadol and nonopioid cohorts across outcomes. Discussion:Although pain severity was reduced over time in all cohorts, opioid users showed less improvement in pain-related interference with daily living, functioning, depression, and insomnia. Overall, the findings show little support for the long-term use of opioid medications in patients with fibromyalgia given the poorer outcomes across multiple assessment domains associated with this cohort.

Pain Management in Primary Care: Strategies to Mitigate Opioid Misuse, Abuse, and Diversion

Abstract Pain is among the most common reasons patients seek medical attention, and the care of patients with pain is a significant problem in the United States. Acute pain (mild-to-moderate intensity) represents one of the most frequent complaints encountered by primary care physicians (PCPs) and accounts for nearly half of patient visits. However, the overall quality of pain management remains unacceptable for millions of US patients with acute or chronic pain, and underrecognition and undertreatment of pain are of particular concern in primary care. Primary care physicians face dual challenges from the emerging epidemics of undertreated pain and prescription opioid abuse. Negative impacts of untreated pain on patient activities of daily living and public health expenditures, combined with the success of opioid analgesics in treating pain provide a strong rationale for PCPs to learn best practices for pain management. These clinicians must address the challenge of maintaining therapeutic access for patients with a legitimate medical need for opioids, while simultaneously minimizing the risk of abuse and addiction. Safe and effective pain management requires clinical skill and knowledge of the principles of opioid treatment as well as the effective assessment of risks associated with opioid abuse, addiction, and diversion. Easily implementable patient selection and screening, with selective use of safeguards, can mitigate potential risks of opioids in the busy primary practice setting. Primary care physicians can become advocates for proper pain management and ensure that all patients with pain are treated appropriately.

Burden of illness and treatment patterns for patients with fibromyalgia.

OBJECTIVE   This study was designed to describe burden of illness and treatment patterns, and to examine the patient, physician, and care factors associated with the treatment choices of individuals receiving new prescriptions for fibromyalgia (FM). DESIGN   This is a baseline assessment of the Real-World Examination of Fibromyalgia: Longitudinal Evaluation of Costs and Treatments (REFLECTIONS), a prospective observational study. Baseline data (including a physician survey, a patient visit form, and computer-assisted telephone interviews) were collected from July 2008 through May 2010 in 58 care settings in the United States, including Puerto Rico. RESULTS   Patients (N = 1,700) were mostly female (94.6%) and white (82.9%). Mean age was 50.4 years and mean duration of illness was 5.6 years. Mean Fibromyalgia Impact Questionnaire total score was 54.4 (range 0-80), and Brief Pain Inventory average pain severity level was 5.5 (range 0-10). Patients reported high annual health care use and numerous work limitations related to FM. Patients were taking 182 unique types of medications prescribed for FM, including duloxetine (26.8%), nonsteroidal anti-inflammatory drugs (26.6%), pregabalin (24.5%), opioids (24.2%), tramadol (15.3%), benzodiazepines (15.2%), cyclobenzaprine (12.9%), milnacipran (8.9%), and others. Most patients took more than one medication concurrently (77.8%). Type of current medications used was most strongly associated with medication history and physician specialty. CONCLUSIONS   Burden of illness was high for patients with FM, and treatment patterns were highly variable. Importantly, the treatments with the most evidence to support their use were not always the most frequently chosen.

Safety and Efficacy of Duloxetine in the Treatment of Diabetic Peripheral Neuropathic Pain in Older Patients

OBJECTIVE We present a post-hoc analysis of the safety and efficacy of duloxetine, a selective serotonin/norepinephrine reuptake inhibitor, for treatment of diabetic peripheral neuropathic pain (DPNP) in older patients. METHODS Data from three double-blind, placebo-controlled trials in adult patients with DPNP were pooled and stratified by age (<65, >or=65 years). Patients were randomized to duloxetine (DLX) 60 mg once-daily, 60 mg twice-daily, or placebo for 12 weeks, followed by a 52-week extension phase (re-randomization to routine care or DLX 120 mg/day). Intent-to-treat analyses were used for safety and efficacy assessment. RESULTS In the acute phase, overall TEAE rates did not differ significantly by age. A greater percentage of older patients discontinued due to TEAEs (P<0.001), regardless of treatment group. Duloxetine improved weekly mean 24-hour average pain scores versus placebo in both age groups (P<0.01). In the extension phase, a significant therapy-by-age interaction (P<0.05) was observed in overall TEAE rate; with routine care, 86.6% of older patients had >or=1 TEAE versus 74.6% of younger patients. CONCLUSIONS Although TEAEs more frequently lead to discontinuation in older patients, duloxetine was well tolerated and efficacious for treatment of DPNP regardless of age. These data suggest duloxetine may be beneficial for treatment of DPNP in patients>or=65.

Clinical overview of fibromyalgia.

Fibromyalgia (FM) is a complex disorder that affects up to 5% of the general population worldwide, more frequently in women than in men. In addition to chronic widespread pain, patients with FM usually experience other characteristic symptoms, including fatigue, disturbed sleep, stiffness, reduced functioning, dyscognition, and depressed mood. Many patients also have comorbid conditions such as depression, irritable bowel syndrome, temporomandibular disorder, or migraine. Although the etiology of FM remains unclear, evidence suggests that biologic, genetic, and environmental factors are involved. The variability of symptoms and the frequency of comorbidities among patients with FM make this a difficult disorder to diagnose. Diagnosis may be further complicated by the stigmatization of this disorder among treatment providers, the health insurance industry, and the general population. Treating chronic pain disorders such as FM can be time consuming and costly, and other issues such as polypharmacy, treatment adherence, and access to treatment often need to be addressed. The aim of this article is to provide physicians with a general overview of FM, including a brief review of the pathophysiology that explains the biologic and genetic bases of this disorder. Also included is a synopsis of new diagnostic criteria and other useful diagnostic tools and a discussion of various treatment challenges and strategies.