A systematic review of the effectiveness of policies restricting access to pregabalin.

BACKGROUND: Formularies often employ restriction policies to reduce pharmacy costs. Pregabalin, an alpha-2-delta ligand, is approved for treatment of fibromyalgia (FM); neuropathic pain (NeP) due to postherpetic neuralgia (PHN), diabetic peripheral neuropathy (pDPN), spinal cord injury; and as adjunct therapy for partial onset seizures. Pregabalin is endorsed as first-line therapy for these indications by several US and EU medical professional societies. However, restriction policies such as prior authorization (PA) and step therapy (ST) often favor less costly generic pain medications over pregabalin. METHODS: A structured literature search (PubMed, past 11 years) was conducted to evaluate whether restriction policies against pregabalin support real-world economic and healthcare utilization benefits. RESULTS: Search criteria identified three claims analyses and a modeling study that evaluated patients with NeP and/or FM with and without PA restrictions; three other studies included patients with FM and NeP in plans with ST requirements, and one evaluated a mail order requirement program. All studies evaluated outcomes during follow-up periods of 6 months or longer. Overall, PA, ST, and mail order restriction policies effectively reduced pregabalin usage, but the effects were inconsistent with reducing pharmacy costs and were non-significant for total disease-related medical costs. Two studies (one PA; one ST) reported significantly higher disease-related costs in restricted plans. The modeling study failed to demonstrate cost savings with PA. Opioid usage was higher in PA-restricted plans (two studies). The US Centers for Disease Control and Prevention and several professional NeP guidelines recommend opioid use only in cases when other non-opioid pain therapies have proven ineffective. New US Government taskforce guidelines now seek to reduce opioid exposure. Additionally, in both ST studies, gabapentin utilization (a common ST edit) was significantly increased. Both studies had substantial proportions of FM and pDPN patients and the only pain condition gabapentin is approved to treat in the United States is PHN. CONCLUSION: PA and ST restriction policies significantly decrease utilization of pregabalin, but do not consistently demonstrate cost savings for US health plans. More research is needed to evaluate whether these policies may lead to increased opioid usage as found in some studies. TRIAL REGISTRATION: N/A.

Burden of illness associated with peripheral and central neuropathic pain among adults seeking treatment in the United States: a patient-centered evaluation.

OBJECTIVE: The aim of this study was to evaluate patient-reported burden associated with peripheral and central neuropathic pain (NeP) by pain severity and NeP condition. DESIGN: Six hundred twenty-four subjects with one of six NeP conditions were recruited during routine office visits. Subjects consented to retrospective chart review and completed a one-time questionnaire (including EuroQol-5 dimensions, 12-item Short-Form Health Survey, Brief Pain Inventory-Short Form, Medical Outcomes Study Sleep Scale, Hospital Anxiety and Depression Scale, and demographic and clinical characteristics). Pain severity scores were used to stratify subjects by mild, moderate, and severe pain. Summary statistics and frequency distributions were calculated. Differences by severity level were compared using Kruskal-Wallis (continuous variables) and chi-square or Fisher's exact test (categorical variables). Effect size was computed with Cohen's d (mild vs severe). RESULTS: Subjects' mean age was 55.5. The majority (80.8%) had moderate or severe pain. Patient-reported outcomes (health status, physical and mental health, pain interference with function, sleep, anxiety, and depression) were significantly worse among subjects with greater pain severity (all P < 0.0001). Severe pain subjects were negatively impacted by ≥30% in each outcome compared with mild pain subjects; standardized effect size was moderate for anxiety (0.59) and large (>0.95) for all others. The observed burden was most substantial among chronic low back pain-NeP, although the pattern of disease burden was similar across the six NeP conditions. CONCLUSIONS: Subjects across NeP conditions exhibited high pain levels, which were significantly associated with poor function, compromised health status and sleep, and increased anxiety and depression. Results indicate substantial patient burden across broad NeP, particularly among subjects with severe pain.

Medical and psychological risks and consequences of long-term opioid therapy in women.

BACKGROUND: Long-term opioid use has increased substantially over the past decade for U.S. women. Women are more likely than men to have a chronic pain condition, to be treated with opioids, and may receive higher doses. Prescribing trends persist despite limited evidence to support the long-term benefit of this pain treatment approach. PURPOSE: To review the medical and psychological risks and consequences of long-term opioid therapy in women. METHOD: Scientific literature containing relevant keywords and content were reviewed. RESULTS AND CONCLUSIONS: Long-term opioid use exposes women to unique risks, including endocrinopathy, reduced fertility, neonatal risks, as well as greater risk for polypharmacy, cardiac risks, poisoning and unintentional overdose, among other risks. Risks for women appear to vary by age and psychosocial factors may be bidirectionally related to opioid use. Gaps in understanding and priorities for future research are highlighted.

Use and costs of prescription medications and alternative treatments in patients with osteoarthritis and chronic low back pain in community-based settings.

OBJECTIVE: To evaluate the use and direct medical costs of pharmacologic and alternative treatments for patients with osteoarthritis (OA) and chronic low back pain (CLBP). METHODS: The LifeLink™ Health Plan Claims Database was used to identify patients ≥18 years old, diagnosed with OA (N = 112,951) or CLBP (N = 101,294). Of these patients, 64,085 with OA and 47,386 with CLBP received pain-related treatments during CY2008 and were selected for inclusion. For patients in both cohorts, pharmacologic and alternative treatments, and direct medical costs were examined during CY2008. RESULTS: Opioids were the most frequently prescribed medication (>70%) in both groups, followed by nonselective nonsteroidal anti-inflammatory drugs (>50%). Over 30% received antidepressants, >20% received benzodiazepines, and 15% in each group received sedative hypnotics. Use of alternative treatments was as follows: chiropractor, OA 11%, CLBP 34%; physical therapy, 20% in both groups; transcutaneous electrical nerve stimulations (TENS), OA 14%, CLBP 22%; acupuncture, hydrotherapy, massage therapy, and biofeedback, <3% in both groups. Mean (SD) total healthcare costs among these patients were, OA: $15,638 ($22,595); CLBP: $11,829 ($20,035). Pharmacologic therapies accounted for approximately 20% of these costs, whereas alternative treatments accounted for only 3% to 4% of the total costs. CONCLUSIONS: Patients with OA and CLBP used a variety of pain-related and adjunctive medications. Although, alternative treatments are widely recommended, we found limited use of several of these in clinical practice, potentially due to the source of our data (commercial claims). Further research is needed to ascertain the extent to which such therapies contribute to the total costs of OA and CLBP management.

Research approaches for evaluating opioid sparing in clinical trials of acute and chronic pain treatments: Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials recommendations.

ABSTRACT: Randomized clinical trials have demonstrated the efficacy of opioid analgesics for the treatment of acute and chronic pain conditions, and for some patients, these medications may be the only effective treatment available. Unfortunately, opioid analgesics are also associated with major risks (eg, opioid use disorder) and adverse outcomes (eg, respiratory depression and falls). The risks and adverse outcomes associated with opioid analgesics have prompted efforts to reduce their use in the treatment of both acute and chronic pain. This article presents Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus recommendations for the design of opioid-sparing clinical trials. The recommendations presented in this article are based on the following definition of an opioid-sparing intervention: any intervention that (1) prevents the initiation of treatment with opioid analgesics, (2) decreases the duration of such treatment, (3) reduces the total dosages of opioids that are prescribed for or used by patients, or (4) reduces opioid-related adverse outcomes (without increasing opioid dosages), all without causing an unacceptable increase in pain. These recommendations are based on the results of a background review, presentations and discussions at an IMMPACT consensus meeting, and iterative drafts of this article modified to accommodate input from the co-authors. We discuss opioid sparing definitions, study objectives, outcome measures, the assessment of opioid-related adverse events, incorporation of adequate pain control in trial design, interpretation of research findings, and future research priorities to inform opioid-sparing trial methods. The considerations and recommendations presented in this article are meant to help guide the design, conduct, analysis, and interpretation of future trials.

AAAPT Diagnostic Criteria for Acute Pain Following Breast Surgery.

Acute pain after breast surgery decreases the quality of life of cancer survivors. Previous studies using a variety of definitions and methods report prevalence rates between 10% and 80%, which suggests the need for a comprehensive framework that can be used to guide assessment of acute pain and pain-related outcomes after breast surgery. A multidisciplinary task force with clinical and research expertise performed a focused review and synthesis and applied the 5 dimensional framework of the AAAPT (Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks [ACTTION], American Academy of Pain Medicine [AAPM], American Pain Society [APS] Pain Taxonomy) to acute pain after breast surgery. Application of the AAAPT taxonomy yielded the following: 1) Core Criteria: Location, timing, severity, and impact of breast surgery pain were defined; 2) Common Features: Character and expected trajectories were established in relevant surgical subgroups, and common pain assessment tools for acute breast surgery pain identified; 3) Modulating Factors: Biological, psychological, and social factors that modulate interindividual variability were delineated; 4) Impact/Functional Consequences: Domains of impact were outlined and defined; 5) Neurobiologic Mechanisms: Putative mechanisms were specified ranging from nerve injury, inflammation, peripheral and central sensitization, to affective and social processing of pain. PERSPECTIVE: The AAAPT provides a framework to define and guide improved assessment of acute pain after breast surgery, which will enhance generalizability of results across studies and facilitate meta-analyses and studies of interindividual variation, and underlying mechanism. It will allow researchers and clinicians to better compare between treatments, across institutions, and with other types of acute pain.

Unique aspects of clinical trials of invasive therapies for chronic pain.

Nearly all who review the literature conclude that the role of invasive procedures to treat chronic pain is poorly characterized because of the lack of "definitive" studies. The overt nature of invasive treatments, along with the risks, technical skills, and costs involved create challenges to study them. However, these challenges do not completely preclude evaluating invasive procedure effectiveness and safety using well-designed methods. This article reviews the challenges of studying outcomes of invasive therapies to treat pain and discuss possible solutions. Although the following discussion can apply to most invasive therapies to treat chronic pain, it is beyond the scope of the article to individually cover every invasive therapy used. Therefore, most of the examples focus on injection therapies to treat spine pain, spinal cord stimulation, and intrathecal drug therapies.

Characteristics of patients with neuropathic pain syndromes screened by the painDETECT questionnaire and diagnosed by physician exam.

BACKGROUND: The aim of this study was to identify the clinical characteristics, treatment usage, and health outcomes of US adults diagnosed with neuropathic pain (NeP) by experienced physicians. METHODS: Adults with scores exceeding the threshold for probable NeP (painDETECT ≥19) and diagnosed with NeP by a qualified physician completed a questionnaire that included comorbid conditions, pain symptoms and experiences, medication use, health status (3-level EuroQol 5 Dimensions (EQ-5D-3L]: health utilities index and visual analog scale), pain severity and interference with functioning (Brief Pain Inventory), and work and activity impairment (Work Productivity and Activity Impairment questionnaire). Descriptive analyses were performed for each NeP subtype. RESULTS: Participants (n=295) were predominantly female (64.4%), middle-aged (53.9%), and white (51.5%). Chronic low back pain was the most frequently diagnosed major NeP syndrome (n=166), followed by diabetic peripheral neuropathy (n=58), post-trauma neuropathy (n=47), post-surgical neuropathy (n=28), and central NeP (n=23). An additional 45 participants were diagnosed, but did not meet the criteria for the aforementioned subtypes. Participants could be diagnosed with multiple subtypes. Across each NeP subtype, patients reported high rates of comorbid disease, including arthritis (range: 39.1%-64.3%) and high blood pressure (range: 26.1%-69.0%), as well as symptomology that included numbness (range: 68.1%-91.4%) and changes in muscular strength (range: 24.1%-65.2%). The majority of patients reported back pain (range: 77.8%-95.7%) and arthritis/joint pain (range: 68.1%-78.6%). The most commonly reported types of NeP pain medication were non-steroidal anti-inflammatory drugs (range: 43.1%-70.2%), weak opioids (range: 22.2%-39.3%), and strong opioids (range: 8.7%-28.6%). All six NeP groups generally reported similar levels of dysfunction on all self-report measures. The most notable finding was that the EuroQol-5D-3L health utilities index scores for each of the six groups were lower than the US norms by a clinically important amount. CONCLUSION: These exploratory findings indicate that patients with NeP across different etiologies are medically complex and experience impaired function across multiple domains.

Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations.

UNLABELLED: A consensus meeting was convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to provide recommendations for interpreting clinical importance of treatment outcomes in clinical trials of the efficacy and effectiveness of chronic pain treatments. A group of 40 participants from universities, governmental agencies, a patient self-help organization, and the pharmaceutical industry considered methodologic issues and research results relevant to determining the clinical importance of changes in the specific outcome measures previously recommended by IMMPACT for 4 core chronic pain outcome domains: (1) Pain intensity, assessed by a 0 to 10 numerical rating scale; (2) physical functioning, assessed by the Multidimensional Pain Inventory and Brief Pain Inventory interference scales; (3) emotional functioning, assessed by the Beck Depression Inventory and Profile of Mood States; and (4) participant ratings of overall improvement, assessed by the Patient Global Impression of Change scale. It is recommended that 2 or more different methods be used to evaluate the clinical importance of improvement or worsening for chronic pain clinical trial outcome measures. Provisional benchmarks for identifying clinically important changes in specific outcome measures that can be used for outcome studies of treatments for chronic pain are proposed. PERSPECTIVE: Systematically collecting and reporting the recommended information needed to evaluate the clinical importance of treatment outcomes of chronic pain clinical trials will allow additional validation of proposed benchmarks and provide more meaningful comparisons of chronic pain treatments.

Pregabalin in the treatment of refractory neuropathic pain: results of a 15-month open-label trial.

OBJECTIVE: Neuropathic pain associated with postherpetic neuralgia (PHN) and painful diabetic peripheral neuropathy (DPN) can be intractable and may not respond to commonly used treatments, such as tricyclic antidepressants (TCAs) and opioids. This long-term, open-label study was a preliminary evaluation of pregabalin for patients whose pain had been judged refractory to other treatments for neuropathic pain. DESIGN: Patients had previously participated in double-blind, placebo-controlled, randomized trials of pregabalin in DPN and PHN. They had moderate to severe neuropathic pain despite treatment with gabapentin, a TCA, and a third medication (e.g., other anticonvulsants, opioid, selective serotonin reuptake inhibitor, tramadol). Flexible-dosage pregabalin 150-600 mg/day was taken for 3-month periods followed by 3- to 28-day pregabalin "drug holidays," with an analysis up to 15 months (five treatment cycles). Pain intensity was measured using the visual analog scale of the Short-Form McGill Pain Questionnaire. RESULTS: In total, 81 patients were included in this analysis. Pregabalin 150-600 mg/day was associated with clinically meaningful and sustained pain reduction during each treatment cycle. During pregabalin "drug holidays," pain quickly returned to baseline levels; it was reduced again when pregabalin was reinstated. CONCLUSIONS: These results suggest that pregabalin may be beneficial in patients with neuropathic pain who have had an unsatisfactory response to treatment with other medications.

Recommendations for the management of herpes zoster.

The objective of this article is to provide evidence-based recommendations for the management of patients with herpes zoster (HZ) that take into account clinical efficacy, adverse effects, impact on quality of life, and costs of treatment. Systematic literature reviews, published randomized clinical trials, existing guidelines, and the authors' clinical and research experience relevant to the management of patients with HZ were reviewed at a consensus meeting. The results of controlled trials and the clinical experience of the authors support the use of acyclovir, brivudin (where available), famciclovir, and valacyclovir as first-line antiviral therapy for the treatment of patients with HZ. Specific recommendations for the use of these medications are provided. In addition, suggestions are made for treatments that, when used in combination with antiviral therapy, may further reduce pain and other complications of HZ.

Classification of patients with pain based on neuropathic pain symptoms: comparison of an artificial neural network against an established scoring system.

Wider use of pain assessment tools that are specifically designed for certain types of pain--such as neuropathic pain--contribute an increasing amount of information which in turn offers the opportunity to employ advanced methods of data analysis. In this manuscript, we present the results of a study where we employed artificial neural networks (ANNs) in an analysis of pain descriptors with the goal of determining how an approach that uses a specific symptoms-based tool would perform with data from the real world of clinical practice. We also used traditional statistics approaches in the form of established scoring systems as well as logistic regression analysis for the purpose of comparison. Our results confirm the clinical experience that groups of pain descriptors rather than single items differentiate between patients with neuropathic and non-neuropathic pain. The accuracy obtained by ANN analysis was only slightly higher than that of the traditional approaches, indicating the absence of nonlinear relationships in this dataset. Data analysis with ANNs provides a framework that extends what current approaches offer, especially for dynamic data, such as the rating of pain descriptors over time.

The prevalence of probable neuropathic pain in the US: results from a multimodal general-population health survey.

BACKGROUND: The prevalence of neuropathic pain (NeP) has been estimated within specific health conditions; however, there are no published data on its broad prevalence in the US. The current exploratory study addresses this gap using the validated PainDetect questionnaire as a screener for probable NeP in a general-population health survey conducted with a multimodal recruitment strategy to maximize demographic representativeness. MATERIALS AND METHODS: Adult respondents were recruited from a combination of Internet panels, telephone lists, address lists, mall-based interviews, and store-receipt invitations using a random stratified-sampling framework, with strata defined by age, sex, and race/ethnicity. Older persons and minorities were oversampled to improve prevalence estimates. Results were weighted to match the total adult US population using US Census data. Demographic information was collected, and respondents who experienced physical pain in the past 12 months completed the PainDetect and provided additional pain history. A cutoff score of 19 or greater on the PainDetect was used to define probable NeP. RESULTS: A total of 24,925 respondents (average response rate 2.5%) provided demographic data (52.2% female, mean age 51.5 years); 15,751 respondents reported pain (63.7%), of which 2,548 (15.7%, 95% confidence interval 14.9%-16.5%) had probable NeP based on the PainDetect, which was 10% (95% confidence interval 9.5%-10.5%) of all respondents. Among those reporting pain, the prevalence of probable NeP among Blacks and Hispanics was consistently higher than Whites in each age- and sex group. The highest prevalence among those with pain was among male Hispanics 35-44 years (32.4%) and 45-54 years (24.2%) old. The most commonly used medications reported by those with probable NeP were nonsteroidal anti-inflammatory drugs (44.2%), followed by weak opioids (31.7%), antiepileptics (10.9%), and strong opioids (10.9%). CONCLUSION: This is the first study to provide an estimate of the prevalence of probable NeP in the US, showing significant variation by age and ethnicity.

Interventional therapies in the management of complex regional pain syndrome.

Invasive procedures have long held a place in the therapeutic armamentarium for the management of complex regional pain syndrome (CRPS). However, this has evolved considerably, particularly as research into the mechanisms of CRPS has called into question long-held presumptions about the key role of sympathetic dysfunction in the syndrome. This review summarizes some of the key information currently available about interventional treatments, including nerve blocks, spinal cord and peripheral nerve stimulation, chemical and surgical sympathectomies, and deep brain stimulation. The potential roles for these procedures in facilitating functional rehabilitation goals that are primary to the treatment of CRPS are emphasized.

Burden of HIV-Related Neuropathic Pain in the United States.

BACKGROUND: HIV-related neuropathic pain (HIV-NeP) is common; however, the burden of HIV-NeP is not well-understood. METHODS: The cross-sectional study aimed to characterize the HIV-NeP burden. A total of 103 patients with HIV-NeP recruited during routine office visits completed a questionnaire to assess patient-reported outcomes, including pain severity, health status, sleep, mood, and lost productivity. Physicians completed a 6-month retrospective chart review. RESULTS: The sample was predominantly male and not employed for pay. A majority (75.7%) of patients experienced moderate or severe pain. Pain interference, general health, physical health, and depression were worse among patients with more severe pain (all Ps < .006). Most (87.4%) patients were prescribed at least 1 medication for NeP. HIV-related neuropathic pain was associated with 36.1% work impairment. Adjusted annualized costs increased with increasing pain severity (P < .0001). CONCLUSION: The impact of HIV-NeP on health status, physical function, and depression increases with severity, resulting in substantial clinical and economic burden.

Efficacy and Safety of Pregabalin in the Treatment of Patients With Painful Diabetic Peripheral Neuropathy and Pain on Walking.

OBJECTIVES: This randomized, double-blind, placebo-controlled, multicenter, 2-period crossover study (two 6-week treatment periods separated by a 2-week washout period) evaluated the efficacy and safety of pregabalin (150 to 300 mg/d) for treatment of pain and pain on walking in patients with painful diabetic peripheral neuropathy (DPN) who experienced pain while walking. METHODS: Co-primary efficacy endpoints were: (1) mean pain score (last 7 daily pain diary scores, 0 to 10 numeric rating scale at end of each treatment period) and (2) DPN pain on walking (0 to 10 numeric rating scale immediately after walking 50 feet [15.2 m] on flat surface). Secondary endpoints included other pain parameters, patient-reported sleep, health-related quality of life, and safety measures. RESULTS: Two hundred three patients were treated (pregabalin, n=198; placebo, n=186), with no statistically significant treatment difference for pregabalin versus placebo in the co-primary efficacy endpoints, mean DPN pain (P=0.0656) and mean DPN pain on walking (P=0.412). A carryover effect was observed. Analysis of co-primary endpoints for period 1 showed significant treatment difference for DPN pain (P=0.034) and DPN pain on walking (P=0.001). Treatment with pregabalin resulted in significant improvements versus placebo on prespecified patient global impression of change (end of period 1; P=0.002), and sleep interference rating scale (end of period 2; P=0.011). Adverse events were more frequent with pregabalin than with placebo and caused discontinuation in 13 (6.6%) pregabalin patients versus 5 (2.7%) placebo patients. DISCUSSION: Failure to meet the co-primary objectives may be related to carryover effect from period 1 to period 2, lower pregabalin dose (150 to 300 mg/d), and/or placebo response in painful DPN.

Body motion during repetitive isodynamic lifting: a comparative study of normal subjects and low-back pain patients.

To quantify performance differences between patients with low-back pain (LBP) and a control group during their performance of a repetitive isodynamic lifting task. Case-control study was done. LBP patients were recruited and tested at an outpatient ambulatory chronic pain rehabilitation program before treatment was begun. Fifty-three LBP patients who had prolonged back pain and 53 age and gender matched pain-free control subjects. Overall lifting performance measures included weight lifting and number of lifts completed; kinematic measures of hip and knee movements during lifting were described by hyperbolic tangent models, and included static measures of starting and ending angles, and dynamic measures of midpoint, falltime, and lift speed. Control subjects completed significantly more lifts and lifted more weight than patients. Starting hip flexion was greater for controls and starting knee flexion was greater for patients, indicating that patients used more of a leg lift. Patients and controls also differed significantly on dynamic measures, particularly lifting speed and hip and knee temporal midpoints. Major static and dynamic motion differences were found between LBP patients and controls as they performed repetitive lifting under a constant load. These findings indicate that body motion parameters, in addition to more common strength and endurance measures, are necessary to describe the impact of persistent LBP on a person's lifting abilities.

Use of gabapentin for postherpetic neuralgia: results of two randomized, placebo-controlled studies.

BACKGROUND: Postherpetic neuralgia (PHN), which affects up to 70% of elderly persons with herpes zoster, can have debilitating effects, including physical and social disability and significant psychological distress. A variety of agents have been used, either singly or in combination, to control PHN, including topical and oral analgesics, antidepressants, and antiepileptic drugs (AEDs). However, PHN often proves refractory to these therapies. OBJECTIVE: This article reviews available data on the use of the newer AED gabapentin for the control of PHN. METHODS: A MEDLINE search was undertaken to identify all randomized, placebo-controlled trials on the use of gabapentin in PHN. The search terms were gabapentin and postherpetic neuralgia. RESULTS: The literature search identified 2 published studies of the efficacy of gabapentin in a total of 563 patients with PHN that had persisted for at least 3 months after the healing of herpes zoster rash. The studies employed multiple outcome measures, including visual analog and Likert scales for pain intensity, and quality-of-life and functional measures that included the Medical Outcomes Study 36-item Short Form Health Survey (SF-36) and the Profile of Mood States. At maximum target dosages of 1800 to 3600 mg/d, gabapentin produced significant reductions in mean daily pain scores compared with placebo on both visual analog(P < 0.001) and Likert scales (P < 0.01). Improvements were also seen on the SF-36 subscales for physical functioning, bodily pain, vitality, and mental health(P < 0.01). CONCLUSION: Gabapentin may provide benefits in terms of alleviation of pain and overall quality of life in patients with chronic PHN.

Pain severity and the economic burden of neuropathic pain in the United States: BEAT Neuropathic Pain Observational Study.

BACKGROUND: As with many chronic conditions, patients with neuropathic pain (NeP) are high consumers of health care resources. However, limited literature exists on the economic burden of NeP, including its impact on productivity. The aim of this study was to characterize health care resource utilization, productivity, and costs associated with NeP by pain severity level in US adults. METHODS: Subjects (n=624) with painful diabetic peripheral neuropathy, human immunodeficiency virus-related peripheral NeP, post-trauma/post-surgical NeP, spinal cord injury with NeP, chronic low back pain with NeP, and small fiber neuropathy were recruited during routine office visits to US community-based general practitioners and specialists. Clinicians captured clinical characteristics, NeP-related medications, and health care resource utilization based on 6-month retrospective medical chart review. Subjects completed questionnaires on demographics, pain/symptoms, costs, and productivity. Brief Pain Inventory pain severity scores were used to classify subjects by mild, moderate, or severe pain. Annualized NeP-related costs (adjusted for covariates) were estimated, and differences across pain severity groups were evaluated. RESULTS: In total, 624 subjects were recruited (mean age 55.5±13.7 years; 55.4% male), and 504/624 (80.8%) reported moderate or severe pain. Statistically significant differences were observed across pain severity levels for number of comorbidities, prescription medications, physician office visits, and lost productivity (all P≤0.0001). At all pain severity levels, indirect costs were the primary cost driver. After adjusting for demographic and clinical variables, total mean (95% confidence interval [CI]) annualized direct medical costs to payers, direct costs to subjects, and indirect costs per subject were US$6,016 (95% CI 5,316-6,716), US$2,219 (95% CI 1,919-2,519), and US$19,000 (95% CI 17,197-20,802), respectively, with significant differences across pain severity levels. CONCLUSION: Subjects with NeP, mainly those showing moderate or severe pain, had significant associations between pain severity and NeP-related health care resource utilization, productivity, and costs. The economic burden, particularly indirect costs, was highest among those with severe pain and higher than previously reported in studies of specific NeP conditions.

Health status, function, productivity, and costs among individuals with idiopathic painful peripheral neuropathy with small fiber involvement in the United States: results from a retrospective chart review and cross-sectional survey.

OBJECTIVE: To characterize the burden of idiopathic painful peripheral neuropathy with small fiber involvement (idiopathic SFN) by pain severity in the US. METHODS: One hundred previously diagnosed idiopathic SFN subjects were enrolled during routine office visits. Subjects completed a one-time questionnaire, and investigators reported clinical characteristics and healthcare resource use, based on 6 month retrospective chart review. Annualized direct and indirect costs were estimated. Results were stratified across pain severity groups. RESULTS: Mean age was 63.5 years; 53.0% were female; 76.0% had moderate or severe pain. Most common comorbidities were sleep disturbance/insomnia (37.0%), anxiety (34.0%), and depressive symptoms (33.0%). Overall mean health status (0.59; -0.11-1.00 scale), physical and mental health (31.7 and 45.6, respectively, 0-100 scale), sleep index (45.1; 0-100 scale), and pain interference with function (5.0; 0-10 scale) differed by pain severity, with worse outcomes among those with greater pain (all p < 0.002). 84.0% were prescribed ≥1 SFN medication. 16.0% were employed; mean overall work impairment was 36.9%. Annualized average adjusted direct and indirect costs per subject ($8055 and $13,733, respectively) differed by pain severity. CONCLUSIONS: Idiopathic SFN subjects with pain experience moderate or severe pain, which negatively impacts health status, function, and productivity, and leads to substantial direct and indirect costs.