Alec B. O'Connor

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.

Treatment of Neuropathic Pain: An Overview of Recent Guidelines

A number of different treatments for neuropathic pain have been studied, but the literature is sizable, rapidly evolving, and lacks important information about practical aspects of patient management. Under the auspices of the International Association for the Study of Pain (IASP) Neuropathic Pain Special Interest Group (NeuPSIG), a consensus process was used to develop evidence-based guidelines for the pharmacologic management of neuropathic pain that take into account clinical efficacy, adverse effects, impact on health-related quality of life, convenience, and costs. On the basis of randomized clinical trials, medications recommended as first-line treatments for neuropathic pain included certain antidepressants (i.e., tricyclic antidepressants and dual reuptake inhibitors of both serotonin and norepinephrine), calcium channel alpha(2)-delta ligands (i.e., gabapentin and pregabalin), and topical lidocaine. Opioid analgesics and tramadol were recommended as second-line treatments that can be considered for first-line use in selected clinical circumstances. Other medications that generally would be used as third-line treatments include certain other antidepressant and antiepileptic medications, topical capsaicin, mexiletine, and N-methyl-d-aspartate receptor antagonists. Two other national and international associations recently published pharmacologic treatment guidelines for neuropathic pain, which are summarized and contrasted with the NeuPSIG recommendations. Recent guidelines for the use of neurostimulation for the treatment of neuropathic pain also are summarized. For all treatments for neuropathic pain, long-term studies, head-to-head comparisons, and studies of treatment combinations are a priority for future research.

Neuropathic Pain : Quality-of-Life Impact, Costs and Cost Effectiveness of Therapy

AbstractA number of different diseases or injuries can damage the central or peripheral nervous system and produce neuropathic pain (NP), which seems to be more difficult to treat than many other types of chronic pain. As a group, patients with NP have greater medical co-morbidity burden than age- and sex-adjusted controls, which makes determining the humanistic and economic burden attributable to NP challenging.Health-related quality of life (HR-QOL) is substantially impaired among patients with NP. Patients describe pain-related interference in multiple HR-QOL and functional domains, as well as reduced ability to work and reduced mobility due to their pain. In addition, the spouses of NP patients have been shown to experience adverse social consequences related to NP. In randomized controlled trials, several medications have been shown to improve various measures of HR-QOL. Changes in HR-QOL appear to be tightly linked to pain relief, but not to the development of adverse effects. However, in cross-sectional studies, many patients continue to have moderate or severe pain and markedly impaired HR-QOL, despite taking medications prescribed for NP. The quality of NP treatment appears to be poor, with few patients receiving recommended medications in efficacious dosages.The substantial costs to society of NP derive from direct medical costs, loss of the ability to work, loss of caregivers’ ability to work and possibly greater need for institutionalization or other living assistance. No single study has measured all of these costs to society for chronic NP. The cost effectiveness of various interventions for the treatment or prevention of different types of NP has been assessed in several different studies. The most-studied diseases are post-herpetic neuralgia and painful diabetic neuropathy, for which tricyclic antidepressants (both amitriptyline and desipramine) have been found to be either cost effective or dominant relative to other strategies.Increasing the use of cost-effective therapies such as tricyclic antidepressants for post-herpetic neuralgia and painful diabetic neuropathy may improve the HR-QOL of patients and decrease societal costs. Head-to-head clinical trials comparing NP therapies are needed to help assess the relative clinical efficacy of treatments, ideally using HR-QOL and utility outcomes. The full costs to society of NP, including productivity loss costs, have not been determined for chronic NP. Improved relative efficacy, utility and cost estimates would facilitate future cost-effectiveness research in NP.

Interventional management of neuropathic pain: NeuPSIG recommendations

&NA; Neuropathic pain (NP) is often refractory to pharmacologic and noninterventional treatment. On behalf of the International Association for the Study of Pain Neuropathic Pain Special Interest Group, the authors evaluated systematic reviews, clinical trials, and existing guidelines for the interventional management of NP. Evidence is summarized and presented for neural blockade, spinal cord stimulation (SCS), intrathecal medication, and neurosurgical interventions in patients with the following peripheral and central NP conditions: herpes zoster and postherpetic neuralgia (PHN); painful diabetic and other peripheral neuropathies; spinal cord injury NP; central poststroke pain; radiculopathy and failed back surgery syndrome (FBSS); complex regional pain syndrome (CRPS); and trigeminal neuralgia and neuropathy. Due to the paucity of high‐quality clinical trials, no strong recommendations can be made. Four weak recommendations based on the amount and consistency of evidence, including degree of efficacy and safety, are: 1) epidural injections for herpes zoster; 2) steroid injections for radiculopathy; 3) SCS for FBSS; and 4) SCS for CRPS type 1. Based on the available data, we recommend not to use sympathetic blocks for PHN nor radiofrequency lesions for radiculopathy. No other conclusive recommendations can be made due to the poor quality of available data. Whenever possible, these interventions should either be part of randomized clinical trials or documented in pain registries. Priorities for future research include randomized clinical trials, long‐term studies, and head‐to‐head comparisons among different interventional and noninterventional treatments.

Healthcare Costs of Acute and Chronic Pain Associated with a Diagnosis of Herpes Zoster

OBJECTIVES: To determine the healthcare costs of acute and chronic pain associated with herpes zoster.

Building Comparative Efficacy and Tolerability Into the FDA Approval Process

THE US FOOD AND DRUG ADMINISTRATION (FDA) “IS responsible for protecting the public health by assuring the safety, efficacy, and security” of drugs and medical devices and for helping provide the public with the “science-based information” it needs to use drugs and devices to improve health. Under the current Code of Federal Regulations (CFR), new drug approval is typically based on demonstration of efficacy in 2 or more randomized clinical trials (RCTs), often in comparison with placebo; high-risk device approval appears to be based on considerably weaker evidence of safety and efficacy. Given the continued progress of science, approval of a new drug or device implies to physicians and the general public that the product represents an advance over older treatments. The current FDA standards for approval fail to assess whether newly approved drugs and devices are less efficacious or less well-tolerated than existing alternatives. This raises the possibility that patients may be harmed by receiving a newly approved treatment instead of an alternative with established efficacy and safety.

Health Care Expenditure Burden of Persisting Herpes Zoster Pain

OBJECTIVES Pain can persist long after the resolution of herpes zoster, but little is known regarding its health care costs. The objective of this study was to determine the health care expenditures associated with persisting pain following herpes zoster by comparing expenditures for patients with postherpetic neuralgia or subacute herpetic neuralgia with a control group without these conditions. METHODS Health care expenditures attributable to persisting pain in herpes zoster patients were calculated using Thomson-Medstats MarketScan databases to examine commercial, Medicare, and Medicaid claims for inpatient and outpatient services and outpatient prescription drugs. RESULTS Excess annualized costs were

A Cost-Effectiveness Comparison of Desipramine, Gabapentin, and Pregabalin for Treating Postherpetic Neuralgia

4,917 for commercially insured patients,

Association of pain score documentation and analgesic use in a pediatric emergency department.

2,696 for Medicare patients, and