Brett R. Stacey

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.

Efficacy of Gabapentin in Migraine Prophylaxis

Objective.—To compare gabapentin with placebo for use as a prophylactic agent in patients with migraine (with or without aura).

The Burden of Chronic Low Back Pain Clinical Comorbidities, Treatment Patterns, and Health Care Costs in Usual Care Settings

Study Design. Retrospective analysis of an insurance claims database. Objective. To examine the comorbidities, treatment patterns, health care resource utilization, and direct medical costs of patients with chronic low back pain (CLBP) in clinical practice. Summary of Background Data. Although the socioeconomic impact of CLBP is substantial, characterization of comorbidities, pain-related pharmacotherapy, and health care resource use/costs of patients with CLBP relative to non-CLBP controls have been infrequently documented. Methods. Using the LifeLink Health Plan Claims Database (IMS Health Inc., Watertown, MA), patients with CLBP, defined using the International Classification of Diseases, Ninth Revision, Clinical Modification, were identified and matched (age, sex, and region) with non-CLBP individuals. Comorbidities, pain-related pharmacotherapy, and health care service use/costs (pharmacy, outpatient, inpatient, total) were compared for the 2 groups during 2008. Results. A total of 101,294 patients with CLBP and controls were identified (55% women; mean age was 47.2 ± 11.6 years). Relative to controls, patients with CLBP had a greater comorbidity burden including a significantly higher (P < 0.0001) frequency of musculoskeletal and neuropathic pain conditions and common sequelae of pain such as depression (13.0% vs. 6.1%), anxiety (8.0% vs. 3.4%), and sleep disorders (10.0% vs. 3.4%). Pain-related pharmacotherapy was significantly greater (P < 0.0001) among patients with CLBP including opioids (37.0% vs. 14.8%; P < 0.0001), nonsteroidal anti-inflammatory drugs (26.2% vs. 9.6%; P < 0.0001), and tramadol (8.2% vs. 1.2%; P < 0.0001). Prescribing of “adjunctive” medications for treating conditions associated with pain (i.e., depression, anxiety, and insomnia) was also significantly greater (P < 0.0001) among patients with CLBP; 36.3% of patients received combination therapy. Health care costs were significantly higher in the CLBP cohort (P < 0.0001), reflecting greater resource utilization. Total direct medical costs were estimated at

Interventional management of neuropathic pain: NeuPSIG recommendations

8386 ±

Considerations for improving assay sensitivity in chronic pain clinical trials: IMMPACT recommendations

17,507 in the CLBP group and

Pregabalin for Postherpetic Neuralgia: Placebo-Controlled Trial of Fixed and Flexible Dosing Regimens on Allodynia and Time to Onset of Pain Relief

3607 ±

Burden of illness associated with painful diabetic peripheral neuropathy among adults seeking treatment in the US: Results from a retrospective chart review and cross-sectional survey

10,845 in the control group; P < 0.0001). Conclusion. Patients with CLBP are characterized by greater comorbidity and economic burdens compared with those without CLBP. This economic burden can be attributed to greater prescribing of pain-related medications and increased health resource utilization.

Management of Patient-Controlled Analgesia : A comparison of primary surgeons and a dedicated pain service

&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.

Economic and humanistic burden of post-trauma and post-surgical neuropathic pain among adults in the United States

A number of pharmacologic treatments examined in recent randomized clinical trials (RCTs) have failed to show statistically significant superiority to placebo in conditions in which their efficacy had previously been demonstrated. Assuming the validity of previous evidence of efficacy and the comparability of the patients and outcome measures in these studies, such results may be a consequence of limitations in the ability of these RCTs to demonstrate the benefits of efficacious analgesic treatments vs placebo (“assay sensitivity”). Efforts to improve the assay sensitivity of analgesic trials could reduce the rate of falsely negative trials of efficacious medications and improve the efficiency of analgesic drug development. Therefore, an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials consensus meeting was convened in which the assay sensitivity of chronic pain trials was reviewed and discussed. On the basis of this meeting and subsequent discussions, the authors recommend consideration of a number of patient, study design, study site, and outcome measurement factors that have the potential to affect the assay sensitivity of RCTs of chronic pain treatments. Increased attention to and research on methodological aspects of clinical trials and their relationships with assay sensitivity have the potential to provide the foundation for an evidence‐based approach to the design of analgesic clinical trials and expedite the identification of analgesic treatments with improved efficacy and safety.