Stephanie Mathieson

Trial of Pregabalin for Acute and Chronic Sciatica

BACKGROUND Sciatica can be disabling, and evidence regarding medical treatments is limited. Pregabalin is effective in the treatment of some types of neuropathic pain. This study examined whether pregabalin may reduce the intensity of sciatica. METHODS We conducted a randomized, double‐blind, placebo‐controlled trial of pregabalin in patients with sciatica. Patients were randomly assigned to receive either pregabalin at a dose of 150 mg per day that was adjusted to a maximum dose of 600 mg per day or matching placebo for up to 8 weeks. The primary outcome was the leg‐pain intensity score on a 10‐point scale (with 0 indicating no pain and 10 the worst possible pain) at week 8; the leg‐pain intensity score was also evaluated at week 52, a secondary time point for the primary outcome. Secondary outcomes included the extent of disability, back‐pain intensity, and quality‐of‐life measures at prespecified time points over the course of 1 year. RESULTS A total of 209 patients underwent randomization, of whom 108 received pregabalin and 101 received placebo; after randomization, 2 patients in the pregabalin group were determined to be ineligible and were excluded from the analyses. At week 8, the mean unadjusted leg‐pain intensity score was 3.7 in the pregabalin group and 3.1 in the placebo group (adjusted mean difference, 0.5; 95% confidence interval [CI], ‐0.2 to 1.2; P=0.19). At week 52, the mean unadjusted leg‐pain intensity score was 3.4 in the pregabalin group and 3.0 in the placebo group (adjusted mean difference, 0.3; 95% CI, ‐0.5 to 1.0; P=0.46). No significant between‐group differences were observed with respect to any secondary outcome at either week 8 or week 52. A total of 227 adverse events were reported in the pregabalin group and 124 in the placebo group. Dizziness was more common in the pregabalin group than in the placebo group. CONCLUSIONS Treatment with pregabalin did not significantly reduce the intensity of leg pain associated with sciatica and did not significantly improve other outcomes, as compared with placebo, over the course of 8 weeks. The incidence of adverse events was significantly higher in the pregabalin group than in the placebo group. (Funded by the National Health and Medical Research Council of Australia; PRECISE Australian and New Zealand Clinical Trials Registry number, ACTRN12613000530729.)

Neuropathic pain screening questionnaires have limited measurement properties. A systematic review

OBJECTIVES The Douleur Neuropathique 4 (DN4), ID Pain, Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), PainDETECT, and Neuropathic Pain Questionnaire have been recommended as screening questionnaires for neuropathic pain. This systematic review aimed to evaluate the measurement properties (eg, criterion validity and reliability) of these questionnaires. STUDY DESIGN AND SETTING Online database searches were conducted and two independent reviewers screened studies and extracted data. Methodological quality of included studies and the measurement properties were assessed against established criteria. A modified Grading of Recommendations Assessment, Development and Evaluation approach was used to summarize the level of evidence. RESULTS Thirty-seven studies were included. Most studies recruited participants from pain clinics. The original version of the DN4 (French) and Neuropathic Pain Questionnaire (English) had the most number of satisfactory measurement properties. The ID Pain (English) demonstrated satisfactory hypothesis testing and reliability, but all other properties tested were unsatisfactory. The LANSS (English) was unsatisfactory for all properties, except specificity. The PainDETECT (English) demonstrated satisfactory hypothesis testing and criterion validity. In general, the cross-cultural adaptations had less evidence than the original versions. CONCLUSION Overall, the DN4 and Neuropathic Pain Questionnaire were most suitable for clinical use. These screening questionnaires should not replace a thorough clinical assessment.

PRECISE - pregabalin in addition to usual care for sciatica: study protocol for a randomised controlled trial.

BackgroundSciatica is a type of neuropathic pain that is characterised by pain radiating into the leg. It is often accompanied by low back pain and neurological deficits in the lower limb. While this condition may cause significant suffering for the individual, the lack of evidence supporting effective treatments for sciatica makes clinical management difficult. Our objectives are to determine the efficacy of pregabalin on reducing leg pain intensity and its cost-effectiveness in patients with sciatica.Methods/DesignPRECISE is a prospectively registered, double-blind, randomised placebo-controlled trial of pregabalin compared to placebo, in addition to usual care. Inclusion criteria include moderate to severe leg pain below the knee with evidence of nerve root/spinal nerve involvement. Participants will be randomised to receive either pregabalin with usual care (n = 102) or placebo with usual care (n = 102) for 8 weeks. The medicine dosage will be titrated up to the participant’s optimal dose, to a maximum 600 mg per day. Follow up consultations will monitor individual progress, tolerability and adverse events. Usual care, if deemed appropriate by the study doctor, may include a referral for physical or manual therapy and/or prescription of analgesic medication. Participants, doctors and researchers collecting participant data will be blinded to treatment allocation. Participants will be assessed at baseline and at weeks 2, 4, 8, 12, 26 and 52. The primary outcome will determine the efficacy of pregabalin in reducing leg pain intensity. Secondary outcomes will include back pain intensity, disability and quality of life. Data analysis will be blinded and by intention-to-treat. A parallel economic evaluation will be conducted from health sector and societal perspectives.DiscussionThis study will establish the efficacy of pregabalin in reducing leg pain intensity in patients with sciatica and provide important information regarding the effect of pregabalin treatment on disability and quality of life. The impact of this research may allow the future development of a cost-effective conservative treatment strategy for patients with sciatica.Trial registrationClinicalTrial.gov, ACTRN 12613000530729

Anticonvulsants in the treatment of low back pain and lumbar radicular pain: a systematic review and meta-analysis

BACKGROUND: The use of anticonvulsants (e.g., gabapentin, pregabalin) to treat low back pain has increased substantially in recent years despite limited supporting evidence. We aimed to determine the efficacy and tolerability of anticonvulsants in the treatment of low back pain and lumbar radicular pain compared with placebo. METHODS: A search was conducted in 5 databases for studies comparing an anticonvulsant to placebo in patients with nonspecific low back pain, sciatica or neurogenic claudication of any duration. The outcomes were self-reported pain, disability and adverse events. Risk of bias was assessed using the Physiotherapy Evidence Database (PEDro) scale, and quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Data were pooled and treatment effects were quantified using mean differences for continuous and risk ratios for dichotomous outcomes. RESULTS: Nine trials compared topiramate, gabapentin or pregabalin to placebo in 859 unique participants. Fourteen of 15 comparisons found anticonvulsants were not effective to reduce pain or disability in low back pain or lumbar radicular pain; for example, there was high-quality evidence of no effect of gabapentinoids versus placebo on chronic low back pain in the short term (pooled mean difference [MD] −0.0, 95% confidence interval [CI] −0.8 to 0.7) or for lumbar radicular pain in the immediate term (pooled MD −0.1, 95% CI −0.7 to 0.5). The lack of efficacy is accompanied by increased risk of adverse events from use of gabapentinoids, for which the level of evidence is high. INTERPRETATION: There is moderate- to high-quality evidence that anticonvulsants are ineffective for treatment of low back pain or lumbar radicular pain. There is high-quality evidence that gabapentinoids have a higher risk for adverse events. Protocol registration: PROSPERO-CRD42016046363

PRECISE — pregabalin in addition to usual care: statistical analysis plan

BackgroundSciatica is a severe, disabling condition that lacks high quality evidence for effective treatment strategies. This a priori statistical analysis plan describes the methodology of analysis for the PRECISE study.Methods/designPRECISE is a prospectively registered, double blind, randomised placebo controlled trial of pregabalin compared to placebo, in addition to usual care in patients with sciatica. The aim of this study is to determine the efficacy and cost-effectiveness of pregabalin in reducing leg pain intensity (primary outcome). Secondary outcomes include disability (key secondary), back pain intensity, quality of life, participants’ perceived global effect, work absenteeism and health utilisation. Information about medication usage and tolerability are also collected. Outcomes are collected over one year (weeks 2, 4, 8, 12, 26 and 52). Double data entry will be conducted for primary and key secondary outcomes. Other outcomes will be checked using a risk-based approach. Analyses will be consistent with the intention-to-treat principle. Statistical tests will be two-tailed with a p value <0.05 considered significant. Group allocation will remain masked until analyses and interpretation are finalised. Repeated-measure linear mixed models will assess the effect of treatment (pregabalin versus placebo) on primary and secondary outcomes at all time points. Fixed effects will include group allocation, visit as a categorical variable and the interaction between group and visit. Covariates will include baseline leg pain and symptom duration, with an interaction term between baseline leg pain and visit. Pairwise differences between groups will be tested at weeks 8 and 52. The number of serious adverse events and adverse events will be reported, and the proportion of patients per group who have at least one event will be compared using Fisher’s exact test. An economic evaluation will be conducted if there is a treatment effect on the primary outcome at week 8. A subgroup analysis will assess whether presenting features of neuropathic pain at baseline modify the treatment effect of leg pain at week 8.DiscussionThis statistical analysis plan provides detailed methodology for the analysis of the PRECISE study, which aims to deliver much needed evidence about effective and affordable management of sciatica.Trial registrationAustralian and New Zealand Clinical Trials Registry (ACTRN12613000530729. Registered 13 May 2013)

Combination Drug Therapy for the Management of Low Back Pain and Sciatica: Systematic Review and Meta-Analysis

Combining medicines may give greater pain relief and/or improved tolerability. We conducted a systematic review to investigate the effects of combination drug therapy in patients with low back pain and/or sciatica on pain, disability, and adverse events. Databases and trial registers were searched from inception to July 27, 2017, for randomized trials of (sub)acute or chronic back pain or sciatica participants that were administered combination drug therapy compared with monotherapy or placebo. Of the 27 studies included, most combinations (21 of 23) consisted of single trials. Most combinations had no or small effect on pain and disability. A clinically important difference was found in one combination, buprenorphine plus pregabalin versus buprenorphine for chronic back pain at immediate (mean difference = -23.30; 95% confidence interval = -27.68 to -18.92) and short (mean difference = -27.60; 95% confidence interval = -31.70 to -23.50) terms; however, the quality of evidence was low. There was no statistically significant increased risk of serious adverse events. When the risk of adverse events was statistically significant, it favored monotherapy or placebo. There is no clear evidence to support any combination drug therapy for the management of low back pain and sciatica due to the limited number of studies and overall low quality of evidence. Perspective: Combining medicines may give greater pain relief and/or improved tolerability compared with single-ingredient medicines. However, the lack of studies and overall low quality of evidence limit the recommendation of combination drug therapy for the management of low back pain and sciatica.