pregabalin and Sciatica

This SR aims to assess the effectiveness of pregabalin and gabapentin on pain and disability caused by acute sciatica and the adverse events associated with their clinical use.. Systematic review.. Electronic databases of Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Clinical Trials.gov were searched from their inception until March 1st of 2021.. Randomized trials (RCT) with adults>18 years old with acute sciatica for a minimum of 1 week and a maximum of 1 year (at least moderate pain).. The outcomes were pain, disability and adverse events. Data was summarized using odds ratio and mean difference. GRADE was used to calculate the level of evidence.. Eight RCT involving 747 participants were included. The effect of pregabalin was assessed in 3 RCT and in one three-arm trial (pregabalin vs limaprost vs a combination of limaprost and pregabalin). Two trials assessed the effect of gabapentin compared with placebo and one compared with tramadol. One study assessed the effect of gabapentin vs pregabalin in a crossover head-to-head trial. A statistically significant improvement on leg pain at 2 weeks and leg pain with movement at 3 and 4 months was found in a RCT comparing gabapentin with placebo. There were no statistically differences on the remaining time periods assessed for leg pain, low back pain and functional disability.. This SR provides clear evidence for lack of effectiveness of pregabalin and gabapentin for sciatica pain management. In view of this, its routine clinical use cannot be supported.

Topics: Adolescent; Adult; Analgesics; Gabapentin; Humans; Low Back Pain; Pregabalin; Sciatica

The gabapentinoid drugs gabapentin and pregabalin were originally developed as antiseizure drugs but now are prescribed mainly for treatment of pain. For gabapentin, the only pain-related indication approved by the US Food and Drug Administration (FDA) is postherpetic neuralgia. For pregabalin, FDA-approved indications related to pain are limited to postherpetic neuralgia, neuropathic pain associated with diabetic neuropathy or spinal cord injury, and fibromyalgia. Despite these limited indications, gabapentin and pregabalin are widely prescribed off-label for various other pain syndromes. Such use is growing, possibly because clinicians are searching increasingly for alternatives to opioids.. This report summarizes the limited published evidence to support off-label gabapentinoid uses, describes clinical cases in which off-label use is problematic, and notes how review articles and guidelines tend to overstate gabapentinoid effectiveness.. Clinicians who prescribe gabapentinoids off-label for pain should be aware of the limited evidence and should acknowledge to patients that potential benefits are uncertain for most off-label uses.

Topics: Analgesics; Diabetic Neuropathies; Drug Approval; Fibromyalgia; Gabapentin; Humans; Low Back Pain; Minimal Clinically Important Difference; Neuralgia; Neuralgia, Postherpetic; Off-Label Use; Pain; Pain Measurement; Pregabalin; Radiculopathy; Sciatica; Spinal Cord Injuries

Whilst pregabalin (PGB) and gabapentin (GBP) are both used to treat neuropathic pain, their relative role in sciatica is unclear. Our aim was to extensively review the roles of PGB and GBP in treating sciatica. The efficacy, side effects (SE) profile and cost of PGB and GBP in neuropathic pain states were reviewed with special reference to sciatica. Eleven articles matched the criteria: seven systematic reviews, one retrospective cross-sectional study, one placebo-controlled-crossover study, one randomized placebo-controlled double-blind study and one case report. GBP and PGB appeared to demonstrate comparable efficacy and SE. However, the amount and quality of evidence was low, and only indirect comparisons were available. Importantly, no direct "head-to-head" study existed. Globally, costs varied widely (by up to 31 times) and unpredictably (PGB cheaper than GBP, or vice versa). Formulary regulator rulings were globally disparate; however, many exclusively favoured the more expensive drug (whether GBP or PGB). No studies assessed PGB-GBP interchange. Weak evidence suggests that efficacy and SE with GBP and PGB are probably similar; however, firm conclusions are precluded. Despite weak data, and having cited minor titration, but definite cost, advantages, UK National Institute for Health and Clinical Excellence favoured PGB over GBP. Given that no evidence supports unhindered PGB-GBP interchange, neither drug should probably be favoured. Prospective "head-to-head" studies are urgently required to provide robust evidence-based knowledge for choice of GBP or PGB in sciatica.

Topics: Amines; Analgesics; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; Humans; Neuralgia; Pregabalin; Sciatica; Treatment Outcome

To estimate the healthcare resource utilisation of an Australian cohort of people with sciatica and explore individual-level factors associated with expenditure.. Healthcare utilisation (services and medication) data from a randomised, double-blind, placebo-controlled trial of pregabalin in patients with sciatica (n = 185) were analysed to estimate healthcare expenditure of participants over 12 months. Associations between key baseline socio-economic, pain and quality of life characteristics and healthcare expenditure were examined using generalised linear imputation models.. On average, participants accessed AUD$1,134 of healthcare over the year, predominantly made up of $114 of medication and $914 of health services, which included $418 of physiotherapy services. Participants randomised to receive pregabalin incurred higher expenditure ($1,263 compared to $1,001 for placebo), which was largely driven by pregabalin ($158) and greater health services ($107). Healthcare expenditure was significantly higher for participants prescribed pregabalin, earning greater than $1,700 per week ($88,400 per year) and reporting poorer quality of life (physical and mental).. Our results suggest inefficiency in the use of healthcare resources due to increased healthcare resource utilisation in people with sciatica treated with pregabalin, compared to placebo. Costs of treating sciatica varied based on individual quality of life and socio-economic characteristics.

Topics: Australia; Health Expenditures; Humans; Pregabalin; Quality of Life; Sciatica

Optimal pharmacologic treatment for chronic sciatica (CS) is currently unclear. While gabapentin (GBP) and pregabalin (PGB) are both used to treat CS, equipoise exists. Nevertheless, pharmaceutical regulation authorities typically subsidize one drug over the other. This hinders interchange wherever the favored drug is either ineffective or ill-tolerated.. To assess GBP vs PGB head to head for the treatment of CS.. A preplanned interim analysis of a randomized, double-blind, double-dummy crossover trial of PGB vs GBP for management of CS at half the estimated final sample size was performed in a single-center, tertiary referral public hospital. A total of 20 patients underwent randomization from March 2016 to March 2018, and 2 were excluded with 1 lost to follow-up and the other requiring urgent surgery unrelated to the study. Patients attending a specialist neurosurgery clinic with unilateral CS were considered for trial recruitment. Chronic sciatica was defined as pain lasting for at least 3 months radiating into 1 leg only to, at, or below the knee level. Imaging (magnetic resonance imaging with or without computed tomography) corroborating a root-level lesion concordant with symptoms and/or signs was determined by the trial clinician. Inclusion criteria included patients who had not used GBP and PGB and were 18 years or older. Analyses were intention to treat and began February 2018.. Randomly assigned participants received GBP (400 mg to 800 mg 3 times a day) then PGB (150 mg to 300 mg twice daily) or vice versa, each taken for 8 weeks. Crossover followed a 1-week washout.. The primary outcome was pain intensity (10-point visual analog scale) at baseline and 8 weeks. Secondary outcomes included disability (using the Oswestry Disability Index) and severity/frequency of adverse events.. The total trial population (N = 18) consisted mostly of men (11 [61%]) with a mean (SD) age of 57 (16.5) years. A third of the cohort were smokers (5 [28%]), and more than half consumed alcohol (12 [67%]). Gabapentin was superior to PGB, with fewer and less severe adverse events. Both GBP (mean [SD], 7.54 [1.39] to 5.82 [1.72]; P < .001) and PGB (mean [SD], 7.33 [1.30] to 6.38 [1.88]; P = .002) displayed significant visual analog pain intensity scale reduction and Oswestry Disability Index reduction (mean [SD], 59.22 [16.88] to 48.54 [15.52]; P < .001 for both). Head to head, GBP showed superior visual analog pain intensity scale reduction (mean [SD], GBP: 1.72 [1.17] vs PGB: 0.94 [1.09]; P = .035) irrespective of sequence order; however, Oswestry Disability Index reduction was unchanged. Adverse events for PGB were more frequent (PGB, 31 [81%] vs GBP, 7 [19%]; P = .002) especially when PGB was taken first.. Pregabalin and GBP were both significantly efficacious. However, GBP was superior with fewer and less severe adverse events. Gabapentin should be commenced before PGB to permit optimal crossover of medicines.. anzctr.org.au Identifier: ACTRN12613000559718.

Topics: Adult; Aged; Analgesics; Chronic Pain; Cross-Over Studies; Double-Blind Method; Female; Gabapentin; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Pregabalin; Sciatica

There is currently an absence of high-grade evidence regarding the treatment of chronic sciatica (CS). Whilst gabapentin (GBP) and pregabalin (PGB) are both currently used to treat CS, equipoise exists regarding their individual use. In particular, no head-to-head study of GBP and PGB in CS exists. Despite equipoise, most countries' formulary regulatory authorities typically favour one drug for subsidy over the other. This hinders interchange wherever the favoured drug is either ineffective or not tolerated. The primary aim of this study is to conduct a head-to-head comparison of the efficacy of PGB versus GBP for CS based on outcomes on a visual analogue scale (VAS) and the Oswestry Disability Index (ODI).. We are conducting a prospective, randomised, double-blind, double-dummy cross-over study. Included patients will be over 18 years old and have unilateral CS with radiological confirmation of corresponding neural compression/irritation. Pregnant women, those with major organ disease, or those with creatinine clearance < 60 ml/minute will be excluded. Patients will continue their current pain medication at study onset, conditional upon dosage consistency during the prior 30 days. Each drug will be titrated up to a target dose (GBP 400-800 mg three times daily, PGB 150-300 mg twice daily) and taken for 8 weeks. The first drug will then be ceased; however, cross-over will be deferred pending a 1-week washout period. Drug efficacy will be assessed using the VAS and ODI. Results of the Health Locus of Control Scale and side effect frequency/severity will be used to determine psychological functioning. Assuming the hypothesis that PGB will display a superior effect, the sample size required is n = 38 with 80% power and a 5% type I error rate. Results will be analysed via intention-to-treat methodology.. This study will establish the efficacy of PGB compared with GBP in reducing pain in people with sciatica and lead to greater understanding of the treatment options available.. Australian and New Zealand Clinical Trials Registry, 12613000559718 . Registered on 17 May 2013.

Topics: Cross-Over Studies; Data Collection; Double-Blind Method; Gabapentin; Humans; Pregabalin; Prospective Studies; Randomized Controlled Trials as Topic; Sample Size; Sciatica

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.. 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.. 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.. 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 .).

Topics: Adult; Aged; Analgesics; Back Pain; Disability Evaluation; Dizziness; Double-Blind Method; Female; Humans; Male; Middle Aged; Pain Measurement; Pregabalin; Quality of Life; Sciatica; Treatment Failure

Topics: Analgesics; Double-Blind Method; Humans; Middle Aged; Pain; Pain Measurement; Pregabalin; Sciatica

Sciatica 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.. PRECISE 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.. This 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.. Australian and New Zealand Clinical Trials Registry (ACTRN12613000530729. Registered 13 May 2013).

Topics: Analgesics; Data Interpretation, Statistical; Double-Blind Method; Humans; Outcome Assessment, Health Care; Pregabalin; Prospective Studies; Sample Size; Sciatica

Sciatica 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.. PRECISE 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.. This 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.. ClinicalTrial.gov, ACTRN 12613000530729.

Topics: Analgesics; Clinical Protocols; Combined Modality Therapy; Cost-Benefit Analysis; Disability Evaluation; Double-Blind Method; Drug Costs; gamma-Aminobutyric Acid; Humans; New South Wales; Pain Measurement; Predictive Value of Tests; Pregabalin; Prospective Studies; Quality of Life; Research Design; Sciatica; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Treatment Outcome

Patients with unilateral sciatica have heightened responses to intradermal capsaicin compared to pain-free volunteers. No studies have investigated whether this pain model can screen for novel anti-neuropathic agents in patients with pre-existing neuropathic pain syndromes.. This study compared the effects of pregabalin (300 mg) and the tetracycline antibiotic and glial attenuator minocycline (400 mg) on capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia in patients with unilateral sciatica on both their affected and unaffected leg.. Eighteen patients with unilateral sciatica completed this randomised, double-blind, placebo-controlled, three-way cross-over study. Participants received a 10 µg dose of capsaicin into the middle section of their calf on both their affected and unaffected leg, separated by an interval of 75 min. Capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were recorded pre-injection and at 5, 20, 40, 60 and 90 min post-injection. Minocycline tended to reduce pre-capsaicin injection values of hyperalgesia in the affected leg by 28% (95% CI 0% to 56%). The area under the effect time curves for capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were not affected by either treatment compared to placebo. Significant limb differences were observed for flare (AUC) (-38% in affected leg, 95% CI for difference -19% to -52%). Both hand dominance and sex were significant covariates of response to capsaicin.. It cannot be concluded that minocycline is unsuitable for further evaluation as an anti-neuropathic pain drug as pregabalin, our positive control, failed to reduce capsaicin-induced neuropathic pain. However, the anti-hyperalgesic effect of minocycline observed pre-capsaicin injection is promising pilot information to support ongoing research into glial-mediated treatments for neuropathic pain. The differences in flare response between limbs may represent a useful biomarker to further investigate neuropathic pain. Inclusion of a positive control is imperative for the assessment of novel therapies for neuropathic pain.

Topics: Adult; Analysis of Variance; Capsaicin; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; gamma-Aminobutyric Acid; Humans; Hyperalgesia; Injections, Intradermal; Male; Middle Aged; Minocycline; Pain; Pregabalin; Sciatica; Time Factors; Treatment Outcome

Topics: Adult; Cross-Over Studies; Gabapentin; Humans; Low Back Pain; Pregabalin; Sciatica

Topics: Adult; Cross-Over Studies; Gabapentin; Humans; Low Back Pain; Pregabalin; Sciatica

Topics: Humans; Low Back Pain; Peer Review; Physiatrists; Pregabalin; Sciatica

Topics: Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Diskectomy; Humans; Intervertebral Disc Displacement; Lumbar Vertebrae; Male; Middle Aged; Physical Therapy Modalities; Pregabalin; Sciatica

Topics: Analgesics; gamma-Aminobutyric Acid; Humans; Pregabalin; Sciatica

Topics: Analgesics; gamma-Aminobutyric Acid; Humans; Pain Measurement; Pregabalin; Sciatica; Treatment Outcome

Topics: Analgesics; gamma-Aminobutyric Acid; Humans; Pain Measurement; Pregabalin; Sciatica; Treatment Outcome

Topics: Analgesics; gamma-Aminobutyric Acid; Humans; Pain Measurement; Pregabalin; Sciatica; Treatment Outcome

Topics: Humans; Pain; Pain Measurement; Pregabalin; Quality of Life; Sciatica

Topics: Analgesics; gamma-Aminobutyric Acid; Humans; Pregabalin; Sciatica

The effects of pregabalin on neuropathic pain relief and the serum visfatin level were assessed using an experimental model of neuropathy in a study conducted on 40 male mice with sciatic nerve constriction. The mice were randomly assigned to 4 groups, each with 10 mice. The mice were subjected to experimental chronic partial constriction of the sciatic nerve and compared to sham-operated, saline-treated control mice (group I). The experimental groups (II-IV) were subjected to partial constriction of the left sciatic nerve. A series of behavioral tests, electrophysiological studies and biochemical measures were performed after 3 weeks of daily oral treatment with pregabalin (20 and 40 mg/kg in groups III and IV, respectively). The study revealed the actions of pregabalin against the nociceptive effects of chronic sciatic nerve constriction in mice (p < 0.01), including replenishment of the glutathione level (p < 0.05) and reduction of the serum visfatin level. No significant effect on the tissue malondialdehyde level was found for any of the pregabalin doses. The percentage differences in the maximum tetanic force between the ipsilateral and contra lateral legs were significant in both pregabalin-treated groups (p < 0.05). We concluded that pregabalin reduced the serum visfatin level and produced a dose-dependent antinociceptive antioxidant effect.

Topics: Analgesics; Animals; Behavior, Animal; Biomarkers; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Electrophysiological Phenomena; Glutathione; Hyperalgesia; Male; Malondialdehyde; Mice; Muscle, Skeletal; Nicotinamide Phosphoribosyltransferase; Pregabalin; Sciatica

Pregabalin is an anti-convulsant that successfully treats many neuropathic pain syndromes, although the mechanism of its anti-hyperalgesic action remains elusive. This study aims to help delineate pregabalin's anti-hyperalgesic mechanisms. We assessed the effectiveness of pregabalin at decreasing mechanical and cold hypersensitivity induced in a rat model of neuropathic pain. Thus, we compared the effectiveness of pre- or post-treatment with systemic or intrathecal (i.t.) pregabalin at reducing the development and maintenance of the neuropathic pain symptoms. Pregabalin successfully decreased mechanical and cold hypersensitivity, as a pre-treatment, but was less effective at suppressing cold hypersensitivity when administered as a post-treatment. Furthermore, both i.t. and systemic administration of pregabalin were effective in reducing the behavioral hypersensitivity, with the exception of systemic post-treatment on cold hypersensitivity. We also examined pregabalin's effects at inhibiting hind paw formalin-induced nociception in naïve rats and formalin-induced release of excitatory amino acids in the spinal cord dorsal horn (SCDH) both in naïve rats and in rats with neuropathic pain. Pregabalin dose-dependently reduced nociceptive scores in the formalin test. We also present the first evidence that pregabalin reduces the formalin-induced release of glutamate in SCDH. Furthermore, i.t. pregabalin reduces the enhanced noxious stimulus-induced spinal release of glutamate seen in neuropathic rats. These data suggest that pregabalin reduces neuropathic pain symptoms by inhibiting the release of glutamate in the SCDH.

Topics: Analgesics; Animals; Chromatography, High Pressure Liquid; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Administration Schedule; Electrochemistry; gamma-Aminobutyric Acid; Glutamic Acid; Hyperalgesia; Male; Microdialysis; Pain Measurement; Pain Threshold; Physical Stimulation; Pregabalin; Rats; Rats, Long-Evans; Sciatica; Spinal Cord; Spinal Cord Injuries; Statistics, Nonparametric; Time Factors