Benefits and safety of gabapentinoids in chronic low back pain: A systematic review and meta-analysis of randomized controlled trials.
ABSTRACT: Chronic Low Back Pain (CLBP) is very common, with a lifetime prevalence between 51% and 80%. In majority, it is nonspecific in nature and multifactorial in etiology. Pregabalin (PG) and Gabapentin (GB) are gabapentinoids that have demonstrated benefit in neuropathic pain conditions. Despite no clear rationale, they are increasingly used for nonspecific CLBP. They necessitate prolonged use and are associated with adverse effects and increased cost. Recent guidelines from the National Health Service (NHS), England, expressed concerns on their off-label use, in addition to the risk of misuse. We aimed to assess the effectiveness and safety of gabapentinoids in adult CLBP patients.Electronic databases of MEDLINE, EMBASE, and Cochrane were searched from their inception until December 20th, 2016. We included randomized control trials reporting the use of gabapentinoids for the treatment of CLBP of >3 months duration, in adult patients. Study selection and data extraction was performed independently by paired reviewers. Outcomes were guided by Initiative on Methods, Measurement and Pain Assessment in Clinical Trials guidelines, with pain relief and safety as the primary outcomes. Meta-analyses were performed for outcomes reported in 3 or more studies. Outcomes were reported as mean differences (MDs) or risk ratios (RRs) with their corresponding 95% confidence intervals (CIs), and I2 in percentage representing the percentage variability in effect estimates that could be explained by heterogeneity. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to assess the quality of evidence.Out of 1,385 citations, eight studies were included. Based on the interventions and comparators, studies were analyzed in 3 different groups. GB compared with placebo (3 studies, n = 185) showed minimal improvement of pain (MD = 0.22 units, 95% CI [-0.5 to 0.07] I2 = 0%; GRADE: very low). Three studies compared PG with other types of analgesic medication (n = 332) and showed greater improvement in the other analgesic group (MD = 0.42 units, 95% CI [0.20 to 0.64] I2 = 0; GRADE: very low). Studies using PG as an adjuvant (n = 423) were not pooled due to heterogeneity, but the largest of them showed no benefit of adding PG to tapentadol. There were no deaths or hospitalizations reported. Compared with placebo, the following adverse events were more commonly reported with GB: dizziness-(RR = 1.99, 95% CI [1.17 to 3.37], I2 = 49); fatigue (RR = 1.85, 95% CI [1.12 to 3.05], I2 = 0); difficulties with mentation (RR = 3.34, 95% CI [1.54 to 7.25], I2 = 0); and visual disturbances (RR = 5.72, 95% CI [1.94 to 16.91], I2 = 0). The number needed to harm with 95% CI for dizziness, fatigue, difficulties with mentation, and visual disturbances were 7 (4 to 30), 8 (4 to 44), 6 (4 to 15), and 6 (4 to 13) respectively. The GRADE evidence quality was noted to be very low for dizziness and fatigue, low for difficulties with mentation, and moderate for visual disturbances. Functional and emotional improvements were reported by few studies and showed no significant improvements.Existing evidence on the use of gabapentinoids in CLBP is limited and demonstrates significant risk of adverse effects without any demonstrated benefit. Given the lack of efficacy, risks, and costs associated, the use of gabapentinoids for CLBP merits caution. There is need for large high-quality trials to more definitively inform this issue.PROSPERO CRD42016034040.
Project description:Duloxetine has demonstrated efficacy in chronic low back pain (CLBP). We examined the predictors of response to duloxetine for CLBP.This was a post hoc analysis of pooled data from 4 double-blind, ran-domized, placebo-controlled trials of duloxetine (60 mg/day for 12-14 weeks) in adult patients with CLBP. Primary outcome was proportion of patients with ≥30% reduction in Brief Pain Inventory (BPI) average pain ("pain reduction") at 12-14 weeks. The proportion of patients with ≥30% and ≥50% (secondary outcome) pain reduction in duloxetine and placebo groups was compared. Variables for responder analyses were early improvement (≥15% pain reduction at Week 2), sex, age, baseline BPI average pain score, duration of CLBP, and number of painful body sites according to the Michigan Body Map (≥2 vs 1 [isolated CLBP]; 1 trial); relative risk (RR) and 95% confidence interval (CI) were calculated.Compared with placebo (n = 653), a greater proportion of duloxetine-treated patients (n = 642) achieved ≥30% (59.7% vs 47.8%; P < 0.001) and ≥50% pain reduction (48.6% vs 35.1%; P < 0.001). Among duloxetine-treated patients, early improvement was associated with greater likelihood of ≥30% (RR [95% CI], 2.91 [2.30-3.67]) or ≥50% (3.24 [2.44-4.31]) pain reduction. Women were slightly more likely than men to achieve ≥30% (RR [95% CI], 1.14 [1.00-1.30]) or ≥50% (1.17 [0.99-1.38]) pain reduction. Response rates were similar between age, CLBP duration, and baseline BPI average pain score subgroups. Patients with ≥2 painful sites were more likely to respond to duloxetine 60 mg relative to placebo than patients with isolated CLBP (RR, duloxetine vs placebo [95% CI]: ≥30% reduction, ≥2 painful sites 1.40 [1.18-1.66], isolated CLBP 1.07 [0.78-1.48]; ≥50% reduction, ≥2 painful sites 1.51 [1.20-1.89], isolated CLBP 1.23 [0.81-1.88]).Early pain reduction was indicative of overall response. Patients with multiple painful sites had more benefit from duloxetine than patients with isolated CLBP.
Project description:BACKGROUND:Common complications of pediatric strabismus surgery, including emergence agitation (EA), postoperative nausea and vomiting (PONV), and postoperative pain, may be prevented using dexmedetomidine, which is an anxiolytic and analgesic. This systematic review and meta-analysis assessed the effects of dexmedetomidine in patients who had undergone pediatric strabismus surgery. METHOD:Five databases were searched for randomized controlled trials published from database inception to April 2020 that compared dexmedetomidine use with placebo or active comparator use and evaluated EA, PONV, or postoperative pain incidence (main outcomes) in patients who had undergone pediatric strabismus surgery. Oculocardiac reflex (OCR) incidence and postanesthesia care unit (PACU) stay duration were considered as safety outcomes. All meta-analyses were performed using a random-effects model. RESULTS:In the nine studies meeting our inclusion criteria, compared with placebo use, dexmedetomidine use reduced EA incidence [risk ratio (RR): 0.39; 95% confidence interval (CI): 0.25-0.62, I2 = 66%], severe EA incidence (RR: 0.27, 95% CI: 0.17-0.43, I2 = 0%), PONV incidence (RR: 0.33, 95% CI: 0.21-0.54, I2 = 0%), analgesia requirement (RR: 0.38, 95% CI: 0.25-0.57, I2 = 0%), and pain scores (standardized mean difference: -1.02, 95% CI: -1.44 to -0.61, I2 = 75%). Dexmedetomidine also led to lower EA incidence in the sevoflurane group than in the desflurane group (RR: 0.26 for sevoflurane vs. 0.45 for desflurane). Continuous dexmedetomidine infusion (RR: 0.19) led to better EA incidence reduction than did bolus dexmedetomidine infusion at the end of surgery (RR: 0.26) or during the peri-induction period (RR: 0.36). Compared with placebo use, dexmedetomidine use reduced OCR incidence (RR: 0.63; I2 = 40%). No significant between-group differences were noted for PACU stay duration. CONCLUSION:In patients who have undergone pediatric strabismus surgery, dexmedetomidine use may alleviate EA, PONV, and postoperative pain and reduce OCR incidence. Moreover, dexmedetomidine use does not affect the PACU stay duration.
Project description:BACKGROUND:Chronic low back pain (cLBP) affects millions of Americans and costs billions. Studies suggest a link between cLBP and joint hypermobility. METHODS:We conducted cross-sectional primary analyses of joint hypermobility and cLBP, lumbar spine osteoarthritis (OA), and lumbar facet joint OA (FOA) in 3 large studies-the Generalized Osteoarthritis Study, Genetics of Generalized Osteoarthritis Study, and Johnston County Osteoarthritis Project (total n = 5072). Associations of joint hypermobility and Beighton trunk flexion with cLBP and lumbar OA were estimated using separate adjusted logistic regression models. Adjusted pooled odds ratios (pORs) and 95% confidence intervals (CIs) were then summarized-using random effect univariate, multivariate crude, and adjusted models-and heterogeneity was determined (I2 statistic). RESULTS:In univariate models, hypermobility was associated with symptomatic FOA (pOR = 0.64 [95% CI 0.44, 0.93]) but this result was not found in the multivariate models. In multivariate adjusted models, hypermobility was not significantly associated with cLBP and lumbar OA, but trunk flexion was inversely associated with cLBP (pOR = 0.40 [95% 0.26, 0.62]), spine OA (pOR = 0.66 [95% CI 0.50, 0.87]), symptomatic spine OA (pOR = 0.39 [95% CI 0.28, 0.53]), and symptomatic FOA (pOR = 0.53 [95% CI 0.37, 0.77]). Generally, between-study heterogeneity was moderate-high. CONCLUSIONS:Hypermobility was not associated with cLBP or lumbar OA. The inverse association of trunk flexion with cLBP and lumbar OA may indicate a role for a flexible spine in avoiding or managing these conditions.
Project description:Gabapentinoid drugs, which include gabapentin and pregabalin, play an established role in the management of neuropathic pain. However, whether preoperative administration of gabapentinoids has a beneficial role in controlling acute pain after spinal surgery is unknown. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the efficacy and safety of the preoperative use of gabapentinoids (gabapentin and pregabalin) for the treatment of acute postoperative pain following spinal surgery.In March 2017, a systematic computer-based search was conducted in PubMed, EMBASE, Web of Science, Cochrane Library, and Google databases. RCTs comparing gabapentinoids (gabapentin and pregabalin) with placebo in patients undergoing spine surgery were retrieved. The primary endpoint was the visual analogue scale (VAS) score with rest or mobilization at 6, 12, 24, and 48 hours and cumulative morphine consumption at 24 and 48 hours. The secondary outcomes were complications of nausea, vomiting, sedation, dizziness, headache, urine retention, pruritus, and visual disturbances. After tests for publication bias and heterogeneity among studies were performed, data were aggregated for random-effects models when necessary.Sixteen clinical studies (gabapentin group n = 8 and pregabalin group n = 8) were ultimately included in the meta-analysis. Gabapentinoids were associated with reduced pain scores at 6, 12, 24, and 48 hours. Similarly, gabapentinoids were associated with a reduction in cumulative morphine consumption at 24 and 48 hours. Furthermore, gabapentinoids can significantly reduce the occurrence of nausea, vomiting, and pruritus. There were no significant differences in the occurrence of sedation, dizziness, headache, visual disturbances, somnolence, or urine retention.Preoperative use of gabapentinoids was able to reduce postoperative pain, total morphine consumption, and morphine-related complications following spine surgery. Further studies should determine the optimal dose and whether pregabalin is superior to gabapentin in controlling acute pain after spine surgery.
Project description:BACKGROUND:Migraine has been recognized as one of common diseases in the world whose current treatment options are not ideal. Lasmiditan, an oral 5-hydroxytryptamine (HT)1F receptor agonist, appears more promising for the acute treatment of migraine because of considerably better effect profiles with no severe adverse events (AEs). This review aimed to systematically evaluate the efficacy and safety of lasmiditan from the results of randomized controlled trials (RCTs). METHODS:PubMed, Cochrane Library, Embase were searched on lasmiditan for the acute treatment of migraine from inception of the databases to Feb 1, 2020. Pain free and pain relief, global impression (very much/much better), and no/mild disability at 2?h in efficacy; total treatment-emergent adverse events (TEAEs), dizziness, nausea, fatigue, paraesthesia and somnolence in safety were extracted from the included studies. A systematic review and meta-analysis was performed using Review Manager Software version 5.3 (RevMan 5.3). RESULTS:Four RCTs with a total of 4960 subjects met our inclusion criteria. The overall effect estimate showed that lasmiditan was significantly superior to placebo in terms of pain free (RR 1.71, 95% CI 1.55-1.87), pain relief (RR 1.40, 95% CI 1.33-1.47), global impression (very much/much better) (RR 1.55, 95% CI 1.44-1.67), and no/mild disability (RR 1.15, 95% CI 1.10-1.20) at 2?h. For the safety, significant number of patients experienced TEAEs with lasmiditan than with placebo (RR 2.77, 95% CI 2.53-3.03), most TEAEs were central nervous system (CNS)-related and included dizziness (RR 5.81, 95% CI 4.72-7.14), nausea (RR 2.58, 95% CI 1.87-3.57), fatigue (RR 5.38, 95% CI 3.78-7.66), paraesthesia (RR 4.48, 95% CI 3.33-6.02), and somnolence (RR 2.82, 95% CI 2.18-3.66). CONCLUSIONS:This meta-analysis suggests that lasmiditan is effective for the acute treatment of migraine with a higher incidence of CNS-related adverse reactions compared with placebo. Long-term, open-label, multi-dose trials are required to verify the current findings.
Project description:A systematic review and meta-analysis was conducted to explore the effect of a eutectic mixture of local anaesthetics (EMLA) on pain reduction during extracorporeal shockwave lithotripsy (ESWL). PubMed, Web of Science, Embase, EBSCO, and Cochrane library databases (updated March 2020) were searched for randomised controlled trials (RCTs) assessing the effect of EMLA for patients that underwent ESWL. The search strategy and study selection process were managed according to the PRISMA statement. Six RCTs were included in the meta-analysis. Overall, the results indicated that EMLA significantly reduced pain compared to the control group (RR = -2.98, 95% CI = -5.82 to -0.13, P = 0.04) with a heterogeneity of I2 = 57% (P = 0.04). Subgroup analysis showed that EMLA did not significantly reduce pain when the patients took an analgesic premedication (RR = -1.46, 95% CI = -5.89 to 2.98, P = 0.52) with a heterogeneity of I2 = 38% (P = 0.52). Conversely, studies without premedication showed a significant pain relief effect (RR = -4.08, 95% CI = -7.36 to -0.65, P = -0.80) with a heterogeneity of I2 = 48% (P = 0.14). Most studies showed there was no difference in the patient's need for analgesics. EMLA was effective for reducing pain during EWSL. However, this analgesic effect was limited and did not reduce the need for analgesics.
Project description:BACKGROUND:Chronic low back pain (CLBP) is a common and often disabling musculoskeletal condition. Yoga has been proven to be an effective therapy for chronic low back pain. However, there are still controversies about the effects of yoga at different follow-up periods and compared with other physical therapy exercises. OBJECTIVE:To critically compare the effects of yoga for patients with chronic low back pain on pain, disability, quality of life with non-exercise (e.g. usual care, education), physical therapy exercise. METHODS:This study was registered in PROSPERO, and the registration number was CRD42020159865. Randomized controlled trials (RCTs) of online databases included PubMed, Web of Science, Cochrane Central Register of Controlled Trials, Embase which evaluated effects of yoga for patients with chronic low back pain on pain, disability, and quality of life were searched from inception time to November 1, 2019. Studies were eligible if they assessed at least one important outcome, namely pain, back-specific disability, quality of life. The Cochrane risk of bias tool was used to assess the methodological quality of included randomized controlled trials. The continuous outcomes were analyzed by calculating the mean difference (MD) or standardized mean difference (SMD) with 95% confidence intervals (CI) according to whether combining outcomes measured on different scales or not. RESULTS:A total of 18 randomized controlled trials were included in this meta-analysis. Yoga could significantly reduce pain at 4 to 8 weeks (MD = -0.83, 95% CI = -1.19 to -0.48, p<0.00001, I2 = 0%), 3 months (MD = -0.43, 95% CI = -0.64 to -0.23, p<0.0001, I2 = 0%), 6 to 7 months (MD = -0.56, 95% CI = -1.02 to -0.11, p = 0.02, I2 = 50%), and was not significant in 12 months (MD = -0.52, 95% CI = -1.64 to 0.59, p = 0.36, I2 = 87%) compared with non-exercise. Yoga was better than non-exercise on disability at 4 to 8 weeks (SMD = -0.30, 95% CI = -0.51 to -0.10, p = 0.003, I2 = 0%), 3 months (SMD = -0.31, 95% CI = -0.45 to -0.18, p<0.00001, I2 = 30%), 6 months (SMD = -0.38, 95% CI = -0.53 to -0.23, p<0.00001, I2 = 0%), 12 months (SMD = -0.33, 95% CI = -0.54 to -0.12, p = 0.002, I2 = 9%). There was no significant difference on pain, disability compared with physical therapy exercise group. Furthermore, it suggested that there was a non-significant difference on physical and mental quality of life between yoga and any other interventions. CONCLUSION:This meta-analysis provided evidence from very low to moderate investigating the effectiveness of yoga for chronic low back pain patients at different time points. Yoga might decrease pain from short term to intermediate term and improve functional disability status from short term to long term compared with non-exercise (e.g. usual care, education). Yoga had the same effect on pain and disability as any other exercise or physical therapy. Yoga might not improve the physical and mental quality of life based on the result of a merging.
Project description:Dezocine is considered to be an alternative medication for managing postoperative pain. The aim of this study was to assess the efficacy and safety of this drug in this regard.Medline, EMBASE and the Cochrane Central Register of Control Trials (CENTRAL) were searched to identify all randomized controlled trials (RCTs) that compare dezocine with placebo or dezocine with morphine on postoperative pain. The data were extracted and pooled using Mantel-Haenszel random effects model. Heterogeneity was tested using the I2 statistic with values >50% and Chi2 test with P ? 0.05 indicating obvious heterogeneity between the studies.Seven trials evaluating 665 patients were included. The number of patients with at least 50% pain relief was increased (N = 234; RR 3.04, 95% CI 2.27 to 4.08) and physician (N = 465; RR 2.84, 95% CI 1.66 to 4.84) and patient satisfaction (N = 390; RR 2.81, 95% CI 1.85 to 4.26) were improved following the administration of dezocine compared with the placebo. The effects of dezocine were similar to those of morphine in terms of the number of patients reporting at least 50% pain relief within 2-6 h after surgery (N = 235; RR 1.29, 95% CI 1.15 to 1.46) and physician (N = 234; RR 1.18, 95% CI 0.93 to 1.49) and patient (N = 158; RR 1.33, 95% CI 0.93 to 1.92) satisfaction. While, the number of patients with at least 50% pain relief within 0-1 h after surgery increased following dezocine compared with morphine treatment (N = 79; RR 1.45, 95% CI 1.18 to 1.77). There was no difference in the incidence of postoperative nausea and vomiting (PONV) following dezocine treatment compared with the placebo (N = 391; RR 1.06, 95% CI 0.42 to 2.68) or morphine treatment (N = 235; RR 0.65, 95% CI 0.14 to 2.93).Dezocine is a promising analgesic for preventing postoperative pain, but further studies are required to evaluate its safety.
Project description:Introduction:Catheter ablation has shown to reduce mortality in patient with atrial fibrillation (AF) and heart failure (HF) with reduced ejection fraction. Its effect on mortality in patients without HF has not been well elucidated. Methods:Thirteen randomized controlled trials encompassing 3856 patients were selected using PubMed, Embase and the CENTRAL till April 2019. Estimates were reported as random effects risk ratio (RR) with 95% confidence intervals (CI). Results:Compared with medical therapy, catheter ablation did not reduce the risk of all-cause mortality (RR, 0.86, 95% CI, 0.62-1.19, P=0.36; I2=0), stroke (RR, 0.55, 95% CI, 0.18-1.66, P=0.29; I2=0), need for cardioversion (RR, 0.84, 95% CI, 0.66-1.08, P=0.17; I2=0) or pacemaker (RR, 0.59, 95% CI, 0.34-1.01, P=0.06; I2=0). However, ablation reduced the RR of cardiac hospitalization (0.37, 95% CI, 0.18-0.77, P=0.01; I2=86), and recurrent atrial arrhythmia (0.46, 95% CI, 0.35-0.60, P<0.001; I2=87). There were non-significant differences among treatment groups with respect to major bleeding (RR, 1.89, 95% CI, 0.59-6.08, P=0.29; I2=15), and pulmonary vein stenosis (RR, 3.00, 95% CI, 0.83-10.87, P=0.09; I2=0), but had significantly higher rates of pericardial tamponade (RR, 4.46, 95 % CI, 1.70-11.72, P<0.001; I2=0). Conclusions:Catheter ablation did not improve survival compared with medical therapy in patients with AF without HF. Catheter ablation reduced cardiac hospitalization and recurrent atrial arrhythmia at the expense of pericardial tamponade.
Project description:OBJECTIVE:Our aim was to assess the safety of cyclooxygenase-2 (COX-2) inhibitors in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials. METHODS:A comprehensive literature search was undertaken in the databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with COX-2 inhibitors in patients with OA were eligible for inclusion. Two authors appraised titles, abstracts and full-text papers for suitability and then assessed the studies for random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data and selective outcomes reporting. The primary outcomes of interest were gastrointestinal disorders, cardiac disorders, vascular disorders, nervous system disorders, skin and subcutaneous tissue disorders, hepatobiliary disorders, renal and urinary disorders, as well as overall severe and serious AEs, drug-related AEs and mortality. Secondary outcomes were withdrawals due to AEs (i.e. the number of participants who stopped the treatment due to an AE) and total number of AEs (i.e. the number of patients who experienced any AE at least once). RESULTS:Database searches identified 2149 records from which, after exclusions, 40 trials were included in the meta-analysis. The use of COX-2 inhibitors in OA was associated with a significant increased risk of drug-related AEs compared with placebo (relative risk (RR) 1.26, 95% CI 1.09-1.46; I2 = 24%). The risk of upper gastrointestinal complications (including dyspepsia, gastritis and heartburn) was significantly increased with COX-2 inhibitors versus placebo (RR 1.19, 95% CI 1.03-1.38; I2 = 0%), particularly for abdominal pain, which increased by 40% with COX-2 inhibitors (RR 1.40, 95% CI 1.08-1.80; I2 = 0%). The risk of hypertension increased by 45% overall (RR 1.45, 95% CI 1.01-2.10; I2 = 25%); however, when rofecoxib was removed from the analysis the risk of hypertension in the COX-2 inhibitor group was no longer significant (RR 1.21, 95% CI 0.80-1.83; I2 = 20%). The overall risk of heart failure and edema was increased by nearly 70% with COX-2 inhibitors versus placebo (RR 1.68, 95% CI 1.22-2.31; 0%) and this level of risk did not change appreciably when rofecoxib was excluded (RR 1.67, 95% CI 1.21-2.29; 0%). CONCLUSIONS:In our analysis, COX-2 inhibitors were associated with an increased risk of upper gastrointestinal AEs, especially abdominal pain. We also found an increased risk of cardiovascular AEs with COX-2 inhibitors, namely hypertension, heart failure and edema.