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Clinical Autonomic Research : Official... Aug 2019Diabetic neuropathy is a common and disabling disorder, and there are currently no proven effective disease-modifying treatments. Physical activity and dietary... (Review)
Review
PURPOSE
Diabetic neuropathy is a common and disabling disorder, and there are currently no proven effective disease-modifying treatments. Physical activity and dietary interventions in patients with diabetes and diabetic neuropathy have multiple beneficial effects and are generally low risk, which makes lifestyle interventions an attractive treatment option. We reviewed the literature on the effects of physical activity and dietary interventions on length-dependent peripheral neuropathy and cardiac autonomic neuropathy in diabetes.
METHODS
The electronic database PubMed was systematically searched for original human and mouse model studies examining the effect of either dietary or physical activity interventions in subjects with diabetes, prediabetes, or metabolic syndrome.
RESULTS
Twenty studies are included in this review. Fourteen studies were human studies and six were in mice. Studies were generally small with few controlled trials, and there are no widely agreed upon outcome measures.
CONCLUSIONS
Recent research indicates that dietary interventions are effective in modifying diabetic neuropathy in animal models, and there are promising data that they may also ameliorate diabetic neuropathy in humans. It has been known for some time that lifestyle interventions can prevent the development of diabetic neuropathy in type 2 diabetes mellitus subjects. However, there is emerging evidence that lifestyle interventions are effective in individuals with established diabetic neuropathy. In addition to the observed clinical value of lifestyle interventions, there is emerging evidence of effects on biochemical pathways that improve muscle function and affect other organ systems, including the peripheral nerve. However, data from randomized controlled trials are needed.
Topics: Animals; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Diet, Healthy; Exercise; Humans; Overweight; Risk Reduction Behavior
PubMed: 31076938
DOI: 10.1007/s10286-019-00607-x -
Diabetes/metabolism Research and Reviews Jan 2016Prevention of foot ulcers in patients with diabetes is extremely important to help reduce the enormous burden of foot ulceration on both patient and health resources. A... (Review)
Review
BACKGROUND
Prevention of foot ulcers in patients with diabetes is extremely important to help reduce the enormous burden of foot ulceration on both patient and health resources. A comprehensive analysis of reported interventions is not currently available, but is needed to better inform caregivers about effective prevention. The aim of this systematic review is to investigate the effectiveness of interventions to prevent first and recurrent foot ulcers in persons with diabetes who are at risk for ulceration.
METHODS
The available medical scientific literature in PubMed, EMBASE, CINAHL and the Cochrane database was searched for original research studies on preventative interventions. Both controlled and non-controlled studies were selected. Data from controlled studies were assessed for methodological quality by two independent reviewers.
RESULTS
From the identified records, a total of 30 controlled studies (of which 19 RCTs) and another 44 non-controlled studies were assessed and described. Few controlled studies, of generally low to moderate quality, were identified on the prevention of a first foot ulcer. For the prevention of recurrent plantar foot ulcers, multiple RCTs with low risk of bias show the benefit for the use of daily foot skin temperature measurements and consequent preventative actions, as well as for therapeutic footwear that demonstrates to relieve plantar pressure and that is worn by the patient. To prevent recurrence, some evidence exists for integrated foot care when it includes a combination of professional foot treatment, therapeutic footwear and patient education; for just a single session of patient education, no evidence exists. Surgical interventions can be effective in selected patients, but the evidence base is small.
CONCLUSION
The evidence base to support the use of specific self-management and footwear interventions for the prevention of recurrent plantar foot ulcers is quite strong, but is small for the use of other, sometimes widely applied, interventions and is practically nonexistent for the prevention of a first foot ulcer and non-plantar foot ulcer.
Topics: Combined Modality Therapy; Cost of Illness; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Foot; Evidence-Based Medicine; Humans; Patient Compliance; Patient Education as Topic; Precision Medicine; Recurrence; Risk Factors; Self Care; Shoes
PubMed: 26340966
DOI: 10.1002/dmrr.2701 -
Complementary Therapies in Clinical... Feb 2019Honey dressing has been applied in the treatment of diabetic foot ulcers (DFUs). However, there is a lack of research showing ample evidence that honey dressing is more... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Honey dressing has been applied in the treatment of diabetic foot ulcers (DFUs). However, there is a lack of research showing ample evidence that honey dressing is more effective in the treatment of DFUs than other dressings. This study aimed to examine the effects of honey dressing on wound-healing process for DFUs.
METHOD
We searched for evidence regarding honey dressing used in the treatment of DFUs in various databases. We selected randomized controlled trials (RCTs) and quasi-experimental studies for meta-analysis.
RESULTS
The meta-analysis showed that honey dressing effectively shortened the wound debridement time, wound healing time, and bacterial clearance time; it increased the wound healing rate and bacterial clearance rate during the first one to two weeks of use.
CONCLUSION
Our findings suggest that honey dressing effectively promotes healing in DFUs. Further research is needed to elucidate these findings so that this form of treatment can be widely applied.
Topics: Bandages, Hydrocolloid; Diabetic Foot; Honey; Humans; Randomized Controlled Trials as Topic; Wound Healing
PubMed: 30712715
DOI: 10.1016/j.ctcp.2018.09.004 -
Annals of Clinical and Translational... Oct 2019Diabetic neuropathy (DN) is one of the most common complications of diabetes that occurs in more than 67% of individuals with diabetes. Genetic polymorphisms may play an... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Diabetic neuropathy (DN) is one of the most common complications of diabetes that occurs in more than 67% of individuals with diabetes. Genetic polymorphisms may play an important role in DN development. However, until now, the association between genetic polymorphisms and DN risk has remained unknown. We performed a systematic review, meta-analysis, and trial sequential analysis (TSA) of the association between all genetic polymorphisms and DN risk.
METHODS
Relevant published studies examining the relationship between all genetic polymorphisms and DN were obtained based on a designed search strategy up to 28 February 2019. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess overall pooled effects of genetic models as well as in subgroup analyses. Sensitive analysis and publication bias were applied to evaluate the reliability of the study. Moreover, TSA was conducted to estimate the robustness of the results.
RESULTS
We conducted a systematic review of a total of 1256 articles, and then 106 publications reporting on 136 polymorphisms of 76 genes were extracted. We performed 107 meta-analyses on 36 studies involving 12,221 subjects to derive pooled effect estimates for eight polymorphisms. We identified that ACE I>D, MTHFR 1298A/C, GPx-1 rs1050450, and CAT -262C/T were associated with DN, while MTHFR C677T, GSTM1, GSTT1, and IL-10 -1082G/A were not. Sensitivity analysis, funnel plot, and Egger's test displayed robust results. Furthermore, the results of TSA indicated sufficient sample size in studies of ACE, GPx-1, GSTM1, and IL-10 polymorphisms.
INTERPRETATION
Our study assessed the association between ACE I>D, MTHFR C677T, MTHFR 1298A/C, GPx-1 rs1050450, CAT -262C/T, GSTM1, GSTT1, and IL-10 -1082G/A polymorphisms and DN risk. We hope that the data in our research study are used to study DN genetics.
Topics: Clinical Trials as Topic; Diabetic Neuropathies; Humans
PubMed: 31557408
DOI: 10.1002/acn3.50892 -
The Cochrane Database of Systematic... Jan 2019This review updates part of an earlier Cochrane Review titled "Pregabalin for acute and chronic pain in adults", and considers only neuropathic pain (pain from damage to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This review updates part of an earlier Cochrane Review titled "Pregabalin for acute and chronic pain in adults", and considers only neuropathic pain (pain from damage to nervous tissue). Antiepileptic drugs have long been used in pain management. Pregabalin is an antiepileptic drug used in management of chronic pain conditions.
OBJECTIVES
To assess the analgesic efficacy and adverse effects of pregabalin for chronic neuropathic pain in adults.
SEARCH METHODS
We searched CENTRAL, MEDLINE, and Embase for randomised controlled trials from January 2009 to April 2018, online clinical trials registries, and reference lists.
SELECTION CRITERIA
We included randomised, double-blind trials of two weeks' duration or longer, comparing pregabalin (any route of administration) with placebo or another active treatment for neuropathic pain, with participant-reported pain assessment.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed trial quality and biases. Primary outcomes were: at least 30% pain intensity reduction over baseline; much or very much improved on the Patient Global Impression of Change (PGIC) Scale (moderate benefit); at least 50% pain intensity reduction; or very much improved on PGIC (substantial benefit). We calculated risk ratio (RR) and number needed to treat for an additional beneficial (NNTB) or harmful outcome (NNTH). We assessed the quality of the evidence using GRADE.
MAIN RESULTS
We included 45 studies lasting 2 to 16 weeks, with 11,906 participants - 68% from 31 new studies. Oral pregabalin doses of 150 mg, 300 mg, and 600 mg daily were compared with placebo. Postherpetic neuralgia, painful diabetic neuropathy, and mixed neuropathic pain predominated (85% of participants). High risk of bias was due mainly to small study size (nine studies), but many studies had unclear risk of bias, mainly due to incomplete outcome data, size, and allocation concealment.Postherpetic neuralgia: More participants had at least 30% pain intensity reduction with pregabalin 300 mg than with placebo (50% vs 25%; RR 2.1 (95% confidence interval (CI) 1.6 to 2.6); NNTB 3.9 (3.0 to 5.6); 3 studies, 589 participants, moderate-quality evidence), and more had at least 50% pain intensity reduction (32% vs 13%; RR 2.5 (95% CI 1.9 to 3.4); NNTB 5.3 (3.9 to 8.1); 4 studies, 713 participants, moderate-quality evidence). More participants had at least 30% pain intensity reduction with pregabalin 600 mg than with placebo (62% vs 24%; RR 2.5 (95% CI 2.0 to 3.2); NNTB 2.7 (2.2 to 3.7); 3 studies, 537 participants, moderate-quality evidence), and more had at least 50% pain intensity reduction (41% vs 15%; RR 2.7 (95% CI 2.0 to 3.5); NNTB 3.9 (3.1 to 5.5); 4 studies, 732 participants, moderate-quality evidence). Somnolence and dizziness were more common with pregabalin than with placebo (moderate-quality evidence): somnolence 300 mg 16% versus 5.5%, 600 mg 25% versus 5.8%; dizziness 300 mg 29% versus 8.1%, 600 mg 35% versus 8.8%.Painful diabetic neuropathy: More participants had at least 30% pain intensity reduction with pregabalin 300 mg than with placebo (47% vs 42%; RR 1.1 (95% CI 1.01 to 1.2); NNTB 22 (12 to 200); 8 studies, 2320 participants, moderate-quality evidence), more had at least 50% pain intensity reduction (31% vs 24%; RR 1.3 (95% CI 1.2 to 1.5); NNTB 22 (12 to 200); 11 studies, 2931 participants, moderate-quality evidence), and more had PGIC much or very much improved (51% vs 30%; RR 1.8 (95% CI 1.5 to 2.0); NNTB 4.9 (3.8 to 6.9); 5 studies, 1050 participants, moderate-quality evidence). More participants had at least 30% pain intensity reduction with pregabalin 600 mg than with placebo (63% vs 52%; RR 1.2 (95% CI 1.04 to 1.4); NNTB 9.6 (5.5 to 41); 2 studies, 611 participants, low-quality evidence), and more had at least 50% pain intensity reduction (41% vs 28%; RR 1.4 (95% CI 1.2 to 1.7); NNTB 7.8 (5.4 to 14); 5 studies, 1015 participants, low-quality evidence). Somnolence and dizziness were more common with pregabalin than with placebo (moderate-quality evidence): somnolence 300 mg 11% versus 3.1%, 600 mg 15% versus 4.5%; dizziness 300 mg 13% versus 3.8%, 600 mg 22% versus 4.4%.Mixed or unclassified post-traumatic neuropathic pain: More participants had at least 30% pain intensity reduction with pregabalin 600 mg than with placebo (48% vs 36%; RR 1.2 (1.1 to 1.4); NNTB 8.2 (5.7 to 15); 4 studies, 1367 participants, low-quality evidence), and more had at least 50% pain intensity reduction (34% vs 20%; RR 1.5 (1.2 to 1.9); NNTB 7.2 (5.4 to 11); 4 studies, 1367 participants, moderate-quality evidence). Somnolence (12% vs 3.9%) and dizziness (23% vs 6.2%) were more common with pregabalin.Central neuropathic pain: More participants had at least 30% pain intensity reduction with pregabalin 600 mg than with placebo (44% vs 28%; RR 1.6 (1.3 to 2.0); NNTB 5.9 (4.1 to 11); 3 studies, 562 participants, low-quality evidence) and at least 50% pain intensity reduction (26% vs 15%; RR 1.7 (1.2 to 2.3); NNTB 9.8 (6.0 to 28); 3 studies, 562 participants, low-quality evidence). Somnolence (32% vs 11%) and dizziness (23% vs 8.6%) were more common with pregabalin.Other neuropathic pain conditions: Studies show no evidence of benefit for 600 mg pregabalin in HIV neuropathy (2 studies, 674 participants, moderate-quality evidence) and limited evidence of benefit in neuropathic back pain or sciatica, neuropathic cancer pain, or polyneuropathy.Serious adverse events, all conditions: Serious adverse events were no more common with placebo than with pregabalin 300 mg (3.1% vs 2.6%; RR 1.2 (95% CI 0.8 to 1.7); 17 studies, 4112 participants, high-quality evidence) or pregabalin 600 mg (3.4% vs 3.4%; RR 1.1 (95% CI 0.8 to 1.5); 16 studies, 3995 participants, high-quality evidence).
AUTHORS' CONCLUSIONS
Evidence shows efficacy of pregabalin in postherpetic neuralgia, painful diabetic neuralgia, and mixed or unclassified post-traumatic neuropathic pain, and absence of efficacy in HIV neuropathy; evidence of efficacy in central neuropathic pain is inadequate. Some people will derive substantial benefit with pregabalin; more will have moderate benefit, but many will have no benefit or will discontinue treatment. There were no substantial changes since the 2009 review.
Topics: Acute Disease; Adult; Analgesics; Chronic Disease; Diabetic Neuropathies; Dizziness; Humans; Neuralgia; Neuralgia, Postherpetic; Pain; Pregabalin; Randomized Controlled Trials as Topic; Sleepiness
PubMed: 30673120
DOI: 10.1002/14651858.CD007076.pub3 -
Pain Practice : the Official Journal of... Feb 2014Painful diabetic peripheral neuropathy (pDPN) is prevalent among persons with diabetes and increases over time. Published guidelines recommend a number of medications to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Painful diabetic peripheral neuropathy (pDPN) is prevalent among persons with diabetes and increases over time. Published guidelines recommend a number of medications to treat this condition providing clinicians with a variety of treatment options. This study provides a comprehensive systematic review and meta-analysis of published pharmacologic therapies for pDPN.
METHODS
The published literature was systematically searched to identify randomized, controlled trials of all available pharmacologic treatments for pDPN (recommended or nonrecommended) reporting predefined efficacy and safety outcomes. Bayesian fixed-effect mixed treatment comparison methods were used to assess relative therapeutic efficacy and harms.
RESULTS
Data from 58 studies including 29 interventions and 11,883 patients were analyzed. Pain reduction over that of placebo on the 11-point numeric rating scale ranged from -3.29 for sodium valproate (95% credible interval [CrI] = [-4.21, -2.36]) to 1.67 for Sativex (-0.47, 0.60). Estimates for most treatments were clustered between 0 and -1.5 and were associated with more study data and smaller CrIs. Pregabalin (≥ 300 mg/day) was the most effective on the 100-point visual analog scale (-21.88; [-27.06, -16.68]); topiramate was the least (-3.09; [-3.99, -2.18]). Relative risks (RRs) of 30% pain reduction ranged from 0.78 (Sativex) to 1.84 (lidocaine 5% plaster). Analysis of the RR ratio of these 2 treatments reveals marginal significance for Sativex (3.27; [1.07, 9.81]), indicating the best treatment is only slightly better than the worst. Relative risks of 50% pain reduction ranged from 0.98 (0.56, 1.52) (amitriptyline) to 2.25 (1.51, 3.00) (alpha-lipoic acid). RR ratio for these treatments was not statistically different (3.39; [0.88, 3.34]). Fluoxetine had the lowest risk of adverse events (0.94; [0.62, 1.23]); oxycodone had the highest (1.55; [1.45, 1.64]). Discontinuation RRs were clustered around 0.8 to 1.5, with those on the extreme having greater uncertainty.
CONCLUSIONS
Selecting an appropriate pDPN therapy is key given the large number of available treatments. Comparative results revealed relative equivalence among many of the studied interventions having the largest overall sample sizes and highlight the importance of standardization of methods to effectively assess pain.
Topics: Analgesics; Bayes Theorem; Diabetic Neuropathies; Humans; Neuralgia; Randomized Controlled Trials as Topic
PubMed: 23534696
DOI: 10.1111/papr.12054 -
Frontiers in Endocrinology 2023Vascular endothelial growth factors (VEGFs, including VEGF-A, VEGF-B, VEGF-C, VEGF-D and PLGF) have important roles in the development and function of the peripheral... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Vascular endothelial growth factors (VEGFs, including VEGF-A, VEGF-B, VEGF-C, VEGF-D and PLGF) have important roles in the development and function of the peripheral nervous system. Studies have confirmed that VEGFs, especially VEGF-A (so called VEGF) may be associated with the diabetic peripheral neuropathy (DPN) process. However, different studies have shown inconsistent levels of VEGFs in DPN patients. Therefore, we conducted this meta-analysis to evaluate the relationship between cycling levels of VEGFs and DPN.
METHODS
This study searched 7 databases, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, WanFang Database, and Chinese Biomedical Literature (CBM), to find the target researches. The random effects model was used to calculate the overall effect.
RESULTS
14 studies with 1983 participants were included, among which 13 studies were about VEGF and 1 was VEGF-B, so only the effects of VEGF were pooled. The result showed that there were obviously increased VEGF levels in DPN patients compared with diabetic patients without DPN (SMD:2.12[1.34, 2.90], <0.00001) and healthy people (SMD:3.50[2.24, 4.75], <0.00001). In addition, increased circulating VEGF levels were not associated with an increased risk of DPN (OR:1.02[0.99, 1.05], <0.00001).
CONCLUSION
Compared with healthy people and diabetic patients without DPN, VEGF content in the peripheral blood of DPN patients is increased, but current evidence does not support the correlation between VEGF levels and the risk of DPN. This suggests that VEGF may play a role in the pathogenesis and repairment of DPN.
Topics: Humans; Diabetes Mellitus; Diabetic Neuropathies; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor B
PubMed: 37251664
DOI: 10.3389/fendo.2023.1169405 -
Scientific Reports Jan 2021Studies have suggested that hyperbaric oxygen therapy (HBOT) is effective in the healing of diabetic foot ulcer (DFU); however, there is a lack of consensus. Therefore,... (Meta-Analysis)
Meta-Analysis
Studies have suggested that hyperbaric oxygen therapy (HBOT) is effective in the healing of diabetic foot ulcer (DFU); however, there is a lack of consensus. Therefore, to assess the efficacy of HBOT on diabetic foot ulcer among diabetic patients, controlled clinical trials were searched through PubMed, EMBASE, Clinical key, Ovid Discovery, ERMED, Clinical Trials.gov databases for randomized controlled trials (RCTs) and other sources until 15 September 2020. Studies that evaluated the effect of HBOT on diabetic foot ulcer, complete healing, amputation, adverse events, ulcer reduction area, and mortality rate were included. Of 1984 study records screened, 14 studies (768 participants) including twelve RCTs, and two CCTs were included as per inclusion criteria. The results with pooled analysis have shown that HBOT was significantly effective in complete healing of diabetic foot ulcer (OR = 0.29; 95% CI 0.14-0.61; I = 62%) and reduction of major amputation (RR = 0.60; 95% CI 0.39-0.92; I = 24%). Although, it was not effective for minor amputations (RR = 0.82; 95% CI 0.34-1.97; I = 79%); however, less adverse events were reported in standard treatment group (RR = 1.68; 95% CI 1.07-2.65; I = 0%). Nevertheless, reduction in mean percentage of ulcer area and mortality rate did not differ in HBOT and control groups. This review provides an evidence that hyperbaric oxygen therapy is effective as an adjunct treatment measure for the diabetes foot ulcers. These findings could be generalized cautiously by considering methodological flaws within all studies.
Topics: Amputation, Surgical; Controlled Clinical Trials as Topic; Diabetic Foot; Humans; Hyperbaric Oxygenation; Publication Bias; Risk; Treatment Outcome; Wound Healing
PubMed: 33500533
DOI: 10.1038/s41598-021-81886-1 -
BMC Endocrine Disorders Apr 2020Diabetes mellitus (DM) is a global health care problem that can impose a substantial economic burden. Diabetic peripheral neuropathy (DPN) is a common microvascular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetes mellitus (DM) is a global health care problem that can impose a substantial economic burden. Diabetic peripheral neuropathy (DPN) is a common microvascular complication of DM that increases the potential for morbidity and disability due to ulceration and amputation. Though there is a significant amount of variation in the primary studies on DM regarding the prevalence of DPN in Africa. Hence, this study was aimed to estimate the overall prevalence of DPN in DM patients in Africa.
METHODS
PubMed, Scopus, Google Scholar, African Journals OnLine, WHO African Library, and the Cochrane Review were systematically searched online to retrieve related articles. The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines was followed. Heterogeneity across the included studies was evaluated by the inconsistency index (I). Publication bias was examined by funnel plot and Egger's regression test. The random-effect model was fitted to estimate the pooled prevalence of diabetic peripheral neuropathy among patients in Africa. The meta-analysis was performed using the STATA™ Version 14 software.
RESULTS
Twenty-three studies which includes 269,691 participants were included in the meta-analysis. The overall pooled prevalence of diabetic peripheral neuropathy was 46% (95% CI:36.21-55.78%). Based on the subgroup analysis, the highest prevalence of diabetic peripheral neuropathy in DM patients was reported in West Africa at 49.4% (95% CI: 32.74, 66.06).
CONCLUSION
This study revealed that the overall prevalence of diabetic peripheral neuropathy is relatively high in Africa. Hence, DPN needs situation-based interventions and preventive strategies, which are specific to the country. Further meta-analysis is needed to identify associated factors for the occurrence of diabetic peripheral neuropathy.
Topics: Africa; Diabetes Mellitus; Diabetic Neuropathies; Humans; Prevalence; Prognosis; Risk Factors
PubMed: 32293400
DOI: 10.1186/s12902-020-0534-5 -
The Cochrane Database of Systematic... Jun 2017Gabapentin is commonly used to treat neuropathic pain (pain due to nerve damage). This review updates a review published in 2014, and previous reviews published in 2011,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gabapentin is commonly used to treat neuropathic pain (pain due to nerve damage). This review updates a review published in 2014, and previous reviews published in 2011, 2005 and 2000.
OBJECTIVES
To assess the analgesic efficacy and adverse effects of gabapentin in chronic neuropathic pain in adults.
SEARCH METHODS
For this update we searched CENTRAL), MEDLINE, and Embase for randomised controlled trials from January 2014 to January 2017. We also searched the reference lists of retrieved studies and reviews, and online clinical trials registries.
SELECTION CRITERIA
We included randomised, double-blind trials of two weeks' duration or longer, comparing gabapentin (any route of administration) with placebo or another active treatment for neuropathic pain, with participant-reported pain assessment.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed trial quality and potential bias. Primary outcomes were participants with substantial pain relief (at least 50% pain relief over baseline or very much improved on Patient Global Impression of Change scale (PGIC)), or moderate pain relief (at least 30% pain relief over baseline or much or very much improved on PGIC). We performed a pooled analysis for any substantial or moderate benefit. Where pooled analysis was possible, we used dichotomous data to calculate risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or harmful outcome (NNH). We assessed the quality of the evidence using GRADE and created 'Summary of findings' tables.
MAIN RESULTS
We included four new studies (530 participants), and excluded three previously included studies (126 participants). In all, 37 studies provided information on 5914 participants. Most studies used oral gabapentin or gabapentin encarbil at doses of 1200 mg or more daily in different neuropathic pain conditions, predominantly postherpetic neuralgia and painful diabetic neuropathy. Study duration was typically four to 12 weeks. Not all studies reported important outcomes of interest. High risk of bias occurred mainly due to small size (especially in cross-over studies), and handling of data after study withdrawal.In postherpetic neuralgia, more participants (32%) had substantial benefit (at least 50% pain relief or PGIC very much improved) with gabapentin at 1200 mg daily or greater than with placebo (17%) (RR 1.8 (95% CI 1.5 to 2.1); NNT 6.7 (5.4 to 8.7); 8 studies, 2260 participants, moderate-quality evidence). More participants (46%) had moderate benefit (at least 30% pain relief or PGIC much or very much improved) with gabapentin at 1200 mg daily or greater than with placebo (25%) (RR 1.8 (95% CI 1.6 to 2.0); NNT 4.8 (4.1 to 6.0); 8 studies, 2260 participants, moderate-quality evidence).In painful diabetic neuropathy, more participants (38%) had substantial benefit (at least 50% pain relief or PGIC very much improved) with gabapentin at 1200 mg daily or greater than with placebo (21%) (RR 1.9 (95% CI 1.5 to 2.3); NNT 5.9 (4.6 to 8.3); 6 studies, 1277 participants, moderate-quality evidence). More participants (52%) had moderate benefit (at least 30% pain relief or PGIC much or very much improved) with gabapentin at 1200 mg daily or greater than with placebo (37%) (RR 1.4 (95% CI 1.3 to 1.6); NNT 6.6 (4.9 to 9.9); 7 studies, 1439 participants, moderate-quality evidence).For all conditions combined, adverse event withdrawals were more common with gabapentin (11%) than with placebo (8.2%) (RR 1.4 (95% CI 1.1 to 1.7); NNH 30 (20 to 65); 22 studies, 4346 participants, high-quality evidence). Serious adverse events were no more common with gabapentin (3.2%) than with placebo (2.8%) (RR 1.2 (95% CI 0.8 to 1.7); 19 studies, 3948 participants, moderate-quality evidence); there were eight deaths (very low-quality evidence). Participants experiencing at least one adverse event were more common with gabapentin (63%) than with placebo (49%) (RR 1.3 (95% CI 1.2 to 1.4); NNH 7.5 (6.1 to 9.6); 18 studies, 4279 participants, moderate-quality evidence). Individual adverse events occurred significantly more often with gabapentin. Participants taking gabapentin experienced dizziness (19%), somnolence (14%), peripheral oedema (7%), and gait disturbance (14%).
AUTHORS' CONCLUSIONS
Gabapentin at doses of 1800 mg to 3600 mg daily (1200 mg to 3600 mg gabapentin encarbil) can provide good levels of pain relief to some people with postherpetic neuralgia and peripheral diabetic neuropathy. Evidence for other types of neuropathic pain is very limited. The outcome of at least 50% pain intensity reduction is regarded as a useful outcome of treatment by patients, and the achievement of this degree of pain relief is associated with important beneficial effects on sleep interference, fatigue, and depression, as well as quality of life, function, and work. Around 3 or 4 out of 10 participants achieved this degree of pain relief with gabapentin, compared with 1 or 2 out of 10 for placebo. Over half of those treated with gabapentin will not have worthwhile pain relief but may experience adverse events. Conclusions have not changed since the previous update of this review.
Topics: Adult; Amines; Analgesics; Chronic Disease; Chronic Pain; Cyclohexanecarboxylic Acids; Diabetic Neuropathies; Fibromyalgia; Gabapentin; Humans; Neuralgia; Neuralgia, Postherpetic; Numbers Needed To Treat; Randomized Controlled Trials as Topic; gamma-Aminobutyric Acid
PubMed: 28597471
DOI: 10.1002/14651858.CD007938.pub4