Gabapentin Patient Reviews for Small Nerve Peripheral Neuropathy

Context and Policy Issues

Neuropathic pain typically develops equally a result of lesions or disease that results in damage to the nervous organisation including areas such equally the peripheral nervus, the dorsal root ganglion or dorsal root, or the central nervous system.^{ane – 3} Neuropathic pain is characterized past pain in the absence of a stimulus, or where minor stimuli result in exaggerated levels of hurting.ⁱⁱⁱ The neuropathic pain experienced by patients is heterogeneous in etiology, pathophysiology, and clinical appearance. Neuropathic pain relates to a complex combination of sensory deficits including partial or consummate loss of sensation, and symptoms such equally dysaethesia (abnormal awareness, i.eastward., called-for) and paraesthesia (i.due east., tingling, prickling).² Based on sensory profiles, peripheral neuropathic hurting can be grouped into the following three subgroups: sensory loss (small and large fiber function and the presence of paradoxical heat sensation), thermal hyperalgesia (relatively preserved big and small fiber sensory functions in combination with heat and cold hyperalgesia and depression -intensity dynamic mechanical allodynia), and mechanical hyperalgesia (predominant loss of cold and oestrus-sensitive pocket-sized fiber function in combination with blunt pressure level hyperalgesia, pinprick hyperalgesia, and marked and more frequent dynamic mechanical allodynia).^ane

It is estimated that the prevalence of neuropathic pain is between 6.9% and 10% in the general population.⁴ Neuropathic pain is associated with a multitude of weather such as diabetes, shingles, amputation, HIV, and spinal string injury.³ While a number of pharmaceutical therapies exist for neuropathic pain treatment, several drawbacks exist. It is known that patients generally do not answer to non-steroidal anti-inflammatory drugs and resistance or insensitivity to opiates is common and thus non recommended.^{two , iii} Other therapy such equally serotonin and norepinephrine uptake inhibitors, antidepressants, and anticonvulsants are associated with negative side-effects and have limited to minor efficacy.^{2 , 3}

Gabapentin (GBP) is a Health Canada approved antiepileptic drug.⁵ In the U.k., GBP is licensed for the handling of peripheral and key neuropathic hurting in adults and in the Us information technology is marketed for post-herpetic neuralgia (PHN).³ The mechanism of action for GBP relates to its ability to bind with high-affinity to the blastoff-2-delta subunit of voltage-gated calcium channels located throughout the peripheral and cardinal nervous system; thus modifies the release of neurotransmitters and reduces excitability of nerve cells.^{iii , six} It is this mechanism of action that may produce analgesic effect in patients experiencing neuropathic pain.³ While there is evidence to support the use of GBP for patients with diabetic peripheral neuropathy (DPN) and PHN the efficacy for the off-label handling of other atmospheric condition requires examination.^{7 , eight}

The purpose of this study is to review the clinical effectiveness of GBP compared to other therapy (tricyclic antidepressants, serotonin–norepinephrine reuptake inhibitors, carbamazepine, topiramate) or placebo in adults with neuropathic pain.

This study serves as an update to CADTH's 2015⁸ and 2016^ix Rapid Response reports. These previous reports reviewed studies relating to neuropathic pain (non specific to any conditions) and two studies relating to HIV-associated neuropathic hurting, respectively. In the HIV-associated neuropathic pain written report,⁹ the review suggested that gabapentin may improve pain and sleep disturbances, however the pocket-size sample size of each report and limitations in the analyses conducted prevent strong conclusions. In the 2016 study,⁸ almost of the available RCT data pertained to DPN and PHN, information technology was ended that for DPN there was greater reduction in neuropathic hurting and increased risk of adverse events associated with gabapentin compared with placebo. For other conditions there were limited number of RCTs and for some conditions the show was from single RCTs.⁸

Enquiry Question

What is the clinical effectiveness of gabapentin for adults with neuropathic pain?

Primal Findings

The findings from four systematic reviews and ane RCT for gabapentin (GBP) compared to placebo or agile comparators is limited by quantity and quality of evidence for studies on neuropathic pain associated with conditions including chronic lower back hurting, fibromyalgia, mixed neuropathic pain, and nerve injury pain. While some studies reported little to no deviation in pain, the limited data preclude strong conclusions to exist drawn for the clinical efficacy of GBP. For patients with trigeminal neuralgia, conclusions near the efficacy of GBP compared to carbamazepine could not be made. Express bear witness suggests that there is no deviation between GBP and topiramate for the treatment of neuropathic pain. Common adverse events associated with GBP included somnolence, fatigue, drowsiness, and dizziness.

Methods

Literature Search Methods

A express literature search was conducted on key resource including Ovid Medline, Ovid Embase, PubMed, The Cochrane Library, University of York Eye for Reviews and Dissemination (CRD) databases and a focused Internet search. No methodological filters were applied to limit retrieval by publication type. The search was limited to English linguistic communication documents published betwixt Jan 1, 2014 and February ix, 2018.

Selection Criteria and Methods

One reviewer screened citations and selected studies. In the first level of screening, titles and abstracts were reviewed and potentially relevant articles were retrieved and assessed for inclusion. The final choice of full-text articles was based on the inclusion criteria presented in Table 1.

Exclusion Criteria

Articles were excluded if they did not meet the choice criteria outlined in Table 1, they were duplicate publications, they were included in systematic reviews, they were published prior to 2014, or they were included in previous CADTH reports. Articles were excluded if they were solely composed of patients with DPN or PHN.

Disquisitional Appraisal of Individual Studies

The included systematic reviews were critically appraised using AMSTAR 2,¹⁰ and the randomized studies were critically appraised using the Downs and Black Checklist.¹¹ Summary scores were not calculated for the included studies; rather, a review of the strengths and limitations of each included study were described narratively.

Summary of Evidence

Quantity of Enquiry Bachelor

A full of 368 citations were identified in the literature search. Following screening of titles and abstracts, 347 citations were excluded and 21 potentially relevant reports from the electronic search were retrieved for full-text review. Nineteen potentially relevant publications were retrieved from the grey literature search. Of these potentially relevant articles, 35 publications were excluded for various reasons, while five publications met the inclusion criteria and were included in this report. Appendix 1 describes the PRISMA flowchart of the study selection.

Summary of Study Characteristics

The details of the individual study characteristics for the included publications are provided in Appendix two.

Study Design, Aim and Patient Population

Cooper et al. published a Cochrane systematic review to assess the analgesic efficacy of GBP for fibromyalgia pain in adults.¹² This systematic review identified i relevant RCT from 2007 that included 150 patients.

Shanthanna et al. conducted a systematic review to determine the usefulness of either pregabalin or GBP in decreasing hurting and improving function in patients with chronic low back pain.¹³ This systematic review required patients to have predominant chronic low back hurting for three or more months and identified six relevant RCTs (n = 517) with 3 (n = 185) specifically related to GBP published between 2000 and 2016. One of the included GBP RCTs had a crossover design, while the other ii GBP RCTs had a parallel design.

Wiffen et al. published a Cochrane systematic review to assess the analgesic efficacy of GBP for chronic neuropathic pain in adults.ⁱⁱⁱ This systematic review identified 37 relevant RCTs published between 1998 and 2016 that included five,914 patients. The majority of the private trials focused on DPN and PHN. Since this patient population was non included in the nowadays RR, the summary will be on the other patient populations included in the systematic review (i.e., mixed neuropathic pain [one study], nervus injury pain [i study]). Other studies focusing on patient populations for radicular leg hurting, spinal string injury, nervus injury hurting, phantom limb pain, cancer-related neuropathic pain, and HIV-associated sensory neuropathies were described narratively.

Yuan et al. conducted a systematic review to evaluate the safety and efficacy of GBP compared with carbamazepine for the treatment of trigeminal neuralgia.^xiv This systematic review included 16 RCTs published between 2006 and 2014 yielding data from 1,311 patients. The private trials all originated from Mainland china and were published in Chinese.

A RCT by Nazarbaghi et al. published in 2017 followed patients with neuropathic pain attributed to polyneuropathy for 4 weeks.^fifteen This written report was conducted in Iran and included 30 patients. The mean age of patients was 63.6 years, and 40% of patients were female.

Interventions and Comparators

Cooper et al. assessed GBP at whatsoever dose, past any route, compared to placebo or whatsoever other active comparator.¹² The single RCT that was identified used a placebo control.

Shanthanna et al. assessed the following comparing: GBP versus placebo, and pregabalin versus placebo.¹³ A specific dose for GBP was not specified, withal across the three included RCTs GBP was administered at 300 mg once a twenty-four hours and increased on a weekly footing to a maximum dose of 1,200 mg per mean solar day or 15 mg/kg.

Wiffen et al. assessed GBP at in whatsoever dose, by whatever route compared to placebo or any other active comparator.^three The majority of studies used oral GBP or GBP encarbil at 1200 mg or higher daily.

Yuan et al. assessed GBP compared to carbamazepine; dosing was not specified.^fourteen

Nazarbaghi et al. assessed GBP 300 mg/mean solar day to a maximum of 900 mg/twenty-four hours compared to topiramate 50 mg/day to a maximum of 100 mg/day.^fifteen

Outcomes

Across all studies, the outcomes related to pain relief and safety or adverse events. For the systematic reviews by Cooper¹² and Wiffen,³ pain relief was assessed using the following criteria: 30% pain reduction at 12 weeks, 50% pain reduction at 12 weeks, Patient Global Impression of Change - whatsoever category of ''improve'' at 12 weeks (for Cooper et al.) or much/very much improved (for Wiffen et al.). Withdraws, serious agin events, and deaths were also planned outcomes to be assessed. For the Wiffen et al. systematic review, the secondary outcomes were described narratively and not focused on in the review; thus only studies reporting outcomes relevant to the master outcomes volition exist focused on in the CADTH report.

The individual RCTs included in the systematic review by Shanthanna assessed pain relief using a numerical rating scale or visual analogue scale.¹³ For consistency, these scales were converted into a common zero to ten numerical rating scale. Safety was assessed using the occurrence of serious adverse events.

The systematic review by Yuan examined the following outcomes: the effective rate of therapy (efficacy assessed via odds ratio), life satisfaction, and adverse reactions.^xiv

The RCT by Nazarbaghi evaluated severity of pain using a visual analogue scale with the following specifications: 0 (No Distress), 1 (2 cm, Annoying), 2 (four cm, Uncomfortable), 3 (6 cm, Dreadful), iv (8 cm, Horrible) and v (10 cm, Disturbing).¹⁵

Summary of Critical Appraisal

The details of the critical appraisal for the included publications are provided in Appendix 3.

The Cochrane systematic reviews for fibromyalgia past Cooper et al.¹² and neuropathic pain past Wiffen et al.ⁱⁱⁱ were assessed to exist of high quality. Both of these systematic reviews included clear components to the research question (population, intervention, comparator group, event) with the exception of the dosages which were unspecified. The systematic reviews used comprehensive literature search strategies and robust methods. The methods for the systematic reviews were pre-adamant with a registered protocol in place. Additionally, both systematic reviews selected studies and extracted data in duplicate or triplicate independently. For the individual studies included, each systematic review used the Cochrane risk of bias tool and clearly presented the results pertaining blinding, randomization, and allotment concealment. Where appropriate, publication bias was assessed. The Cooper systematic review did not warrant the use of a meta-assay due to identifying a single applicable RCT.¹² The included RCT was judged to have low or unclear take chances of bias. The Wiffen systematic review used appropriate statistical methods for the meta-analysis including the cess of heterogeneity, subgroup analysis, and assessment of the certainty of testify using GRADE (Grading of Recommendations Assessment, Development, and Evaluation). The bulk of the private studies in Wiffen Cochrane systematic review were of moderate quality.

The systematic review for chronic depression back pain by¹³ was generally of loftier quality. The enquiry question was clearly described with the exception of the dosages which were unspecified. A comprehensive literature search strategy and robust methods were used. The methods for the systematic review were pre-determined with a registered protocol in place. The studies were screened and the data was extracted in duplicate independently. The RCTs were assessed using the Cochrane risk of bias tool and aspects including blinding, randomization, and allocation concealment were clearly reported. Publication bias due to low sample size was commented on. Appropriate statistical methods were used for the meta-analysis; statistical heterogeneity was assessed using the Cochrane Q-exam, extracted results of studies were weighted, and sensitivity analysis based on alternate imputation methods was conducted. The quality of evidence was assessed using Course.

The systematic review¹⁴ for GBP compared to carbamazepine for patients with trigeminal neuralgia included a clear enquiry question with the exception of the dosages for both GBP and carbamazepine which were unspecified. A comprehensive literature search strategy was used, and written report choice and data extraction were performed in indistinguishable independently. Some of the statistical methods for the meta-analysis were appropriate, specifically for the investigation of heterogeneity and the adventure of bias. When heterogeneity was present (p-value < 0.10 or I² score > 50%), random-effects models were used. Risk of bias was assessed for individual studies using the Cochrane nomenclature to examine aspects including blinding, randomization, and allotment concealment. Risk of bias was assessed for individual studies using the Cochrane nomenclature, and risk of publication bias for the commonage studies was assessed using Egger'southward regression test.

The RCT^xv for GBP compared to topiramate for patients with neuropathic pain attributed to polyneuropathy included a clear research question. The doses were specified, however the details of the associated titration process were non included. The master written report effect to exist measured was clearly identified in the methods section and the characteristics of the patients were clearly described. The exact probability values were reported. Validity and reliability of the issue (visual analogue scale) were not reported. Issues pertaining to external validity were present (i.eastward., all-encompassing exclusion criteria, recruitment at a single clinic in Iran). The blinding process was not described and a power adding was not provided.

Summary of Findings

What is the clinical effectiveness of gabapentin for adults with neuropathic pain?

For adults with fibromyalgia pain, a systematic review identified a single RCT which indicated some numerical comeback over placebo for patients on GBP for various pain outcomes:49% of patients with fibromyalgia on GBP and 31% of patients on placebo achieved 30% or greater reduction in pain over baseline; 91% of patients on GBP and 47% of patients on placebo accomplished a patient global impression of change any category of "better".¹² More patients on GBP (sixteen%) discontinued the written report due to adverse events compared to placebo (ix%). Overall, the sparseness of evidence and methodological limitations in the individual trial contributed to the quality of testify classified as very low.

For adults with chronic depression back hurting assessed in the systematic review by Shanthanna et al.,¹³ very depression quality of prove indicated minimal improvement of chronic low back pain for GBP compared to placebo (mean deviation = 0.22 units, 95% CI: −0.5 to 0.07), where pain was assessed using a 0 to 10 numerical rating scale.^xiii Very low quality of bear witness indicated increased adventure of dizziness or unsteadiness (RR = 1.99, 95% CI: 1.17 to three.37) and fatigue or languor (RR = one.85, 95% CI: 1.12 to 3.05) for GBP compared to placebo. Moderate quality of testify indicated increased risk of visual disturbances/blurring of vision (RR = v.72, 95% CI: one.94 to 16.91), and low quality of evidence indicated increased risk for difficulty with mentation (RR = three.34, 95% CI: 1.54 to 7.25).

For adults with mixed neuropathic hurting, limited testify from a single report included in the Wiffen et al. Cochrane systematic review³ suggested no significant differences between GBP and placebo for at to the lowest degree 50% pain reduction over baseline (Take chances ratio = 1.45, 95% CI: 0.88 to ii.37).³ For patient global impression of change for the combined much improved or very much improved categories, an improvement was noted for GBP compared to placebo (Take a chance ratio = 2.17, 95% CI: ane.38 to three.41), but not for much improved (Risk ratio = ane.99, 95% CI: 0.92 to iv.28). For adults with nerve injury hurting, limited evidence from a unmarried study suggested no significant differences betwixt GBP and placebo for at to the lowest degree 50% hurting reduction over baseline (Risk ratio = 1.44, 95% CI: 0.65 to 3.22).³ For patient global impression of change for much or very much improved, an improvement was noted for GBP compared to placebo (Run a risk ratio = 2.21, 95% CI: ane.26 to iii.ninety), likewise as for much improved (Risk ratio = 3.6, 95% CI: 1.39 to 9.31).^three Other conditions assessed in this systematic review (radicular leg pain, spinal cord injury, nervus injury pain, phantom limb hurting, cancer-related neuropathic pain, HIV-associated sensory neuropathies) were of depression quality with a small-scale number of studies, participants, and events. For all conditions combined, adverse event withdrawals were more common with GBP (11%) than with placebo (8.ii%) (RR 1.4, (95% CI: 1.one to 1.7).³

For adults with trigeminal neuralgia, low quality evidence indicated that the total effective rate was like for GBP and carbamazepine (OR = 1.60, 95% CI: 1.18 to 2.16; p = 0.002).^fourteen Low quality evidence indicated that the life-satisfaction improvement was greater for GBP compared to carbamazepine (SMD = 0.97, 95% CI: 0.58 to 1.35; p < 0.001). Moderate quality of testify indicated that the adverse reaction rate was lower for GBP compared to carbamazepine (OR = 0.31, 95% CI: 0.24 to 0.41).

For adults with neuropathic pain attributed to polyneuropathy, a unmarried depression-quality RCT reported no significant differences between GBP and topiramate in terms of average reduction of neuropathic pain intensity attributed to polyneuropathy (GBP = 59.7% reduction, topiramate = 55.0% reduction, p = 0.48).^fifteen

Limitations

The systematic reviews were mostly well conducted, however all four did not report the specific dose of GBP or road of administration which could have potentially introduced heterogeneity thus limiting the applicability of the results.

With the exception of limited data, no major limitations to the Cochrane systematic reviews for fibromyalgia¹² or neuropathic pain³ were noted. The systematic review for chronic low back pain¹³ did not reveal whatsoever major limitations.

Limitations related to the statistical methods used in the meta-assay were noted for systematic review that compared GBP to carbamazepine for patients with trigeminal neuralgia.^xiv Firstly, it is unclear if the methods for the meta-assay were established prior to the conduct of the written report; a pre-published protocol was not referenced. It does not appear that weighting was used to business relationship for differences in sample sizes for the primary outcome of total effective rate. In addition, it is unclear if the take a chance estimates extracted were based on fully-adapted models. Sensitivity analyses were non reported or performed to investigate the potential impact of various covariates (i.due east., affliction severity), or the effect of removing low quality studies (i.e., high risk of bias). The private studies included in the systematic review were conducted in Mainland china and therefore information technology is unclear if the results are externally valid to the Canadian population. Sources of funding and conflict of interest were non reported for this systematic review.

The RCT comparison GBP to topiramate for patients with polyneuropathy had a number of limitations including a small-scale sample size (n = 30).^xv Firstly, the interventions were non described in acceptable detail. A limited description indicated that patients received a specific dose at the outset of the trial (GBP 300 mg/day, 50 mg/day topiramate) that was titrated to a maximum (GBP 900 mg/solar day, 100 mg/solar day topiramate) after a 4-week period. However, the details of the titration (i.e., incremental dose increase, duration between dose increases) were non provided. It is unclear if titration was conducted in the same manner between patients in the same handling group. The rationale for the dose was non provided, thus information technology is unclear if the starting and final dosages were equivalent or consistent with the therapeutic norm. The utilize of a visual counterpart scale presents concerns near the validity or reliability as references for its utilize and design were not provided. The external validity of the RCT was limited as participants were recruited from a single neurology clinic in Islamic republic of iran. Additionally, patients were excluded if they had taken other medications (tricyclic antidepressants, mexiletine hydrochloride, carbamazepine, phenytoin, valproate sodium and dextromethorphan drugs) inside 30 days). This trial stated that it was blinded, only did non provide details of the blinding procedure and the parties who were blinded. It was unclear if the trial was sufficiently powered as a ability calculation was not reported. The numerous limitations reduce the robustness of the findings highlighting the demand for caution when interpreting the conclusions.

Conclusions and Implications for Decision or Policy Making

This report serves as an update to CADTH's 2015^viii and 2016^nine Rapid Response reports. These previous reports reviewed neuropathic pain (not specific to any condition) and HIV-associated neuropathic pain, In the HIV-associated neuropathic hurting study, the review suggested that gabapentin may amend pain and sleep disturbances, however the small sample size of each study and limitations in the analyses conducted prevented stiff conclusions. In the 2016 report, near of the available RCT data pertained to DPN and PHN, and information technology was concluded that for DPN at that place was greater reduction in neuropathic hurting and increased chance of agin events associated with gabapentin compared with placebo. For other weather, in that location were limited number of RCTs and for some conditions the evidence was from single RCTs thus highlighting the need for a follow-up CADTH report.^viii

In the current CADTH written report four systematic reviews and one RCT assessed patients with neuropathic hurting associated with a variety of conditions including fibromyalgia, chronic low dorsum pain, mixed neuropathic pain, nervus injury hurting, trigeminal neuralgia, and polyneuropathy. Whether compared to placebo or an active comparator the available literature was limited, thus preventing conclusions to be drawn well-nigh the clinical effectiveness. The included RCT that assessed patients with polyneuropathy, while having several methodological limitations, reported no divergence between GBP and topiramate.

As the focus of this CADTH study was for adults with neuropathic hurting for conditions other than DPN and PHN. The findings for the clinical effectiveness of GBP on neuropathic hurting attributed to other conditions (i.e., fibromyalgia, chronic low back hurting, mixed neuropathic pain, nerve injury pain, and trigeminal neuralgia) were limited by the quantity and quality of individual studies; thus conclusions nigh the clinical effectiveness cannot be drawn. Further loftier-quality report is required to draw conclusions pertaining to the clinical benefits and harms for the use of GBP for neuropathic hurting related to these weather.

References

1.

2.

3.

Wiffen PJ, Derry S, Bong RF, Rice As, Tolle TR, Phillips T, et al. Gabapentin for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017 Jun 9;6:CD007938. [PMC free article: PMC6452908] [PubMed: 28597471]

iv.

v.

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PrNuerontin® (gabapentin): capsules 100 mg, 300 mg, and 400 mg tablets 600 mg and 800 mg [production monograph]. Kirkland (QC): Pfizer Canada Inc.; 2014 Sep 12.

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Cooper TE, Derry S, Wiffen PJ, Moore RA. Gabapentin for fibromyalgia pain in adults. Cochrane Database Syst Rev. 2017 Jan 3;1:CD012188. [PMC complimentary commodity: PMC6465053] [PubMed: 28045473]

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Yuan M, Zhou HY, Xiao ZL, Wang W, Li Forty, Chen SJ, et al. Efficacy and rubber of gabapentin vs. carbamazepine in the treatment of trigeminal neuralgia: a meta-analysis. Pain Pract. 2016 Feb 19;2016:1083–91. [PubMed: 26891784]

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sixteen.

Appendix i. Option of Included Studies

Appendix two. Characteristics of Included Publications

Table 2 Characteristics of Included Systematic Reviews and Meta-Analyses

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Commencement Author, Publication Year, Country	Type and Number of Primary Studies Included, Aim	Population Characteristics	Comparisons	Outcomes
Cooper,12 2017, United Kingdom	1 RCT To assess the analgesic efficacy of gabapentin for fibromyalgia pain in adults and the adverse events associated with its utilize in clinical trials.	Adults with fibromyalgia hurting. n = 150	GBP versus placebo GBP versus active comparator	Pain relief (i.eastward., xxx% hurting reduction at 12 weeks, fifty% pain reduction at 12 weeks, Patient Global Impression of Modify any category of "improve") Adverse events
Shanthanna,13 2017, Canada	6 RCTs (three related to GBP) To decide the usefulness of either pregabalin or GBP in decreasing pain and improving functions, and the potential adverse furnishings of pregabalin and GBP, in patients with predominant chronic low dorsum pain	Developed patients with predominant chronic low back hurting of 3 months or more. north = 517 (NGBP = 185)	GBP versus placebo Pregabalin versus placebo	Pain relief (0 to 10 NRS) Condom (adverse events)
Wiffen,3 2017, United Kingdom	37 double-blind RCTs To appraise the analgesic efficacy and adverse effects of gabapentin in chronic neuropathic pain in adults.	Patients with neuropathic pain. north = 5,914	GBP versus placebo GBP versus active comparator	Hurting relief (i.e., thirty% pain reduction at 12 weeks, l% pain reduction at 12 weeks, Patient Global Impression of Change – much or very much improved) Adverse events
Yuan,fourteen 2016, Prc	16 RCTs To evaluate the condom and efficacy of GBP in comparison with carbamazepine in the treatment of trigeminal neuralgia.	Patients with trigeminal neuralgia. n = 1,311	GBP versus carbamazepine	Effective rate of therapy Life satisfaction Agin reaction

GBP = gabapentin; NRS = numeric rating scale; RCT = randomized controlled trial.

Table 3 Characteristics of Included Clinical Studies

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First Author, Publication Year, Country	Study Blueprint, Length of Follow-upwardly	Patient Characteristics, Sample Size (n)	Intervention	Comparator(s)	Clinical Outcomes
Nazarbaghi,15 2017, Iran	RCT, 4 weeks	Patients with pain attributed to neuropathy Age, mean = 63.6 Female = xl% N = 30	GBP 300 mg/day to a maximum of 900 mg/twenty-four hours	Topiramate 50 mg/twenty-four hours to a maximum of 100 mg/24-hour interval	Severity of pain (visual counterpart scale)

GBP = gabapentin; RCT = randomized controlled trial.

Appendix 3. Critical Appraisal of Included Publications

Tabular array 4 Strengths and Limitations of Systematic Reviews and Meta-Analyses using AMSTAR ii¹⁰

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Strengths	Limitations
Cooper, 201712
The research question included the components of PICO (population, intervention, comparator grouping, outcome) The methods for the systematic review were established prior to the conduct of the study and the protocol was registered A comprehensive literature search strategy was used The study pick and information extraction were performed in indistinguishable independently The included study was described in acceptable detail Chance of bias was assessed for private studies using the Cochrane risk of bias tool, and publication bias was planned to be assessed Sources of funding were reported, and no conflict of interest was present	Dose for intervention was not specified
Shanthanna, 201713
The research question included the components of PICO (population, intervention, comparator group, upshot) The methods for the systematic review were established prior to the conduct of the study and the protocol was registered A comprehensive literature search strategy was used The study selection and data extraction was performed in indistinguishable independently Justification for studies that were excluded was provided The details of the individual studies were provided Risk of bias was assessed for private studies using the Cochrane adventure of bias tool Sources of funding was reported Generally, appropriate statistical methods were used for the meta-assay	Dose for intervention was non specified
Wiffen, 20173
The enquiry question included the components of PICO (population, intervention, comparator grouping, outcome) The methods for the systematic review were established prior to the carry of the study and the protocol was registered A comprehensive literature search strategy was used The study selection was performed in indistinguishable and data extraction was performed in triplicate independently Justification for studies that were excluded was provided The included studies were described in adequate detail Risk of bias was assessed for private studies using the Cochrane risk of bias tool, and publication bias was also assessed Sources of funding were reported, and no conflict of interest was present Statistical methods for the meta-analyses were appropriate	Dose for intervention was not specified
Yuan, 201614
The enquiry question included the components of PICO (population, intervention, comparator group, consequence) A comprehensive literature search strategy was used The study selection and data extraction was performed in duplicate independently Justification for studies that were excluded was provided The details of the private studies were provided Gamble of bias was assessed for individual studies using the Cochrane classification, and risk of publication bias for the collective studies was assessed using Egger's regression examination Some of the statistical methods for the meta-analysis were advisable (i.due east. investigation of heterogeneity)	Dose for intervention and comparator were non specified External validity to Canadian population unclear Unclear if the methods for the meta-assay were established prior to the conduct of the study Sources of funding and conflict of interest were not reported Some of the common statistical methods used in metaanalyses were referred to but non presented (i.e., sensitivity analyses), or not preformed (i.e., analysis omitting low quality studies)

Table v Strengths and Limitations of Randomized Controlled Trials using the Downs and Blackness Checklist¹¹

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Strengths	Limitations
Nazarbaghi, 2017fifteen
The aim of the study was clearly described The main study outcome to be measured was described in the methods section The characteristics of the patients included were clearly described The main findings of the report were clearly described Probability values were reported	The intervention was not conspicuously described (express description of titration process, unclear rationale for initial and final dose) No prove for the validity or reliability of the event (visual counterpart scale) were provided External validity was limited as participants were recruited from a single neurology clinic in Iran, and patients were excluded if they had taken other medications (tricyclic antidepressants, mexiletine hydrochloride, carbamazepine, phenytoin, valproate sodium and dextromethorphan drugs) within 30 days Blinding was stated, only details of the process were not provided Unclear if the trial was sufficiently powered, power calculation was not reported

Appendix 4. Main Written report Findings and Author'southward Conclusions

Tabular array six Summary of Findings of Included Studies

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Main Study Findings	Author's Conclusion
Cooper, 201712
49% of patients with fibromyalgia on GBP and 31% of patients on placebo achieved thirty% or greater reduction in hurting over baseline. 91% of patients on GBP and 47% of patients on placebo achieved a patient global impression of alter any category of "meliorate". 16% of patients on GBP and 9% of patients on placebo discontinued the study because of adverse events.	"We take only very depression quality evidence and are very uncertain about estimates of benefit and harm because of a small amount of data from a single trial. At that place is insufficient evidence to back up or refute the proposition that gabapentin reduces hurting in fibromyalgia." P.216
Shanthanna, 201713
Minimal comeback of chronic low dorsum pain was identified for GBP compared to placebo (mean divergence = 0.22 units, 95% CI: −0.5 to 0.07). The most frequently reported adverse events for handling with GBP were dizziness (RR = 1.99, 95% CI: 1.17 to 3.37), fatigue (RR = i.85, 95% CI: 1.12 to 3.05), difficulties with mentation (RR = three.34, 95% CI: one.54 to 7.25)., and visual disturbances (RR = 5.72, 95% CI: i.94 to 16.91).	"Existing testify on the use of gabapentinoids in chronic low back pain is express and demonstrates significant adventure of adverse furnishings without any demonstrated benefit. Given the lack of efficacy, risks, and costs associated, the use of gabapentinoids for chronic lower back pain merits circumspection." p.215
Wiffen, 2017three
For mixed neuropathic hurting information from one study determined no significant differences betwixt GBP and placebo for at least 50% hurting reduction over baseline (Gamble ratio = 1.45, 95% CI: 0.88 to 2.37). For patient global impression of change for much or very much improved, an comeback was noted for GBP compared to placebo (Risk ratio = 2.17, 95% CI: 1.38 to 3.41), but not for much improved (Risk ratio = ane.99, 95% CI: 0.92 to 4.28). For nerve injury pain data from one study determined no significant differences between GBP and placebo for at least 50% pain reduction over baseline (Risk ratio = 1.44, 95% CI: 0.65 to 3.22). Other atmospheric condition assessed (radicular leg hurting, spinal cord injury, nerve injury pain, phantom limb pain, cancer-related neuropathic pain, HIV-associated sensory neuropathies) were of low quality with a minor number of studies, participants, and events. For all conditions combined, adverse result withdrawals were more common with GBP (11%) than with placebo (viii.2%) (RR 1.4, (95% CI: 1.1 to 1.7). The most frequently reported adverse consequence for treatment with GBP were dizziness (19%), somnolence (14%), peripheral oedema (7%), and gait disturbance (14%).	"Gabapentin at doses of 1800 mg to 3600 mg daily (1200 mg to 3600 mg gabapentin encarbil) can provide proficient levels of hurting relief to some people with postherpetic neuralgia and peripheral diabetic neuropathy. Evidence for other types of neuropathic pain is very limited." p.210
Yuan, 2016fourteen
For patients with trigeminal neuralgia, the total effective charge per unit was similar for GBP and carbamazepine (OR = 1.sixty, 95% CI 1.18 to 2.xvi; p = 0.002). The life-satisfaction improvement was greater for GBP compared to carbamazepine (SMD = 0.97, 95% CI: 0.58 to one.35; p < 0.001). The agin reaction charge per unit was significantly lower in the GBP group compared to the carbamazepine group (OR = 0.31, 95% CI: 0.24 to 0.41; p < 0.001). The adverse reaction rate was lower for GBP compared to carbamazepine (OR = 0.31, 95% CI: 0.24 to 0.41). The most oftentimes reported adverse event for handling with GBP was vertigo, somnolence, fatigue and dizziness; for carbamazepine it was vertigo, somnolence, nausea, and fatigue.	"It is not possible to draw conclusions regarding the efficacy and side furnishings of gabapentin being superior to carbamazepine." p.1090
Nazarbaghi, 2017xv
At that place were no significant differences between GBP and topiramate in terms of average reduction of neuropathic pain intensity attributed to polyneuropathy (GBP = 59.7% reduction, topiramate = 55.0% reduction, p = 0.48). The most oft reported complication for treatment with GBP was drowsiness; for CBZ it was topiramate.	"…there was no clear difference between topiramate and gabapentin, and in cases of intolerance to gabapentin and other drugs such as antidepressants, topiramate tin can be replaced in the handling of neuropathic pain." p.5621

Nearly the Serial

CADTH Rapid Response Study: Summary with Disquisitional Appraisal

Version: i.0

Funding: CADTH receives funding from Canada's federal, provincial, and territorial governments, with the exception of Quebec.

Suggested citation:

Gabapentin for adults with neuropathic hurting: a review of the clinical effectiveness. Ottawa: CADTH; 2018 Mar. (CADTH rapid response report: summary with critical appraisal)

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Source: https://www.ncbi.nlm.nih.gov/books/NBK531934/

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