Trial Of Gabapentin Research Articles

Phase I/II trial of gabapentin plus intranasal ketamine for the prevention and treatment of pain in patients undergoing radiotherapy for head and neck cancer.

Phase I/II trial of gabapentin plus intranasal ketamine for the prevention and treatment of pain in patients undergoing radiotherapy for head and neck cancer.

A phase Ib/II randomized, open-label drug repurposing trial of glutamate signaling inhibitors in combination with chemoradiotherapy in patients with newly diagnosed glioblastoma: the GLUGLIO trial protocol

BackgroundGlioblastoma is the most common and most aggressive malignant primary brain tumor in adults. Glioblastoma cells synthesize and secrete large quantities of the excitatory neurotransmitter glutamate, driving epilepsy, neuronal death, tumor growth and invasion. Moreover, neuronal networks interconnect with glioblastoma cell networks through glutamatergic neuroglial synapses, activation of which induces oncogenic calcium oscillations that are propagated via gap junctions between tumor cells. The primary objective of this study is to explore the efficacy of brain-penetrating anti-glutamatergic drugs to standard chemoradiotherapy in patients with glioblastoma.Methods/designGLUGLIO is a 1:1 randomized phase Ib/II, parallel-group, open-label, multicenter trial of gabapentin, sulfasalazine, memantine and chemoradiotherapy (Arm A) versus chemoradiotherapy alone (Arm B) in patients with newly diagnosed glioblastoma. Planned accrual is 120 patients. The primary endpoint is progression-free survival at 6 months. Secondary endpoints include overall and seizure-free survival, quality of life of patients and caregivers, symptom burden and cognitive functioning. Glutamate levels will be assessed longitudinally by magnetic resonance spectroscopy. Other outcomes of interest include imaging response rate, neuronal hyperexcitability determined by longitudinal electroencephalography, Karnofsky performance status as a global measure of overall performance, anticonvulsant drug use and steroid use. Tumor tissue and blood will be collected for translational research. Subgroup survival analyses by baseline parameters include segregation by age, extent of resection, Karnofsky performance status, O6-methylguanine DNA methyltransferase (MGMT) promotor methylation status, steroid intake, presence or absence of seizures, tumor volume and glutamate levels determined by MR spectroscopy. The trial is currently recruiting in seven centers in Switzerland.Trial registrationNCT05664464. Registered 23 December 2022.

Post-Amputation Pain: Combined Analyses of Randomized Controlled Trials Evaluating Opioids and Gabapentinoids versus Placebo.

An estimated 185,000 patients per year undergo an extremity amputation in the United States (over 500 amputations/day). Prolonged postoperative opioid use, defined as the presence of a filled opioid prescription between 90 and 180 days following the operative amputation procedure, affects nearly 50% of amputees. Moreover, the use of preoperative benzodiazepines, muscle relaxants, anticonvulsants, and antidepressants is strongly linked to prolonged opioid use suggesting new therapeutic strategies are needed. The goal of this study was to better understand how well post-amputation pain is currently treated by selected pharmacologic agents and the success rates of these existing agents. The available literature on PubMed was screened for articles that used randomized-controlled trial (RCT) study designs and gabapentinoids (eg, gabapentin or pregabalin) or opioids (eg, morphine). Two morphine-related RCTs using at least 50% pain reduction responder criteria were combined and qualitatively compared with two gabapentin trials that were previously combined to understand the potential benefits of these drugs in post-amputation pain management compared with placebo. All 4 trials included measured post-amputation pain over a 4- to 6-week acute period. The combined opioid analysis demonstrated a treatment effect that favored morphine (P=0.02) over placebo and indicated the number needed to treat (NNT) of 3.9 (95% CI: 2.5, 9.3) patients. Similarly, the previously combined analysis of gabapentin trials favored gabapentin over placebo and indicated an estimated NNT of 8.9 (95% CI: 5.3, 27.8). Patients undergoing limb amputation have a clear unmet need for more adequate chronic pain control. Given that post-amputation pain is often diagnosed as a chronic condition, persisting for at least 90 days, our data highlight the need for larger sample sizes and longer-term controlled trials to better understand the advantages and disadvantages of chronic use of gabapentinoids and opioids/opioid combination drugs in this patient population.

Harms were detected but not reported in six clinical trials of gabapentin

ObjectivesWe sought to assess and report harms that were observed but not disclosed previously in clinical trials of gabapentin. Study Design and SettingWe reanalyzed individual participant data from six randomized parallel trials of gabapentin for neuropathic pain, and we conducted meta-analyses. Between 1996 and 2003, adult participants were assigned to gabapentin (600 mg–3,600 mg per day) or placebo for 7–14 weeks. We calculated the proportion of participants with: one or more adverse events (AEs), one or more serious AEs, discontinued, discontinued because AEs. We also estimated effects on AEs at three levels of aggregation using COSTART, a hierarchical system for classifying AEs: body system, midlevel system, preferred term. ResultsWe found evidence of important harms that were neither included in published trial reports nor included in systematic reviews. Aggregating related harms led to greater confidence that gabapentin might harm the nervous system and possibly the digestive, metabolic and nutritional, respiratory, sensory, and urogenital body systems. Nervous system harms were more common than previous reports suggest. ConclusionClinical trials identified harms that were not reported publicly, and journal articles overstated uncertainty about harms. Relying on journal articles to evaluate gabapentin's harms could contribute to incomplete and misleading conclusions in systematic reviews and guidelines. To prevent bias arising from the selective nonreporting of results, journal articles should describe how to access data for all harms observed in clinical trials (e.g., by sharing individual participant data).

Gabapentin monotherapy for epilepsy: A review.

Epilepsy is one of the most common chronic neurological disorders, affecting more than 50 million people globally. In this review we summarised the evidence from randomised controlled trials of gabapentin used as monotherapy for the treatment of focal epilepsy, both newly diagnosed and drug-resistant, with or without secondary generalisation. To assess the effects of gabapentin monotherapy for people with epileptic focal seizures with and without secondary generalisation. We searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 24 February 2020) on 25 February 2020. CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRA), and the specialised registers of Cochrane Review Groups including the Cochrane Epilepsy Group. We also searched several Russian databases, reference lists of relevant studies, ongoing trials registers, conference proceedings, and we contacted trial authors. We found five randomised controlled trials (3167 participants) comparing gabapentin to other antiepileptic drugs (AEDs) and differing doses of gabapentin as monotherapy for newly diagnosed focal epilepsy and drug- resistant focal epilepsy with or without secondary generalisation. Two review authors independently applied the inclusion criteria, assessed trial quality, risk of bias, and extracted data. We used the GRADE approach to assess the certainty of evidence and present seven patient-important outcomes in the "Summary of findings" tables. The quality of evidence was very low to moderate due to poor reporting quality, poor trial design, and other risks of bias, such as selective presentation of findings and potential heavy industry input. Better quality research may change our certainty in the effect estimates. None of the included trials reported on the number of people with 50% or greater reduction in seizures and time to withdrawal (retention time) in an extractable way. Gabapentin-treated participants were more likely to withdraw from treatment for any cause (285/539) than those treated with lamotrigine, oxcarbazepine, or topiramate pooled together (695/1317) (RR 1.13, 95% CI 1.02 to 1.25; 3 studies, 1856 participants; moderate-certainty evidence), but not carbamazepine. Fewer people treated with gabapentin withdrew from treatment owing to adverse events (190/525) than those treated with carbamazepine, oxcarbazepine, or topiramate (479/1238), (RR 0.79, 95% CI 0.69 to 0.91; 1763 participants, 3 studies; moderate-certainty evidence), but not lamotrigine.CONCLUSIONGabapentin as monotherapy probably controlled seizures no better and no worse than comparator AEDs (lamotrigine, carbamazepine, oxcarbazepine, and topiramate). Compared to carbamazepine, gabapentin was probably better in retaining people in studies and preventing withdrawals due to adverse events. The most common side effects associated with gabapentin were ataxia (poor co-ordination and unsteady gait), dizziness, fatigue, and drowsiness.

Feasibility of gabapentin as an intervention for neurorecovery after an acute spinal cord injury: Protocol.

This protocol is describing the first ever prospective, mock-efficacy, dose exploration trial design testing the feasibility of administering gabapentin in the acute setting as an intervention for neurorecovery. Gabapentin is an FDA-approved medication for treating seizures and postherpetic neuralgia and is used broadly off-label for neuropathic pain management for many conditions, including spinal cord injury. Emerging data suggests that when given early after spinal cord injury onset and in low-medium doses, gabapentin may have properties that promote recovery of neurological function. The objective of this trial is to assess the feasibility of conducting an efficacy trial in which gabapentin is started early after injury, is restricted in its dose, and is not used for pain management. Forty-two people aged 18 years or older with any level and any severity of spinal cord injury induced by a trauma will be enrolled, randomized, and have the first dose of study medication by 120 h post-injury onset. Participants will be randomly assigned to one of three groups: 600, 1,800 mg/day gabapentin, or placebo. Study medication will be given for a 90-day duration. Blinded assessments will be obtained at 7 days post-injury (baseline), 30 days post-injury (interim), after the 90-day treatment duration/approximately 3 months post-injury (end of treatment), and at 6 months post-injury (end of study). The key analysis parameters will evaluate feasibility of recruitment of target population, delivery of drug treatment protocol, maintenance of blinding, and retention of participants. Outputs from this trial will inform research and clinical practice on the effects of manipulating gabapentin for non-pain management purposes in the acute setting and will guide the development of a properly powered efficacy trial of gabapentin as an intervention for neurorecovery in spinal cord injury. The study was approved by the MetroHealth Institutional Review Board (IRB21-00609) and registered at clinicaltrials.gov prior to enrolling any participants. Dissemination will include peer-reviewed publications, presentations at professional conferences and in the community, and through other healthcare and public venues. www.ClinicalTrials.gov, identifier: NCT05302999; protocol version 1.1 approved 05/23/2022. National Institute on Disability, Independent Living and Rehabilitation Research.

Comparing the Value of Data Visualization Methods for Communicating Harms in Clinical Trials.

In clinical trials, harms (i.e., adverse events) are often reported by simply counting the number of people who experienced each event. Reporting only frequencies ignores other dimensions of the data that are important for stakeholders, including severity, seriousness, rate (recurrence), timing, and groups of related harms. Additionally, application of selection criteria to harms prevents most from being reported. Visualization of data could improve communication of multidimensional data. We replicated and compared the characteristics of 6 different approaches for visualizing harms: dot plot, stacked bar chart, volcano plot, heat map, treemap, and tendril plot. We considered binary events using individual participant data from a randomized trial of gabapentin for neuropathic pain. We assessed their value using a heuristic approach and a group of content experts. We produced all figures using R and share the open-source code on GitHub. Most original visualizations propose presenting individual harms (e.g., dizziness, somnolence) alone or alongside higher level (e.g., by body systems) summaries of harms, although they could be applied at either level. Visualizations can present different dimensions of all harms observed in trials. Except for the tendril plot, all other plots do not require individual participant data. The dot plot and volcano plot are favored as visualization approaches to present an overall summary of harms data. Our value assessment found the dot plot and volcano plot were favored by content experts. Using visualizations to report harms could improve communication. Trialists can use our provided code to easily implement these approaches.

Restoring invisible and abandoned trials of gabapentin for neuropathic pain: a clinical and methodological investigation

IntroductionGabapentin (Neurontin) is prescribed widely for conditions for which it has not been approved by regulators, including certain neuropathic pain conditions. There is limited evidence that gabapentin is safe and...

Gabapentin add-on treatment for drug-resistant focal epilepsy.

This is an updated version of the Cochrane Review previously published in 2018. Epilepsy is a common neurological disorder characterised by recurrent seizures. Most people with epilepsy have a good prognosis and their seizures are well controlled by a single antiepileptic drug, but up to 30% develop drug-resistant epilepsy, especially people with focal seizures. In this review, we summarised the evidence from randomised controlled trials (RCTs) of gabapentin, when used as an add-on treatment for drug-resistant focal epilepsy. To evaluate the efficacy and tolerability of gabapentin when used as an add-on treatment for people with drug-resistant focal epilepsy. For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid) on 11 August 2020. CRS Web includes randomised or quasi-randomised, controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialised Registers of Cochrane Review Groups including Epilepsy. We imposed no language restrictions. Randomised, placebo-controlled, double-blind, add-on trials of gabapentin in people with drug-resistant focal epilepsy. We also included trials using an active drug control group or comparing different doses of gabapentin. Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: seizure frequency, seizure freedom, treatment withdrawal (any reason) and adverse effects. Primary analyses were intention-to-treat. We also undertook sensitivity best-case and worst-case analyses. We estimated summary risk ratios (RR) for each outcome and evaluated dose-response in regression models. We identified no new studies for this update, therefore, the results and conclusions are unchanged. In the previous update of this review, we combined data from six trials in meta-analyses of 1206 randomised participants. The overall risk ratio (RR) for reduction in seizure frequency of 50% or more compared to placebo was 1.89 (95% confidence interval (CI) 1.40 to 2.55; 6 studies, 1206 participants; moderate-certainty evidence). Dose regression analysis (for trials in adults) showed increasing efficacy with increasing dose, with 25.3% (95% CI 19.3 to 32.3) of people responding to gabapentin 1800 mg compared to 9.7% on placebo, a 15.5% increase in response rate (95% CI 8.5 to 22.5). The RR for treatment withdrawal compared to placebo was 1.05 (95% CI 0.74 to 1.49; 6 trials, 1206 participants; moderate-certainty evidence). Adverse effects were significantly associated with gabapentin compared to placebo. RRs were as follows: ataxia 2.01 (99% CI 0.98 to 4.11; 3 studies, 787 participants; low-certainty evidence), dizziness 2.43 (99% CI 1.44 to 4.12; 6 studies, 1206 participants; moderate-certainty evidence), fatigue 1.95 (99% CI 0.99 to 3.82; 5 studies, 1161 participants; low-certainty evidence) and somnolence 1.93 (99% CI 1.22 to 3.06; 6 studies, 1206 participants; moderate-certainty evidence). There was no evidence of a difference for the adverse effects of headache (RR 0.79, 99% CI 0.46 to 1.35; 6 studies, 1206 participants; moderate-certainty evidence) or nausea (RR 0.95, 99% CI 0.52 to 1.73; 4 trials, 1034 participants; moderate-certainty evidence). Overall, the studies were at low to unclear risk of bias due to information on each risk of bias domain not being available. We judged the overall certainty of the evidence (using the GRADE approach) as low to moderate due to potential attrition bias resulting from missing outcome data and imprecise results with wide CIs. Gabapentin has efficacy as an add-on treatment in people with drug-resistant focal epilepsy, and seems to be fairly well-tolerated. However, the trials reviewed were of relatively short duration and provide no evidence for the long-term efficacy of gabapentin beyond a three-month period. The results cannot be extrapolated to monotherapy or to people with other epilepsy types. Further trials are needed to assess the long-term effects of gabapentin, and to compare gabapentin with other add-on drugs.

Gabapentin for Peri-Operative Pain Relief in Office Gynecological Surgery: A Double-Blind Randomized Controlled Trial

Background: This study aims to validate the use of gabapentin in peri-operative pain management for outpatient gynecological (GYN) office procedures using surgical abortion at gestational ages less than 24 weeks. Methods: We conducted a double-blind, randomized, placebo-controlled trial of gabapentin in an ambulatory surgical abortion center. Eligible participants were patients 18 years of age and older, English or Spanish speaking, seeking a surgical elective abortion with pain management consisting of local anesthesia and intravenous sedation at gestational ages from 5 to 23 6/7 weeks. The study site was Birth Control Care Center, an affiliated clinic with the University of Nevada Las Vegas School of Medicine. Patients received routine pain control plus either placebo or gabapentin 600 mg 1 - 2 h prior to surgery. The primary outcome measured was post-operative pain scores using a 100-point (100 mm) visual analog scale at 5 min after the procedure. Additionally, pain scores were obtained at 30 min and 24 h post-procedure. Other secondary outcomes measured were nausea and vomiting at 5 min and 24 h post-procedure. Results: From May 2017 to March 2018, 219 patients were recruited to this study from 400 patients who were offered participation. A total of 109 were randomized to gabapentin and 110 were randomized to placebo. Demographic characteristics, pregnancy history and general health conditions were similar. Pain scores at 5 min, 30 min and 24 h after the procedure were not significantly different between arms (P = 0.28), though pain was reported to decrease between 30 min and 24 h post-procedure (P < 0.001) for both groups. Nausea and vomiting were also not significantly reduced in the gabapentin group (P = 0.32 and 0.47), respectively. Conclusions: Patients who received gabapentin, in combination with the routine intravenous pain control and local anesthesia for office-based surgical abortion did not experience less pain at 5 min, 30 min, nor at 24 h after the procedure, compared to the placebo group. Gabapentin did not appear to reduce pain at 24 h after the procedure and is therefore unlikely to reduce narcotic use in this clinic sample treated with intravenous (IV) sedation. Further, gabapentin was not useful to reduce nausea and vomiting post-operatively in this clinic sample. J Clin Gynecol Obstet. 2020;9(4):96-101 doi: https://doi.org/10.14740/jcgo689

Preoperative Factors Associated with Remote Postoperative Pain Resolution and Opioid Cessation in a Mixed Surgical Cohort: Post Hoc Analysis of a Perioperative Gabapentin Trial.

BackgroundPreoperative patient-specific risk factors may elucidate the mechanisms leading to the persistence of pain and opioid use after surgery. This study aimed to determine whether similar or discordant preoperative factors were associated with the duration of postoperative pain and opioid use.MethodsIn this post hoc analysis of a randomized, double-blind, placebo-controlled trial of perioperative gabapentin vs active placebo, 410 patients aged 18–75 years, undergoing diverse operations underwent preoperative assessments of pain, opioid use, substance use, and psychosocial variables. After surgery, a modified Brief Pain Inventory was administered over the phone daily up to 3 months, weekly up to 6 months, and monthly up to 2 years after surgery. Pain and opioid cessation were defined as the first of 5 consecutive days of 0 out of 10 pain or no opioid use, respectively.ResultsOverall, 36.1%, 19.8%, and 9.5% of patients continued to report pain, and 9.5%, 2.4%, and 1.7% reported continued opioid use at 3, 6, and 12 months after surgery. Preoperative pain at the future surgical site (every 1-point increase in the Numeric Pain Rating Scale; HR 0.93; 95% CI 0.87–1.00; P=0.034), trait anxiety (every 10-point increase in the Trait Anxiety Inventory; HR 0.79; 95% CI 0.68–0.92; P=0.002), and a history of delayed recovery after injury (HR 0.62; 95% CI 0.40–0.96; P=0.034) were associated with delayed pain cessation. Preoperative opioid use (HR 0.60; 95% CI 0.39–0.92; P=0.020), elevated depressive symptoms (every 5-point increase in the Beck Depression Inventory-II score; HR 0.88; 95% CI 0.80–0.98; P=0.017), and preoperative pain outside of the surgical site (HR 0.94; 95% CI 0.89–1.00; P=0.046) were associated with delayed opioid cessation, while perioperative gabapentin promoted opioid cessation (HR 1.37; 95% CI 1.06–1.77; P=0.016).ConclusionSeparate risk factors for prolonged post-surgical pain and opioid use indicate that preoperative risk stratification for each outcome may identify patients needing personalized care to augment universal protocols for perioperative pain management and conservative opioid prescribing to improve long-term outcomes.

Gabapentin as an adjunct to paracervical block for perioperative pain management for first-trimester uterine aspiration: a randomized controlled trial

Pain management approaches during uterine aspiration vary, which include local anesthetic, oral analgesics, moderate sedation, deep sedation, or a combination of approaches. For local anesthetic approaches specifically, we continue to have suboptimal pain control. Gabapentin as an adjunct to pain management has proven to be beneficial in gynecologic surgery. We sought to evaluate the impact of gabapentin on perioperative pain during surgical management of first-trimester abortion or early pregnancy loss with uterine aspiration under local anesthesia. We hypothesized that adding gabapentin to local anesthesia will reduce perioperative and postoperative pain associated with uterine aspiration. Secondary outcomes included tolerability of gabapentin and postoperative pain, nausea, vomiting, and anxiety. We conducted a randomized double-blinded placebo-controlled trial of gabapentin 600 mg given 1 to 2 hours preoperatively among subjects receiving a first-trimester uterine aspiration under paracervical block in an outpatient ambulatory surgery center. There were 111 subjects randomized. The primary outcome was pain at time of uterine aspiration as measured on a 100-mm visual analog scale. Secondary outcomes included pain at other perioperative time points. To assess changes in pain measures, an intention to treat mixed effects model was fit with treatment groups (gabapentin vs control) as a between-subjects factor and time point as a within-subjects factor plus their interaction term. Because of a non-normal distribution of pain scores, the area under the curve was calculated for secondary outcomes with comparison of groups utilizing Mann-Whitney U tests. Among the 111 randomized, most subjects were Black or African American (69.4%), mean age was 26 years (±5.5), and mean gestational age was 61.3 days (standard deviation, 14.10). Mean pain scores at time of uterine aspiration were 66.77 (gabapentin) vs 71.06 (placebo), with a mean difference of-3.38 (P=.51). There were no significant changes in pain score preoperatively or intraoperatively. Subjects who received gabapentin had significantly lower levels of pain at 10 minutes after surgery (mean difference [standard error (SE)]=-13.0 [-5.0]; P=.01) and 30 minutes after surgery (mean difference [SE]=-10.8 [-5.1]; P=.03) compared with subjects who received placebo. Median nausea scores and incidence of emesis pre- and postoperatively did not differ between groups. Similarly, anxiety scores did not differ between groups, before or after the procedure. At 10 and 30 minutes after the procedure, most participants reported no side effects or mild side effects, and this did not differ between groups. Preoperative gabapentin did not reduce pain during uterine aspiration. However, it did reduce postoperative pain, which may prove to be a desired attribute of its use, particularly in cases where postoperative pain may be a greater challenge.

Gabapentin as an Adjunct to Perioperative Pain Management for Surgical Abortion: A Randomized Controlled Trial [10S

INTRODUCTION: The use of gabapentin in the setting of surgical abortion has never been evaluated; however, it is used successfully in similar surgical settings as an adjunct to pain management. We sought to evaluate the impact of Gabapentin on perioperative pain during first trimester abortion with local anesthesia. METHODS: We conducted a randomized double-blinded placebo-controlled trial of gabapentin 600 mg given 1-2 hours pre-operatively among subjects receiving a 1st trimester surgical abortion under paracervical block. The primary outcome was pain on a 100-mm visual analog scale (VAS) measured at 6 time points perioperatively. To assess changes in pain measures, an intention to treat (ITT) mixed effects model was fit with treatment group (Gabapentin vs. Control) as a between-subjects factor and time point as a within-subjects factor plus their interaction term. Using Fisher's exact tests, we examined any group differences in the percentage of patients who reported side effects post procedure. RESULTS: Among the 115 randomized, most subjects were Black/African American (69.6%), average age was 26 years (+/-5.6), and mean gestational age was 61.8 days. There were no significant changes in pain score preoperatively or intraoperatively. Subjects who received gabapentin had significantly lower levels of pain at 10 minutes postsurgery [mean difference (SE) = -13.0 (-5.1), p-value = 0.01] and 30 minutes postsurgery [-10.5 (-5.1), p=0.04] as compared to subjects who received placebo. Side effects were rare, of low severity, with no significant difference between groups. CONCLUSION: Post-operative pain scores were lower among subjects receiving Gabapentin preoperatively compared to placebo, thus improving recovery.

Gabapentin add-on treatment for drug-resistant focal epilepsy.

This is an updated version of the Cochrane Review previously published in 2013.Most people with epilepsy have a good prognosis and their seizures are well controlled by a single antiepileptic drug, but up to 30% develop drug-resistant epilepsy, especially those with focal seizures. In this review, we summarised the evidence from randomised controlled trials (RCTs) of gabapentin, when used as an add-on treatment for drug-resistant focal epilepsy. To evaluate the efficacy and tolerability of gabapentin when used as an add-on treatment for people with drug-resistant focal epilepsy. For the latest update, we searched the Cochrane Register of Studies (CRS Web, 20 March 2018), which includes the Cochrane Epilepsy Group's Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946 to 20 March 2018), ClinicalTrials.gov (20 March 2018) and the World Health Organization International Clinical Trials Registry Platform (ICTRP, 20 March 2018). We imposed no language restrictions. Randomised, placebo-controlled, double-blind, add-on trials of gabapentin in people with drug-resistant focal epilepsy. We also included trials using an active drug control group or comparing different doses of gabapentin. For this update, two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: seizure frequency, seizure freedom, treatment withdrawal (any reason) and adverse effects. Primary analyses were intention-to-treat. We also undertook sensitivity best-case and worst-case analyses. We estimated summary risk ratios (RR) for each outcome and evaluated dose-response in regression models. We included 12 trials representing 2607 randomised participants. We combined data from six trials in meta-analyses of 1206 randomised participants. The overall RR for reduction in seizure frequency of 50% or more compared to placebo was 1.89 (95% confidence interval (CI) 1.40 to 2.55; 6 trials, 1206 participants; moderate-quality evidence). Dose regression analysis (for trials in adults) showed increasing efficacy with increasing dose, with 25.3% (19.3 to 32.3) of people responding to gabapentin 1800 mg compared to 9.7% on placebo, a 15.5% increase in response rate (8.5 to 22.5). The RR for treatment withdrawal compared to placebo was 1.05 (95% CI 0.74 to 1.49; 6 trials, 1206 participants; moderate-quality evidence). Adverse effects were significantly associated with gabapentin compared to placebo. RRs were as follows: ataxia 2.01 (99% CI 0.98 to 4.11; 3 studies, 787 participants; low-quality evidence), dizziness 2.43 (99% CI 1.44 to 4.12; 6 studies, 1206 participants; moderate-quality evidence), fatigue 1.95 (99% CI 0.99 to 3.82; 5 studies, 1161 participants; low-quality evidence) and somnolence 1.93 (99% CI 1.22 to 3.06; 6 studies, 1206 participants; moderate-quality evidence). There were no significant differences for the adverse effects of headache (RR 0.79, 99% CI 0.46 to 1.35; 6 studies, 1206 participants; moderate-quality evidence) or nausea (RR 0.95, 99% CI 0.52 to 1.73; 4 trials, 1034 participants; moderate-quality evidence). Overall, the studies were rated at low to unclear risk of bias due to information on each risk of bias domain not being available. We judged the overall quality of evidence (using the GRADE approach) as low to moderate due to potential attrition bias resulting from missing outcome data and imprecise results with wide confidence intervals. Gabapentin has efficacy as an add-on treatment in people with drug-resistant focal epilepsy. However, the trials reviewed were of relatively short duration and provide no evidence for the long-term efficacy of gabapentin beyond a three-month period. The results cannot be extrapolated to monotherapy or to people with other epilepsy types.

Evaluation of composite responder outcomes of pain intensity and physical function in neuropathic pain clinical trials: an ACTTION individual patient data analysis.

Integrating information on physical function and pain intensity into a composite measure may provide a useful method for assessing treatment efficacy in clinical trials of chronic pain. Accordingly, we evaluated composite outcomes in trials of duloxetine, gabapentin, and pregabalin. Data on 2287 patients in 9 trials for painful diabetic peripheral neuropathy (DPN) and 1513 patients in 6 trials for postherpetic neuralgia (PHN) were analyzed. All trials assessed pain intensity on a 0 to 10 numeric rating scale and physical function with the 10-item subscale of the Short Form-36, ranging 0 to 100 with higher scores indicating better function. Correlation between change in pain intensity from baseline to posttreatment and change in physical function was small in DPN (ρ = -0.22; P < 0.001) and nonsignificant in PHN (ρ = -0.05; P = 0.08). Assay sensitivities of 10 composite outcomes were examined in a random subsample of patients enrolled in pregabalin trials for DPN and PHN. Of these, a responder outcome of ≥50% improvement in pain intensity, or a ≥20% improvement in pain intensity and ≥30% improvement in physical function was not only significantly associated with pregabalin vs placebo in the development cohorts for both pain conditions but also in the validation cohorts. Furthermore, this composite outcome was cross-validated in trials of gabapentin for PHN and duloxetine for DPN, and had slightly lower number needed to treat than a standard responder outcome of ≥50% reduction in pain intensity. In summary, this study identified a composite outcome of pain intensity and physical function that may improve the assay sensitivity of future neuropathic pain trials.

A double-blind, randomized controlled trial of gabapentin vs. placebo for acute pain management in critically ill patients with rib fractures

IntroductionAchieving adequate pain control for rib fractures remains challenging; prescription of alternatives to narcotics is imperative to curtail the current opioid epidemic. Although gabapentin has shown promise following elective thoracic procedures, its efficacy in patients with rib fractures remains unstudied. We hypothesized that gabapentin, as compared to placebo, would both improve acute pain control and decrease narcotic use among critically ill patients with rib fractures. Materials and MethodsAdult patients admitted to the trauma surgery service from November 2016 – November 2017 at an urban, Level I trauma center with one or more rib fractures were randomized to either gabapentin 300mg thrice daily or placebo for one month following their injury. Daily numeric pain scores, opioid consumption, oxygen requirement, respiratory rate, and incentive spirometry recordings during the index admission, as well as and one-month quality of life survey data were abstracted. ResultsForty patients were randomized. The groups were well matched with respect to age, gender, prior narcotic use, tobacco use, and prior respiratory disease. Although the median RibScore did not differ between groups, the gabapentin group had a higher median number of ribs fractured as compared to the placebo group (7 vs. 5, respectively). Degree of pulmonary contusion and injury severity score were similar between groups. Use of loco-regional anesthetic modalities did not differ between groups. Daily numeric pain scores, opioid consumption, oxygen requirement, respiratory rate, and incentive spirometry recordings were similar between both groups. No benefit was observed when adding gabapentin to a multi-modal analgesic regimen for rib fractures. There were no instances of pneumonia, respiratory failure, or mortality in either group. Hospital and intensive care unit length of stay were similar between groups. Both overall and chest-specific quality of life was equivalent between groups at one month follow-up. ConclusionsIn this group of critically ill patients with rib fractures, gabapentin did not improve acute outcomes for up to one month of treatment.

Is gabapentin effective in improving cough-related quality of life in patients with unexplained chronic cough?

Bottom line Gabapentin in doses of 1,200–1,800 mg per day improves cough-related quality of life (QoL, by about 9%) and cough severity (by up to 28%) in patients with unexplained chronic cough (SOR: B, RCT and cohort study). A trial of gabapentin is recommended when benefits outweigh potential risks at an initial dose of 300 mg daily, which may be titrated as tolerated to a maximum dose of 1,800 mg daily in 2 to 3 divided doses (SOR: C, expert opinion).

Randomized trial of standard pain control with or without gabapentin for pain related to radiation-induced mucositis in head and neck cancer.

Radiation-induced mucositis (RIM) in chemoradiotherapy (CRT) for head and neck cancer (HNC) causes severe pain and worsens CRT compliance, QOL and outcome. Following retrospective reports, we conducted a randomized trial of the safety and efficacy of gabapentin for RIM-associated pain during CRT. HNC patients (pts) receiving CRT were randomized to standard pain control (SPC) with acetaminophen and opioids, or SPC plus gabapentin (SPC+G). Gabapentin was maintained at 900mg/day for 4 weeks after CRT. Primary endpoint was maximum visual analogue scale (VAS) score during CRT, and secondary endpoints were total opioid dose, changes in QOL (EORTC QLQ-C30 and QLQ-HN 35) from baseline to 4 weeks after CRT, and adverse events. Twenty-two eligible Stage III or IV pts were randomly assigned to SPC or SPC+G (n=11 each). Twelve were treated in a locally advanced setting and 10 in a postoperative setting. Median maximum VAS scores, median total dose of opioids at maximum VAS and total dose of opioids at 4 weeks after CRT tended to be higher in the SPC+G arm (47 in SPC vs. 74 in SPC+G, p=0.517; 215mg vs. 745.3mg, p=0.880; and 1260mg vs. 1537.5mg, p=0.9438, respectively), without significance. QOL analysis showed significantly worse scores in the SPC+G arm for weight gain (p=0.005). Adverse events related to gabapentin were manageable. This pilot study is the first prospective randomized trial of gabapentin for RIM-related pain. Gabapentin had no apparent beneficial effect. Further research into agents for RIM-related pain is warranted.

Pilot trial of gabapentin for the treatment of benzodiazepine abuse or dependence in methadone maintenance patients

ABSTRACTBackground: Benzodiazepine use disorders are a common clinical problem among methadone maintenance treatment patients and have adverse effects on clinical outcomes. Objectives: To evaluate gabapentin for the outpatient treatment of benzodiazepine abuse or dependence in methadone maintenance patients. Methods: Participants (n = 19) using benzodiazepines at least 4 days per week were enrolled into an 8-week randomized double-blind placebo-controlled outpatient pilot trial. All participants received a manual-guided supportive psychotherapy aimed to promote abstinence. Study medication was titrated over a 2-week period to a maximum dose of gabapentin 1200 mg or placebo three times a day. Benzodiazepine use was assessed using urine toxicology confirmed self-report. Benzodiazepines were not provided as part of study participation; participants were provided guidance to gradually reduce benzodiazepine intake. Results: Sixteen participants had post-randomization data for analysis. Retention at week eight was 50%. The mean dose of gabapentin achieved by titration was 2666 mg/day (SD = ± 1446). There were no significant between group differences on benzodiazepine use outcomes (amount benzodiazepine per day [Mann-Whitney U = 27, p = 0.745], abstinent days per week [U = 28, p = 0.811]) and Clinical Instrument Withdrawal Assessment (CIWA)-benzodiazepines scale (U = 29.0, p = 0.913). One participant in the gabapentin group discontinued study medication because of peripheral edema. Two participants in the placebo group requested admission for inpatient detoxification treatment. Conclusion: In outpatient methadone-maintained patients with benzodiazepine use disorder, gabapentin did significantly decrease benzodiazepine use relative to placebo. The small sample recruited for this trial may have limited the ability to detect a group difference.

A randomized controlled trial of gabapentin for chronic low back pain with and without a radiating component.

Gabapentin is prescribed for analgesia in chronic low back pain, yet there are no controlled trials supporting this practice. This randomized, 2-arm, 12-week, parallel group study compared gabapentin (forced titration up to 3600 mg daily) with inert placebo. The primary efficacy measure was change in pain intensity from baseline to the last week on treatment measured by the Descriptor Differential Scale; the secondary outcome was disability (Oswestry Disability Index). The intention-to-treat analysis comprised 108 randomized patients with chronic back pain (daily pain for ≥6 months) whose pain did (43%) or did not radiate into the lower extremity. Random effects regression models which did not impute missing scores were used to analyze outcome data. Pain intensity decreased significantly over time (P < 0.0001) with subjects on gabapentin or placebo, reporting reductions of about 30% from baseline, but did not differ significantly between groups (P = 0.423). The same results pertained for disability scores. In responder analyses of those who completed 12 weeks (N = 72), the proportion reporting at least 30% or 50% reduction in pain intensity, or at least "Minimal Improvement" on the Physician Clinical Global Impression of Change did not differ significantly between groups. There were no significant differences in analgesia between participants with radiating (n = 46) and nonradiating (n = 62) pain either within or between treatment arms. There was no significant correlation between gabapentin plasma concentration and pain intensity. Gabapentin appears to be ineffective for analgesia in chronic low back pain with or without a radiating component.