Efficacy of topical gabapentin in women with primary macular amyloidosis: A side-by-side triple-blinded randomized clinical trial.

BACKGROUND: Primary cutaneous macular amyloidosis (PCMA) is a chronic pruritic cutaneous disease characterized by heterogeneous extracellular deposition of amyloid protein in the skin. AIMS: This study aimed to evaluate the efficacy of topical 6% gabapentin cream for the treatment of patients with PCMA. MATERIALS AND METHODS: In this triple-blind clinical trial, a total of 34 patients, who were diagnosed with PCMA, treated using two different strategies of topical gabapentin as the active group and vehicle cream as the control group. RESULTS: Pruritus score reduction in both groups was statistically significant compared with the baseline value (p < 0.001). There was a significant pigmentation score reduction in intervention group compared with control group after 1 month of the study (p < 0.001). The differences of pigmentation score changes between the groups were not significant at month 2 (p = 0.52) and month 3 (p = 0.22). CONCLUSIONS: The results of this study suggest that topical gabapentin cream may be effective as a topical agent in the treatment of pruritus associated with PCMA without any significant adverse effects. It is recommended to perform similar studies with a larger sample size and longer duration in both sexes.

Pre-emptive analgesia with methylprednisolone and gabapentin in total knee arthroplasty in the elderly.

The aim of this study is to assess whether administration of gabapentin and methylprednisolone as "pre-emptive analgesia" in a group of patients above 65 years of age would be effective in complex pain management therapy following total knee arthroplasty (TKA). One hundred seventy patients above 65 years were qualified for the study, with exclusion of 10 patients due to clinical circumstances. One hundred sixty patients were randomly double-blinded into two groups: the study group (80 patients) and the control group (80 patients). The study group received as "pre-emptive" analgesia a single dose of 300 mg oral (PO) gabapentin and 125 mg intravenous (IV) methylprednisolone, while the control received a placebo. All patients received opioid and non-opioid analgesic agents perioperatively calculated for 1 kg of total body weight. We measured (1) pain intensity level at rest (numerical rating scale, NRS), (2) life parameters, (3) levels of inflammatory markers (leukocytosis, C reactive protein CRP), and (4) all complications. Following administration of gabapentin and methylprednisolone as "pre-emptive" analgesia, the NRS score at rest was calculated at 6, 12 (p < 0.000001), 18 (p < 0.00004) and 24 (p = 0.005569) h postoperatively. Methylprednisolone with gabapentin significantly decreased the dose of parenteral opioid preparations (p = 0.000006). The duration time of analgesia was significantly longer in study group (p < 0.000001), with CRP values lower on all postoperative days (1, 2 days-p < 0.00001, 3 days-p = 0.00538), and leukocytosis on day 2 (p < 0.0086) and 3 (p < 0.00042). No infectious complications were observed in the first postoperative days; in the control group, one patient manifested transient ischemic attack (TIA). The use of gabapentin and methylprednisolone as a single dose decreased the level of postoperative pain on the day of surgery, the dose of opioid analgesic preparations, and the level of inflammatory parameters without infectious processes.

Results from a randomized, double-blind, placebo-controlled, crossover, multimodal-MRI pilot study of gabapentin for co-occurring bipolar and cannabis use disorders.

Disrupted brain gamma-aminobutyric acid (GABA)/glutamate homeostasis is a promising target for pharmacological intervention in co-occurring bipolar disorder (BD) and cannabis use disorder (CUD). Gabapentin is a safe and well-tolerated medication, FDA-approved to treat other neurological diseases, that restores GABA/glutamate homeostasis, with treatment studies supporting efficacy in treating CUD, as well as anxiety and sleep disorders that are common to both BD and CUD. The present manuscript represents the primary report of a randomized, double-blind, placebo-controlled, crossover (1-week/condition), multimodal-MRI (proton-MR spectroscopy, functional MRI) pilot study of gabapentin (1200 mg/day) in BD + CUD (n = 22). Primary analyses revealed that (1) gabapentin was well tolerated and adherence and retention were high, (2) gabapentin increased dorsal anterior cingulate cortex (dACC) and right basal ganglia (rBG) glutamate levels and (3) gabapentin increased activation to visual cannabis cues in the posterior midcingulate cortex (pMCC, a region involved in response inhibition to rewarding stimuli). Exploratory evaluation of clinical outcomes further found that in participants taking gabapentin versus placebo, (1) elevations of dACC GABA levels were associated with lower manic/mixed and depressive symptoms and (2) elevations of rBG glutamate levels and pMCC activation to cannabis cues were associated with lower cannabis use. Though promising, the findings from this study should be interpreted with caution due to observed randomization order effects on dACC glutamate levels and identification of statistical moderators that differed by randomization order (i.e. cigarette-smoking status on rBG glutamate levels and pMCC cue activation). Nonetheless, they provide the necessary foundation for a more robustly designed (urn-randomized, parallel-group) future study of adjuvant gabapentin for BD + CUD.

Anti-nociceptive effects of ECa 233 a standardized extract of Centella asiatica (L.) Urban on chronic neuropathic orofacial pain in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: ECa 233 is a standardized extract of Centella asiatica (L.) Urban, a herb traditionally used to treat a number of diseases including neurological disorders. Accordingly, ECa 233 showed benefits on animal models of cognitive deficits, chronic stress and Parkinson's disease. Analgesic activity of ECa 233 was shown in Tail's flick test in rodent and relieving aphthous ulcer pain in man. Moreover, acute and sub-chronic toxicity testing in rodents and pharmacokinetic study in healthy volunteers, clinical trial phase I demonstrated good safety profiles of ECa 233. AIM OF THE STUDY: This study aims to evaluate the anti-nociceptive effects of ECa 233 and its synergistic effect with gabapentin on chronic neuropathic orofacial pain after 3 weeks infraorbital nerve chronic constriction injury in mice. The peripheral and central nociceptive activities are also examined. MATERIALS AND METHODS: Chronic neuropathic orofacial pain was induced by 3 weeks infraorbital nerve chronic constriction injury. Mice were treated with ECa 233 (30, 100 and 300 mg/kg) and gabapentin (10 mg/kg) by oral gavage starting on day 21 and going on for 14 consecutive days. Mechanical hyperalgesia and allodynia were measured on day 7, 14, 21, 28 and 35 after infraorbital nerve chronic constriction injury. At the end of the experiment, mice were observed for the sedative effect using the locomotor activity, the calcitonin gen-related peptide in trigeminal ganglion and c-fos expression in trigeminal nucleus caudalis were investigated after euthanasia. RESULTS: Infraorbital nerve chronic constriction injury gradually induced marked ipsilateral mechanical hyperalgesia and allodynia. The maximum hyperalgesia and allodynia response presented on day 21 and the response was remained constant until day 35. Treatment with either 300 mg/kg ECa 233 or 10 mg/kg gabapentin were able to attenuate mechanical hyperalgesia and allodynia. The downregulation of calcitonin gen-related peptide on ipsilateral trigeminal ganglion were observed in ECa 233 at 100 and 300 mg/kg and 10 mg/kg gabapentin-treated groups. The c-fos expression on ipsilateral trigeminal nucleus caudalis was also decreased in 300 mg/kg ECa 233 and 10 mg/kg gabapentin-treated groups. CONCLUSION: ECa 233 reduced hyperalgesia and allodynia by modulating the peripheral calcitonin gen-related peptide expression consequently alleviate the nociceptive activity in trigeminal nucleus caudalis. Further clinical trial to proof ECa 233's efficacy in neuropathic pain in man as well as possible attributable mechanism of action should be further investigated.

Day-of-Surgery Gabapentinoids and Prolonged Opioid Use: A Retrospective Cohort Study of Medicare Patients Using Electronic Health Records.

BACKGROUND: While preoperative gabapentinoids are commonly used in surgical multimodal analgesia protocols, little is known regarding the effects this therapy has on prolonged postsurgical opioid use. In this observational study, we used data from a large integrated health care system to estimate the association between preoperative day-of-surgery gabapentinoids and the risk of prolonged postsurgical opioid use. METHODS: We identified adults age ≥65 years undergoing major therapeutic surgical procedures from a large integrated health care system from 2016 to 2019. Exposure to preoperative gabapentinoids on the day of surgery was measured using inpatient medication administration records, and the outcome of prolonged opioid use was measured using outpatient medication orders. We used stabilized inverse probability of treatment-weighted log-binomial regression to estimate risk ratios and 95% confidence intervals (CIs) of prolonged opioid use, comparing patients who received preoperative gabapentinoids to those who did not and adjusting for relevant clinical factors. The main analysis was conducted in the overall surgical population, and a secondary analysis was conducted among procedures where at least 30% of all patients received a preoperative gabapentinoid. RESULTS: Overall, 13,958 surgical patients met inclusion criteria, of whom 21.0% received preoperative gabapentinoids. The observed 90-day risk of prolonged opioid use following surgery was 0.91% (95% CI, 0.77-1.08). Preoperative gabapentinoid administration was not associated with a reduced risk of prolonged opioid use in the main analysis conducted in a broad surgical population (adjusted risk ratio [adjRR], 1.19 [95% CI, 0.67-2.12]) or in the secondary analysis conducted in patients undergoing colorectal resection, hip arthroplasty, knee arthroplasty, or hysterectomy (adjRR, 1.01 [95% CI, 0.30-3.33]). CONCLUSIONS: In a large integrated health system, we did not find evidence that preoperative gabapentinoids were associated with reduced risk of prolonged opioid use in patients undergoing a broad range of surgeries.

Comparison between acupuncture therapy and gabapentin for chronic pain: a pilot study.

BACKGROUND: We examined whether the effect of true electroacupuncture on pain and functionality in chronic pain participants can be differentiated from that of medication (gabapentin) by analyzing quantitative sensory testing (QST). METHODS: We recruited chronic back and neck pain participants who received six sessions (twice weekly) of true electroacupuncture versus sham electroacupuncture or 3 weeks of gabapentin versus placebo treatment. QST profiles, pain scores, and functionality profile were obtained at baseline (visit 1) and after three sessions (visit 4) or six sessions (visit 7) of acupuncture or 3 weeks of gabapentin or placebo. RESULTS: A total of 50 participants were analyzed. We found no differences in QST profile changes (p = 0.892), pain reduction (p = 0.222), or functionality (p = 0.254) between the four groups. A major limitation of this pilot study was the limited number of study participants in each group. CONCLUSION: This pilot study suggests that a large-scale clinical study with an adequate sample size would be warranted to compare acupuncture and medication therapy for chronic pain management. TRIAL REGISTRATION NUMBER: NCT01678586 (ClinicalTrials.gov).

Toxicity assessment of concurrent gabapentin/pregabalin administration with high-dose melphalan in autologous hematopoietic cell transplant recipients.

A theoretical pharmacokinetic interaction mediated through L-amino acid transporter 1 and 2 exists between gabapentin (GP) and pregabalin (PG) with melphalan. Peripheral neuropathy is a common toxicity of various multiple myeloma regimens commonly utilized prior to autologous hematopoietic cell transplant (auto-HCT) with high-dose melphalan (HD-Mel). Therefore, it is likely concurrent administration of either GP or PG will occur in patients receiving HD-Mel conditioning for auto-HCT, which could potentially increase cellular uptake and worsen the mucosal injury. A retrospective chart review of adult patients from January 2012 to July 2016 who received HD-Mel (140-200 mg/m2) at West Virginia University Medicine was performed to assess toxicity and outcomes in these patients. A total of 80 patients were included in the study, with 30 patients receiving GP or PG and 50 control patients. There were no significant differences in grade 2 or higher mucositis, admissions for nausea/vomiting/diarrhea, intravenous opioid requirements, oral topical therapies, antidiarrheal medication use, rescue anti-emetics, days of nausea or vomiting, pain scores, neutrophil or platelet engraftment, treatment-related mortality, progression-free survival, or overall survival. Our data suggest that it is safe to continue GP/PG therapy throughout HD-Mel therapy, with no negative transplant outcomes. Prospective studies or evaluations of larger databases are necessary to better characterize the clinical effect of concomitant therapy.

Pilot randomized placebo-controlled clinical trial of high-dose gabapentin for alcohol use disorder.

BACKGROUND: Despite advances in the development of pharmacotherapy for alcohol use disorder (AUD), there remains a need for medications that can be administered to actively drinking outpatients to promote a reduction in harmful alcohol consumption. The primary aim of this pilot study was to determine whether high-dose gabapentin (3600 mg/daily) is more effective than placebo in reducing harmful alcohol consumption in outpatients with AUD. METHODS: Forty patients (27 men) who met DSM-IV-TR criteria for alcohol dependence and reporting at least 4 heavy drinking days (HDD) per week were recruited at a single site. Participants were actively drinking at study entry and received double-blind gabapentin (3600 mg/day; n = 19) or placebo (n = 20) for 8 weeks. Study medication was titrated over 5 days and administered in three divided doses (1200 mg three times per day). The proportion of HDD (primary outcome) and percent days abstinent (PDA; secondary outcome) were analyzed using generalized longitudinal mixed models with the predictors being study arm, week, study arm by week interaction, and corresponding baseline drinking measure. RESULTS: There was a significant interaction between study arm and week for the proportion of HDD per week, F (7, 215) = 3.33, p = 0.002 . There was also a significant interaction between study arm and week for PDA per week, F (7, 215) = 3.11, p = 0.004. The overall retention rate was 67.5% with no significant difference in time-to-dropout between treatment groups. There were no serious adverse events. No participants were removed from the trial due to the development of moderate-to-severe alcohol withdrawal (CIWA-Ar ≥ 13). CONCLUSIONS: Gabapentin treatment rapidly titrated to a dosage of 3600 mg/day is associated with a reduction in the proportion of HDD per week and an increase in PDA per week in actively drinking outpatients with AUD. High-dose gabapentin is potentially a feasible approach to treating AUD and deserving of further study.

Combined carvedilol and gabapentin treatment induces a rapid response in red scrotum syndrome.

Red scrotum syndrome (RSS) is a rare dermatologic condition characterized by persistent erythema and analgesia of the male genitalia that cannot be attributed to contact or atopic dermatitis or acute or chronic infections. Treatment of RSS is challenging since it often fails to respond to corticosteroids, antifungals, antivirals, and antibiotics. Several reports described RSS patients who responded to gabapentin, pregabalin, and ?-adrenergic receptor blockers, suggesting a neuropathic etiology. Here we present a refractory RSS case with rapid clinical improvement on a combined carvedilol plus gabapentin therapy. We suggest that RSS manifestations are driven by neurogenic inflammation and that the efficacy of gabapentin/carvedilol relates to the suppression of the neuro-immuno-epidermal axis.

The analgesic evaluation of gabapentin for arthroscopy: A meta-analysis of randomized controlled trials.

INTRODUCTION: The efficacy of gabapentin for pain management of arthroscopy remains controversial. We conduct a systematic review and meta-analysis to explore the influence of gabapentin versus placebo on the postoperative pain intensity of arthroscopy. METHODS: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through April 2020 for randomized controlled trials assessing the effect of gabapentin versus placebo on pain control of arthroscopy. This meta-analysis is performed using the random-effect model. RESULTS: Five randomized controlled trials are included in the meta-analysis. Overall, compared with control group for arthroscopy, gabapentin remarkably decreases pain scores at 24 hour (standard mean difference [SMD]=-0.68; 95% confidence interval [CI]=-1.15 to -0.02; P = .21), analgesic consumption (SMD = -18.24; 95% CI=-24.61 to -11.88; P < .00001), nausea and vomiting (OR = 0.42; 95% CI = 0.21 to 0.84; P = .01), but has no obvious influence on pain scores at 6 h (SMD = -1.30; 95% CI = -2.92 to 0.31; P = .11) or dizziness (OR = 1.12; 95% CI = 0.56 to 2.24; P = .75). CONCLUSIONS: Gabapentin is effective for pain control after arthroscopy.

Gabapentin dependence and withdrawal requiring an 18-month taper in a patient with alcohol use disorder: a case report.

Gabapentin has been widely used to manage post-herpetic neuralgia, peripheral neuropathy, seizure disorders, alcohol use disorder (AUD), alcohol withdrawal, and insomnia. Although usually well tolerated, gabapentin has been reported to cause severe physiologic dependence and withdrawal. Tapering gabapentin in this context poses a significant clinical challenge, with little published information to date on meeting this challenge. This case highlights the need for patient-centered slow tapers in patients with severe gabapentin dependence and withdrawal. We present a 32-year-old female effectively treated for AUD with 1,200 mg daily dose of gabapentin, who developed gabapentin dependence and severe withdrawal. Recognizing her intolerance to gabapentin withdrawal after a brief accidental pause of medication, a taper plan was initiated using the framework of the BRAVO Protocol. On average, she reduced daily gabapentin dose by 100 mg per month until she reached 300 mg. The taper then slowed to 20-30 mg dose decrements per month. For the last 100 mg, she tapered down at 5 mg decrements every one to two weeks to 60 mg, at which point she discontinued gabapentin. The entire taper process took eighteen months. The BRAVO protocol outlines a safe and compassionate strategy. Originally developed for opioids and adapted to benzodiazepines, the use of the Bravo Protocol provides a framework for a gabapentin taper. For patients in whom gabapentin treatment leads to severe dependence and withdrawal, the BRAVO Protocol provides a practical, patient-centered framework for tapering.

Association Between Dual Trajectories of Opioid and Gabapentinoid Use and Healthcare Expenditures Among US Medicare Beneficiaries.

OBJECTIVES: Little is known about relationships between opioid- and gabapentinoid-use patterns and healthcare expenditures that may be affected by pain management and risk of adverse outcomes. This study examined the association between patients' opioid and gabapentinoid prescription filling/refilling trajectories and direct medical expenditures in US Medicare. METHODS: This cross-sectional study included a 5% national sample (2011-2016) of fee-for-service beneficiaries with fibromyalgia, low back pain, neuropathy, or osteoarthritis newly initiating opioids or gabapentinoids. Using group-based multitrajectory modeling, this study identified patients' distinct opioid and gabapentinoid (OPI-GABA) dose and duration patterns, based on standardized daily doses, within a year of initiating opioids and/or gabapentinoids. Concurrent direct medical expenditures within the same year were estimated using inverse probability of treatment weighted multivariable generalized linear regression, adjusting for sociodemographic and health status factors. RESULTS: Among 67 827 eligible beneficiaries (mean age ± SD = 63.6 ± 14.8 years, female = 65.8%, white = 77.1%), 11 distinct trajectories were identified (3 opioid-only, 4 gabapentinoid-only, and 4 concurrent OPI-GABA trajectories). Compared with opioid-only early discontinuers ($13 830, 95% confidence interval = $13 643-14 019), gabapentinoid-only early discontinuers and consistent low-dose and moderate-dose gabapentinoid-only users were associated with 11% to 23% lower health expenditures (adjusted mean expenditure = $10 607-$11 713). Consistent low-dose opioid-only users, consistent high-dose opioid-only users, consistent low-dose OPI-GABA users, consistent low-dose opioid and high-dose gabapentinoid users, and consistent high-dose opioid and moderate-dose gabapentinoid users were associated with 14% to 106% higher healthcare expenditures (adjusted mean expenditure = $15 721-$28 464). CONCLUSIONS: Dose and duration patterns of concurrent OPI-GABA varied substantially among fee-for-service Medicare beneficiaries. Consistent opioid-only users and all concurrent OPI-GABA users were associated with higher healthcare expenditures compared to opioid-only discontinuers.

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

BACKGROUND: 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. OBJECTIVES: To evaluate the efficacy and tolerability of gabapentin when used as an add-on treatment for people with drug-resistant focal epilepsy. SEARCH METHODS: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.

Comparison of therapeutic effects of continuous epidural nerve block combined with drugs on postherpetic neuralgia.

PURPOSE: To compare the therapeutic effects of continuous epidural block combined with drugs and oral drugs alone on postherpetic neuralgia (PHN). METHODS: Ninety-six PHN patients meeting the standard were selected and divided into group A and group B. Patients in group A had epidural block combined with oral administration of gabapentin and oxycodone-acetaminophen, and patients in group B received oral gabapentin and oxycodone-acetaminophen. Visual analogue scale (VAS) and Wisconsin brief pain inventory scores were used to evaluate the patients in group A and group B for 6 times (before treatment, 1 d, 3 d, 7 d, 15 d and 30 d after treatment) respectively, and the complications and adverse reactions of the two treatment methods, as well as the number of cases requiring remedial measures were observed. RESULTS: There were significant differences in VAS and Wisconsin brief pain inventory scores at 1 d, 3 d, 7 d, 15 d and 30 d after treatment between the two groups (p < 0.05). Moreover, the scores before and after treatment decreased with the time of treatment, and there was a significant difference between the two groups at different time points (p < 0.05). No significant adverse reactions were observed in group A except for 1 patient with catheter detachment. Compared with group A, the adverse reactions of group B were more varied and obvious. CONCLUSION: Both treatments have certain effects on PHN, but epidural block combined with drug therapy is more effective, especially for patients with severe pain, early use can quickly relieve pain.

Development and Validation of a Model to Predict Neonatal Abstinence Syndrome.

OBJECTIVES: To develop and validate clinical risk prediction tools for neonatal abstinence syndrome (NAS). STUDY DESIGN: We developed prediction models for NAS based on a set of 30 demographic and antenatal exposure covariates collected during pregnancy. Data (outpatient prescription, vital, and administrative records), were obtained from enrollees in the Tennessee Medicaid Program from 2009 to 2014. Models were created using logistic regression and backward selection based on improvement in the Akaike information criterion, and internally validated using bootstrap cross-validation. RESULTS: A total of 218 020 maternal and infant dyads met inclusion criteria, of whom 3208 infants were diagnosed with NAS. The general population model included age, hepatitis C virus infection, days of opioid used by type, number of cigarettes used daily, and the following medications used in the last 30 day of pregnancy: bupropion, antinausea medicines, benzodiazepines, antipsychotics, and gabapentin. Infant characteristics included birthweight, small for gestational age, and infant sex. A high-risk model used a smaller number of predictive variables. Both models discriminated well with an area under the curve of 0.89 and were well-calibrated for low-risk infants. CONCLUSIONS: We developed 2 predictive models for NAS based on demographics and antenatal exposure during the last 30 days of pregnancy that were able to risk stratify infants at risk of developing the syndrome.

Preoperative Gabapentin Administration and Its Impact on Postoperative Opioid Requirement and Pain in Sinonasal Surgery.

OBJECTIVE: To determine the efficacy of preoperative gabapentin on patient-reported pain levels and postoperative opioid requirements following sinonasal surgery. STUDY DESIGN: Retrospective review. SETTING: Academic institution. METHODS: Patients undergoing sinonasal surgery between July 2019 and January 2020 were followed. Groups were divided into those that received 600 mg of oral gabapentin 1 hour preoperatively (gabapentin) and those that did not (control). Postoperatively, each patient was counseled to use acetaminophen, ibuprofen, and oxycodone as needed for pain control. Patients completed a daily postoperative pain and medication log. Pain was measured by the visual analog scale (VAS) and opioid use by morphine equivalent dose (MED). Chi-square test and Wilcoxon test were used for data analysis. RESULTS: Fifty-seven patients were included (control, n = 28; gabapentin, n = 29). There was no significant difference in age, sex, or baseline Sinonasal Outcome Test-22 scores between the groups. The total MED, postoperative day (POD) 1-2 MED, POD 3-4 MED, and POD 5-6 MED did not differ significantly between the control (17.9, 12.2, 4.6, 1.5) and gabapentin (19.0, 8.9, 7.2, 3.5) groups (P = .98, .25, .16, .44). The mean daily VAS score did not differ significantly between the control (3.1) and gabapentin (2.8) groups (P = .81). The mean daily VAS score decreased significantly in both groups with each successive POD (P = .004). CONCLUSION: Preoperative gabapentin did not significantly reduce postoperative pain or opioid use. Postoperative discomfort following sinonasal surgery is mild, and opioid intake is minimal.

Preoperative Gabapentin for Minimally Invasive Hysterectomy: A Randomized Controlled Trial.

STUDY OBJECTIVE: To evaluate whether a single dose of gabapentin given preoperatively reduces narcotic use 24 hours after minimally invasive hysterectomy (MIH). DESIGN: Randomized controlled trial. SETTING: Single academic-affiliated community hospital. PATIENTS: Women undergoing MIH for benign indications between June 2016 and June 2017. INTERVENTIONS: Subjects were randomized to receive a preoperative regimen of acetaminophen, celecoxib, and gabapentin versus acetaminophen and celecoxib alone. MEASUREMENTS AND MAIN RESULTS: The primary outcome assessed was the total amount of narcotics used at 24 hours after surgery. Secondary outcomes included adverse effects from gabapentin use, total narcotics used, and pain scores at 2 weeks after surgery. A total of 129 women were randomized and eligible for analysis in the gabapentin study arm (n = 68) or the control arm (n = 61). Demographic characteristics and surgical details were similar between groups. Narcotics used at 24 hours after surgery totaling 168 versus 161 oral morphine milligram equivalents in the gabapentin and control groups, respectively, did not significantly differ between groups (p = .60). Total narcotics used and pain scores at 2 weeks after surgery and the rates of adverse effects from gabapentin were also similar between study arms. CONCLUSION: Single-dose, preoperative gabapentin for women undergoing benign MIH does not reduce total opioid use 24 hours after surgery.

Co-prescription of gabapentinoids and opioids among adults with and without osteoarthritis in the United Kingdom between 1995 and 2017.

OBJECTIVES: To produce national and regional estimates and trends for gabapentinoid-opioid co-prescribing rates in patients with OA, both in absolute terms and relative to matched controls without OA. METHODS: Using the UK Clinical Practice Research Datalink database we first constructed age-sex-practice-date 1:1 matched cohorts of patients aged ≥40 years with and without a new diagnosis of OA between 1995-2017 and estimated the relative incidence of a first gabapentinoid prescription. Incident gabapentinoid users in both cohorts were followed to estimate and compare the event rate of gabapentinoid-opioid co-prescription (prescription from both classes within the same 28-day window). RESULTS: The incidence of first gabapentinoid prescription was 3-fold higher in patients with OA than in matched controls [n = 215 357; incidence rate ratio (IRR) 2.93; 95% CI: 2.87, 3.00]. Among incident gabapentinoid users with OA (n = 27 374, median follow-up 3.9 years) the event rate of gabapentinoid-opioid co-prescription was 4.03 (4.02-4.05) per person-year. The rate was higher in OA patients classed as long-term gabapentinoid users (6.24; 6.22-6.26). These rates were significantly higher than in incident gabapentinoid users without OA [adjusted-IRR: 1.29 (1.28-1.30)]. This elevated risk was observed across age, sex, geographic regions, and calendar years, when restricted to strong opioids and to long-term gabapentinoid users, and when co-prescription was defined as within 14 days and same-day prescribing. CONCLUSIONS: Patients with OA not only have a higher risk of being prescribed a gabapentinoid but, once prescribed a gabapentinoid, are also at greater risk of opioid co-prescription. Strict restriction of gabapentinoid-opioid co-prescription, and improved access to, and uptake of, effective non-pharmacological and surgical alternatives for OA are required.

Use of gabapentin in management of postoperative pain after crosslinking / Uso da gabapentina no manejo da dor pós-operatória do crosslinking

ABSTRACT Objective: The objective was to evaluate the efficacy of gabapentin in the management of neuropathic pain in patients with keratoconus, who were treated with fast (10 minutes) epi-off corneal crosslinking (CXL). Methods: This was a prospective, double-blind, randomized study. The sample comprised patients with bilateral progressive keratoconus, aged 12 years or older, who underwent a bilateral epi-off corneal CXL (fast - 10 minutes) procedure. One group was given placebo orally, and the other group received gabapentin 600 mg orally, both preoperatively. The visual analogue scale (VAS) was applied to record postoperative pain up to 48 hours after procedure. The study was conducted at the Belotto Stock Centro Oftalmológico, in the city of Joaçaba, Santa Catarina, Brazil, from June 2018 to September 2019. Results: At no point in the study significant differences were observed between groups, in terms of pain intensity measured by means of the VAS questionnaire, or of opioid use (Paco®), though opioid consumption was 21% lower in the group receiving gabapentin. Conclusion: We concluded gabapentin has no efficacy in postoperative pain control after epi-off corneal CXL (fast - 10 minutes). Although there was no statistically significant difference, the group that received gabapentin suffered less pain, resulting in lower opioid consumption. UTN number: U1111-1256-0330.

RESUMO Objetivo: Avaliar a eficácia do uso da gabapentina no manejo da dor neuropática em pacientes portadores de ceratocone submetidos ao tratamento de crosslinking corneano epi-off fast de 10 minutos. Métodos: Tratou-se de pesquisa prospectiva, duplo-cega, randomizada. A amostra foi composta de pacientes com ceratocone progressivo bilateral, a partir dos 12 anos de idade, submetidos ao procedimento de crosslinking corneano acelerado epi-off fast de 10 minutos bilateral. Um grupo recebeu placebo via oral e o outro, gabapentina 600mg, via oral, ambos no pré-operatório. A Escala Visual Analógica foi aplicada para registrar a dor pós-operatória até 48 horas após o procedimento. A pesquisa foi realizada no período de junho de 2018 a setembro de 2019 em um centro oftalmológico. Resultados: Não foram observadas diferenças estatísticas significativas para ambos os grupos, tanto na intensidade da dor medida pela Escala Visual Analógica, como na redução do uso do opioide (Paco®), em qualquer horário analisado durante um período de 48 horas. No entanto, houve redução de 21% no consumo de opioides pelo grupo que fez uso da gabapentina. Conclusão: A gabapentina não demonstrou eficácia no controle da dor no pós-operatório do crosslinking corneano epi-off fast de 10 minutos. No entanto, observou-se que, mesmo não havendo diferença estatisticamente significativa, houve diminuição da dor no grupo em que foi usada a gabapentina, resultando na redução do consumo de opioides. Número UTN: U1111-1256-0330.

Association of Gabapentinoids With the Risk of Opioid-Related Adverse Events in Surgical Patients in the United States.

Importance: The use of gabapentinoids in multimodal postoperative analgesia is increasing; however, when coadministered with opioids, these drugs may potentiate central nervous system and respiratory depression. Objective: To evaluate the association between perioperative coadministration of gabapentinoids and opioids with inpatient opioid-related adverse events in surgical patients. Design, Setting, and Participants: This cohort study used propensity score trimming, stratification, and weighting of adults admitted for a major surgery between October 2007 and December 2017 who were treated with opioids on the day of surgery and included in the Premier Research database. Data analysis was conducted from February to April 2020. Exposure: Gabapentinoids (gabapentin or pregabalin) coadministered with opioids starting the day of surgery vs opioid therapy without gabapentinoids. Main Outcomes and Measures: Primary outcome was opioid overdose. Secondary outcomes included respiratory complications, unspecified adverse effects of opioid use, and a composite of these 3 outcomes. Patients were followed up for as long as 30 days from the day of surgery until deviation from the initial treatment regimen or discharge. Results: Gabapentinoids with opioids were administered to 892 484 of 5 547 667 eligible admissions (16.1%; mean [SD] age, 63.5 [11.8] years; 353 315 [39.6%] men). Among the 4 655 183 patients who received opioids only, the mean (SD) age was 63.7 (14.7) years, and 1 913 284 (41.1%) were men. Overall, 441 overdose events were identified, with absolute risks of 1.4 per 10 000 patients with gabapentinoid exposure and 0.7 per 10 000 patients receiving opioids only. Following propensity score trimming, the cohort included 737 383 patients exposed to gabapentinoids and 3 002 480 patients receiving opioids only. The primary analysis yielded the adjusted hazard ratio of 1.95 (95% CI, 1.49-2.55), and the number needed to treat for an additional overdose to occur was 16 914 patients (95% CI, 11 556-31 537 patients). Adjusted hazard ratios for secondary outcomes were 1.68 (95% CI, 1.59-1.78) for respiratory complications, 1.77 (95% CI, 1.61-1.93) for unspecified adverse effects of opioids, and 1.70 (95% CI, 1.62-1.79) for the composite outcome. The results were consistent across sensitivity analyses and subgroups identified by key clinical factors. Conclusions and Relevance: In this real-world cohort study of patients who underwent major surgery, concomitant use of gabapentinoids with opioids was associated with increased risk of opioid overdose and other opioid-related adverse events; however, the absolute risk of adverse events was low.