Gabapentin for Postoperative Pain Control and Opioid Reduction in Scrotal Surgery: A Randomized Controlled Clinical Trial.

PURPOSE: To assess the safety and efficacy of gabapentin in reducing postoperative pain among patients undergoing scrotal surgery for male infertility by conducting a randomized, double-blind, placebo-controlled trial. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled trial, healthy men undergoing scrotal surgery with a single surgeon were randomized to receive either (1) gabapentin 600 mg given 2 hours preoperatively and 300 mg taken 3 times a day postoperatively for 3 days, or (2) inactive placebo. The primary outcome measure was difference in postoperative pain scores. Secondary outcomes included differences in opioid usage, patient satisfaction, and adverse events. RESULTS: Of 97 patients screened, 74 enrolled and underwent randomization. Of these, 4 men were lost to follow-up, and 70 were included in the final analysis (35 gabapentin, 35 placebo). Both differences in initial postoperative mean pain score (-1.14, 95% CI -2.21 to -0.08, P = .035) and final mean pain score differences (-1.27, 95% CI -2.23 to -0.32, P = .0097) indicated lower gabapentin pain compared to placebo. There were no statistically significant differences in opioid usage, patient satisfaction, or adverse events. CONCLUSIONS: These data suggest that perioperative gabapentin results in a statistically and clinically significant decrease in pain following scrotal surgery. While there was no evidence of an impact on opioid usage or patient satisfaction, given the low risk of adverse events, it may be considered as part of a multimodal pain management strategy.

Gabapentinoids in Ireland 2010 to 2020: An observational study of trends in gabapentinoid prescribing, law enforcement drug seizures and postmortem toxicology.

AIMS: We explored trends in gabapentinoid prescribing, drug seizures and postmortem toxicology using a national pharmacy claims database, law enforcement drug seizures data and a population-based postmortem toxicology database. METHODS: Gabapentinoid prescribing rates per 100 000 eligible population (2010-2020), annual number of drug seizures involving gabapentinoids (2012-2020) and gabapentinoid detection (positive) rates per 100 postmortem toxicology case (2013-2020) were calculated. Negative binomial regression models were used to evaluate longitudinal trends for gabapentin and pregabalin separately. RESULTS: Gabapentin (adjusted rate ratio [RR] 1.06, 95% confidence interval [CI] 1.05-1.06, P < .001) and pregabalin (adjusted RR 1.08, 95% CI 1.08-1.09, P < .001) prescribing increased annually, with higher rates of pregabalin (vs. gabapentin) observed every year. Drug seizures involving pregabalin also increased over time (RR 1.54 95% CI 1.25-1.90, P < .0001). Of the 26 317 postmortem toxicology cases, 0.92% tested positive for gabapentin, and 6.37% for pregabalin. Detection rates increased for both gabapentin (RR 1.28, 95% CI 1.11-1.48, P < .001) and pregabalin (RR 1.13, 95% CI 1.11-1.48, P < .001) between 2013 and 2020. A total of 1901 cases (7.2%) tested positive for heroin/methadone; this sub-group had a higher detection rate for pregabalin (n = 528, 27.8%) and gabapentin (n = 41, 2.2%) over the study period, with a high burden of codetections for pregabalin with benzodiazepines (peaking at 37.3% in 2018), and pregabalin with prescription opioids (peaking at 28.9% in 2020). CONCLUSION: This study raises concerns regarding the wide availability of pregabalin in Ireland, including a growing illicit supply, and the potential for serious harm arising from poly drug use involving pregabalin among people who use heroin or methadone.

Patterns of gabapentinoid use among long-term opioid users.

OBJECTIVE: Understanding the clinical and demographic profile of patients on gabapentinoids can highlight areas of prescribing disparities, inform clinical practice, and guide future research to optimize effectiveness and safety of gabapentinoids for pain management. We used a national sample of Medicare beneficiaries to examine trends, patterns, and patient-level predictors of gabapentinoid use among long-term opioid users. METHODS: Using a national Medicare sample between 2014 and 2020, we examined factors associated with gabapentinoid use among long-term opioid users. We included Medicare eligible long-term opioid users with no prior gabapentinoid use. The primary outcome was gabapentinoid use after the long-term opioid use episode. Logistic regression was used to test the association with gabapentinoid use for year, age, sex, race/ethnicity, region, Medicare entitlement, low-income status, frailty, pain locations, anxiety, depression, opioid use disorder, and opioid morphine milligrams equivalent. RESULTS: Gabapentinoid use among long-term opioid users increased from 12.6% in 2014 to 16.8% in 2019 (p < .0001). Factors associated with increased gabapentinoid use were Hispanic ethnicity, back pain, nerve pain, and moderate or high opioid usage. Factors associated with decreased gabapentinoid use were older age and Medicare entitlement due to old age. CONCLUSIONS: Variation of gabapentinoid use by socio-demographics and insurance status indicates opportunities to improve pain management and a need for shared therapeutic decision making informed by discussion between pain patients and providers regarding safety and effectiveness of pain therapies. Our findings underscore the need for future research into the comparative effectiveness and safety of gabapentinoids for non-cancer chronic pain in various subpopulations.

Risks of congenital malformations and neonatal intensive care unit admissions with gabapentin use in pregnancy: A cohort study and scoping review with meta-analysis.

BACKGROUND: The increasing and prevalent use of gabapentin among pregnant people highlights the necessity to assess its neonatal safety. OBJECTIVES: This study aimed to investigate the foetal safety of gabapentin during pregnancy using a cohort study and scoping review with a meta-analysis of published evidence. METHODS: We conducted a population-based cohort study using the Manitoba health databases between 1995 and 2019. We examined the association between gabapentin use during pregnancy and the prevalence of major congenital malformations, cardiac and orofacial malformations, and neonatal intensive care unit (NICU) admissions using multivariate regression models. We searched the literature in MEDLINE and EMBASE databases from inception to October 2022 to identify relevant observational studies and conducted a meta-analysis using random-effects models, including our cohort study results. RESULTS: Of the 289,227 included pregnancies, 870 pregnant people were exposed to gabapentin. Gabapentin exposure during the First trimester was not associated with an increased risk of any malformations (adjusted relative risk [aRR]) 1.16 (95% confidence interval [CI] 0.92, 1.46), cardiac malformations (aRR 1.29, 95% CI 0.72, 2.29), orofacial malformations (aRR 1.37, 95% CI 0.50, 3.75), and major congenital malformations (aRR 1.00, 95% CI 0.73, 1.36). whereas exposure during any trimester was associated with an increased NICU admission risk (aRR, 1.99, 95% CI 1.70, 2.32). The meta-analysis of unadjusted results revealed an increased risk of major congenital malformations (RR 1.44, 95% CI 1.28, 1.61, I2 = 0%), cardiac malformations (RR 1.66, 95% CI 1.11, 2.47, I2 = 68%), and NICU admissions (RR 3.15, 95% CI 2.90, 3.41, I2 = 10%), and increased trend of orofacial malformations (RR 1.98, 95% CI 0.79, 5.00, I2 = 0%). CONCLUSIONS: Gabapentin use was associated with an increased risk of NICU admissions in the cohort study and pooled meta-analysis. Clinicians should prescribe gabapentin with caution during pregnancy and further studies are warranted.

Risk of Suicidal Ideation and Behavior Following Early-Onset Idiopathic Restless Legs Syndrome Treatment.

PURPOSE: To estimate incidence rates of suicidal ideation and behavior following treatment initiation with gabapentinoids or dopamine agonists (DAs) in patients with newly diagnosed early-onset idiopathic restless legs syndrome (RLS) and to examine suicidal behavior risk, comparing between those receiving gabapentinoids and DAs. METHODS: A new user retrospective cohort study using MarketScan claims data from 2012 to 2019 was conducted. Exposures were monotherapy gabapentinoids or DAs initiated within 60 days of new RLS diagnosis. Three varying outcome measures of suicidality were examined and incidence rates were calculated for each. A log-binomial regression model the estimated relative risk (RR) of the outcomes with gabapentinoids. Propensity score weighting adjusted for baseline covariates, including age, substance use disorders, hyperlipidemia, antipsychotic use, hypnotic/sedative use, and mood stabilizer use, which were most imbalanced before weighting. RESULTS: The cohort included 6672 patients, with 4986 (74.7%) initiating a DA and 1686 (25.3%) initiating a gabapentinoid. Incidence rates for all outcome measures were higher in the gabapentinoid group (suicidality: 21.6 vs. 10.7 per 1000 person-years; suicidality with self-harm: 23.0 vs. 11.1 per 1000 person-years; overdose- and suicide-related events: 30.0 vs. 15.5 person-years). Associated risk of suicidality (adjusted RR, 1.27 [95% CI, 0.86-1.88]); suicidality with self-harm (adjusted RR, 1.30 [95% CI, 0.89-1.90]); or overdose- and suicide-related events (adjusted RR, 1.30 [95% CI, 0.93-1.80]) was not significant with gabapentinoids. CONCLUSIONS: Incidence rates for suicidal ideation and behavior were higher among the gabapentinoid group, although increased risk was not detected after adjustment. A possible signal cannot be ruled out given limitations of the data and rarity of the outcome.

Gabapentin-induced Multifocal Myoclonus.

BACKGROUND: Gabapentin is the most commonly preferred agent for neuropathic pain in general practice as it is usually well tolerated, but occasionally, its toxicity may occur at standard doses, especially in elderly individuals, even without any prior comorbidities. CASE: We present an elderly male with normal renal parameters, who was started on gabapentin for neuropathic pain. He developed multifocal myoclonus all over the body within few days after starting gabapentin and subsided completed after withdrawal of the drug. CONCLUSION: Acute hyperkinetic movement disorders such as multifocal or segmental myoclonus in elderly patients warrant a prompt review of recent drug history, especially gabapentin, even in the background of normal renal function.

Deprescribing interventions for gabapentinoids in adults: A scoping review.

The emerging issue of rising gabapentinoid misuse is being recognized alongside the lack of current evidence supporting the safe and effective deprescribing of gabapentinoids. This scoping review aimed to assess the extent and nature of gabapentinoid deprescribing interventions in adults, either in reducing dosages, or prescribing of, gabapentinoids. Electronic databases were searched on 23 February 2022 without restrictions. Eligible studies included randomized, non-randomized and observational studies that assessed an intervention aimed at reducing/ceasing the prescription/use of a gabapentinoid in adults for any indication in a clinical setting. The research outcomes investigated the type of intervention, prescribing rates, cessations, patient outcomes and adverse events. Extracted outcome data were categorized as either short (≤3 months), intermediate (>3 but <12 months) or long (≥12 months) term. A narrative synthesis was conducted. The four included studies were conducted in primary and acute care settings. Interventions were of dose-reducing protocols, education and/or pharmacological-based approaches. In the randomized trials, gabapentinoid use could be ceased in at least one third of participants. In the two observational trials, gabapentinoid prescribing rates decreased by 9%. Serious adverse events and adverse events specifically related to gabapentinoids were reported in one trial. No study included patient-focused psychological interventions in the deprescribing process, nor provided any long-term follow-up. This review highlights the lack of existing evidence in this area. Due to limited available data, our review was unable to make any firm judgements on the most effective gabapentinoid deprescribing interventions in adults, highlighting the need for more research in this area.

Alcohol-related posterior reversible encephalopathy syndrome: a case report of a patient managed with a benzodiazepine-sparing regimen for alcohol withdrawal.

We report a case of posterior reversible encephalopathy syndrome (PRES) during treatment for alcohol withdrawal syndrome with gabapentin and clonidine. The patient developed severe hypertension, confusion and tremor, culminating in bilateral vision loss and a seizure. Imaging revealed posterior cerebral edema. Treatment with benzodiazepines, antihypertensives, and anti-seizure medications led to resolution. One year later, imaging showed resolution of the findings. We review the associated literature and propose the recognition of a PRES sub-entity, Alcohol-Related PRES (ARPRES), which can appear in the setting of alcohol withdrawal syndrome, chronic alcohol use, and acute alcohol intoxication, with or without hypertension.

The effect of gabapentin and pregabalin administration on memory in clinical and preclinical studies: a meta-analysis and systematic review.

BACKGROUND: Today, gabapentinoids such as Gabapentin (GBP) and pregabalin (PGB) are widely used as painkillers. This may alter the function of the nervous system; hence their results may include a difference in memory and processes that end in memory formation. This study aims to conclude whether gabapentinoids can alter memory or not by reviewing and analyzing clinical and preclinical studies. MATERIAL AND METHODS: A comprehensive search was carried out in databases including PUBMED, EMBASE, SCOPUS, and Web of Science. In the included studies, memory was measured as an outcome variable in clinical or preclinical studies. RESULT: A total of 21 articles (4 clinical, 17 preclinical) were included in the meta-analysis by STATA Software. The results showed that memory changes under the influence of GBP. Both the administrated dosage and the time of administration are important in the final results and latency time of retention. GBP administration in healthy animals increased latency time, whereas if the administration of GBP took place exactly before training, the latency time increased slightly. Short-term administration of PGB in healthy volunteers is accompanied by transient side effects on the CNS. However, the number and homogeneity of the studies were not such that a meta-analysis could be performed on them. CONCLUSION: Clinical and preclinical studies showed that PGB administration did not confirm its improving memory effect. GBP administration in healthy animals increased latency time and improved memory. Although it depended on the time of administration.

Efficacy and Safety of Gabapentin on Postoperative Pain Management After Bariatric Surgery: A Systematic Review and Meta-Analysis.

PURPOSE: Examine the efficacy and safety of perioperative gabapentin in bariatric surgical patients. DESIGN: Systematic Review and Meta-analysis. METHODS: An exhaustive search was conducted using PubMed, Cochrane Library, MEDLINE, CINAHL, Google Scholar, and other gray literature. Only randomized controlled trials evaluating the use of gabapentin in bariatric surgery were included. Risk ratio (RR) and mean difference (MD) were used to estimate outcomes with suitable effect models. Quality of evidence was assessed using the Risk of Bias and GRADE system. FINDINGS: Four trials consisting of 283 patients were analyzed. The use of gabapentin significantly lowered the cumulative pain score in the first 24 hours after surgery by an average of 1.04 (MD, -1.04; 95% CI, -1.45 to -0.63; P < .00001). Gabapentin also reduced the overall morphine equivalent consumption by 7.89 mg (MD, -7.89; 95% CI, -13.56 to -2.2; P = .006). However, gabapentin did not affect the incidence of PONV (RR, 0.61; 95% CI, 0.38-1.00; P = .05), somnolence (RR, 1.25; 95% CI, 0.57-2.73; P = .57), dizziness (RR, 1.01; 95% CI, 0.40-2.54; P = .99), and headache (RR, 0.76; 95% CI, 0.25-2.30; P = .62). Substantial heterogeneity, imprecision of the effect size, and potential publication bias were limitations of this review. CONCLUSIONS: The use of gabapentin is effective in the management of postoperative pain in bariatric surgery. However, there is limited data regarding the opioid-sparing effect and adverse effect profiles of gabapentin in the bariatric surgical population.

[Drug abuse of pregabalin - state of the situation, risks and means of control]. / Détournement de la prégabaline à des fins toxicomaniaques - état de la situation, risques et moyens de lutte.

Pregabalin is an anticonvulsant widely used for the treatment of epilepsy and neuropathic pain. However, there is a growing concern about its misuse, particularly among drug users and patients with substance use disorders (SUD). It is often used in combination with other psychoactive molecules and at levels well above the recommended doses. Increasing cases of overdose and death associated with the misuse of pregabalin have been reported worldwide. Therefore, raising prescribers' awareness of this scourge is mandatory and the role of the pharmacist is crucial in reducing this phenomenon.

Clinical characteristics of antiepileptic-induced liver injury in patients from the DILIN prospective study.

BACKGROUND & AIMS: Antiepileptic drugs (AEDs) are a common cause of drug-induced liver injury (DILI). Over the last few decades, several newer AEDs were approved for marketing in the United States, and they are increasingly prescribed for indications other than seizures. Contemporaneous data related to trends and characteristics of AED-related liver injury are sparse. METHODS: We report the trends, characteristics, and outcomes of patients with AED-related DILI enrolled into the DILIN Prospective Study between 2004 and 2020. RESULTS: Among 1,711 participants with definite, highly likely, or probable DILI, 66 (3.9%) had AED-related DILI (lamotrigine [n = 18], phenytoin [n = 16], carbamazepine [n = 11], valproate [n = 10], gabapentin [n = 4], and others [n = 7]). The frequency of AED-related liver injury significantly decreased during the study period (from 8.5% of cases during 2004-2007 to 2.6% during 2015-2020, p = 0.01). AEDs other than phenytoin were commonly prescribed for non-seizure indications. Compared to non-AEDs, patients with AED-related liver injury were younger (mean age 38.5 vs. 50.1 years-old, p <0.001) and more likely African American (27% vs. 12%, p = 0.008). DRESS was common with liver injury caused by lamotrigine, phenytoin, and carbamazepine, but not valproate or gabapentin. Liver injury severity was moderate to severe in the majority: 5 died, and 3 underwent orthotopic liver transplantation (OLT). No patient with lamotrigine-related DILI, including 13 with hepatocellular jaundice, died or needed OLT, while 3 out of 16 patients (19%) with phenytoin-related DILI either died or required OLT. CONCLUSION: The frequency of AED-related liver injury significantly decreased over the last 2 decades in our experience. AED-related liver injury has several distinctive features, including a preponderance in African American patients and those with immunoallergic skin reactions, with outcomes depending on the type of AED involved. LAY SUMMARY: Medications used to treat epilepsy may sometimes cause severe liver injury. However, several new medications have been approved over the last 2 decades and they may not be as toxic to the liver as older antiepileptic medications (AEDs). This study shows that overall liver injury due to AEDs is decreasing, likely due to decreasing use of older AEDs. Liver injury due to AEDs appears to be more common in African Americans and is commonly associated with allergic skin reactions.

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.

Higher-Dose Gabapentinoids and the Risk of Adverse Events in Older Adults With CKD: A Population-Based Cohort Study.

RATIONALE & OBJECTIVE: Gabapentinoids are opioid substitutes whose elimination by the kidneys is reduced as kidney function declines. To inform their safe prescribing in older adults with chronic kidney disease (CKD), we examined the 30-day risk of serious adverse events according to the prescribed starting dose. STUDY DESIGN: Population-based cohort study. SETTING & PARTICIPANTS: 74,084 older adults (64% women; median age, 79 [interquartile range, 73-85] years) with CKD (defined for this study as an estimated glomerular filtration rate <60 mL/min/1.73 m2 and excluding those receiving dialysis) and a newly prescribed gabapentinoid between 2008 and 2020 in Ontario, Canada. EXPOSURE: Higher-dose gabapentinoids (gabapentin >300 mg/d or pregabalin >75 mg/d) versus lower-dose gabapentinoids (gabapentin ≤300 mg/d or pregabalin ≤75 mg/d). OUTCOMES: The primary composite outcome was the 30-day risk of a hospital visit with encephalopathy, a fall, or a fracture or a hospitalization with respiratory depression. ANALYTICAL APPROACH: Comparison groups were balanced on indicators of baseline health using inverse probability of treatment weighting using propensity score analysis that generated a pseudosample for the reference group with a distribution of measured covariates similar to the exposed group. Weighted risk ratios were estimated using modified Poisson regression, and weighted risk differences were estimated using binomial regression. Prespecified subgroup analyses were conducted by estimated glomerular filtration rate category and type of gabapentinoid. RESULTS: Among 74,084 patients identified with CKD and a new prescription for gabapentin or pregabalin, 41% started at >300 or >75 mg/d, respectively. From this set of patients, a weighted study population with a size of 61,367 was generated. Patients who started at a higher dose had a higher 30-day risk of the primary outcome than patients who started at lower dose. Within the weighted population, the numbers of events for higher versus lower dose were 585 of 30,660 (1.9%) versus 462 of 30,707 (1.5%), respectively. The weighted risk ratio was 1.27 (95% CI, 1.13-1.42), and the weighted risk difference was 0.40% (95% CI, 0.21%-0.60%). In subgroup analyses, neither multiplicative nor additive interactions were statistically significant. LIMITATIONS: Residual confounding. CONCLUSIONS: In this population-based study, starting a gabapentinoid at a higher versus a lower dose was associated with a slightly higher risk of a hospital visit with encephalopathy, a fall, or a fracture or hospitalization with respiratory depression. If verified, these risks should be balanced against the benefits of using a higher-dose gabapentinoid.

Cardiovascular risk of gabapentin and pregabalin in patients with diabetic neuropathy.

BACKGROUND: Gabapentin and pregabalin are commonly prescribed medications to treat pain in patients with diabetic neuropathy. Gabapentin and pregabalin can cause fluid retention, which is hypothesized to be associated with cardiovascular diseases. However, whether long-term use of gabapentin and pregabalin is associated with adverse cardiovascular diseases remains unknown. This study aims to examine the association between gabapentin use, pregabalin use and several adverse cardiovascular events. METHODS: This retrospective cohort study used propensity score matching within patient electronic health records (EHRs) from a multicenter database with 106 million patients from 69 health care organizations in the US. The study population comprised 210,064 patients who had a diagnosis of diabetic neuropathy and were prescribed diabetic neuropathy medications in their EHRs. The exposure cohort comprised patients who were prescribed gabapentin or pregabalin to treat diabetic neuropathy. The comparison cohort comprised patients who were not prescribed either gabapentin or pregabalin but were prescribed other drugs to treat diabetic neuropathy. The outcomes of interest were myocardial infarcts, strokes, heart failure, peripheral vascular disease, and venous thromboembolic events. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for 3-month and 5-year risk for adverse cardiovascular events between the propensity score-matched cohorts. RESULTS: Both gabapentin and pregabalin were associated with increased risk of 5-year adverse cardiovascular events compared with the comparison group. In patients prescribed gabapentin, the highest risk was observed for deep venous thrombosis (HR: 1.58, 95% CI 1.37-1.82), followed by pulmonary embolism (HR: 1.5, 95% CI 1.27-1.76), peripheral vascular disease (HR: 1.37, 95% CI 1.27-1.47), stroke (HR: 1.31, 95% CI 1.2-1.43), myocardial infarction (HR: 1.25, 95% CI 1.14-1.38) and heart failure (HR: 1.14, 95% CI 1.07-1.21). In patients prescribed pregabalin, the highest risk was observed for deep venous thrombosis (HR: 1.57, 95% CI 1.31-1.88), followed by peripheral vascular disease (HR: 1.35, 95% CI 1.22-1.49), myocardial infarction (HR: 1.29, 95% CI 1.13-1.47), pulmonary embolism (HR: 1.28, 95% CI 1.04-1.59), stroke (HR: 1.26, 95% CI 1.12-1.42), and heart failure (HR: 1.2, 95% CI 1.11-1.3). There were significant associations between short-term (3 month) gabapentin use and heart failure, myocardial infarction, peripheral vascular disease, deep venous thrombosis, and pulmonary embolism. Short-term (3 month) pregabalin use was associated with deep venous thrombosis, peripheral vascular disease. CONCLUSION: In patients with diabetic neuropathy who were prescribed gabapentin and pregabalin, there is an increased risk for heart failure, myocardial infarction, peripheral vascular disease, stroke, deep venous thrombosis, and pulmonary embolism with long-term use. Our findings suggest that increased risk for adverse cardiovascular events, along with other side effects, the efficacy of pain control and the degree of tolerance of the patient, should be considered when prescribing gabapentin and pregabalin long-term in patients with diabetic neuropathy.

Fatalities associated with gabapentinoids in England (2004-2020).

The gabapentinoids were reclassified as Schedule II medications and Class C drugs in the UK in 2019 due to their potential misuse. In this study we examined deaths following gabapentinoid use in England reported to the National Programme on Substance Abuse Deaths. A total of 3051 deaths were reported (gabapentin: 913 cases; pregabalin: 2322 cases [both detected in 184 cases]). Prescribed and illicitly obtained gabapentinoids accounted for similar proportions of deaths (gabapentin illicit 38.0%, prescribed 37.1%; pregabalin illicit 41.0%, prescribed 34.6%). Opioids were co-detected in most cases (92.0%), and co-prescribed in a quarter (25.3%). Postmortem blood gabapentinoid concentrations were commonly (sub)therapeutic (65.0% of gabapentin cases; 50.8% of pregabalin cases). In only two cases was gabapentinoid toxicity alone attributed in causing death. Gabapentinoids alone rarely cause death. Clinically relevant doses can, however, prove fatal, possibly by reducing tolerance to opioids. Doctors and patients should be aware of this interaction. Gabapentinoid-opioid co-prescribing needs urgent revision.

Gabapentinoid dosing and adverse events in patients with chronic kidney disease.

BACKGROUND: Gabapentinoids (GPs) are frequently prescribed in individuals with chronic kidney disease (CKD); however, their exclusive renal elimination warrants dose adjustments to decrease risk of toxicity. This study evaluated GP prescribing patterns and whether excessive dosing was associated with increased incidence of gabapentinoid-related adverse events (GRAEs). MATERIALS AND METHODS: A retrospective analysis of adult CKD and end-stage kidney disease (ESKD) patients hospitalized from 2014 to 2020 and receiving GPs was conducted. Patients were grouped based on whether the average daily dose prescribed was higher than recommended (inappropriately dosed, (ID)) or as recommended (appropriately dosed (AD)) for CKD stage. The occurrence of GRAEs was compared between groups. Patient characteristics, CKD stage, and hospital length of stay (LOS) were evaluated to determine association with GRAEs. RESULTS: The 200 patients included were predominantly female (51%), black (72%), CKD 5/ESKD (84%), and prescribed gabapentin (90%) with a mean age 61 ± 14 years. For the 111 (55%) patients in the AD group and 89 (45%) in the ID group there was no statistically significant difference in GRAEs (18 vs. 19%, p = 0.84). GRAEs were associated with older age (66 vs. 61 years; p < 0.001), seizure history (14% for GRAE vs. 3% for no GRAE, p = 0.02), and concomitant antipsychotic use (24% for GRAE vs. 5% for no GRAE; p < 0.001) but not with CKD severity. LOS was significantly longer for patients experiencing a GRAE (8.5 vs. 5.3 days; p < 0.001). CONCLUSION: Appropriate dosing of GPs is particularly important to minimize the risk of adverse events in patients of older age, with a history of seizures, or concomitant antipsychotic use. There is a need for prescriber education given the high frequency of inappropriate GP dosing observed in patients with advanced kidney disease.

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.

Association Between Gabapentinoids and Postoperative Pulmonary Complications in Patients Undergoing Thoracic Surgery.

OBJECTIVE: Perioperative gabapentinoids in general surgery have been associated with an increased risk of postoperative pulmonary complications (PPCs), while resulting in equivocal pain relief. This study's aim was to examine the utilization of gabapentinoids in thoracic surgery to determine the association of gabapentinoids with PPCs and perioperative opioid utilization. DESIGN: A multicenter retrospective cohort study. SETTING: Hospitals in the Premier Healthcare Database from 2012 to 2018. PARTICIPANTS: A total of 70,336 patients undergoing elective open thoracotomy, video-assisted thoracic surgery, and robotic-assisted thoracic surgery. INTERVENTIONS: Propensity score analyses were used to assess the association between gabapentinoids on day of surgery and the primary composite outcome of PPCs, defined as respiratory failure, pneumonia, reintubation, pulmonary edema, and noninvasive and invasive ventilation. Secondary outcomes included invasive and noninvasive ventilation, hospital mortality, length of stay, opioid consumption on day of surgery, and average daily opioid consumption after day of surgery. RESULTS: Overall, 8,142 (12%) patients received gabapentinoids. The prevalence of gabapentin on day of surgery increased from 3.8% in 2012 to 15.9% in 2018. Use of gabapentinoids on day of surgery was associated with greater odds of PPCs (odds ratio [OR] 1.19, 95% CI 1.11-1.28), noninvasive mechanical ventilation (OR 1.30, 95% CI 1.16-1.45), and invasive mechanical ventilation (OR 1.14, 95% CI 1.02-1.28). Secondary outcomes indicated no clinically meaningful associations of gabapentinoid use with opioid consumption, hospital mortality, or length of stay. CONCLUSIONS: Perioperative gabapentinoid administration in elective thoracic surgery may be associated with a higher risk of PPCs and no opioid-sparing effect.

[Efficacy analysis of lidocaine plaster combined with gabapentin in the treatment of herpes zoster neuralgia].

Objective: To evaluate the efficacy and safety of lidocaine plaster combined with gabapentin in the treatment of herpes zoster neuralgia (HZN). Methods: A total of 93 patients diagnosed with HZN from June 4, 2021 to January 5, 2022 in the Department of Pain Clinic of Nanjing Drum Tower Hospital were selected, and their gender was not limited. They were divided into 3 groups by random number table method: group A (n=32) prescribed gabapentin alone, group B (n=30) lidocaine plaster alone, and group C (n=31) lidocaine plaster combined with gabapentin. After excluding patients who did not meet the criteria, there were 28 cases in group A, 28 cases in group B, and 29 cases in group C. The visual analogue scale (VAS), the short-form McGill pain questionnaire (SF-MPQ) score, and drug dosage and adverse reaction in each group at pre-treatment (T0), post-treatment in one week (T1), in two weeks (T2), in four weeks (T4), and in 12 weeks (T12) were recorded and evaluated; Pittsburgh Sleep Quality Index (PSQI) score and Medical Outcomes Study short-form 36 (SF-36) score at T0, T4, and T12 were recorded. Adverse reactions and drug dosage in each group were documented. Repeated measures ANOVA was used to compare the curative effects of the three groups at different time points before and after treatment. Results: The ages of the three groups of patients were (67.8±10.0), (60.9±11.4) and (63.5±12.5) years old respectively (P=0.318), and the proportions of men were 46.4 % (13 cases), 35.7% (10 cases) and 44.8 % (13 cases), respectively (P=0.472). After treatment, the VAS scores and SF-MPQ scores of patients in the three groups were decreased at each time point compared with those before treatment (all P<0.05), the VAS and SF-MPQ scores of patients in group C at T12 time point were 1.2±0.4 and 5.2±2.4 respectively, which were lower than those of patients in groups A and B (both P<0.05). The dosages of gabapentin and lidocaine plaster in group C were lower than those in groups A and B at each time point after treatment (all P<0.05). The PSQI scores of patients in the three groups at T4 and T12 were lower than those before treatment (all P<0.05). The PSQI scores of patients in group C at T4 and T12 were 5.7±1.2 and 4.5±1.2, which were lower than those of patients in groups A and B. (all P<0.05), The SF-36 scores of patients in three groups at T4 and T12 were higher than those before treatment (all P<0.05), and the SF-36 scores of group C at T4 and T12 were 91.7±8.5, 93.1±6.3, which were higher than that of patients in groups A and B (both P<0.05). The incidence of adverse reactions in the three groups were 35.7% (9 cases), 10.7% (3 cases), and 13.8% (4 cases) respectively (P<0.05), the adverse reactions in groups B and C were less than those in group A (P<0.05), and there was no statistical difference between groups B and C (P>0.05). Conclusion: Lidocaine plaster combined with gabapentin has better analgesic effect in the treatment of HZN, with less incidence of adverse reactions, and can reduce the dosage of systemic drugs, improve patients' sleep and quality of life, and thus could provide a safe and effective method for the treatment of HZN.