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Background: Gabapentinoids are among the most widely prescribed pain medications worldwide. However, there is growing evidence of harms associated with their use. The aim of this study was to systematically review and synthesise qualitative research exploring lived experiences of gabapentinoid (pregabalin and/or gabapentin) misuse and symptoms of dependence., Methods: Six databases (MEDLINE, Scopus, Web of Science, CINAHL, EMBASE, PsycINFO) and grey literature sources were searched from inception to September 2023. The methodological quality of included studies was appraised using a modified 11-item version of the Critical Appraisal Skills Programme qualitative checklist, and higher quality studies were prioritised in the thematic synthesis. Confidence in the overall findings of the review was assessed using the GRADE-CERQual approach. The review was prospectively registered on PROSPERO (CRD42023401832)., Results: Twenty-six articles representing 21 original studies were included. The majority used interview methods and were of high methodological quality. Motives for gabapentinoid misuse included getting high, potentiating or offsetting the effects of other drugs, self-medicating for pain, distress, insomnia, or withdrawal symptoms, and substituting for another drug. Symptoms of dependence included the rapid development of tolerance and a severe withdrawal syndrome often involving psychiatric symptoms. Harms including dissociation, loss of consciousness, and overdose were generally reported as a consequence of polysubstance use. Confidence in most of the review findings was moderate with low confidence in one finding., Conclusion: This review provides rich qualitative insights into the potential motives for gabapentinoid misuse as well as the diverse lived experiences of dependence symptomatology. Considering the increasing prescribing of these medications globally, and the potential for public health challenges resulting from misuse, the findings of this review can be used to develop more effective harm reduction strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Sedation before veterinary visits is advocated to help reduce fear and anxiety in cats and facilitate safe handling. The aim of this study was to evaluate the effectiveness of trazodone, gabapentin and a trazodone/gabapentin combination for oral sedation in healthy feline patients before blood donation., Methods: A total of 21 cats were included in the study. Baseline sedation scores were obtained, and cats were randomly assigned to receive oral trazodone at 5 mg/kg (T), oral gabapentin at 10 mg/kg (G), their combination (TG) or placebo (control group). A sedation score was obtained 1 h after drug administration. A blood sample was obtained at the time of blood collection for quantification of drug plasma concentrations. Agreement between observers was tested with a Cohen's Kappa test. Sign tests to compare change within treatment and a Skilling-Mack rank ANOVA to test for differences between groups were performed to compare pre- and post-sedation scores as well as a magnitude of differences over time between the groups. A Spearman's rank correlation coefficient test was used to correlate sedation scores with drug plasma concentrations., Results: Post-sedation final scores were significantly higher only in the T ( P  = 0.022) and TG groups ( P <0.001). The magnitude of change between pre- and post-sedation scores was larger in the TG ( P <0.0032) and T groups ( P <0.038) compared with the control group. There were no other significant differences between the groups. There was no correlation between drug plasma concentrations and sedation scores in any of the groups., Conclusions and Relevance: Administration of oral trazodone alone at 5 mg/kg or in combination with gabapentin at 10 mg/kg resulted in significant sedation in healthy cats with no evident side effects. The degree of sedation was more profound when both drugs were combined, but a gabapentin dose of 10 mg/kg alone failed to provide significant sedation in this population., Competing Interests: Conflict of interestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Few studies report outcomes for enhanced recovery pathways in ambulatory anorectal surgery. We hypothesize that an ambulatory anorectal enhanced recovery pathway with multimodal analgesia can reduce postoperative opioid use., Objective: To compare postoperative opioid use in patients undergoing ambulatory anorectal surgery who receive multimodal analgesia versus standard of care without multimodal analgesia., Design: A prospective randomized trial of patients undergoing elective anal fistula or hemorrhoid surgery from September 2018 to May 2022., Setting: Urban teaching hospital., Patients: Adults aged 18 to 70 years undergoing elective anal fistula or hemorrhoid surgery from September 2018 to May 2022., Intervention: Multimodal enhanced recovery pathway including preoperative and postoperative nonopioid analgesia with oral acetaminophen, gabapentin, and ketolorac., Main Outcome Measures: Primary end point was oral opioid use during the first postoperative week. Secondary end points included maximum pain and nausea scores, adverse events, and emergency room or hospital admissions during the first 30 days postoperatively., Results: Of the 109 enrolled patients, 20 were lost to follow-up. The remaining 89 patients had a median age of 38 years (range, 20-67) and included 41 women (46%). There were no significant differences between the enhanced recovery protocol arm and non-enhanced recovery protocol arm in terms of preoperative and surgical characteristics. The primary end point of this study, that is, oral morphine milligram equivalents use during the first week, was significantly higher among patients in the non-enhanced recovery protocol arm (79 mg; range, 0-600) than patients in the enhanced recovery protocol arm (8 mg; range, 0-390; p = 0.002). On subgroup analysis, both fistula and hemorrhoid surgery patients assigned to the non-enhanced recovery protocol arm took significantly higher oral morphine milligram equivalents in the first week than patients in the enhanced recovery protocol arm. There was no significant difference in secondary end points., Limitations: Patients and providers were not blinded. Our findings are limited to hemorrhoid and fistula surgery and may not be applicable to other anorectal procedures., Conclusions: Enhanced recovery protocols including multimodal analgesia should be used in elective anal fistula and hemorrhoid surgery to decrease postoperative opioid use. See the Video Abstract ., Clinical Trial Registration: ClinicalTrials.gov ID NCT03738904., Implementacin De Protocolo De Recuperacin Acelerada Multimodal En Ciruga Anorrectal Ambulatoria Un Estudio Aleatorizado: ANTECEDENTES:Pocos estudios reportan resultados de programas de recuperación acelerada en la cirugía anorrectal ambulatoria. Presumimos que un programa anorrectal ambulatorio de recuperación acelerada con analgesia multimodal puede reducir el uso posoperatorio de opioides.OBJETIVO:Comparar el uso posoperatorio de opioides en pacientes sometidos a cirugía anorrectal ambulatoria que reciben analgesia multimodal versus atención estándar sin analgesia multimodal.DISEÑO:Un estudio prospectivo aleatorizado de pacientes sometidos a cirugía electiva de fístula anal o hemorroides desde septiembre de 2018 hasta mayo de 2022.LUGAR: Hospital universitario urbano.PACIENTES:Adultos de 18 a 70 años sometidos a cirugía electiva de fístula anal o hemorroides desde septiembre de 2018 hasta mayo de 2022.INTERVENCIÓN:Programa de recuperación acelerada multimodal que incluye analgesia no opioide pre y posoperatoria con paracetamol oral, gabapentina y ketoloraco.PRINCIPALES MEDIDAS DE RESULTADO:El resultado principal fue el uso de opioides orales durante la primera semana postoperatoria. Los resultados secundarios incluyeron puntuaciones máximas de dolor y náuseas, eventos adversos e ingresos a la sala de emergencias o al hospital durante los primeros 30 días después de la operación.RESULTADOS:De los 109 pacientes incluidos, 20 se perdieron durante el seguimiento. Los 89 pacientes restantes tenían una mediana de edad de 38 (rango, 20-67) años e incluían 41 (46%) mujeres. No hubo diferencias significativas entre los grupos del protocolo de recuperación acelerada (Grupo E) y del protocolo de recuperación no acelerada (Grupo NE) en términos de características preoperatorias y quirúrgicas. El resultado principal del estudio, el uso de MME oral durante la primera semana, fue significativamente mayor entre los pacientes del grupo NE (79 mg; rango: 0-600) que los pacientes del grupo E (8 mg; rango: 0-390) ( p = 0,002). En el análisis de subgrupos, los pacientes de cirugía de fístula y hemorroides asignados al grupo NE tomaron MME oral significativamente más alto en la primera semana que los pacientes del grupo E. No hubo diferencias significativas en los resultados secundarios.LIMITACIONES:Los pacientes y proveedores no fueron cegados. Nuestros hallazgos se limitan a la cirugía de hemorroides y fístulas y pueden no ser aplicables a otros procedimientos anorrectales.CONCLUSIONES:Se deben utilizar protocolos de recuperación acelerada que incluyan analgesia multimodal en la cirugía electiva de fístula anal y hemorroides para disminuir el uso posoperatorio de opioides. (Traducción- Dr. Francisco M. Abarca-Rendon )CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov ID NCT03738904., (Copyright © The ASCRS 2024.)

Cold atmospheric plasma (CAP) has been employed as a therapy against both acute and chronic skin lesions, contaminated or not, and has effects on angiogenesis and reepithelialization promoting healing. In this context, the present study aimed to evaluate the effects of a CAP jet associated with pharmacological treatment described by the 2015 AAHA/AAFP pain management guidelines and the 2022 WSAVA guidelines for the recognition, assessment, and treatment of pain, on the healing of chronic skin lesions caused by a pruritic reaction resulting from post-surgical neuropathic pain. To this end, a single CAP application was performed on a feline patient with a 6 months old recurrent contaminated cervical skin lesions along with administration of ketamine (10 µg/kg/min) following the prescription of prednisone (1 mg/kg, SID, 6 days), gabapentin (8 mg/kg, BID, 60 days) and amitriptyline (0.5 mg /kg, SID, 60 days). A single application of plasma associated with an NMDA antagonist, anti-inflammatory steroid, tricyclic antidepressant and gabapentinoid thus provided a significant improvement in the macroscopic appearance of the lesion within 10 days, and the owner reported the cessation of intense itching within the first four hours after treatment and a consequent improvement in the animal's quality of life. The medical treatment was finished almost a year since the writing of this paper, without clinical or reported recurrent signs of the condition. Therefore, we observed that single dose CAP application associated with ketamine, gabapentin, amitriptyline and prednisone leads to significant healing of chronically infected skin lesions resulting from post-surgical neuropathic pain., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Clinical appointment generates stress in feline patients, influencing the frequency of veterinary care with the species. The purpose of this study was to assess serum cortisol in cats submitted to oral gabapentin and integrative practices during clinical care. Twenty cats were evaluated in three clinical appointments, one week apart. All cats were submitted to treatments: placebo (PL), gabapentin (GA), and integrative practices (IP) (music therapy, pheromone therapy, and chromotherapy). GA and PL were administered by the owners 90 min before transportation to the veterinary teaching hospital, and IP were applied 30 min before clinical care. Cats were physically examined at all timepoints, and blood samples were collected for cortisol measurement. Serum cortisol levels ranged from 0.49 µg/dL to 17.99 µg/dL. Mean cortisol concentrations when cats received PL (7.6 µg/dL) were higher than when cats received GA (4.9 µg/dL) and IP (4.1 µg/dL). There was a statistical difference in cortisol levels when cats receiving PL and GA were compared (p = 0.03) and between PL and IP (p = 0.005). The study showed that feline serum cortisol levels were lower when cats received the treatments to IP (integrative practices) and GA (gabapentin), demonstrating that these are applicable methods for reducing stress of feline patients in clinical evaluation., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Gabapentin is an antiepileptic drug that alleviates neuropathic pain. Its oral use reduces the intensity of pruritus in patients receiving chronic dialysis therapy. However, it could lead to toxicity because of the patients' renal deficiency. In this study, we assessed the use of gabapentin topical in treating pruritus in dialysis patients., Methods: This randomized, triple-blinded trial was performed on 80 patients divided into two groups randomly (40 in each group). In intervention group, 92.5% of the patients were on hemodialysis. Patients in intervention and control groups were provided with 5% gabapentin and placebo topical creams every 2 weeks for a month. Both Visual Analog Scale and 12-item Pruritus Severity Score questionnaire were used to evaluate itching intensity and score before treatment, a month, and 2 months after starting treatment in both groups. In addition, the effect of itching on quality of life was investigated with the same questionnaire., Findings: Eighty patients (40 in each group) participated in our study. No complication was found in our intervention group. Itching score significantly decreased after a month and 2 months of follow-up in intervention group (p < 0.001)., Discussion: Our results showed that 5% gabapentin topical cream can be effective in reducing itching in different areas of the body. None of our patients reported complications., (© 2024 International Society for Hemodialysis.)

Objective: To determine the pharmacokinetics and physiological effects following oral and intravenous (IV) administration of gabapentin in goats., Study Design: Prospective, crossover study with a 3 week washout period between treatments., Animals: A total of eight healthy, client-owned, female goats., Methods: Gabapentin (10 mg kg -1 ) was administered to goats either orally or IV. Gabapentin concentrations were measured in serum samples collected 0-96 hours post-administration using liquid chromatography-quadrupole time-of-flight mass spectrometry. Heart rate, respiratory rate, blood pressure and temperature were recorded before and throughout the study. Correlations of the mean serum concentrations of gabapentin to those of each physiological parameter were determined using the Pearson method., Results: The mean and standard deviation of oral bioavailability for gabapentin was 60.9 ± 11.2%. Maximum serum concentration of gabapentin was lower following oral (1.19 ± 0.29 μg mL -1 ) than after IV administration (59.76 ± 14.38 μg mL -1 , p < 0.0001). Half-lives were longer following PO (8.18 ± 0.57 hours) than after IV administration (1.79 ± 0.06 hours, p < 0.0001). Time to maximum concentration was 6.86 ± 2.27 hours following oral administration. Heart rate was inversely correlated with serum gabapentin concentrations. Slight ataxia was observed in three animals, and one became recumbent following IV gabapentin., Conclusions and Clinical Relevance: Gabapentin is well-absorbed following oral administration to goats but yielded significantly lower serum concentrations than the IV route. The longer half-life of gabapentin following oral than after IV administration may result from prolonged absorption throughout the caprine gastrointestinal tract. IV gabapentin may cause slight ataxia in some goats., (Copyright © 2024 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

This study evaluated the influence of gabapentin on sedation, propofol dosage, and physiological variables in cats premedicated with acepromazine and methadone. Thirty-four cats were randomly assigned to receive 100 mg of oral gabapentin (Gabapentin group) or placebo (Control group) 100 min before intramuscular premedication with acepromazine (0.05 mg/kg) plus methadone (0.3 mg/kg). Variables recorded included sedation, using the Dynamic Interactive Visual Analog Scale (DIVAS, range 0-100 mm) and a Numeric Descriptive Scale (NDS, range 0-14), heart rate, respiratory rate and Doppler systolic arterial pressure (SAP). All variables were measured before (T0), 100 min after administration of gabapentin or placebo (T1), and 30 min after premedication (T2). Physiological variables were also recorded after anesthetic induction with propofol (T3). At T2, NDS scores were higher in Gabapentin than the Control group [median (interquartile range): 4 (2-5) versus 2 (1-4), p = 0.028], whereas DIVAS scores were not significantly different [Control: 9 (4-13); Gabapentin: 12 (5-32)]. Despite the significant difference between groups in NDS scores, overall sedation scores were mild at T1 and T2 regardless of gabapentin administration. The propofol dosage did not differ between groups. The most concerning adverse effect was arterial hypotension (SAP < 90 mmHg), recorded only at T3 in 71% of cats in the Control group and 100% in the Gabapentin group, without significant difference between groups. Administration of gabapentin before premedication with acepromazine and methadone in healthy cats did not result in a clinically significant influence on sedation levels, physiological variables, or propofol dosage required for anesthesia induction., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background:  Nuss procedure for pectus excavatum is a minimally invasive, but painful procedure. Recently, intercostal nerve cryoablation has been introduced as a pain management technique., Materials and Methods:  In this cohort study, we compared the efficacy of multimodal pain management strategies in children undergoing a Nuss procedure. The effectiveness of intercostal nerve cryoablation combined with patient-controlled systemic opioid analgesia (PCA) was compared with continuous epidural analgesia (CEA) combined with PCA. The study was conducted between January 2019 and July 2022. Primary outcome was length of stay (LOS), and secondary outcomes were operation room time, postoperative pain, opioid consumption, and gabapentin use., Results:  Sixty-six consecutive patients were included, 33 patients in each group. The cryoablation group exhibited lower Numeric Rating Scale (NRS) pain scores on postoperative day 1 and 2 ( p  = 0.002, p  = 0.001) and a shorter LOS (3 vs. 6 days ( p  < 0.001). Cryoablation resulted in less patients requiring opioids at discharge (30.3 vs. 97.0%; p  < 0.001) and 1 week after surgery (6.1 vs. 45.4%; p  < 0.001)). In the CEA group, gabapentin use was more prevalent (78.8 vs. 18.2%; p  < 0.001) and the operation room time was shorter (119.4 vs. 135.0 minutes; p  < .010). No neuropathic pain was reported., Conclusions:  Intercostal nerve cryoablation is a superior analgesic method compared with CEA, with reduced LOS, opioid use, and NRS pain scores. The prophylactic use of gabapentin is redundant., Competing Interests: S.A.B. works as a proctor for cryotherapy in pectus patients contracted by the company Atricure., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Objective: Benign prostatic hyperplasia (BPH) is a common chronic disease affecting the health of the urinary system and the quality of life in older adults. Plasmakinetic resection of the prostate (PKRP) is one of the important surgical procedures for treating BPH; However, older adults may experience anesthesia complications and postoperative pain. This retrospective study aimed to assess the effects of preoperative oral gabapentin on anesthesia outcomes in older adults with BPH undergoing PKRP and to provide detailed clinical evidence for improving the impact of surgical treatment., Methods: The medical records of 178 older adults with BPH who underwent PKRP in Tianjin Hospital from March 2021 to March 2023 were retrospectively analyzed. After excluding 18 patients who did not meet the inclusion criteria, 160 patients were finally included in the study. According to preoperative use of gabapentin, patients were divided into the observation group (n = 75, received gabapentin) and the control group (n = 85, did not receive gabapentin). The baseline data, visual analog scale (VAS) scores, postoperative Ramsay Sedation Scale (RSS) scores, and incidence of adverse reactions were collected., Results: There were no significant differences observed between the two groups in terms of age, body mass index, prostate volume, surgery duration, International Prostate Symptom Score (IPSS), American Society of Anesthesiologists (ASA) classification, history of hypertension and diabetes mellitus, VAS scores at postoperative 36 hours and 48 hours, and RSS scores at postoperative 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, and 48 hours ( p > 0.05). Compared to the control group, the observation group had significantly lower VAS scores at postoperative 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours ( p < 0.001), and the incidence of adverse reactions was significantly lower within 24 hours after surgery ( p < 0.05)., Conclusions: Preoperative administration of gabapentin before PKRP could reduce pain severity and the incidence of adverse reactions and improve anesthetic effects in older adults with BPH, which is conducive to postoperative recovery., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s).)

Objectives: To investigate the efficacy and safety of pulsed radiofrequency of the dorsal root ganglion combined with ozone injection for treating acute herpes zoster (HZ) neuralgia in middle-aged and elderly adults., Methods: A total of 164 middle-aged and elderly patients with acute HZ were randomly assigned to 2 groups: the pulsed radiofrequency combined with ozone injection group (group A) and the pulsed radiofrequency group (group B). The therapeutic effects were evaluated using Numeric Rating Scale (NRS) scores and the average doses of gabapentin (mg/d) preoperatively and 1 day, 2 weeks, 4 weeks, 12 weeks, and 24 weeks postoperatively. The incidence of clinically significant postherpetic neuralgia (PHN) and complications in the 2 groups were recorded., Results: The data showed that the NRS scores and the doses of gabapentin after treatment were significantly lower when compared with the baseline values in both groups. Compared with group B, the NRS scores and the doses of postoperative gabapentin were significantly lower in group A. The incidence of PHN was significantly lower at weeks 4, 12, and 24 in group A than in group B. No adverse reactions occurred in either of the 2 groups post-treatment., Conclusions: The results indicated that ozone injection in the dorsal root ganglion combined with pulsed radiofrequency therapy was more effective in treating acute HZ neuralgia in middle-aged and elderly adults. It provides patients with longer-lasting pain relief, decreased incidence of PHN and the doses of medication, and improved quality of life than with Pulsed Radiofrequency treatment., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

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, I 2  = 0%), cardiac malformations (RR 1.66, 95% CI 1.11, 2.47, I 2  = 68%), and NICU admissions (RR 3.15, 95% CI 2.90, 3.41, I 2  = 10%), and increased trend of orofacial malformations (RR 1.98, 95% CI 0.79, 5.00, I 2  = 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., (© 2024 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Gabapentin is used for the treatment of many conditions, including seizures, pain, and anxiety. Increasing reports of nonprescribed use suggest that gabapentin may elicit positive subjective effects. The present study was conducted to examine the subjective effects of gabapentin using rats trained to discriminate either a 30.0 mg/kg or 300.0 mg/kg dose of gabapentin versus vehicle on a two-choice drug discrimination task. Both doses of gabapentin were established as discriminative stimuli, and the 300.0 mg/kg dose was more readily established compared to the 30.0 mg/kg dose. Full substitution (> 80% gabapentin-lever responding) occurred by the training drug and by the gabapentinoid compound pregabalin. Partial substitution (> 20% gabapentin-lever responding) was shown by the opioid compounds morphine and fentanyl, and dose combinations of the opioid receptor antagonist naltrexone with the gabapentin training doses reduced the percentage of gabapentin-lever responding to below 80%. Partial substitution for both training doses of gabapentin occurred with the cannabinoid Δ⁹-tetrahydrocannabinol. The barbiturate compound pentobarbital and the benzodiazepine compound diazepam were only tested for substitution for the 300.0 mg/kg dose of gabapentin and these compounds produced full substitution. These findings demonstrate that gabapentin establishes a robust discriminative cue and exhibits stimulus effects closely similar to pregabalin, pentobarbital, and diazepam. Since pregabalin, pentobarbital, and diazepam carry a risk of problematic use and are classified as controlled substances, further evaluations of gabapentin's risks in this regard are warranted. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

We purposed to explore the consequences of the use quercetin and fisetin alone and in combination with pregabalin and gabapentin, which are used in the management of neuropathic pain, and on neuropathic pain in general. The anti-allodynic effect of various doses (5, 10, and 20 mg/kg) of quercetin and fisetin, both singly and in combination with pregabalin and gabapentin, was evaluated by developing a neuropathic pain model induced by chronic constrictive nerve damage in rats. The effectiveness of these flavonoids was investigated by combining them with gabapentin (50 mg/kg) and pregabalin (15 mg/kg), choosing the effectual dose of 10 mg/kg and the dose of 5 mg/kg, which did not show significant antiallodynic effects. In groups combined with gabapentin and pregabalin, it was determined that they showed a significant antiallodynic effect compared with 50 mg/kg gabapentin and 15 mg/kg pregabalin. In conclusion, in our combination studies, it was observed that the effectiveness of gabapentin and pregabalin, was increased and the duration of effect was prolonged when used with lower doses of flavonoids. Based on these findings; it is possible to say that quercetin and fisetin are potential agents that can be used alone or in combination with other effective treatments to alleviate neuropathic pain., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Patients are often switched between generic formulations of the same drug, but in some cases generic interchangeability is questioned. For generic drugs to be approved, bioequivalence with the innovator drug should be demonstrated, but evidence of bioequivalence is not required in the intended patient population or relative to other approved generics., Aim: We aim to identify pathophysiological pharmacokinetic subpopulations for whom there is a difference in comparative bioavailability compared to a healthy population., Methods: We used simulated exposures from a nonparametric model of multiple generics and the originator gabapentin. Exposure was simulated for virtual populations with pharmacokinetic characteristics beyond those of healthy subjects with regard to rate of absorption, volume of distribution and reduced renal function. Virtual parallel design bioequivalence studies were performed using a random sample of 24 simulated subjects, with standard acceptance criteria., Results: Results indicated increased pharmacokinetic variability for patient populations with a lower rate of absorption or a reduced renal function, but no change in the average comparable bioavailability ratio. This increased variability results in a reduced likelihood of demonstrating bioequivalence. Observations were similar for comparisons between all different formulations, as well as between subjects who received the identical formulation in a repeated fashion. No relevant effect was observed for simulations with increased volume of distribution., Conclusion: Our simulations indicate that the reduced likelihood of demonstrating bioequivalence for subjects with altered pharmacokinetics is not influenced by a formulation switch, nor does the average comparable bioavailability ratio change, therefore these results support generic interchangeability and current approval requirements for generics., (© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Introduction: Gabapentin has been used in enhanced recovery after surgery (ERAS) pathways for pain control for patients undergoing ambulatory uro-oncologic surgery; however, it may cause undesirable side effects. We studied the causal association between gabapentin and rapidity of recovery and perioperative pain management after minimally invasive uro-oncologic surgery., Methods: We identified 2397 patients ≤ 65 years undergoing prostatectomies or nephrectomies between 2018 and 2022; 131 (5.5%) did not receive gabapentin. We tested the effect of gabapentin use on time of discharge and perioperative opioid consumption, respectively, using multivariable linear regression adjusting for potential confounders including age, gender, BMI, American Society of Anesthesiologists score, and surgery type., Results: On adjusted analysis, we found no evidence of a difference in discharge time among those who did vs did not receive gabapentin (adjusted difference 0.07 hours shorter on gabapentin; 95% CI -0.17, 0.31; P = .6). There was no evidence of a difference in intraoperative opioid consumption by gabapentin receipt (adjusted difference -1.5 morphine milligram equivalents; 95% CI -4.2, 1.1; P = .3) or probability of being in the top quartile of postoperative opioid consumption within 24 hours (adjusted difference 4.2%; 95% CI -4.8%, 13%; P = .4). We saw no important differences in confounders by gabapentin receipt suggesting causal conclusions are justified., Conclusions: Our confidence intervals did not include clinically meaningful benefits from gabapentin, when used with an ERAS protocol, in terms of length of stay or perioperative opioid use. These results support the omission of gabapentin from ERAS protocols for minimally invasive uro-oncologic surgeries.

Background: Although gabapentin has been increasingly prescribed to older adults, the relation between gabapentin initiation and longer-term neurocognitive changes is not well understood. Thus, this study aimed to examine the association of gabapentin initiation with cognitive and motor function decline in older adult participants with cognitive impairment., Methods: A retrospective cohort study was conducted using the National Alzheimer's Coordinating Center Uniform Data Set (2005-March 2023). Participants with cognitive impairment at the visit of gabapentin initiation (i.e., index visit) were included. Using the incidence density sampling method, up to nine non-users were randomly selected for each initiator. Cognitive decline over 1 year was defined as any increase in Clinical Dementia Rating global score (CDR ® GLOB) or a 1-point increase in CDR ® sum of boxes (CDR ® SB). Functional status decline over 1 year was defined as at least a 3-point increase in the Functional Activities Questionnaire (FAQ) sum or a 0.3-point increase of mean of FAQ. Motoric decline over 1 year was defined as new clinician reports of gait disorder, falls, and slowness. To mitigate confounding and selection bias, joint stabilized inverse probability of treatment weights and censoring weights were used. Analyses compared index with index + 1 and index + 2 visits., Results: For the study of cognitive and functional status decline, we included 505 initiators (mean age [SD] 78.8 [7.4]; male = 45%) and 4545 non-users (79.2 [7.6]; 50.1%). For the study of motor decline, we included 353 initiators (78.3 [7.2]; 42.8%) and 3177 non-users (78.5 [7.4]; 48.1%). Gabapentin initiation was not statistically associated with decline on CDR ® GLOB, CDR ® SB, FAQ sum, or mean FAQ at the index + 1 or index + 2 visits. However, gabapentin initiation was significantly associated with increased odds of new falls at the index + 2 visit (odds ratio [95% confidence interval] 2.5 [1.3, 4.6])., Conclusions: Over 1 or 2 years of follow-up, gabapentin initiation was not associated with decline in cognitive or functional status but was associated with increased odds of falling among research participants with cognitive impairment., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Gabapentin is used in goats to treat chronic pain associated with lameness. However, pharmacokinetic data and clinical effectiveness trials are lacking. The objective of the study was to describe the pharmacokinetics of gabapentin in goats following a single oral dose. Six Spanish-crossbred goats were enrolled. Each goat was administered gabapentin at a target dose of 15 mg/kg per os. Serial blood samples were collected out to 60 h post-gabapentin administration for plasma gabapentin concentration determination. Plasma samples were analyzed for gabapentin concentration using ultra-high-pressure liquid chromatography coupled with mass spectroscopy. Individual animal pharmacokinetic outcomes were determined using non-compartmental analysis. Gabapentin was detectable in the plasma of all goats at 60 h post-administration. The mean (±SD) C max was 2.01 ± 0.62 μg/mL which occurred at 8.47 ± 1.9 h. The mean terminal half-life (T 1 / 2 ) and mean resident time were determined to be 8.52 ± 1.8 and 18.7 ± 4.0 h, respectively. This study indicates gabapentin is absorbed from the gastrointestinal tract of goats. Further research is needed to determine an optimal dose for clinical efficacy in goats., (© 2024 The Authors. Journal of Veterinary Pharmacology and Therapeutics published by John Wiley & Sons Ltd.)

Background: Gabapentin supplementation may have some potential in pain control after lumbar laminectomy and discectomy, and this meta-analysis aims to explore the impact of gabapentin supplementation on postoperative pain management for lumbar laminectomy and discectomy., Methods: PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched, and we included randomized controlled trials assessing the effect of gabapentin supplementation on the pain control of lumbar laminectomy and discectomy., Results: Five randomized controlled trials were finally included in the meta-analysis. Overall, compared with control intervention for lumbar laminectomy and discectomy, gabapentin supplementation was associated with significantly lower pain scores at 2 hours (MD = -2.75; 95% CI = -3.09 to -2.41; P < .00001), pain scores at 4 hours (MD = -2.28; 95% CI = -3.36 to -1.20; P < .0001), pain scores at 24 hours (MD = -0.70; 95% CI = -0.86 to -0.55; P < .00001) and anxiety score compared to control intervention (MD = -1.32; 95% CI = -1.53 to -1.11; P < .00001), but showed no obvious impact on pain scores at 12 hours (MD = -0.58; 95% CI = -1.39 to 0.22; P = .16). In addition, gabapentin supplementation could significantly decrease the incidence of vomiting in relative to control intervention (OR = 0.31; 95% CI = 0.12-0.81; P = .02), but they had similar incidence of nausea (OR = 0.51; 95% CI = 0.15-1.73; P = .28)., Conclusions: Gabapentin supplementation benefits to pain control after lumbar laminectomy and discectomy., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Objectives: Gabapentin has shown promise as a potential agent for the treatment of alcohol withdrawal syndrome. We aimed to evaluate the effectiveness of gabapentin as a benzodiazepine-sparing agent in patients undergoing alcohol withdrawal treatment in all the hospitals of a large tertiary healthcare system. Materials and Methods: Medical records of patients admitted to the hospital for alcohol withdrawal management between 1 January 2020 and 31 August 2022 were reviewed. Patients were divided into two cohorts: benzodiazepine-only treatment who received benzodiazepines as the primary pharmacotherapy and gabapentin adjunctive treatment who received gabapentin in addition to benzodiazepines. The outcomes assessed included the total benzodiazepine dosage administered during the treatment and the length of hospital stay. The statistical models were calibrated to account for various factors. Results: A total of 4364 patients were included in the final analysis. Among these, 79 patients (1.8%) received gabapentin in addition to benzodiazepines, and 4285 patients (98.2%) received benzodiazepines only. Patients administered gabapentin required significantly lower average cumulative benzodiazepine dosages, approximately 17.9% less, compared to those not receiving gabapentin (median 2 mg vs. 4 mg of lorazepam equivalent dose ( p < 0.01)). However, there were no significant differences in outcomes between the two groups. Conclusions: Our findings demonstrate that using gabapentin with benzodiazepine was associated with a reduction in the cumulative benzodiazepine dosage for alcohol withdrawal. Considering gabapentin as an adjunctive therapy holds promise for patients with comorbidities who could benefit from reducing benzodiazepine dose. This strategy warrants further investigation.

Objectives: To evaluate the efficacy of post-operative gabapentin administration as an analgesic agent and its effect on narcotic use after orthopedic surgery in an outpatient sports medicine practice by comparing patients prior to and after initiating the routine use of gabapentin as part of a standardized post-operative pain medication regimen. We hypothesized that adding gabapentin to a multimodal post-operative pain regimen would decrease the number of requested pain medication refills and have no detrimental effect on Visual Analogue Scale and Single Assessment Numerical Evaluation scores at these early post-operative visits., Methods: All outpatient surgical patients, <90 years of age, undergoing outpatient orthopedic surgery by the study's senior author were included between 08/05/2021 and 02/22/2022. Patients were allowed 1 narcotic refill post-operatively and only in the first 3 weeks. The primary outcome was difference in percentage of patients who requested a narcotic refill within 3 weeks post-op. Two- and 6-week Visual Analogue Scale and Single Assessment Numerical Evaluation scores, and baseline health and demographic data. T-tests were run on continuous variables, Chi-Square or Fisher's Exact Test were run on dichotomous variables, and Mann-Whitney U test was run on all other categorical variables. Statistical significance was set at P  < .05 for all tests., Results: There was a significant difference in narcotic refills at 3 weeks: 23 pre-gabapentin patients and 9 post-gabapentin patients (22.8% vs 9.0%, respectively: P  = .006). There were no differences between 2- and 6-week Visual Analogue Scale and 2-week Single Assessment Numerical Evaluation scores. There was a significant difference in 6-week SANE between groups: mean difference = 6.4 ( P  = .027) though less than the established MCID., Conclusion: Addition of gabapentin to a post-operative multimodal pain regimen reduced the use of narcotics after orthopedic sports medicine surgeries while also providing equivalent pain control.

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., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Sleep deprivation is a prevalent problem in critically ill patients, which leads to delayed recovery and delirium. Slow-wave sleep (SWS) is essential to energy restoration, tissue repair, and immune system strengthening. This study aimed to investigate the effects of gabapentin on SWS in critically ill patients. We performed a prospective open-label randomized controlled study to compare SWS and the clinical outcomes of gabapentin versus a control intervention in critically ill adult patients admitted to the intensive care unit (ICU) within 24 h. The patients' characteristics and sleep-related outcomes were recorded. The sleep-related outcomes, namely, bispectral analysis (BIS), the Richards-Campbell Sleep Questionnaire (RCSQ), and insulin-like growth factor-1 (IGF-1) levels, were evaluated. Furthermore, clinical outcomes and safety were assessed. Sixty patients from 348 cases were eligible for randomization. On day 3 of the study, patients in the gabapentin group had significantly increased SWS (66.79 vs. 0.00 min; p < 0.001), total sleep time (TST) (331.39 vs. 46.16 min; p = 0.001), RCSQ score (55.05 ± 20.18 vs. 32.80 ± 15.31; p < 0.001), and IGF-1 concentrations (84.33 ± 12.40 vs. 44.00 ± 10.20 ng/mL, p < 0.001) compared with the control group. Improvements in clinical outcomes, such as delirium, ICU-free days, and mechanical ventilator-free days, were observed; however, these differences did not reach statistically significant. Gabapentin at bedtime increased SWS, TST, and IGF-1 concentrations in critically ill patients. This regimen might be beneficial to critically ill patients for improving their sleep quality., (© 2024 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Objectives: The aim of the present study was to assess the effect of gabapentin on blood pressure (BP) in cats with and without chronic kidney disease (CKD)., Methods: A randomized, blinded, placebo-controlled crossover study was performed. A total of 29 cats were included: 13 cats with stable CKD (IRIS stage 2-4) and 16 apparently healthy cats (serum creatinine <1.6 mg/dl and urine specific gravity >1.035). The cats were evaluated twice, approximately 1 week apart, and BP (Doppler sphygmomanometry) was obtained 3 h after cats received either a single dose of gabapentin 10mg/kg PO or placebo. For each cat, BP readings were obtained at each visit using the same Doppler and sphygmomanometer unit, and the same cat holder and Doppler operator, in the same location., Results: After administration of a single dose of gabapentin (10 mg/kg PO), BP was significantly lower (median 122 mmHg, range 82-170) than after administration of the placebo (median 150 mmHg, range 102-191; P  = 0.001). In the CKD subgroup, BP was significantly lower after administration of gabapentin (median 129 mmHg, range 96-170) than after administration of the placebo (median 155 mmHg, range 102-191; P  = 0.008). In the healthy cat subgroup, BP was significantly lower after administration of gabapentin (median 121 mmHg, range 82-139) than after administration of the placebo (median 137 mmHg, range 102-177; P  = 0.002). The median change in BP was -12 mmHg (range -95 to 10) for healthy cats and -12 mmHg (range -43 to 21) for cats with CKD (no significant difference between subgroups)., Conclusions and Relevance: Gabapentin may decrease arterial BP in cats with and without CKD and these findings should be taken into account when gabapentin is administered to patients in which measurement of BP is needed., Competing Interests: Conflict of interestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To assess the level of anxiolysis achieved by alprazolam and gabapentin in hospitalized cats prior to elective ovariohysterectomy and to evaluate the sedative effects of these agents., Animals: 60 client-owned female cats classified as American Society of Anesthesiologists physical status 1, admitted for elective ovariohysterectomy at a veterinary teaching hospital., Methods: The cats were prospectively and randomly allocated into 3 groups. Ninety minutes before evaluation, group G received gabapentin (100 mg/cat), group A received alprazolam (0.125 mg/cat), and group P received no medication (placebo). Stress, enclosure activity, and sedation scores were blindly evaluated., Results: Stress scores were similar in cats treated with gabapentin and alprazolam and gabapentin-treated cats had significantly lower stress score than those of the placebo group. Enclosure activity levels did not differ among the groups. Additionally, gabapentin and alprazolam resulted in similar sedation levels 90 minutes after treatment, which differed significantly compared to placebo., Clinical Relevance: The results of this study suggest that gabapentin provides similar anxiolysis in cats to that of alprazolam when evaluated 90 minutes after administration. Although no difference was noted in sedation levels between gabapentin and alprazolam, both induced deeper sedation than placebo.

Background: Antipsychotics are commonly used to treat delirium but can adversely affect the extrapyramidal and cardiac conduction systems. Antipsychotic use has also been reported to be associated with increased mortality in older adults. Therefore, alternative and adjunct medications for delirium are necessary. We retrospectively assessed the efficacy and safety of gabapentin (GBP) as an alternative and adjunct medication for delirium., Methods: We retrospectively investigated the records of patients with delirium treated with GBP (71 patients; median age, 81 years; interquartile range, 76-87.5 years; 54.9% males) at a general hospital. We examined duration to delirium improvement, as assessed by the Intensive Care Delirium Screening Checklist (ICDSC) and DSM-5 criteria, as well as adverse events., Results: The median (interquartile range) GBP dose was 200 mg (150-350 mg) /day. A total of 71.8% and 85.9% of the patients failed to meet the diagnostic criteria for delirium at 2 days and 5 days after initial administration, respectively (p<0.05). In subgroup analysis, patients with a history of epilepsy or cerebrovascular disease responded better to GBP than did those without such histories, suggesting that patients with abnormal/borderline neuronal activity respond to GBP even though they do not exhibit seizures. GBP did not induce extrapyramidal symptoms, cardiac conduction disturbances, hyperglycemia, or epilepsy but caused sleepiness and myoclonus., Conclusions: GBP may improve delirium with fewer adverse effects and may be a safe alternative or adjunct treatment for delirium. Dosage adjustment may be necessary to prevent sleepiness.

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 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., (© 2022. The Author(s).)

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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., (© 2021 Society for the Study of Addiction.)

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).

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/m 2 ) 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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2021 International Anesthesia Research Society.)

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.

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., (© 2021 by the Research Society on Alcoholism.)

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., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

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.

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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.

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., (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

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., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

A 23-year-old woman diagnosed with type 1 diabetes mellitus in 2011 came to our outpatient office because of an inability to walk correctly. She was under a basal bolus insulin regimen. In the summer of 2016, she experienced a rapid improvement in her glycaemic control. A few weeks later, she started to complain of a severe burning pain in the soles of her feet (pain score 10/10). Neither macrovascular nor microvascular complications were detected. The patient was forced to walk barefoot due to an intense pain using shoes or socks and used to soak her feet in water for several hours daily. She also developed severe intolerance to environmental heat, both indoors and outdoors. A diagnosis of treatment-induced diabetic neuropathy was made. The patient was admitted to a general ward to start pain therapy. After a 6-month course of different neuropathic pain drugs, the patient was able to walk autonomously again., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Hundreds of patients are treated for burn injuries each year at University of Wisconsin School of Medicine and Public Health. Pain management is particularly challenging during dressing changes and following skin grafting procedures. We performed a retrospective chart review from January 2011 through June 2018 to evaluate the effect of nonopioid analgesic medications on opioid use in nonintubated patients. Our primary outcome was the change in opioid use following the procedure. We found that most patients (69%) report severe pain (Numeric Rating Scale ≥7) immediately after autologous skin grafting. On average, patients required an additional 52 mg of oral morphine equivalents (ME) in the 24 h after the procedure compared with the 24 h before. The use of perioperative nonopioid analgesia varied between patients (acetaminophen 29%, gabapentin 29%, ketamine 35%, and all three 8%). Patients who received either gabapentin or a combination of acetaminophen, gabapentin, and ketamine had a smaller increase in their opioid use than patients who did not receive the medications (-25 ME, 95% confidence interval [-46, -4]; P = .018 and -47 ME, [-81, -11]; P = .010, respectively). These results support using a combination of acetaminophen, gabapentin, and ketamine for perioperative analgesia in burn patients undergoing autologous skin grafting., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)