Dose Of Gabapentin Research Articles

Pain Control and Opioid Consumption in Patients Undergoing Total Hip or Knee Arthroplasty Receiving a Preoperative Low Dose of Gabapentin

Background: Meta-analyses and randomized controlled trials were inconclusive regarding the role of gabapentinoids in patients undergoing joint arthroplasties. The aim of the present study was to investigate the effect of a preoperative low dose of gabapentin in patients undergoing total hip (THA) and knee arthroplasties (TKA). Methods: A retrospective observational study was conducted on 135 patients undergoing THA and TKA at the National Orthopedic Hospital Cappagh, Dublin, from July to December 2022. The primary outcome was the assessment of numerical rating scores (NRS) for postoperative pain at various time intervals. Results: During the observation period, 55 patients received a preoperative dose of gabapentin, while 80 patients did not. Statistically significant differences in numerical rating scores (NRS) were found at 6 (3 vs. 0, p < 0.001), 12 (4 vs. 2, p < 0.001), 18 (4 vs. 3, p < 0.001), and 24 h (4 vs. 3, p = 0.010) after surgery, in favor of the group receiving gabapentin. A reduction in opioid consumption, measured as morphine equivalents, was also noted in the gabapentin group (40 vs. 30 mg, p = 0.040). Conclusions: A low preoperative dose of gabapentin was associated with reduced postoperative pain and opioid consumption in patients undergoing TKA and THA, without impacting hospital stay. Prospectively designed trials are encouraged to assess the safety and effect on pain control of a preoperative low dose of gabapentin.

COMPARISON OF TWO DIFFERENT DOSES OF ORAL GABAPENTIN FOR POST OPERATIVE ANALGESIA IN LOWER LIMB SURGERY UNDER SPINAL ANAESTHESIA

Background: Pre-emptive analgesia is a technique of pain control where treatment is initiated before intervention and operational during the surgical procedure in order to reduce the physiological consequences of nociceptive transmission provoked by the procedure. Gabapentin has demonstrated analgesic effects in clinical trials as a preemptive analgesic in acute postoperative pain management with very few side effects. Owing to the protective effect of gabapentin on the nociceptive pathways, preemptive analgesia has the potential to be more effective and hence reduce postoperative pain and development of chronic pain. Objective: We therefore designed this study to compare two different doses of Oral Gabapentin (300mg and 600mg) given as pre-emptive analgesic for post-operative pain relief in lower limb surgeries under spinal anaesthesia. Method: After the approval from ethical committee this prospective randomized double blinded clinical study was conducted over a period of two years in department of anaesthesia in M.G.M.s medical college, Aurangabad. Randomly allocated two groups were given Oral Gabapentin 300mg and 600mg respectively, one hour prior to giving spinal anaesthesia for post operative analgesia in lower limb surgeries. Conclusion: There is no statistically significant difference between group G300 (gabapentin 300mg) and group G600 (gabapentin 600mg) regarding age, gender, duration of analgesia (i.e. demand for first rescue analgesic), total dose of analgesics in first twenty four hours after surgery, duration of sensory block (i.e. L1 regression), highest ramsay sedation score and VAS scores. No significant difference was seen in cases hemodynamic stability and incidence of side effects.

Formulation and characterization of cholesterol-based nanoparticles of gabapentin protecting from retinal injury.

This study aimed to prepare cholesterol and stearic acid-based solid lipid nanoparticles of gabapentin (GAB-SLNs) for protection against streptozotocin (STZ)-induced retinal injury in rats. We prepared four preparations of GAB-SLNs using a hot high-shear homogenization ultrasonication process, and the best formulation was selected and tested for biological activity. The retinal injury was brought in male adult albino rats while gabapentin doses continued for 6weeks. Six groups of rats were assigned as the vehicle, diabetic, diabetic + gabapentin (10-20mg/kg), and diabetic + GAB-SLNs (10-20mg/kg). GAB-SLN#2 was selected as the optimized formulation with high entrapment efficacy (EE%, 98.64% ± 1.97%), small particle size (185.65 ± 2.41nm), high negative Zeta potential (-32.18 ± 0.98mV), low polydispersity index (0.28 ± 0.02), and elevated drug release (99.27% ± 3.48%). The TEM image of GAB-SLN#2 revealed a smooth surface with a spherical shape. GAB-SLNs provided greater protection against retinal injury than free gabapentin as indicated by the histopathology data which demonstrated more organization of retinal layers and less degeneration in ganglion cell layer in rats treated with GAB-SLN#2. Further, GAB-SLN#2 reduced the inflammatory proteins (IL-6/JAK2/STAT3) and vascular endothelial growth factor (VEGF). The preparation of GAB-SLNs enhanced the physical properties of gabapentin and improved its biological activity as a neuroprotectant. Further studies are warranted to validate this technique for the use of oral gabapentin in other neurological disorders.

Gabapentin for Delirium in Infants in the Neonatal Intensive Care Unit

OBJECTIVE A protocol was developed for neonatal intensive care unit (NICU) delirium: Step 1, gabapentin for pain or melatonin for sleep; Step 2, add on other Step 1 agent; Step 3, antipsychotics. The purpose of this study was to describe the utility and dosing of gabapentin for NICU delirium. METHODS Retrospective evaluation of NICU patients from January 1, 2021–December 31, 2022 who received >1 dose of gabapentin based on the delirium protocol. Data collection included demographics, gabapentin regimen, and concomitant sedatives and analgesics. The primary objective was to identify the number of patients receiving gabapentin for Step 1 or Step 2. Secondary objectives included identifying the number of patients requiring antipsychotics (Step 3), the gabapentin regimen, comparison of Échelle de Douleur et d'Inconfort du Nouveau-né (EDIN), Cornell Assessment of Pediatric Delirium (CAPD), and Withdrawal Assessment Tool-1 (WAT-1) scores 72 hours pre- and post-gabapentin initiation, and comparison of opioids, clonidine, and melatonin 24 hours pre- and 72 hours post-gabapentin initiation. Wilcoxon signed rank tests were employed with significance defined at p < 0.05. RESULTS Twenty-nine patients were studied. The majority (n = 22; 75.9%) received gabapentin for Step 1; no patients required Step 3. The median initial dose was 14.4 mg/kg/day divided every 8 hours. Twelve (41.4%) required increase to a median of 16.9 mg/kg/day. A significant decrease in EDIN and WAT-1 scores was noted, but there was no change in CAPD scores or opioid, clonidine, or melatonin doses pre- versus post-gabapentin. CONCLUSION The majority received gabapentin at a median dose of 14 mg/kg/day as Step 1 for delirium. Gabapentin was associated with a significant decrease in pain and withdrawal scores.

Evaluation of the sedative properties of oral trazodone, gabapentin or their combination in healthy cats.

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. 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. 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. 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.

Gabapentin Dosing Guidance: a Multimodal Approach to Topical and Oral Concomitant Therapy

As researchers in pain management search for safer alternatives to oral analgesics, transdermal or externally applied analgesic options are becoming increasingly available. The search for therapeutic alternatives is fueled by not only the risk of misuse of opioids and similar CNS depressant drugs, but also the impact that chronic pain has on a patient’s quality of life. In this review, we determine an approach by which topical and oral gabapentin can be used safely and effectively, either as monotherapy, or as synergistic concomitant therapy.

Efficacy and Safety of Different Preemptive Analgesia Measures in Pain Management after Laparoscopic Cholecystectomy: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

The purpose of this systematic review and network meta-analysis was to evaluate the efficacy and safety of different preemptive analgesia measures given before laparoscopic cholecystectomy (LC) for postoperative pain in patients. We conducted a comprehensive search in databases including PubMed, Web of Science, Embase, and the Cochrane Library up to March 2024, and collected relevant research data on the 26 preemptive analgesia measures defined in this article in LC surgery. Outcomes included postoperative Visual Analogue Scores (VAS) at different times (2, 6, 12, and 24h), opioid consumption within 24h post-operation, time to first rescue analgesia, incidence of postoperative nausea and vomiting (PONV), and incidence of postoperative headache or dizziness. Forty-nine articles involving 5987 patients were included. The network meta-analysis revealed that multimodal analgesia, nerve blocks, pregabalin, and gabapentin significantly reduced postoperative pain scores at all postoperative time points and postoperative opioid consumption compared to placebo. Tramadol, pregabalin, and gabapentin significantly extended the time to first rescue analgesia. Ibuprofen was the best intervention for reducing PONV incidence. Tramadol significantly reduced the incidence of postoperative headache or dizziness. Subgroup analysis of different doses of pregabalin and gabapentin showed that compared to placebo, pregabalin (300mg, 150mg) and gabapentin (600mg, 300mg, and 20mg/kg) were all more effective without significant differences in efficacy between these doses. Higher doses increased the incidence of PONV and postoperative headache and dizziness, with gabapentin 300mg having a lower adverse drug reaction (ADR) incidence. Preemptive analgesia significantly reduced postoperative pain intensity, opioid consumption, extended the time to first rescue analgesia, and decreased the incidence of PONV and postoperative headache and dizziness. Multimodal analgesia, nerve blocks, pregabalin, and gabapentin all showed good efficacy. Gabapentin 300mg given preoperatively significantly reduced postoperative pain and ADR incidence, recommended for preemptive analgesia in LC. PROSPERO CRD42024522185.

Discriminative stimulus properties of two training doses of gabapentin in rats: Substitution by pregabalin, diazepam, and pentobarbital.

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).

The use of low doses of gabapentin in patients with neuropathic pain and with thrombocytopenia

Introduction. Approximately 21–27% of patients with blood system diseases receive opioid analgesics, with neuropathic pain being one of the most common reasons for prescription. Gabapentin is used as a first-line drug for neuropathic pain (NP), but has been poorly studied in patients with blood system diseases.The objective was to study the effectiveness and safety of gabapentin in patients with blood system diseases with chronic pain.Materials and methods. A single-center, prospective observational study included 24 patients with thrombocytopenia and pain between October 2017 and October 2022. The patients’ age ranged from 18 to 71 years (median 40 years). All patients with blood system diseases: non-tumor blood system diseases (aplastic anemia) in 8% (n = 2), myeloid tumor blood system diseases (acute myeloid leukemia) in 34% (n = 8), lymphoid tumor blood system diseases (acute lymphoblastic leukemia, follicular lymphoma, diffuse B – large cell lymphoma, T-cell lymphomas, multiple myeloma) in 58% (n = 14). All patients had thrombocytopenia less than 150∙109/l, 66% (n = 16) had less than 90∙109/l. All patients were diagnosed with neuropathic pain (NP), localized according to the neuroanatomical distribution and accompanied by sensory disturbances typical of NP. The localization of pain was different, pain predominated in the lower extremities (63% (n = 15), 95% CI: 43 – 79%), caused by peripheral polyneuropathy of predominantly toxic origin (vincristine, bortezomib), and pain was also caused by the course of the underlying disease: cephalalgia and neck pain, this pain was caused by compression of the nerve structures by the lymph nodes, postherpetic neuralgia, trigeminal neuralgia caused by tumor growth. All patients had intractable, high-intensity pain requiring trimeperidine at a dose of 20–40 mg/day. All patients were prescribed gabapentin therapy at a dose of 900–1200 mg/day.Results. When taking gabapentin in the study group of patients (n = 24), already on the 3rd day, there was a clinically and statistically significant decrease in pain intensity: 1) by median: from the initial 6 to 4 points, p = 0.01 (and up to 3 points by 7th day of therapy) and 2) on average: from initial 6.5 to 3.9 points, p = 0.01 (and up to 3.2 points by the 7th day). Stratification of the dynamics of pain intensity reduction by type of blood system disease (BSD) shows that the decrease by day 3 (sustained and further by day 7) was clinically and statistically significant (p = 0.01) for groups of patients with lymphoid and myeloid BSD, and clinically and approximately statistically significant in patients (n = 2) with non-tumor BSD. Analgesic therapy using small doses of gabapentin gave a pronounced, stable positive effect (pain intensity statistically significantly decreased by an average of 50%). After 7 days of gabapentin therapy, a decrease in the opioid dose was noted in 52% of patients. Side effects were dominated by drowsiness 67% (n = 16), dizziness 32% (n = 8).Conclusion. The results of this study indicate that gabapentin is effective in the treatment of chronic neuropathic pain in patients with BSD and is safe when used in minimal/average therapeutic doses within the daily dosing ranges established by the official instructions for use.

Computed Tomography-Guided Dorsal Root Ganglion Ozone Injection Combined With Pulsed Radiofrequency for Acute Herpes Zoster Neuralgia Treatment of Middle-aged and Elderly People: A Randomized, Double-blinded, Controlled Trial.

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. 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. 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. 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.

Association of Opioid Use Disorder Diagnosis with Management of Acute Low Back Pain: A Medicare Retrospective Cohort Analysis.

Practice guidelines recommend nonpharmacologic and nonopioid therapies as first-line pain treatment for acute pain. However, little is known about their utilization generally and among individuals with opioid use disorder (OUD) for whom opioid and other pharmacologic therapies carry greater risk of harm. To determine the association between a pre-existing OUD diagnosis and treatment of acute low back pain (aLBP). Retrospective cohort study using 2016-2019 Medicare data. Fee-for-service Medicare beneficiaries with a new episode of aLBP. The main independent variable was OUD diagnosis measured prior to the first LBP claim (i.e., index date). Using multivariable logistic regressions, we assessed the following outcomes measured within 30days of the index date: (1) nonpharmacologic therapies (physical therapy and/or chiropractic care), and (2) prescription opioids. Among opioid recipients, we further assessed opioid dose and co-prescription of gabapentin. Analyses were conducted overall and stratified by receipt of physical therapy, chiropracticcare, opioidfills, or gabapentin fills during the6months before the index date. We identified 1,263,188 beneficiaries with aLBP, of whom 3.0% had OUD. Two-thirds (65.8%) did not receive pain treatments of interest at baseline. Overall, nonpharmacologic therapy receipt was less prevalent and opioid and nonopioid pharmacologic therapies were more common among beneficiaries with OUD than those without OUD. Beneficiaries with OUD had lower odds of receiving nonpharmacologic therapies (aOR = 0.62, 99%CI = 0.58-0.65) and higher odds of prescription opioid receipt (aOR = 2.24, 99%CI = 2.17-2.32). OUD also was significantly associated with increased odds of opioid doses ≥ 90 morphine milligram equivalents/day (aOR = 2.43, 99%CI = 2.30-2.56) and co-prescription of gabapentin (aOR = 1.15, 99%CI = 1.09-1.22). Similar associations were observed in stratified groups though magnitudes differed. Medicare beneficiaries with aLBP and OUD underutilized nonpharmacologic pain therapies and commonly received opioids at high doses and with gabapentin. Complementing the promulgation of practice guidelines with implementation science could improve the uptake of evidence-based nonpharmacologic therapies for aLBP.

Can targeting TSP-1 with gabapentin enhance survival in glioblastoma? A 20-year retrospective cohort study.

2048 Background: Molecularly-defined cellular subpopulations of glioblastoma secrete high levels of the synaptogenic protein thrombospondin-1 (TSP-1) which promotes functional integration of tumor into neural circuity. A greater extent of glioma-neuronal crosstalk portends worse survival for patients. In preclinical studies, gabapentin was shown to inhibit TSP-1, in turn disrupting neuronal synaptogenesis and neuronal activity-dependent glioblastoma proliferation; however, clinical survival data is lacking. We aim to determine whether treatment with gabapentin is associated with improved survival and reduced serum TSP-1 in a retrospective cohort of patients with IDH-wildtype glioblastoma. Methods: Newly-diagnosed, IDH-wildtype glioblastoma patients who received care at the UCSF Brain Tumor Center between 1997-2017 were included in this study. Kaplan-Meier curves and multivariate Cox proportional-hazards models, controlled for age, MGMT promoter methylation status, preoperative tumor volume, and extent of resection, were used for survival analyses. Differences in serum TSP-1 measured by ELISA for gabapentin treated patients and matched non-gabapentin treated controls were assessed using unpaired two-tailed student’s t-test. Control samples were matched 2:1 by age, tumor volume, and extent of resection. After 2005, patients were treated with chemoradiation with concurrent and adjuvant temodar. Results: Among 379 adult patients with glioblastoma, 36 (9.5%) were treated with gabapentin. The median daily dose of gabapentin was 600 mg (IQR: 300-900 mg). There were no significant differences between gabapentin treated and non-gabapentin treated patients by age (0.06), sex (p=0.14), or race (p=0.52). Median overall survival for gabapentin treated and non-gabapentin treated patients was 20.8 months (IQR: 11.7 - 32.1) and 14.7 months (IQR: 8.9-23.5), respectively (p= 0.02). On Kaplan-Meier survival analysis, overall survival was longer for gabapentin treated patients compared with non-gabapentin treated patients (p=0.005). In the multivariate Cox proportional-hazards model, gabapentin use was associated with decreased hazard of death (HR 0.67, p=0.030). Mean serum TSP-1 in gabapentin-treated patients was significantly lower than in the matched control group (10181 ng/ml vs 17015 ng/ml, p=0.017). Conclusions: Gabapentin use is associated with a survival benefit for patients with glioblastoma, possibly mediated through a reduction in TSP-1. This promising result lays the foundation for future prospective studies to further evaluate TSP-1 as a circulating prognostic biomarker as well as to explore the therapeutic benefits of gabapentin as a life-prolonging treatment for patients with newly diagnosed glioblastoma.

Association between gabapentin use and risk of dementia in adults with chronic pain: A nested case-control study

Study objectiveTo explore the association between gabapentin use and the risk of dementia in patients with chronic pain, considering the rising concerns of dementia in an aging population and the potential cognitive impacts of chronic pain management. DesignA nested case-control study utilizing data from a longitudinal health insurance database. SettingThe study is based on a longitudinal health insurance database spanning 2000–2019 in Taiwan. PatientsA total of 201,492 patients aged 50 years and older diagnosed with chronic pain between 2001 and 2017 were included. The study focused on individuals with chronic pain, excluding those diagnosed with dementia a year before or after their chronic pain diagnosis. InterventionAnalysis of gabapentin prescription history was conducted, considering the cumulative dose from the chronic pain diagnosis date to the dementia diagnosis date or equivalent period for controls. MeasurementData included demographics, gabapentin prescription history, and comorbidities. Logistic regression was used to estimate odds ratios for dementia risk. Main resultsNo significant difference in the risk of dementia was found between low and high cumulative doses of gabapentin. The adjusted odds ratio for dementia risk associated with gabapentin use was 0.91 (95 % C.I. 0.83–1.01), indicating no substantial increase in risk. ConclusionLong-term Gabapentin therapy for chronic pain is not associated with a differential risk of dementia across dosage levels, irrespective of age or gender. Further study into its potential cognitive impacts is essential.

Use of gabapentin for neuropathic pain therapy: A view from perspective of evidence-based medicine

The aim of the study was to analyze the literature sources for pharmacodynamic and pharmacokinetic features of gabapentin, providing its use in patients with neuropathic pain, as well as a comparative evaluation of its efficacy and safety when used in different doses.Materials and methods. PubMed, Google Scholar, EMBASE, ResearchGate scientific information network and elibrary.ru databases were used as search resources. The keywords used for the search were “gabapentin”, “mechanism of action”, “gabapentin targets”, “gabapentin pharmacodynamics”, “pharmacokinetics”, “pharmacokinetic parameters”, “neuropathic pain”, and “randomized clinical trials”. The depth of the search was 26 years (from 1998 to 2024). This review resulted in 87 literature sources.Results. Neuropathic pain (NeP) is one of the most common types of chronic pain, characterized by a high prevalence among people of the working age. Effective pharmacotherapy aimed at eliminating the pain syndrome is a key tool for improving the quality of life and preserving the work capacity of patients. Heterogeneity of etiologic factors involved in the genesis of NeP indicates the need to use drugs the analgesic effect of which is based on weakening the transmission of pain impulses in the CNS. In clinical trials, gabapentin has demonstrated efficacy in reducing the severity of pain in patients with postherpetic NeP, painful diabetic neuropathy and many other conditions accompanied by NeP. The dose of gabapentin 300 mg/day is the initial dose in the therapy of NeP and requires a further slow titration depending on the patient’s response to therapy and tolerability of the drug, especially in elderly and senile patients, as well as in patients with an impaired renal function. According to the published data, the most pronounced analgesic effect is achieved in the patients against the background of the gabapentin administration at a dose of 3600 mg/day.Conclusion. Gabapentin is the drug of choice in the management of patients with NeP of different etiology and intensity. A satisfactory safety profile and pharmacodynamic effects make gabapentin possible, despite the long history of its use, to remain a relevant drug used by a wide range of physicians, specialties, for pharmacotherapy of NeP patients.

Abstract PO3-12-12: Axial Neuropathy in Two Breast Cancer Patients receiving Fam-trastuzumab deruxtecan: A Case Report

Abstract Introduction. Fam-trastuzumab deruxtecan (T-DXd) is FDA approved for metastatic HER2-positive (HER2+) and HER2-low breast cancer (BC). Peripheral neuropathy is a side effect of T-DXd, with an incidence of 13%. Here we discuss two BC patients (pts) who presented with paresthesias of the trunk after receiving T-DXd. Case 1. A 51-year-old female with Stage IIIB cT4N2M0 left BC, estrogen receptor positive (ER+), progesterone receptor positive (PR+) and HER2+ was treated with neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP), followed by mastectomy and axillary lymph node dissection, with downstaging to ypT3N2a disease. She was enrolled on a clinical trial comparing T-DXd with standard treatment for HER2+ BC with residual disease after neoadjuvant therapy, and was randomized to T-DXd arm. She also received adjuvant proton radiation therapy to the chest wall. One week after her third cycle of T-DXd she developed Grade 3 paresthesias on her trunk and proximal upper and lower extremities, stating she could not bend over or perform activities of daily living. She did not experience associated weakness or peripheral neuropathy. Symptoms improved to Grade 1 after initiation of gabapentin and delay of cycle 4 T-DXd by one week. She resumed T-DXd with dose reduction per protocol, and increase in gabapentin dose. She was seen by neurology who localized her sensory findings to T5-T9. She was recommended to undergo MRI spine, but was unable to do so, due to presence of tissue expander. Paresthesias have been controlled on dose reduced T-DXd and continued gabapentin. Case 2. A 56-year-old female with ER+, PR+, HER2-negative BC initially diagnosed in 1990, with local recurrence in 2005, treated with mastectomy, adjuvant chemotherapy, and adjuvant endocrine therapy, followed by development of metastatic disease to lung, liver, bone and skin in 2017. She received multiple lines of endocrine therapy, including aromatase inhibitors and fulvestrant, with cdk4/6 inhibitors and everolimus, but either progressed or was intolerant to all treatments. Skin biopsy in 2022 confirmed metastatic BC, which was ER+, PR+, and HER2 low (IHC2+, FISH nonamplified). She then received T-DXd, with clinical and radiographic response to treatment. After cycle 8 T-DXd, the patient was hospitalized for severe burning pain of her trunk and skin. Radiologic evaluation, including CT chest, abdomen, pelvis, and MRI spine, did not show an etiology of her pain, and showed stable metastatic disease to liver and bones, without evidence of cord or nerve root compression. Symptoms improved on pregabalin. She received an additional cycle of T-DXd with dose reduction, but ultimately declined further treatment. Symptoms resolved within 5 months of discontinuation of T-DXd. Discussion. These cases represent unusual events of axial neuropathy in two BC patients receiving T-DXd. Given the similarity of their symptoms, these findings may represent an unusual adverse effect of T-DXd. As the indications for T-DXd continue to expand, clinicians should be aware of this uncommon potential toxicity. Citation Format: Lauren Botero, Katharine McNeill, Della Makower. Axial Neuropathy in Two Breast Cancer Patients receiving Fam-trastuzumab deruxtecan: A Case Report [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-12-12.

Assessment of the effect of gabapentin on blood pressure in cats with and without chronic kidney disease.

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). 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. 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). 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.

Open-label observational study of effectiveness and tolerability of ipidacrine in treatment of patients with diabetic polyneuropathy (DIAMANT study)

Diabetic polyneuropathy (DPN) is one of the most common complications of diabetes mellitus, leading to the development of flaccid paresis, neuropathic pain syndrome, sensitive ataxia, as well as trophic disorders in the distal parts of the lower extremities.The purpose of the randomized, open-label, comparative, prospective study was to evaluate the effectiveness and tolerability of ipidacrine in the complex treatment of patients with DPN.Materials and methods. Patients with DPN (n = 60) were randomized into 2 groups. Both groups received basic therapy (alpha-lipoic acid, B vitamins, gabapentin); in the treatment of patients of the main group (n = 30), in addition, ipidacrine was used (Ipidacrine-SZ, North Star Co., Russia). We have analyzed the intensity of pain syndrome (VAS-P), the average daily dosage of gabapentin, and the results of the neuropathic dysfunctional scale (modified version, NDSm), Pittsburgh Sleep Quality Index, PSQI), Global Rating of Change Scale (GROC), the results of electroneuromyography (ENMG). The total duration of the observation and treatment period was 2 months.Results. After 2 months of therapy in the main group of patients, compared with the control group, there was significantly more complete pain control (VAS-P: 3.0 ± 0.9 vs 3.6 ± 0.8), a decrease in the average daily dosage of gabapentin (390 vs 500 mg/day), reduction in the severity of clinical manifestations of polyneuropathic syndrome (NDSm: 4.4 ± 1.0 vs 4.9 ± 1.0 points) and improvement in sleep quality (PSQI: 6.8 ± 1.3 vs 7.9 ± 1.7). According to ENMG data, patients in the main group showed a significant improvement in the neurophysiological parameters of both motor and sensory fibers, which was significantly more pronounced compared to the control group. A significantly larger proportion of patients in the main group assessed the improvement from the therapy as ‘pronounced’ (GROC: 10/33.3 % vs 6/20.0 %).Conclusions. The use of ipidacrine in complex therapy of patients with DPN can significantly reduce the clinical manifestations of disease and improve the neurophysiological parameters of the peripheral nerves of the lower extremities. Ipidacrine can be considered as a basic drug for the treatment of patients with neurological complications of diabetes mellitus.

Usefulness of Gabapentin as an Alternative/Adjunct Therapy for Delirium: A Retrospective Observational Study.

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. 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. 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. 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.

Evaluating Gabapentin Dosing, Efficacy and Safety in Infants

OBJECTIVE Gabapentin for management of neuropathic pain, irritability, neonatal abstinence syndrome, rescue sedation, feeding intolerance and visceral hyperalgesia in infants has grown over the past decade. There remains little guidance for indications, initiation, titration and maintenance dosing trends and assessment of outcomes. The primary objective was to describe gabapentin dosing, and the secondary objectives were to identify outcomes to assess efficacy and describe weaning practices. METHODS A retrospective single-center study was performed in infants younger than 1 year who received gabapentin at Boston Children’s Hospital between 2015 and 2021. The primary outcome was indication, initiation and maximum gabapentin dose. Secondary outcomes included mortality, adverse reactions and impact on feeding volumes, weight-for-age Z-scores and face, legs, activity, cry, consolability (FLACC) scores. Descriptive statistics were utilized. RESULTS Sixty-six infants received gabapentin at a mean ± SD age of 5.5 ± 2.7 months (range of 0–11 months). The mean ± SD initiation dose of gabapentin was 8.6 ± 5.4 mg/kg/day with a median interval of 24 hours (8–24 hours). The maximum mean dose was 23.2 ± 14.4 mg/kg/day at a median interval of every 8 hours (8 hours). The most common indications for initiation were irritability, rescue sedation, and visceral hyperalgesia. There was a statistical improvement in weight-for-age Z scores from 24 hours prior to gabapentin initiation to 2 weeks after the maximum dose of gabapentin (−2.23 ± 1.78 to −1.66 ± 1.91, p &amp;lt; 0.001) and a reduction in FLACC scores (2.29 ± 1.64 to 1.52 ± 1.76, p = 0.007) from 24 hours prior to gabapentin initiation to 3 days after the maximum dose of gabapentin. Three patients experienced minor adverse events. CONCLUSIONS Gabapentin was well tolerated in infants. Initial gabapentin dosing of 5 mg/kg/dose every 24 hours appears safe and consistent with other published studies in infants. The improvement in outcomes with few adverse events suggests a beneficial role for gabapentin.

Commentary on the Low Dose Gabapentin for Behavioral Symptoms in Dementia with Lewy Bodies Case Series, Brief Review of Pharmacology and A Hypothesis

Over 5 million people in the United States [1] and over 35 million people worldwide [2] suffer from dementia and its prevalence is expected to increase.