Gabapentin for Pain in Pediatric Palliative Care.

OBJECTIVE: Gabapentin is commonly used to treat pain in children receiving pediatric palliative care. This study describes the real-world use of gabapentin and the associated benefits and adverse effects/events (AEs). METHODS: A prospective, multicenter cohort of standardized data collection after a clinical decision was made to use gabapentin for managing neuropathic or nociplastic pain in children attended on by a pediatric palliative care service. It was conducted across 11 sites in seven countries including hospital, inpatient, and outpatient services. Clinical outcomes were graded using pain scales validated for age and cognitive ability and the National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE) at baseline, 14 days, 28 days, six weeks and 12 weeks after initiation of gabapentin. Ad-hoc safety reporting continued throughout the study. RESULTS: Data were collected from 127 children with a median age of 4.7 years (IQR 0.1-17.9); 61% had a neurological disorder, 21% advanced cancer and the cohort had a high level of disability (Lansky/Karnofsky performance score 37.1). Gabapentin was prescribed at standard pediatric doses. On average, 76% of children had a reduction in pain and 42% experienced a potential AE. The mean pain score decreased from 6.0 (SD 2.6) at baseline to 3.3 (SD 2.4) at 14 days and 1.8 (SD 1.8) after 12-weeks of gabapentin therapy. Ten percent had increased pain at each time point. AEs did not increase when individual changes over time were accounted for except for somnolence (7%). Serious AEs attributable to gabapentin were possible or probable in 3% of children. CONCLUSIONS: Gabapentin prescribed at standard doses for advanced cancer and severe neurological injury in children under a pediatric palliative care service was associated with generally improved pain intensity at previously described levels of adverse effects.

Gabapentin and oral antidepressants for chronic pruritus: a prospective cohort study evaluating efficacy and side effects in daily dermatological practice.

BACKGROUND: Chronic pruritus is frequently seen in daily dermatological practice and is associated with marked impact on quality of life. Research on the use of gabapentin and oral antidepressants in daily dermatological practice is scarce. OBJECTIVE: To evaluate the efficacy and safety of gabapentin and oral antidepressants in patients with chronic pruritus in daily clinical practice. METHODS: A prospective observational single-center cohort study was conducted including adult patients with chronic pruritus and an indication for systemic treatment between June 2016 and May 2019. RESULTS: Systemic treatment with gabapentin and/or antidepressants was initiated in 31 patients with severe chronic pruritus (median average pruritus NRS score 7.0), in which most cases no underlying origin was identified (83.9%). In patients treated with gabapentin 900-1800 mg/day (N = 25), median average pruritus NRS decreased to 5.5 (IQR 3.0) after 4 weeks and remained stable up to 24 weeks of treatment. Efficacy of antidepressants was variable, with the highest response after initiation of amitriptyline, nortriptyline, and mirtazapine. Side effects were frequently observed in both gabapentin and antidepressant treatments; however, were mostly mild and temporary. LIMITATIONS: This was a single-site observational study, with limited sample size. CONCLUSION: Treatment with gabapentin and antidepressants should be considered in patients with chronic pruritus unresponsive to conventional treatment.

Effectiveness of oral clonidine and gabapentin on peripheral neuropathy in diabetic patients in southwestern Iran: a randomized clinical trial.

BACKGROUND: Peripheral neuropathy is not only the most prevalent consequence of diabetes but also the main reason for foot ulceration, disability, and amputation. Therefore, the current study aims to determine the effectiveness of oral clonidine and gabapentin on peripheral neuropathy in diabetic patients. METHODS: This 12-week, randomized, and parallel-group trial was conducted to compare the efficacy of oral clonidine and gabapentin with gabapentin alone in diabetic patients in southwest Iran during the first half of 2021. Thirty patients with type 2 diabetes with peripheral neuropathy as assessed by a visual analog scale (VAS) and divided into two groups of 15 patients, treated for up to three months. The data were analyzed using SPSS-21 software. In order to report the results, descriptive indices, independent t-test, one-way analysis of covariance (ANCOVA) and analysis of variance with repeated measures were used. RESULTS: The mean and standard deviation of the age of the participants in the clonidine + gabapentin group was equal to 50.20 ± 7.44, and in the gabapentin group was equal to 50.47 ± 7.57 (t = 0.10, P-value = 0.923). This research showed a significant difference between the clonidine + gabapentin group and with gabapentin group in terms of neuropathic pain and the severity of neuropathic pain (P < 0.001). CONCLUSIONS: According to this research results, clonidine + gabapentin can reduce neuropathic pain and the severity of neuropathic pain in diabetic patients. Therefore, it is recommended that healthcare professionals with diabetes expertise prescribe these medications to reduce neuropathic pain and its severity. TRIAL REGISTRATION: This study was registered in the Iranian Clinical Trials System with the ID (IRCT20211106052983N1) on 14/01/2022.

Abuse and addiction in gabapentinoid drug users for neuropathic pain.

OBJECTIVE: Gabapentinoids are gamma-aminobutyric acid analogue agents used in the treatment of neuropathic pain. They are increasingly being abused to achieve euphoric and dissociative effects. This study aimed to determine drug misuse/abuse and related factors in patients who used gabapentinoids for neuropathic pain. PATIENTS AND METHODS: This study included 140 patients over the age of 18. Patients were excluded from the study if they had aphasia, dementia, or diseases that led to aphasia or cooperative and cognitive dysfunction. They were also excluded if they lacked sufficient information about how long or at what dosage they had been using the drug. The Beck Depression Inventory and Beck Anxiety Inventory were used to evaluate depression and anxiety states. The patients' levels of drug abuse were determined according to the definitions provided in the terminology for misuse, abuse, and related events. RESULTS: The mean age of the patients was 56.78 ± 14.45 years, and 52.1% of them were females. While 57.9% of the patients used pregabalin, 42.1% of the patients used gabapentin. For the median (min-max) of the dataset, the pregabalin dose was 300 (50-600) mg/day, and the gabapentin dose was 900 (300-2,400) mg/day. Abuse was present in 17.9% of the patients. Risk factors for gabapentinoid abuse were smoking, alcohol, and antidepressant use, anxiety and depression, living alone, and drug dose and duration of use. CONCLUSIONS: Before prescribing drugs and managing the treatment process in a controlled manner, questioning patients about their risk factors can reduce the rate of abuse.

The safety and efficacy of gabapentinoids in the management of neuropathic pain: a systematic review with meta-analysis of randomised controlled trials.

BACKGROUND: There are increasing concerns regarding the abusive potential of gabapentinoids putting at risk patients with neuropathic pain requiring long-term pain management. The evidence to support this is rather inconcusive. AIM: This systematic review aimed to evaluate the safety and efficacy of gabapentinoids in the management of neuropathic pain with a focus on randomised controlled trials (RCTs) and categorising the side effects according to the body systems they were affecting. METHOD: Searches were conducted in MEDLINE (PubMed), EMBASE, Web of Science, PsycoINFO, and CINAHL (EBSCO), and included RCTs to identify and critically appraise studies investigating safety and therapeutic effects of gabapentionoids in adults with neuropathic pain. Data extraction was conducted using an established Cochrane form and the risk-of-bias tool was used in the assessment of quality. RESULTS: 50 studies (12,398 participants) were included. The majority of adverse events pertained to the nervous system (7 effects) or psychiatric (3 effects) disorders. There were more adverse effects reported with pregabalin (36 effects) than with gabapentin (22 effects). Six pregabalin studies reported euphoria as a side effect, while no studies reported euphoria with gabapentin. This was the only side effect that may correlate with addictive potential. Gabapentioids were reported to significantly reduce pain compared to placebo. CONCLUSION: Despite RCTs documenting the adverse events of gabapentionoids on the nervous system, there was no evidence of gabapentinoid use leading to addiction, suggesting an urgent need to design studies investigating their abusive potential.

Misuse of gabapentinoids (pregabalin and gabapentin) in patients with neuropathic pain related to spinal cord injury.

OBJECTIVE: To investigate the misuse of gabapentinoids (pregabalin and gabapentin) in patients with neuropathic pain related to spinal cord injury. STUDY DESIGN: Cross-sectional study. SETTING: Outpatient clinic in a physical therapy and rehabilitation hospital. PARTICIPANTS: 127 patients, aged 18-70 years, who had neuropathic pain related to spinal cord injury (SCI) and disease duration of at least 12 months. OUTCOME MEASURES: Gabapentinoid use disorder of the patients was determined based on the DSM-5 diagnostic criteria for substance-related disorders. Patients were divided into 2 groups as those with drug misuse and those without drug misuse. Demographic and clinical information of the patients were compared between the groups. Factors associated with drug misuse were analyzed. RESULTS: The misuse rate was 81.9% in patients using pregabalin and 69.69% in patients using gabapentin. Duration of disease and the Leeds assessment of neuropathic symptoms and signs (LANSS) score were statistically significantly higher in the drug misuse group. A statistically significant difference was found between the groups in terms of marital status, education and income level, and smoking and alcohol use. A statistically significant relationship was observed between drug misuse and duration of disease and LANSS score. CONCLUSION: Misuse of gabapentinoids is prevalent in patients with neuropathic pain related to spinal cord injury. The duration of disease and the severity of NP are associated with misuse. Clinicians should exercise caution when prescribing gabapentinoids to patients with SCI.

Gabapentin Use During Pregnancy and Lactation With and Without Concurrent Opioid Exposure: Considerations and Future Directions.

Gabapentin is a γ-aminobutyric acid analog formally indicated for the treatment of epilepsy and neuropathic pain that is gaining increased popularity. Gabapentin has been historically considered a safe medication, including during pregnancy and lactation, with low reported concerns for misuse and use disorders. However, new empirical efforts are revealing concerns regarding the safety of widespread gabapentin use, particularly in pregnancy and for individuals with a propensity toward substance misuse. The Food and Drug Administration's full prescribing information report on gabapentin provides concerning preclinical data and then states that gabapentin is potentially "developmentally toxic" and has an unknown risk of birth impacts. Concerns have also been raised surrounding in utero exposure to gabapentin due to the onset and presentation of atypical and/or difficult to control withdrawal signs and symptoms in neonates, including those dually exposed to opioids, as well as neonatal exposure to gabapentin via breastmilk. Moreover, nonprescribed gabapentin use has become an increasing problem, with opioid use disorder being the greatest risk factor for such misuse. This article summarizes the current literature regarding gabapentin use during pregnancy and related prenatal and neonatal exposure outcomes with special consideration for interactions between gabapentin and opioid use. Taken together, the current literature suggests that gabapentin use should be considered with caution during pregnancy and during the post-partum period. Well-controlled, prospective research studies are needed to determine the extent of the risks and benefits of prescribed and nonprescribed gabapentin exposure to pregnant people and their neonates.

Gabapentin-Induced Overflow Urinary Incontinence: A Case Report and Review of the Literature.

Gabapentin (GBP) is a structural analog of gamma-aminobutyric acid (GABA) that is commonly used in palliative care for symptom management indications including neuropathic pain syndromes, hiccups, cough, and anxiety. An uncommon adverse effect of GBP is urinary incontinence (UI). We report the case of a 61-year-old male with metastatic non-small cell lung cancer who developed probable overflow UI while receiving 1200 mg/day of GBP for chemotherapy-induced peripheral neuropathy. The patient self-tapered GBP to 600 mg/day which resolved the overflow UI, but resulted in poorly controlled bilateral foot pain. The palliative care physician rotated the patient to pregabalin 150 mg/day and his bilateral foot pain improved after his regimen was titrated to 200 mg/day. The patient did not experience overflow UI while taking pregabalin despite the similar pharmacology and comparable doses to GBP. We believe this is the first case report to describe subsequent achievement of pain control by substituting pregabalin without recurrence of UI. Healthcare professionals should consider GBP as a potential cause when evaluating patients presenting with new onset overflow UI.

The risk of fragility fractures following initiation of gabapentin and pregabalin-A Danish, nationwide, high-dimensional propensity score-matched cohort study.

Gabapentin and pregabalin have been associated with an increased risk of fragility fractures. Due to differences in pharmacokinetics, we aimed to assess the fracture-risk difference between the two medicines. We performed a Danish nationwide new user, high-dimensional propensity score-matched cohort study to assess the 90-day risk of fragility fractures among adults, from January 1996 to December 2018. We applied a high-dimensional propensity score to match new users of gabapentin with new users of pregabalin in a 1:1 intention-to-treat approach. Hazard ratios (HRs), incidence rates (IRs) and incidence rate difference (IRD) were obtained. We identified 388 236 eligible patients of which 294 223 and 98 869 initiated gabapentin and pregabalin, respectively. We included 48 272 matched pairs for further analysis. The mean age was 56 (IQR 44-69) years, and the average follow-up was approximately 11 500 person-years (PY). The IRs of fragility fractures were 23.7 (95%CI 21.0-26.7) and 23.2 (95%CI 20.5-26.2) per 1000 PY for gabapentin and pregabalin-exposed patients, respectively. This yielded an HR of 1.02 (95%CI 0.86-1.21) when using gabapentin as the intervention drug and pregabalin as the reference drug. The IRD was estimated to 0.5 PY (95%CI -3.5-4.5). In conclusion, short-term risk of fragility fractures among gabapentin initiators was not different compared to those initiating pregabalin.

Gabapentinoids and Acetaminophen as Adjuvants for Managing Postoperative Pain.

With the current opiate epidemic in the United States, there is renewed interest in evaluating non-opiate adjuvant medications as effective alternatives for the prevention and treatment of postoperative pain. A systematic review of randomized, controlled trials on Pub Med, Medline, and Embase was conducted looking on postoperative pain management from 2008 to 2018. Studies were included if they used a gabapentenoid with or without acetaminophen and evaluated supplemental opiate use. All adult (18 years or older) surgical populations were considered for inclusion, and fourteen clinical trials met inclusion criteria. Gabapentenoid dosing varied among studies. In nine of fourteen studies, there was a finding of superiority as compared to placebo in managing postoperative pain and decreasing supplemental opiate use. Pregabalin was used in twelve of the fourteen studies and gabapentin was used in two of the fourteen studies. Of the nine studies that found a benefit from using a gabapentoid, all included pregabalin. While the rate of adverse effects was low in all studies, it was found to increase as dosages increased. Results support that pregabalin has a role in decreasing postoperative pain intensity and supplemental opiate use; however, the optimal dose or dosing regimen is not yet well understood.

Is gabapentin effective and safe in the treatment of chronic pelvic pain in women: a systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: Chronic pelvic pain (CPP) affects 2.1-24% of women, causing physical and psychological damage to women around the world. Based on the efficacy of gabapentin in the treatment of chronic pain, we conducted this study to evaluate the efficacy and safety of gabapentin in reducing pain in women with CPP. METHODS: Systematic searches were performed in the electronic databases of PubMed, Embase, Web of Science, Scopus, Cochrane, and Clinicalkey databases. Studies focused on comparing the efficacy of gabapentin and placebo in the treatment of female CPP patients were included. RevMan 5.4 was used to analyze the results and risk of bias. Two investigators independently selected eligible studies and extracted related pain scores and side effects for meta-analysis. RESULTS: In total, 4 RCTs were enrolled in the meta-analysis, totaling 425 patients. Among patients receiving gabapentin, the average pain scores in 3 and 6 months were significantly lower than those in the placebo group(p < 0.00001). The results showed that there was no statistical difference between gabapentin and placebo in the reduction of pain scores from baseline(p = 0.41). The incidence of side effects in the gabapentin group was significantly higher than that in the placebo group (p < 0.00001). CONCLUSION: This systematic review and meta-analysis demonstrated that for women with CPP, gabapentin was significantly different from placebo in average pain scores at 3 and 6 months. However, the two drugs did not differ in the reduction in pain scores from baseline. Gabapentin can bring more significant side effects, whether they are common side effects or serious side effects.

Patient Case Report: Gabapentin-Induced Hypoglycemia.

PURPOSE: Gabapentin is an analog of gamma-aminobutyric acid (GABA), but its complete mechanism is not well understood. Common adverse effects from gabapentin include somnolence, sedation, and dizziness. Hyperglycemia is listed as a possible adverse drug reaction in the labeling. Case reports describe hypoglycemia in patients with diabetes, peritoneal dialysis, and/or incomplete medication records. The following case report details a hypoglycemia episode as a potential result of a gabapentin use in a patient without diabetes. SUMMARY: A 47-year old, 68 kg, white female presented to the emergency department with altered mental status. Her blood glucose level was 33 mg/dL. Gabapentin was started 1 week prior to the hypoglycemia episode. Her past medical history, concomitant medications, and other laboratory findings were not likely causes of her severe hypoglycemia. CONCLUSION: Gabapentin appears to have effects on several voltage-gated calcium channels. Hypoglycemia may be due to gabapentin binding to the alpha2delta subunit of the calcium channels in the pancreas. Future research should investigate gabapentin and the potential for hypoglycemia.

Lesser Known Uses of γ-Aminobutyric Acid Analogue Medications in Otolaryngology.

OBJECTIVES/HYPOTHESIS: In otolaryngology, γ-aminobutyric acid (GABA) analogues have been previously analyzed for their roles in neuropathic pain, chronic cough, tinnitus, and perioperative analgesia. The primary aim of this study is to comprehensively summarize and synthesize the existing evidence for lesser known uses of gabapentin and pregabalin in otolaryngology. STUDY DESIGN: A scoping review conducted of the available English-language literature was performed by two authors through April 1, 2021. METHODS: The Preferred Reporting Items for Systematic Review and Meta-Analysis criteria were followed, and a quality assessment of included studies was performed using the Methodological Index for Non-Randomized Studies. RESULTS: Ten studies met inclusion criteria. Three studies found that gabapentin may reduce gastrostomy tube usage and improve swallowing function in head and neck cancer patients undergoing radiation therapy (RT). Three studies suggested that gabapentin may help reduce opiate use when used as a primary analgesic in patients with radiation-induced mucositis. One study demonstrated that pregabalin-reduced trismus severity in patients with radiotherapy-induced trismus. One study demonstrated gabapentin may be useful in patients with phonasthenia. Two studies demonstrated that GABA analogues may be a useful adjunct in patients with globus pharyngeus in the context of likely laryngeal sensory neuropathy. CONCLUSIONS: The most promising potential uses for GABA analogues identified in this review are for improving swallowing, trismus, and narcotic overuse after RT. The benefit of GABA analogues for improving nonorganic voice disorders is also promising while the benefit for globus pharyngeus when possibly related to laryngeal sensory neuropathy is inconclusive. Laryngoscope, 132:954-964, 2022.

Is gabapentin a safe and effective treatment for nonneuropathic pain?

ABSTRACT: A review of the recent literature found that compared with placebo or other pain medications, gabapentin did not significantly reduce nonneuropathic pain. The drug also is associated with an increased risk of adverse reactions, including somnolence, dizziness, and nausea. Given the lack of efficacy and risk of adverse reactions, gabapentin should not be used for nonneuropathic pain.

[Hepatotoxicity probably associated with gabapentin]. / Hepatotoxicidad probablemente asociada a gabapentina.

BACKGROUND: Gabapentin is an anticonvulsant medication used as an adjuvant in the treatment of neuropathic pain; few cases have been reported in which it causes acute liver injury. CLINICAL CASE: 56-year-old male patient with a history of chronic kidney disease on hemodialysis and narrowing of the spinal canal under treatment with gabapentin, who presented acute liver injury probably secondary to a dose of gabapentin; however, it remitted with the suspension of said drug. CONCLUSION: Gabapentin lacks liver metabolism; the mechanism by which it produces liver injury is still unknown; however, there are reports of hepatotoxicity associated with its administration, so its use must be individualized for each patient.

INTRODUCCIÓN: la gabapentina es un fármaco anticonvulsivante utilizado como adyuvante en el tratamiento del dolor neuropático; se han reportado pocos casos en los cuales es causa de lesión hepática aguda. CASO CLÍNICO: paciente masculino de 56 años de edad con antecedente de enfermedad renal crónica en hemodiálisis y diagnóstico de canal lumbar estrecho en tratamiento con gabapentina, quien presentó lesión hepática aguda, probablemente secundaria a la dosis de gabapentina; sin embargo, remitió posterior a la suspensión de dicho fármaco. CONCLUSIÓN: la gabapentina carece de metabolismo hepático; el mecanismo por el cual produce lesión hepática aún es desconocido; sin embargo, existen reportes de hepatotoxicidad asociada a su administración, por lo que su utilización deberá individualizarse para cada paciente.

Gabapentin controlled substance status.

Gabapentin is approved to treat postherpetic neuralgia and epilepsy with partial-onset seizures. The large majority of gabapentin prescribing is off label. Gabapentin may be abused for euphoria, potentiating the high from opiates, reduction of alcohol cravings, a cocaine-like high, as well as sedation or sleep. Individuals at the highest risk for abusing gabapentin include those with opioid abuse, mental illness, or previous history of prescription drug abuse. States are now taking action to track gabapentin use through prescription monitoring programs, and some states have reclassified it as a Schedule V controlled substance. This commentary summarizes gabapentin's abuse potential, identifies state-level actions regarding gabapentin monitoring, and discusses possible clinical implications and ways to enhance patient safety when prescribing gabapentin.