Prevalence of opioid and nonopioid pain management therapies among Medicare beneficiaries with musculoskeletal pain conditions from 2016 to 2019.

INTRODUCTION: Pain treatment guidelines prioritize nonopioid therapies over opioid medications to prevent opioid-related harms. We examined trends in receipt and intensity of nonpharmacologic, nonopioid medication, and opioid therapies among Medicare beneficiaries. METHODS: Using a 20% national random sample of Medicare data from 2016 to 2019, we identified fee-for-service beneficiaries with ≥2 diagnoses of back, neck, fibromyalgia, or osteoarthritis/joint pain annually. We excluded beneficiaries with cancer. We calculated annual proportions of beneficiaries who received physical therapy (PT), chiropractic care, gabapentin, and opioids, overall and in demographic, geographic, and clinical subgroups. We estimated the intensity of therapies using the annual number of visitsor prescription fills, prescription days' supply, and opioid dose. RESULTS: During 2016-2019, PT receipt increased (22.8% to 25.5%) and the mean number of visits among recipients of PT went from 12 to 13. Chiropractic receipt (~18%) and mean annual visits (~10) remained unchanged. The prevalence of gabapentin receipt was stable at ~22% and the mean annual number of fills was unchanged though gabapentin days increased slightly. Opioid prescribing decreased (56.7% to 46.5%) and reductions in opioid dose and duration were observed. Opioid receipt was high among beneficiaries who were under 65 years, American Indian/Alaska Native, Black/African American, or had opioid use disorder (OUD), in whom nonpharmacologic therapies were also received the least. CONCLUSION: Utilization of nonopioid therapies lagged opioids among Medicare beneficiaries with musculoskeletal pain, with limited changes from 2016 to 2019. As opioid prescribing declines and alternative pain therapy receipt remains low, there are potential increasing risks of pain going untreated or undertreated and individuals seeking illicit opioids to alleviate their pain.

Provider-directed analgesia for dental pain.

INTRODUCTION: Extraction of impacted molar teeth is a common procedure performed by oral surgeons and general dentists, with postoperative pain being a significant adverse event post-surgery. If mismanaged, pain can lead to complications that impact oral and systemic health. The current scourge of the opioid epidemic has ushered in a new era of provider-directed analgesic (PDA) therapy in dentistry. AREAS COVERED: This article provides an in-depth review on the major pharmacological and therapeutic properties of established and alternative analgesics used to manage dental pain. EXPERT OPINION: Substantial evidence-based literature shows a combination of a non-steroidal anti-inflammatory drug (NSAID; e.g. ibuprofen) and acetaminophen provides superior pain relief than single-agent or combination opioid regimens. However, there are clinical scenarios (e.g. severe pain) where a short-course opioid prescription is appropriate in select patients, for which a 2-3-day treatment duration is typically sufficient. Alternative agents (e.g. caffeine, gabapentin, phytotherapies), typically in combination with established agents, can mitigate postoperative dental pain. Some evidence suggests preemptive therapies (e.g. corticosteroids, NSAIDs) reduce amounts of postsurgical analgesic consumption and might lessen opioid prescription burden. In summary, this comprehensive review provides an opportune update on the evolving landscape of pharmacotherapy for acute postsurgical dental pain, informing best practices for PDA in the dental setting.

Comparison the effect of valerian and gabapentin on RLS and sleep quality in hemodialysis patients: A randomized clinical trial.

INTRODUCTION: This study aimed to compare the effect of valerian and gabapentin on restless legs syndrome (RLS) and sleep quality in HD patients. METHODS: In this cross over clinical trial study, 40 HD patients allocated into a valerian and gabapentin group. In the first phase of the study, Group A received valerian and Group B received gabapentin 1 h before bedtime for 1 month. In the second phase, the two groups' treatment regimen was swapped. After a 1-month washout period, the same process was repeated on the crossover groups. RESULTS: After the first phase, the mean score of RLS was lower in the gabapentin group. But there was no statistically significant difference between the two groups in terms of sleep quality score before and after the first and second interventions. CONCLUSION: Gabapentin is more effective than valerian in improving RLS, but both are equally effective in improving sleep quality.

Uremic pruritus: pathophysiology, clinical presentation, and treatments.

Uremic pruritus is one of the most common and bothersome symptoms in patients with end-stage renal disease. Most patients with uremic pruritus experience a prolonged and relapsing course and significant impairments of quality of life. The pathophysiology of uremic pruritus is not completely understood. A complex interplay among cutaneous biology and the nervous and immune systems has been implicated, with the involvement of various inflammatory mediators, neurotransmitters, and opioids. Uremic pruritus treatment outcomes are often unsatisfactory. Clinical trials have mostly been small in scale and have reported inconsistent results. Recent evidence shows that gabapentinoids, nalfurafine, and difelikefalin are effective for relieving uremic pruritus in hemodialysis patients. This review provides an overview of the epidemiology and proposed mechanisms of uremic pruritus, then highlights the manifestations of and clinical approach to uremic pruritus. Current evidence regarding treatment options, including topical treatments, treatment of underlying disease, phototherapy, and systemic treatments, is also outlined. With a better understanding of uremic pruritus, more therapeutic options can be expected in the near future.

From HDAC to Voltage-Gated Ion Channels: What's Next? The Long Road of Antiepileptic Drugs Repositioning in Cancer.

Cancer is a major health burden worldwide. Although the plethora of molecular targets identified in the last decades and the deriving developed treatments, which significantly improved patients' outcome, the occurrence of resistance to therapies remains the major cause of relapse and mortality. Thus, efforts in identifying new markers to be exploited as molecular targets in cancer therapy are needed. This review will first give a glance on the diagnostic and therapeutic significance of histone deacetylase (HDAC) and voltage gated ion channels (VGICs) in cancer. Nevertheless, HDAC and VGICs have also been reported as molecular targets through which antiepileptic drugs (AEDs) seem to exert their anticancer activity. This should be claimed as a great advantage. Indeed, due to the slowness of drug approval procedures, the attempt to turn to off-label use of already approved medicines would be highly preferable. Therefore, an updated and accurate overview of both preclinical and clinical data of commonly prescribed AEDs (mainly valproic acid, lamotrigine, carbamazepine, phenytoin and gabapentin) in breast, prostate, brain and other cancers will follow. Finally, a glance at the emerging attempt to administer AEDs by means of opportunely designed drug delivery systems (DDSs), so to limit toxicity and improve bioavailability, is also given.

Uptake of antiepileptic drugs in forskolin-induced differentiated BeWo cells: alteration of gabapentin transport.

Previous studies have indicated that the expression levels of several transporters are altered during placental trophoblast differentiation. However, changes in the transport activities of therapeutic agents during differentiation must be comprehensively characterised. Antiepileptic drugs, including gabapentin (GBP), lamotrigine (LTG), topiramate, and levetiracetam, are increasingly prescribed during pregnancy. The objective of this study was to elucidate differences in the uptake of antiepileptic drugs during the differentiation process.Human placental choriocarcinoma BeWo cells were used as trophoblast models. For differentiation into syncytiotrophoblast-like cells, cells were treated with forskolin.The uptake of GBP and LTG was lower in differentiated BeWo cells than in undifferentiated cells. In particular, the maximum uptake rate of GBP transport was decreased in differentiated BeWo cells. Furthermore, GBP transport was trans-stimulated by the amino acids His and Met. We investigated the profiles of amino acids in undifferentiated and differentiated BeWo cells. Supplementation with His and Met, which demonstrated trans-stimulatory effects on GBP uptake, restored GBP uptake in differentiated cells. The findings of this study suggest that drug transport in BeWo cells can be altered before and after differentiation, and that the altered GBP uptake could be mediated by the intracellular amino acid status.

Treating Severe Refractory and Augmented Restless Legs Syndrome.

Restless legs syndrome (RLS) is a sensory-motor neurologic disorder present to a clinically significant degree in 2% to 3% of the adult population, more commonly with advancing age and in women, that dramatically affects sleep and quality of life. Addressing factors that worsen RLS (eg, iron deficiency, antidepressant or antihistamine administration, OSA) is an important first step in treatment. RLS can generally be well treated with medications such as the alpha2-delta calcium channel ligands (A2Ds) gabapentin, pregabalin, and gabapentin enacarbil or, if these are poorly tolerated or lack efficacy, the dopamine agonists (DAs) pramipexole, ropinirole, or rotigotine. Oral or IV iron supplementation is often efficacious as initial treatment in patients with low normal serum indexes. However, at least one-third of patients do not achieve acceptable symptom relief from initial treatments. Furthermore, DAs, the most commonly used medications for RLS, commonly produce augmentation, a progressive, long-term, iatrogenic worsening of RLS symptoms characterized by increasing severity as well as temporal and anatomic extension of symptoms. If dopaminergic augmentation of RLS is present, substitution of an A2D or opioid for the DA is the primary goal. However, given the profound rebound RLS and insomnia that occurs with even small dose reductions of DAs, the initial change should be the addition of one of these alternate treatments. Once adequate doses, or symptom relief, are achieved with the second agent, subsequent very slow down-titration and discontinuation of the DA is often possible and can lead to dramatic long-term relief of RLS symptoms and improvement in sleep.

Small Molecules as Modulators of Voltage-Gated Calcium Channels in Neurological Disorders: State of the Art and Perspectives.

Voltage-gated calcium channels (VGCCs) are widely expressed in the brain, heart and vessels, smooth and skeletal muscle, as well as in endocrine cells. VGCCs mediate gene transcription, synaptic and neuronal structural plasticity, muscle contraction, the release of hormones and neurotransmitters, and membrane excitability. Therefore, it is not surprising that VGCC dysfunction results in severe pathologies, such as cardiovascular conditions, neurological and psychiatric disorders, altered glycemic levels, and abnormal smooth muscle tone. The latest research findings and clinical evidence increasingly show the critical role played by VGCCs in autism spectrum disorders, Parkinson's disease, drug addiction, pain, and epilepsy. These findings outline the importance of developing selective calcium channel inhibitors and modulators to treat such prevailing conditions of the central nervous system. Several small molecules inhibiting calcium channels are currently used in clinical practice to successfully treat pain and cardiovascular conditions. However, the limited palette of molecules available and the emerging extent of VGCC pathophysiology require the development of additional drugs targeting these channels. Here, we provide an overview of the role of calcium channels in neurological disorders and discuss possible strategies to generate novel therapeutics.

Non-opioid pharmacologic treatment of chronic spinal cord injury-related pain.

Purpose: Spinal cord injury-related pain is often a severe debilitating condition that adversely affects the patient's physical health, psychological wellbeing and quality of life. Opioid medications have historically been prescribed to this population with great frequency. As opioid abuse disorder becomes an ever-worsening public health issue, more attention must be placed upon non-opioid options. This paper reviews non-opioid medications to be considered when treating spinal cord injury-related pain. The pertinent literature is reviewed, and the advantages and pitfalls of various medication options are discussed in the complicated context of the individual with a spinal cord injury.Methods: Peer-reviewed journal articles and medication package insert data are reviewed.Results:. The non-opioid medications with the greatest evidence for efficacy in the treatment of chronic spinal cord injury-related pain are drawn from the antiepileptic drug and antidepressant categories though the specific selection must be nuanced to the particular individual patient. More research is required to understand the role of calcitonin, lithium, and marijuana in treating spinal cord injury-related pain.Conclusions: The complex clinical situation of each individual patient must be weighed against the risks and benefits of each medication, as reviewed in this paper, to determine the ideal treatment strategy for chronic spinal cord injury-related pain.

Punicalagin and ellagic acid containing Punica granatum L. fruit rind extract prevents vincristine-induced neuropathic pain in rats: an in silico and in vivo evidence of GABAergic action and cytokine inhibition.

Objectives: We aimed to investigate the protective potential of Punica granatum L. fruit rind extract (PFE) containing punicalagin (10.3% W/W), ellagic acid (EA) (2.7%W/W) in vincristine (75 µg/kg i.p.)- induced neuropathic pain in Wistar rats.Methods: Docking simulation studies were done on the three-dimensional (3D) structure of the GABAA and PPAR γ receptor for the binding of EA as well as punicalagin docking studies on TNF-α, and IL-6. The Present Study conceptualized a test battery to evaluate the behavioral, biochemical and histological changes.Results: Vincristine -induced significant cold allodynia, mechanical hyperalgesia, and functional deficit on 12th and 21st days. It also increased in the levels of TNF-α (Tumor necrosis factor-α), IL-6 (Interleukin-6), and MPO (Myeloperoxidase). Administration of PFE (100 and 300 mg/kg, p.o.), EA (50 mg/kg), and gabapentin (100 mg/kg) attenuated Vincristine-induced behavioral and biochemical changes significantly (P < .05). PFE showed better antinociceptive activity to EA. The histopathological evaluation also revealed the protective effects of PFE. Pretreatment of bicuculline (selective antagonist of GABAA receptors) reversed antinociceptive action of PFE, but administration of γ aminobutyric acid potentiated the action of PFE. PPAR-γ antagonist BADGE did not modify the effect of PFE. Docking results revealed that EA properly positioned into GABA and PPARγ binding site and acts as a partial agonist. Docking score of Punicalagin found to be - 9.02 kcal/mol and - 8.32 kcal/mol on IL-6 and TNFα respectively.Discussion: Conclusively, the attenuating effect of PFE may be attributed to the GABAergic system, cytokine inhibition, and anti-inflammatory activities.

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

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

Treatment for alcohol use disorder among persons with and without HIV in a clinical care setting in the United States.

BACKGROUND: Alcohol use disorders (AUD) can lead to poor health outcomes. Little is known about AUD treatment among persons with HIV (PWH). In an integrated health system in Northern California, 2014-2017, we compared AUD treatment rates between PWH with AUD and persons without HIV (PWoH) with AUD. METHODS: Using Poisson regression with GEE, we estimated prevalence ratios (PRs) comparing the annual probability of receiving AUD treatment (behavioral intervention or dispensed medication), adjusted for sociodemographics, psychiatric comorbidities, insurance type, and calendar year. Among PWH, we examined independent AUD treatment predictors using PRs adjusted for calendar year only. RESULTS: PWH with AUD (N = 633; 93% men, median age 49) were likelier than PWoH with AUD (N = 7006; 95% men, median age 52) to have depression (38% vs. 21%) and a non-alcohol substance use disorder (SUD, 48% vs. 25%) (both P < 0.01). Annual probabilities of receiving AUD treatment were 45.4% for PWH and 34.4% for PWoH. After adjusting, there was no difference by HIV status (PR 1.02 [95% CI 0.94-1.11]; P = 0.61). Of treated PWH, 59% received only a behavioral intervention, 5% only a medication, and 36% both, vs. 67%, 4%, 30% for treated PWoH, respectively. Irrespective of HIV status, the most common medication was gabapentin. Among PWH, receiving AUD treatment was associated with having depression (PR 1.78 [1.51-2.10]; P < 0.01) and another SUD (PR 2.68 [2.20-3.27]; P < 0.01). CONCLUSIONS: PWH with AUD had higher AUD treatment rates than PWoH with AUD in unadjusted but not adjusted analyses, which may be explained by higher psychiatric comorbidity burden among PWH.

Efficacy of pharmacologic treatment in tinnitus patients without specific or treatable origin: A network meta-analysis of randomised controlled trials.

BACKGROUND: Although tinnitus has a prevalence between 20 and 42.8%, the currently recommended management for tinnitus, such as tinnitus support and psychologic therapies, are relatively time-consuming and expensive. Several new pharmacologic treatments designed for tinnitus patients without specific origin had been developed but their efficacy remains unclear. METHODS: The current Network Meta-Analysis (NMA) of randomised controlled trials (RCTs) was conducted to evaluate the efficacy of different pharmacologic treatments for tinnitus management in tinnitus patients without specific or treatable origin (i.e. primary tinnitus). Databases were searched from inception to April 5th, 2021. All network meta-analytic procedures were conducted under the frequentist model. We calculated the effect size of outcomes with different rating scales with standardized mean difference. PROSPERO registration: CRD42020177742. FINDINGS: Overall, 36 RCTs were included with 2,761 participants. The main results revealed that pharmacologic interventions with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) and those with anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) were associated with superior improvement in tinnitus severity and response rate compared to placebo/control. Oral amitriptyline were associated with the highest improvement in tinnitus severity and the fourth highest response rate. None of the investigated interventions was associated with different changes in quality of life compared to placebo/control. All the investigated treatments were associated with similar drop-out rate to placebo/control. INTERPRETATION: The current NMA suggests a potential role for treatments with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) or anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) as the preferable effective treatments for tinnitus without specific or treatable origin. FUNDING: none.

[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 as an adjunct to paracervical block for perioperative pain management for first-trimester uterine aspiration: a randomized controlled trial.

BACKGROUND: Pain management approaches during uterine aspiration vary, which include local anesthetic, oral analgesics, moderate sedation, deep sedation, or a combination of approaches. For local anesthetic approaches specifically, we continue to have suboptimal pain control. Gabapentin as an adjunct to pain management has proven to be beneficial in gynecologic surgery. We sought to evaluate the impact of gabapentin on perioperative pain during surgical management of first-trimester abortion or early pregnancy loss with uterine aspiration under local anesthesia. OBJECTIVE: We hypothesized that adding gabapentin to local anesthesia will reduce perioperative and postoperative pain associated with uterine aspiration. Secondary outcomes included tolerability of gabapentin and postoperative pain, nausea, vomiting, and anxiety. STUDY DESIGN: We conducted a randomized double-blinded placebo-controlled trial of gabapentin 600 mg given 1 to 2 hours preoperatively among subjects receiving a first-trimester uterine aspiration under paracervical block in an outpatient ambulatory surgery center. There were 111 subjects randomized. The primary outcome was pain at time of uterine aspiration as measured on a 100-mm visual analog scale. Secondary outcomes included pain at other perioperative time points. To assess changes in pain measures, an intention to treat mixed effects model was fit with treatment groups (gabapentin vs control) as a between-subjects factor and time point as a within-subjects factor plus their interaction term. Because of a non-normal distribution of pain scores, the area under the curve was calculated for secondary outcomes with comparison of groups utilizing Mann-Whitney U tests. RESULTS: Among the 111 randomized, most subjects were Black or African American (69.4%), mean age was 26 years (±5.5), and mean gestational age was 61.3 days (standard deviation, 14.10). Mean pain scores at time of uterine aspiration were 66.77 (gabapentin) vs 71.06 (placebo), with a mean difference of -3.38 (P=.51). There were no significant changes in pain score preoperatively or intraoperatively. Subjects who received gabapentin had significantly lower levels of pain at 10 minutes after surgery (mean difference [standard error (SE)]=-13.0 [-5.0]; P=.01) and 30 minutes after surgery (mean difference [SE]=-10.8 [-5.1]; P=.03) compared with subjects who received placebo. Median nausea scores and incidence of emesis pre- and postoperatively did not differ between groups. Similarly, anxiety scores did not differ between groups, before or after the procedure. At 10 and 30 minutes after the procedure, most participants reported no side effects or mild side effects, and this did not differ between groups. CONCLUSION: Preoperative gabapentin did not reduce pain during uterine aspiration. However, it did reduce postoperative pain, which may prove to be a desired attribute of its use, particularly in cases where postoperative pain may be a greater challenge.

Effect of gabapentin on sleep-deprivation-induced disruption of prepulse inhibition.

RATIONALE: There are controversial reports on the effects of gabapentin in respect to psychotic symptoms. Prepulse inhibition of the acoustic startle response is an operational measure of sensorimotor gating. In laboratory rodents, deficits in sensorimotor gating are used to model behavioral endophenotypes of schizophrenia. Sleep deprivation disrupts prepulse inhibition and can be used as a psychosis model to evaluate effects of gabapentin. OBJECTIVES: This study aimed to investigate behavioral effects of gabapentin in both naïve and sleep-deprived rats. METHODS: Sleep deprivation was induced in male Wistar rats by using the modified multiple platform technique in a water tank for 72 h. The effect of water tank itself was studied in a sham group. The effects of oral acute and subchronic (4.5 days) gabapentin doses (25, 100, or 200 mg/kg/day) on sensorimotor gating and locomotor activity was evaluated by prepulse inhibition test and locomotor activity test, respectively. Plasma gabapentin levels of some groups and body weights of all groups were also assessed. RESULTS: Sleep deprivation disrupted prepulse inhibition, increased locomotor activity, reduced gabapentin plasma levels, and body weights. Some gabapentin doses disrupted sensorimotor gating irrespective of sleep condition. Some gabapentin doses increased locomotor activity in non-sleep-deprived rats and decreased locomotor activity in sleep-deprived rats. On the contrary, gabapentin did not normalize sleep deprivation-induced disruption in sensorimotor gating. CONCLUSIONS: Sleep deprivation via modified multiple platform technique could be used as an animal model for psychosis. Gabapentin may have dose- and duration-dependent effects on sensorimotor gating and locomotor activity.

Successful Management of Glioblastoma Chemotherapy-Associated Dysgeusia with Gabapentin.

Dysgeusia is a frequent, yet underreported side effect of chemotherapy for cancer. We report here the first use of gabapentin in two glioblastoma patients who developed dysgeusia following intra-arterial administration of carboplatin or oral administration of lomustine, respectively. Treatment initiation was followed by resolution of taste alteration within weeks. Both patients reported significant improvement in their quality of life and regained weight, allowing further chemotherapy cycles. We hypothesized that in these two cases, chemotherapy impeded gustatory cells turnover and function, resulting in a gustatory "deafferentation-like" syndrome which was successfully addressed by the medication.

Combination Therapy of Gabapentin and N-Acetylcysteine Against Posttraumatic Epilepsy in Rats.

Traumatic brain injury (TBI) is a major public health problem worldwide that is associated with increased mortality and morbidity. Posttraumatic epilepsy (PTE) is one of the sequelae of TBI. The aim of this study was to investigate the role of N-acetylcysteine (NAC) as an adjuvant on the efficacy of levetiracetam (LEV) and gabapentin (GBP) in PTE model encouraged by pentylenetetrazol (PTZ) after mild-TBI in male Sprague-Dawley rats. Mild-TBI was performed by the weight-drop method in male Sprague-Dawley rats. PTE model was developed by injecting PTZ (30+15+15 mg/kg, 30 min intervals, i.p.) 7 days after head trauma. After the development of posttraumatic seizures, the rats were treated with NAC (100 mg/kg), LEV (50 mg/kg), GBP (100 mg/kg), NAC+LEV and NAC+GBP intraperitoneally for 14 days. Seizures related to PTE were scored by video-EEG recording. Motor performance of the animals was also evaluated in the rotarod test. 50 mg/kg LEV and 100 mg/kg GBP reduced seizures related to PTE. LEV alone (p = 0.009), but the administration of GBP+NAC (p = 0.015) was more effective on PTE-related seizure control. However, GBP+NAC application adversely affected the fall latency in the rotarod test. In terms of trauma-related seizure control, there was no statistically significant difference between the use of prophylactic LEV and symptomatic LEV. LEV alone or the combination of GBP with NAC provides more effective seizure control in the PTE facilitated by PTZ. On the other hand, the use of prophylactic LEV did not have any extra effect on posttraumatic seizure development and control.

Use of Gabapentin in the Treatment of Substance Use and Psychiatric Disorders: A Systematic Review.

Objective: Gabapentin (GBP) is an anticonvulsant medication that is also used to treat restless legs syndrome (RLS) and posttherapeutic neuralgia. GBP is commonly prescribed off-label for psychiatric disorders despite the lack of strong evidence. However, there is growing evidence that GBP may be effective and clinically beneficial in both psychiatric disorders and substance use disorders. This review aimed to perform a systematic analysis of peer-reviewed published literature on the efficacy of GBP in the treatment of psychiatric disorders and substance use disorders. Methods: This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The PubMed and Ovid MEDLINE literature databases were screened and filtered by using specific search terms and inclusion/exclusion criteria. The full texts of selected studies were subsequently retrieved and reviewed. The search terms generated 2,604 results from the databases. After excluding all duplicates, 1,088 citations were left. Thereafter, we applied inclusion and exclusion criteria; a total of 54 papers were retained for detailed review. Results: This literature review concludes that GBP appears to be effective in the treatment of various forms of anxiety disorders. It shows some effectiveness in bipolar disorder as an adjunctive therapeutic agent, while the evidence for monotherapy is inconclusive. In substance use disorders, GBP is effective for acute alcohol withdrawal syndrome (AWS) with mild to moderate severity; it reduces cravings, improves the rate of abstinence, and delays return to heavy drinking. GBP may have some therapeutic potential in the treatment of opioid addiction and cannabis dependence, but there is limited evidence to support its use. No significant benefit of GBP has been conclusively observed in the treatment of OCD, PTSD, depression, or cocaine and amphetamine abuse. Conclusion: GBP appears to be effective in some forms of anxiety disorders such as preoperative anxiety, anxiety in breast cancer survivors, and social phobia. GBP has shown to be safe and effective in the treatment of alcohol dependence. However, the literature suggests that GBP is effective as an adjunctive medication rather than a monotherapy. More clinical trials with larger patient populations are needed to support gabapentin's off-label use in psychiatric disorders and substance use disorders. It is worth noting that numerous clinical studies that are discussed in this review are open-label trials, which are inherently less rigorously analyzed. Therefore, more extensive investigations are required to examine not only the efficacy of GBP, but also its safety and tolerance.