Successful Synergistic Use of Gabapentin With Other Antiepileptic Drugs in the Management of Lance-Adams Syndrome Complicated by Alcohol Withdrawal Seizures: A Case Report.

OBJECTIVE: Lance-Adams syndrome is a rare and debilitating disorder characterized by successful cardiopulmonary resuscitation resulting in myoclonus activity. Alcohol withdrawal seizures from alcohol use disorder may further exacerbate Lance-Adams syndrome. We aim to present a case of Lance-Adams syndrome complicated by alcohol withdrawal seizures and successfully treated with a combination of valproate, clonazepam, and gabapentin. MATERIALS AND METHODS: The patient's electronic medical record, direct patient care experiences, and a comprehensive literature search were used for this case report. We report a 41-year-old male patient with Lance-Adams syndrome with concurrent alcohol use disorder. Treatment was improved when adding gabapentin for alcohol use disorder treatment, alongside combination antiepileptic therapy. A PubMed search was conducted to examine Lance-Adams syndrome case reports of successful combination antiepileptic therapy, with a secondary evaluation of patients with concurrent alcohol use disorder. RESULTS: The literature search yielded 18 articles, which resulted in 21 individual cases in which combination antiepileptic drug therapy was successful in treating myoclonus secondary to Lance-Adams syndrome; however, none of the case reports utilized gabapentin synergistically. One case described Lance-Adams syndrome complicated by alcohol consumption and similar to our patient, the patient used alcohol to abolish myoclonic activity. CONCLUSIONS: To the best of our knowledge, this is the first case report documenting a patient with Lance-Adams syndrome and concurrent alcohol use disorder, with a positive effect of gabapentin use. Gabapentin, when used for alcohol use disorder treatment, may be an appropriate adjunct agent in the management of patients receiving combination antiepileptic therapy for the treatment of Lance-Adams syndrome.

Long-term outcome of alcohol withdrawal seizures.

BACKGROUND AND PURPOSE: Alcohol withdrawal seizures (AWS) are a well-known complication of chronic alcohol abuse, but there is currently little knowledge of their long-term relapse rate and prognosis. The aims of this study were to identify risk factors for AWS recurrence and to study the overall outcome of patients after AWS. METHODS: In this retrospective single-center study, we included patients who were admitted to the Emergency Department after an AWS between January 1, 2013 and August 10, 2021 and for whom an electroencephalogram (EEG) was requested. AWS relapses up until April 29, 2022 were researched. We compared history, treatment with benzodiazepines or antiseizure medications (ASMs), laboratory, EEG and computed tomography findings between patients with AWS relapse (r-AWS) and patients with no AWS relapse (nr-AWS). RESULTS: A total of 199 patients were enrolled (mean age 53 ± 12 years; 78.9% men). AWS relapses occurred in 11% of patients, after a median time of 470.5 days. Brain computed tomography (n = 182) showed pathological findings in 35.7%. Risk factors for relapses were history of previous AWS (p = 0.013), skull fractures (p = 0.004) at the index AWS, and possibly epileptiform EEG abnormalities (p = 0.07). Benzodiazepines or other ASMs, taken before or after the index event, did not differ between the r-AWS and the nr-AWS group. The mortality rate was 2.9%/year of follow-up, which was 13 times higher compared to the general population. Risk factors for death were history of AWS (p < 0.001) and encephalopathic EEG (p = 0.043). CONCLUSIONS: Delayed AWS relapses occur in 11% of patients and are associated with risk factors (previous AWS >24 h apart, skull fractures, and pathological EEG findings) that also increase the epilepsy risk, that is, predisposition for seizures, if not treated. Future prospective studies are mandatory to determine appropriate long-term diagnostic and therapeutic strategies, in order to reduce the risk of relapse and mortality associated with AWS.

[Assessment of alcohol withdrawal syndrome: new perspectives]. / Az alkoholmegvonásos szindróma ellátása: új perspektívák.

Alcohol withdrawal syndrome is one of the most important consequences of alcohol use disorder, a complex neuropsychiatric disorder, which is firstly treated in non-specific and secondly in psychiatric/addictive in- or outpatient units. On the other hand, alcohol withdrawal syndrome is one of the most important outcomes of the severity of alcohol use disorder, further, it can lead to the development of alcohol-related seizure and delirium tremens. Hence, early recognition and optimal treatment of alcohol withdrawal syndrome have a critical importance. Therefore, the main goal of the present review was - by systematically summarizing the scientific data published during the past two decades - to form a unique diagnostic and therapeutic algorithm. During the recognition and the course of alcohol withdrawal syndrome, the Clinical Institute Withdrawal Assessment for Alcohol, Revised scale, while in the risk assessment the Prediction of Alcohol Withdrawal Severity Scale are the recommended psychometric tools. Benzodiazepines are the key elements of the pharmacotherapy of alcohol withdrawal syndrome. Many studies have evaluated that diazepam, chlordiazepoxide, lorazepam and oxazepam with distinct indications have sufficient evidence in the treatment of alcohol withdrawal syndrome. However, in the past few years some authors have recommended the importance of non-benzodiazepine medications. The efficacy of propofol, phenobarbital, carbamazepin, oxcarbamazepin and alpha-2 receptor agonists in the treatment of alcohol withdrawal syndrome have been revealed. Furthermore, it has been evaluated that benzodiazepines are recommended in the treatment of alcohol-related seizure and delirium tremens. In the present review, our aim was to construct a unique, up-to-date diagnostic and therapeutic algorithm by summarizing the related papers published during the past two decades. Hence this scheme may be useful in the optimal treatment of patients diagnosed with alcohol use disorder and it could help to conduct further clinical researches. Orv Hetil. 2023; 164(38): 1487-1496.

Prevention of alcohol withdrawal seizure recurrence and treatment of other alcohol withdrawal symptoms in the emergency department: a rapid review.

BACKGROUND: Patients who experience harms from alcohol and other substance use often seek care in the emergency department (ED). ED visits related to alcohol withdrawal have increased across the world during the COVID-19 pandemic. ED clinicians are responsible for risk-stratifying patients under time and resource constraints and must reliably identify those who are safe for outpatient management versus those who require more intensive levels of care. Published guidelines for alcohol withdrawal are largely limited to the primary care and outpatient settings, and do not provide specific guidance for ED use. The purpose of this review was to synthesize published evidence on the treatment of alcohol withdrawal syndrome in the ED. METHODS: We conducted a rapid review by searching MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (1980 to 2020). We searched for grey literature on Google and hand-searched the conference abstracts of relevant addiction medicine and emergency medicine professional associations (2015 to 2020). We included interventional and observational studies that reported outcomes of clinical interventions aimed at treating alcohol withdrawal syndrome in adults in the ED. RESULTS: We identified 13 studies that met inclusion criteria for our review (7 randomized controlled trials and 6 observational studies). Most studies were at high/serious risk of bias. We divided studies based on intervention and summarized evidence narratively. Benzodiazepines decrease alcohol withdrawal seizure recurrence and treat other alcohol withdrawal symptoms, but no clear evidence supports the use of one benzodiazepine over another. It is unclear if symptom-triggered benzodiazepine protocols are effective for use in the ED. More evidence is needed to determine if phenobarbital, with or without benzodiazepines, can be used safely and effectively to treat alcohol withdrawal in the ED. Phenytoin does not have evidence of effectiveness at preventing withdrawal seizures in the ED. CONCLUSIONS: Few studies have evaluated the safety and efficacy of pharmacotherapies for alcohol withdrawal specifically in the ED setting. Benzodiazepines are the most evidence-based treatment for alcohol withdrawal in the ED. Pharmacotherapies that have demonstrated benefit for treatment of alcohol withdrawal in other inpatient and outpatient settings should be evaluated in the ED setting before routine use.

Derivation and validation of a multivariable model, the alcohol withdrawal triage tool (AWTT), for predicting severe alcohol withdrawal syndrome.

BACKGROUND: Alcohol withdrawal and its consequences are a common concern for the large numbers of patients who present to emergency departments (EDs) with alcohol use disorders. While the majority of patients who go on to develop alcohol withdrawal experience only mild symptoms, a small proportion will experience seizures or delirium tremens. The aim of this study was to develop a tool to predict the need for hospital admission in patients at risk for alcohol withdrawal using only objective criteria that are typically available during the course of an ED visit. METHODS: We conducted a retrospective study at an academic medical center. Our primary outcome was severe alcohol withdrawal syndrome (SAWS), which we defined as a composite of delirium tremens, seizure, or use of high benzodiazepine doses. All candidate predictors were abstracted from the electronic health record. A logistic regression model was constructed using the derivation dataset to create the alcohol withdrawal triage tool (AWTT). RESULTS: Of the 2038 study patients, 408 20.0 %) developed SAWS. We identified eight independent predictors of SAWS. Each of the predictors in the regression model was assigned one point. Summing the points for each predictor generated the AWTT score. An AWTT score of 3 or greater was defined as high risk based on sensitivity of 90 % and specificity of 47 % for predicting SAWS. CONCLUSIONS: We were able to identify a set of objective, timely, independent predictors of SAWS. The predictors were used to create a novel clinical prediction rule, the AWTT.

Genotype Differences in Sensitivity to the Anticonvulsant Effect of the Synthetic Neurosteroid Ganaxolone during Chronic Ethanol Withdrawal.

Sensitivity to anticonvulsant effects of the γ-aminobutyric acidA receptor-active neurosteroid allopregnanolone (ALLO) during ethanol withdrawal varies across genotypes, with high sensitivity in genotypes with mild withdrawal and low sensitivity in genotypes with high withdrawal. The present studies determined whether the resistance to ALLO during withdrawal in mouse genotypes with high handling-induced convulsions (HICs) during withdrawal could be overcome with use of ganaxolone (GAN), the metabolically stable derivative of ALLO. In separate studies, male and female Withdrawal Seizure-Prone (WSP-1) and DBA/2J (D2) mice were exposed to air (controls) or 72-h ethanol vapor and then were scored for HICs during withdrawal (hourly for the first 12 h, then at hours 24 and 25). After the HIC scoring at hours 5 and 9, mice were injected with 10 mg/kg GAN or vehicle. Area under the HIC curve (AUC) for hours 5-12 was analyzed. In control WSP-1 mice, GAN significantly reduced AUC by 52% (males) and 63% (females), with effects that were absent or substantially reduced during withdrawal. In contrast, GAN significantly reduced AUC in both control and ethanol-withdrawing male and female D2 mice. AUC was decreased by 81% (males) and 70% (females) in controls and by 35% (males) and 21% (females) during withdrawal. The significant anticonvulsant effect of GAN during withdrawal in D2 but not WSP-1 mice suggests that different mechanisms may contribute to ALLO insensitivity during withdrawal in these two genotypes. Importantly, the results in D2 mice suggest that GAN may be a useful treatment for ethanol withdrawal-induced seizures.

[Management of alcohol withdrawal]. / Prise en charge du sevrage alcoolique.

This article proposes an update and summary of current knowledge in the management of alcohol withdrawal, based on a review of recent literature. The issues open to debate and the areas whith new developments will be addressed, such as: the entry into treatment, the withdrawal setting, the withdrawal medications, the various possible protocols and the introduction of relapse prevention treatments.

Cet article propose une actualisation et un résumé du savoir-faire dans la prise en charge du sevrage éthylique, sur base d'une revue de la littérature récente. Les questions qui prêtent à débat et les domaines où des nouveautés se présentent y sont abordés : l'entrée en traitement, le lieu du sevrage, la médication de sevrage ainsi que les différents protocoles possibles, l'instauration des traitements de prévention des rechutes.

Anticonvulsants as monotherapy or adjuncts to treat alcohol withdrawal: A systematic review.

BACKGROUND: This systematic review evaluates current literature on anticonvulsants to treat alcohol withdrawal symptoms (AWS). METHODS: We performed a literature search of PubMed, MEDLINE, PsycINFO, EMBASE, and Cochrane collaboration databases through September 30, 2016. The search was not restricted by patients' age. Articles published in English or with official English translations were included. RESULTS: We found 16 double-blind randomized controlled trials (RCTs) that evaluated the use of anticonvulsants as treatment of AWS. Available data indicates that anticonvulsants are as effective as sedatives/hypnotics in treating mild or moderate AWS. Two studies evaluated the use of anticonvulsants as adjuncts. Combining anticonvulsants with sedatives decreases the quantity of sedatives required and AWS may resolve quicker. There is some data that anticonvulsants can be used to treat AWS as monotherapy. Fourteen of these studies assessed adverse effects of these medications; 13 studies identified minor adverse effects and one found the adverse effects to be intolerable. CONCLUSIONS: Available evidence indicates that anticonvulsants have good efficacy as monotherapy and as adjuncts with sedatives/hypnotics in treating mild to moderate AWS.

Alcohol withdrawal syndrome: diagnostic and therapeutic methods.

Alcohol withdrawal syndrome (AWS) is a medical emergency, rare in the general population, but very common among alcoholic individuals, which can lead to severe complications when unrecognized or late treated. It represents a clinical condition which can evolve in few hours or days following an abrupt cessation or reduction of alcohol intake and is characterized by hyperactivity of the autonomic nervous system resulting in the development of typical symptoms. According to DSM-5 criteria, the alcohol withdrawal syndrome is defined as such: if patients present at least two of typical signs and symptoms. The Clinical Institute Withdrawal Assessment of Alcohol Scale, revised version (CIWA-Ar), is the tool for assessing the severity of AWS. The support to patient with AWS includes pharmacological intervention as well as general support, restoration of biochemical imbalances and specific therapy. Regarding the pharmacological treatment, benzodiazepines represent the gold standard, in particular long-acting benzodiazepines, administered with a gradual reduction up to cessation.

Adjunctive Use of Ketamine for Benzodiazepine-Resistant Severe Alcohol Withdrawal: a Retrospective Evaluation.

INTRODUCTION: Benzodiazepine (BZD)-resistant alcohol withdrawal remains a challenge for most institutions due to limited evidence with available agents. One published study currently exists utilizing the N-methyl-D-aspartate antagonist, ketamine, for alcohol withdrawal. OBJECTIVE: The purpose of our study was to evaluate the effect of adjunctive ketamine continuous infusion on symptom control and lorazepam infusion requirements for BZD-resistant alcohol withdrawal patients in the intensive care unit. METHODS: A retrospective review was conducted of patients receiving ketamine adjunctively with a lorazepam infusion for severe alcohol withdrawal between August 2012 and August 2014. Outcomes included time to symptom control, lorazepam infusion requirements, ketamine initial and maximum daily infusion rates, and adverse effects of ketamine. RESULTS: Thirty patients were included in the analysis. Mean time to initiation of ketamine after the initiation of a lorazepam infusion was 41.4 h. All patients achieved initial symptom control within 1 h of ketamine initiation. Median initial ketamine infusion rate was 0.75 mg/kg/h and the average maximum daily rate was 1.6 mg/kg/h. Significant decreases in lorazepam infusion rates from baseline were observed at 24 h (- 4 mg/h; p = 0.01) after ketamine initiation. No patients experienced documented CNS adverse effects. Two patients experienced hypertension and no patients experienced tachycardia related to ketamine. CONCLUSION: Adjunctive ketamine could provide symptom control for BZD-refractory patients and may potentially reduce lorazepam infusion requirements. Future studies to determine optimal dosing, timing of initiation, and place in therapy for BZD-resistant alcohol withdrawal are needed. The mechanism of action via the NMDA receptor with ketamine may provide benefit for BZD-resistant alcohol withdrawal.

Topiramate-induced acute liver injury: A rare adverse effect.

Idiosyncratic drug-induced liver injury (DILI) is damage to liver occurring at recommended dose of a drug in contrast to toxic or predictable DILI. Although it is common in first-generation antiepileptic drugs (AEDs), it is rare in newer AEDs such as topiramate. Topiramate commonly causes neurological adverse effects such as psychomotor slowing and somnolence. Hepatotoxicity by topiramate is rare and has been previously reported in combination with other drugs such as valproate and carbamazepine. Here, we report a case of topiramate-induced asymptomatic elevation of liver enzymes in an adult man diagnosed with alcohol dependence syndrome and alcohol withdrawal complicated with seizures.

Alcohol-use disorders: diagnosis and management of physical complications. Last updated: 2017

This guideline covers care for adults and young people (aged 10 years and older) with physical health problems that are completely or partly caused by an alcohol-use disorder. It aims to improve the health of people with alcohol-use disorders by providing recommendations on managing acute alcohol withdrawal and treating alcohol-related conditions. In April 2017, we reviewed the evidence for corticosteroid treatment for people with severe alcohol-related hepatitis and changed recommendation 1.3.3.1. MHRA advice on antiepileptic drugs in pregnancy: In May 2021, we linked to the updated MHRA safety advice on antiepileptic drugs in pregnancy in the recommendation on treatment for acute alcohol withdrawal. NICE has also produced guidelines on alcohol-use disorders: prevention and alcohol-use disorders: diagnosis, assessment and management of harmful drinking (high-risk drinking) and alcohol dependence.

Diazepam in the Treatment of Moderate to Severe Alcohol Withdrawal.

Benzodiazepines ameliorate or prevent the symptoms and complications of moderate to severe alcohol withdrawal, which can include autonomic hyperactivity, agitation, combativeness, hallucinations, seizures, delirium, and death. The benzodiazepines most commonly used for this purpose are lorazepam, chlordiazepoxide, oxazepam, and diazepam. It is widely asserted that no member of this group is superior to the others for treatment of alcohol withdrawal. However, of these, diazepam has the shortest time to peak effect, which facilitates both rapid control of symptoms and accurate titration to avoid over-sedation. Furthermore, diazepam and its active metabolite, desmethyldiazepam, have the longest elimination half-lives, so their levels decrease in a gradual, self-tapering manner, resulting in a smoother withdrawal, i.e., a lower incidence and severity of both breakthrough symptoms and rebound phenomena, including a possibly decreased seizure risk. Importantly, the fear of increased risk of over-sedation with diazepam compared with other benzodiazepines is based on a misunderstanding of its pharmacokinetics and is unfounded. Similarly, the notion that diazepam should be avoided in patients with liver disease and elderly patients to avoid prolonged over-sedation is based on no more than conjecture. In fact, there is clinical evidence that diazepam is safe for the treatment of alcohol withdrawal in these patients when administered using a simple symptom-based approach. There is one instance in which diazepam should not be used: when intramuscular administration is the only option, the lipophilicity of diazepam can result in slow absorption-either lorazepam or, when rapid control of symptoms is required, midazolam should be used. The comparative pharmacokinetics of the benzodiazepines used in the treatment of alcohol withdrawal together with a comprehensive review of the literature on their use strongly suggest that diazepam should be the preferred benzodiazepine for the treatment of patients experiencing moderate to severe alcohol withdrawal under most circumstances.

[Benzodiazepines should still be first-line treatment for alcohol withdrawal].

In this review, we summarize the evidence for benzodiazepines and barbiturates as alcohol withdrawal treatment and outline a treatment guideline. A number of randomized controlled trials (RCTs) indicate that benzodiazepine treatment decreases alcohol withdrawal seizures and is safe. For barbiturates, only a few RCTs have been undertaken, and barbiturates were not found to be superior to benzodiazepines. Consequently, we suggest that benzodiazepines should still be first-line treatment for alcohol withdrawal.

The Role of Barbiturates for Alcohol Withdrawal Syndrome.

BACKGROUND: Benzodiazepine-resistant cases of alcohol withdrawal syndrome are common, and therefore alternate treatments are needed. OBJECTIVE: Our aim was to conduct a systematic review of published reports on the use of barbiturates for alcohol withdrawal syndrome. METHODS: We performed a systematic literature search of PUBMED for relevant citations that described the use of barbiturates either alone or in conjunction with other pharmacological agents to treat alcohol withdrawal syndrome. RESULTS: A total of 15 citations were identified; 2 citations looked at barbiturates alone; 1 found barbiturates effective in an emergency department setting at treating seizures and preventing return visits. A second showed that barbiturates caused a relatively low rate of respiratory depression. Further, 5 citations compared barbiturates with benzodiazepines; 1 suggested that they were better at treating severe withdrawal, and another showed they were more effective at preventing seizures; 4 citations found they were as effective as benzodiazepines, but 1 found a higher rate of respiratory depression. Also, 3 citations compared a combination of barbiturates and benzodiazepines to benzodiazepines alone; 1 showed decreased ventilation, another showed fewer intensive care unit admissions, and a third showed better symptom control; 3 citations described detailed reports of barbiturate protocols. Lastly, 2 citations compared barbiturates with other agents and found them equivalent. CONCLUSION: Barbiturates provide effective treatment for alcohol withdrawal syndrome. In particular, they show promise for use in the emergency department and for severe withdrawal in the intensive care unit. Respiratory depression does not appear to be exceedingly common. Additional studies are needed to clarify the role of barbiturates in alcohol withdrawal syndrome.

Alcohol withdrawal syndrome in medical patients.

The authors provide a critical review focusing on pharmacotherapy of alcohol withdrawal syndrome in hospitalized patients who are not critically ill. They outline recommendations for patient assessment and monitoring.