• Energy Research

AbstractBackground and AimsAnti‐seizure medications (ASMs) have been used historically as treatment options in alcohol withdrawal syndrome (AWS). In the past 10 years, there have been no large‐scale meta‐analyses comparing ASMs with placebo or the current AWS treatment standard, benzodiazepines. We aimed to evaluate the efficacy and tolerability of ASMs in AWS.MethodsSystematic review and meta‐analysis of randomised controlled trials (RCTs) via searching Medline, Embase and PsychINFO from database inception to March 2020 involving adults age >18 years with AWS. We included 24 RCTs reporting on a total of 2223 participants. Efficacy outcomes included the number of participants experiencing AWS related seizures or delirium, Clinical Institute Withdrawal Assessment for Alcohol–Revised (CIWA‐Ar) score reduction and rescue medication requirements. Tolerability outcomes included adverse event rate and dropout because of adverse events, alongside severe and life‐threatening adverse event rates. Quality was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE).ResultsThere was no evidence of significant improvements in any efficacy outcomes when comparing ASMs with placebo or benzodiazepines. When compared with benzodiazepines, ASMs demonstrated significantly increased odds of requiring rescue medications (OR = 3.50, 95% CI = 1.32, 9.28; P = 0.012). When comparing ASMs with placebo, there were significantly more dropouts because of adverse events (OR = 1.86, 95% CI = 1.05, 3.28; P = 0.034). Most results were of very low quality with the majority of included studies conducted before 2000.ConclusionsThis systematic review and meta‐analysis found no evidence to support general first line clinical use of anti‐seizure medications in alcohol withdrawal syndrome treatment.

AbstractIntroductionThis study investigates whether there is a relationship between alcohol and cocaine use in deaths where suicide by self‐injury is the suspected cause of death.MethodsAdults referred by coroners to the Imperial College London Toxicology Unit for toxicological analysis between 2012 and 2016 were reviewed for inclusion criteria. Those who died by self‐injury reasoned to be deliberate were included in the analysis. Femoral blood alcohol concentration (BAC) and presence of cocaine or benzoylecognine (a metabolite of cocaine) in blood and/or urine were tabulated and odds ratios calculated.ResultsA total of 1722 decedents met inclusion criteria. BAC was ≥50 mg/dL in 29% of decedents. Cocaine was detected in 8.4% of cases. The likelihood of testing positive for cocaine increased with BAC and was most frequent between 100 and 199 mg/dL, consistent with moderate to severe intoxication (odds ratio 5.88, 95% confidence interval 3.80, 9.09; P ≤ 0.001) compared to those with BAC <10 mg/dL.Discussion and ConclusionsThis study demonstrates a correlation between increasing BAC and likelihood of cocaine use prior to suspected suicide, up to a level consistent with severe intoxication. Cocaine use was found in a high proportion of cases relative to the general population reporting regular use. This pattern of drug and alcohol use has previously been given little attention in suicide prevention strategies and clinical prioritisation.

Drug and alcohol dependence are global problems with substantial societal costs. There are few treatments for relapse prevention and therefore a pressing need for further study of brain mechanisms underpinning relapse circuitry. The Imperial College Cambridge Manchester (ICCAM) platform study is an experimental medicine approach to this problem: using functional magnetic resonance imaging (fMRI) techniques and selective pharmacological tools, it aims to explore the neuropharmacology of putative relapse pathways in cocaine, alcohol, opiate dependent, and healthy individuals to inform future drug development. Addiction studies typically involve small samples because of recruitment difficulties and attrition. We established the platform in three centres to assess the feasibility of a multisite approach to address these issues. Pharmacological modulation of reward, impulsivity and emotional reactivity were investigated in a monetary incentive delay task, an inhibitory control task, and an evocative images task, using selective antagonists for µ-opioid, dopamine D3 receptor (DRD3) and neurokinin 1 (NK1) receptors (naltrexone, GSK598809, vofopitant/aprepitant), in a placebo-controlled, randomised, crossover design. In two years, 609 scans were performed, with 155 individuals scanned at baseline. Attrition was low and the majority of individuals were sufficiently motivated to complete all five sessions ( n=87). We describe herein the study design, main aims, recruitment numbers, sample characteristics, and explain the test hypotheses and anticipated study outputs.