Benzo Research Articles

Four good reasons to choose ketamine in the emergency department. A case series and literature review

Ketamine is a fast-acting N-methyl-D-aspartate (NMDA) receptor antagonist that can be used in a range of clinical scenarios in the pre-hospital setting and emergency department (ED). When compared with other anesthetic agents, ketamine has many unique properties, such as the ability to produce dose-dependent analgesic and anesthetic effects with a wide margin of safety. Ketamine may be used in the ED for sedation, pain management, and acute agitation treatment in the cases of benzodiazepine (BDZ)-resistant alcohol withdrawal syndrome (AWS) and substance use disorder. To highlight the efficacy and safety of ketamine, we reviewed the literature, starting with a description of four different cases of patients who presented to our ED and were treated with ketamine.

Effective reduction of long term benzodiazepine and other drugs usage for insomnia through cognitive behavioral therapy, muscle stretching session, tDCS, binaural beats, and aromatherapy: a case series

Effective reduction of long term benzodiazepine and other drugs usage for insomnia through cognitive behavioral therapy, muscle stretching session, tDCS, binaural beats, and aromatherapy: a case series

Insomnia Guidelines—The European Update 2023

The last ten years have seen the development and publication of numerous national and international guidelines devoted to the diagnosis and treatment of insomnia. These include guidelines by the American College of Physicians (ACP), the American Academy of Sleep Medicine (AASM), the British Sleep Society (BSS), the German Sleep Society (GSS), and the European Sleep Research Society (ESRS). Though coming from very diverse authors and backgrounds, these guidelines by and large agree concerning the therapeutic recommendations: cognitive behavioral treatment of insomnia (CBT-I), a multicomponent psychotherapeutic intervention, is unequivocally recommended as a first-line treatment. In this report, we will focus on the most recent guideline update from the ESRS, which was published in November 2023. After suggesting a careful diagnostic procedure, CBT-I, both applied face to face (F2F) or digitally (dCBT-I), is again recommended as a first-line treatment based on the available evidence. Hypnotic medications like benzodiazepines (BZ), benzodiazepine receptor agonists (BZRA), sedating antidepressants, and others are approved for short-term-treatment of up to four weeks. Orexin receptor antagonists (i.e., daridorexant) and prolonged release melatonin are considered as options for longer-term treatment when carefully considering the advantages and disadvantages. Both light therapy and exercise regimens were viewed as promising; however, they still lack convincing evidence for the time being. Given the fact that not every patient responds satisfactorily or even remits following CBT-I or other treatment options, the research agenda calls for the development and evaluation of new therapeutic avenues and combination therapies.

Automated enzymatic hydrolysis of urine samples for improved systematic toxicological analysis of drug-facilitated sexual assault cases.

Drug-facilitated sexual assault (DFSA) is characterized by victim incapacitation due to intoxicating substances. Detection of single drug exposure from DFSA requires a systematic toxicological analysis strategy including sensitive methods covering a broad spectrum of substances. The aim of this study was to develop and validate an UHPLC-MS/MS screening method for analysis of samples from DFSA cases and incorporate an automated enzymatic pre-treatment of urine samples into a robotic sample preparation for an efficient laboratory workflow. The screening method included 144 drugs of abuse, pharmaceuticals, and metabolites relevant to DFSA. The use of a recombinant enzyme showed an efficient glucuronide hydrolysis with an average parent drug recovery of 97%. Investigation of matrix effect showed no pronounced ion enhancement or suppression for most analytes (96%), and extraction recovery was above 80% for 97% of analytes. Process efficiency ranged from 50% to 138% for most analytes. The LODs ranged from 0.0001 mg/L to 2 mg/L depending on analyte, and most analytes met the SOFT recommended minimum performance limits. The validated method was applied to authentic suspected DFSA cases (n = 38). Results showed that drugs of abuse, benzodiazepines, and antidepressants were most commonly found in suspected DFSA cases. Incorporation of an automated enzymatic hydrolysis step during sample preparation enables a fast and simple workflow for simultaneous analysis of blood and urine samples for an improved systematic toxicological analysis strategy for DFSA cases.

Chronic benzodiazepine usage among older people: prevalence, indications, and treatment modifications in patients admitted to an acute geriatric unit.

To investigate the prevalence and indications of benzodiazepines (BZD) usage among patients admitted to an acute geriatric unit and assess changes in prescriptions. BZD indications were documented reviewing clinical records, with appropriateness assessed based on the STOPP-START criteria. Changes in BZD prescriptions were recorded at discharge and 3 months later. Among the 366 patients included (mean age: 92.8years, 68% females), 91 (24.9%) were on BZD upon admission, being inappropriate in 93.4%. At discharge,BZD discontinuation was observed in 40.7% and dose reduction initiated in 57.4%. Among patients discharged without prescriptions, 10.8% resumed their use at 3months. Of those discharged with BZD tapering, 74.1% were still on them 3months later. The majority of patients employing BZD lacked a medical indication. Admission to a geriatric ward resulted in successful discontinuation or dose reduction for most patients but was not maintained in the outpatient setting.

Phenobarbital treatment of alcohol withdrawal in the emergency department: A systematic review and meta-analysis.

Despite frequent treatment of alcohol withdrawal syndrome (AWS) in the emergency department (ED), evidence for phenobarbital (PB) as an ED alternative therapy is mixed. We conducted a systematic review and meta-analysis comparing safety and efficacy of PB to benzodiazepines (BZDs) for treatment of AWS in the ED. We searched articles and references published in English in PubMed, Web of Science, and Embase from inception through May 2022. We included randomized trials and cohort studies comparing treatment with PB to BZD controls and excluded studies focused on non-AWS conditions. Review was conducted by two blinded investigators and a third author; eight of 59 (13.6%) abstracts met inclusion criteria for review and meta-analysis using a random-effects model. Treatment superiority was evaluated through utilization, pharmacologic, and clinical outcomes. Primary outcomes for meta-analysis were the proportion of patients (1) admitted to the intensive care unit (ICU), (2) admitted to the hospital, (3) readmitted to the ED after discharge, and (4) who experienced adverse events. Eight studies (two randomized controlled trials, six retrospective cohorts) comprised data from 1507 patients in 2012 treatment encounters for AWS. All studies were included in meta-analysis for adverse events, seven for hospital admission, five for ICU admission, and three for readmission to the ED after discharge. Overall methodological quality was low-moderate, risk of bias moderate-high, and statistical heterogeneity moderate. Pooled relative risk of ICU admission for those treated with PB versus BZD was 0.92 (95% confidence interval [CI] 0.54-1.55). Risk for admission to the hospital was 0.98 (95% CI 0.89-1.07) and for any adverse event was 1.1 (95% CI 0.78-1.57); heterogeneity prevented meta-analysis for ED readmission. The current literature base does not show that treatment with PB significantly reduces ICU admissions, hospital admissions, ED readmissions, or adverse events in ED patients with AWS compared with BZDs alone.

High-dose benzodiazepine use and QTc interval prolongation, a latent class analysis study

Benzodiazepine (BDZ) addiction is a widespread and multifaceted phenomenon. For many patients, especially females, the concomitant use of other drugs also increases their risk of QTc prolongation, possibly leading to complications such as seizures and even sudden death. However, the relationship between BDZ use and QTc prolongation is currently unclear. The present study aims to examine patterns of polysubstance use among a sample of Italian adults with BDZ dependence in relation with their QTc prolongation risk. We used Latent Class Analysis (LCA) on data collected from 251 inpatients of the Addiction Medicine Unit in Verona to group patients into three classes according to their substance use and their QTc prolongation risk. Results showed no significant relationship between QTc prolongation and BDZ use in any of the classes considered. We conclude that BDZs, even if used long-term and at high dosages, can be considered safe in terms of cardiovascular complications for patients.

Passiflora incarnata L., herba, in benzodiazepine tapering: long-term safety and efficacy in a real-world setting.

Chronic and inappropriate benzodiazepine (BDZ) prescription and intake represent an important health and social concern worldwide. The aim of our study was to investigate the safety and efficacy of P. incarnata L., herba in reducing BDZ misuse in a real-world population of depressed and anxious patients in a long-term treatment with BDZs. Over an 18-month period (from July 2021 to December 2022), we previously conducted a retrospective and naturalistic study on euthymic outpatients with a diagnosis of anxiety or depression and chronically taking BDZs. In this study we contacted patients 12 months after their enrollment in the previous study to assess their disease status and their BDZs and P. incarnata intake. Our findings support the effectiveness of a dry extract of P. incarnata L., herba, as an add-on treatment during BDZ tapering in patients with anxiety or depression. We confirmed this effect to be sustained over time, and P. incarnata showed to be easily discontinued with no rebound, withdrawal or psychological dependence effect. The absence of side effects and adverse events confirmed the safety of P. incarnata in a real-world population. Personality disorders confirmed to be a relevant risk factor for maintaining addictive behavior, even when symptoms associated to withdrawal seem to be not particularly relevant. We confirmed the possible effectiveness of P. incarnata as an add-on treatment in BDZ reduction. Further studies may be helpful to better investigate the promising properties of P. incarnata in the management of relevant clinical issues, such as anxiety disorders and addiction, that are classically known to benefit from GABAergic treatments.

Elucidation of Degradation Behavior of Nitrazepam, a Benzodiazepine Drug, under Basic Conditions: Study on Degradability of Drugs in Stomach (IV).

This study investigates the stability of nitrazepam (NZP), a benzodiazepine drug, under basic conditions, since alkaline putrefactive amines and ammonia are produced once bodies are left to decompose for a long period postmortem after a murder involving NZP or an accidental overdose of NZP. The degradation of NZP in an aqueous alkaline solution was investigated by LC/photodiode array detector (PDA) where the NZP degradation product was isolated and purified by solid-phase extraction using Oasis® MCX, and its chemical structure was determined by LC/time-of-flight (TOF)-MS, NMR spectroscopy, and single-crystal X-ray crystallography. The results revealed that NZP was immediately degraded under basic conditions with 2-amino-5-nitrobenzophenone being an intermediate which further degraded to provide 2-hydroxy-5-nitrobenzophenone as the final degradation product. These results are expected to be useful in clinical chemistry and forensic science, such as the detection of drugs during postmortem examination and suspected addiction.

Use and misuse of psychoactive medicines: a descriptive cross-sectional study in a densely populated region of Portugal.

Although psychoactive medicines (PMed) are needed in several psychiatric conditions, their use and misuse bear risks. We aimed at estimating the prevalence of PMed use and misuse. Data on all PMed prescribed in 2017 and dispensed in community pharmacies of the Lisbon and Tagus Valley region of Portugal (ARSLVT) were extracted from ARSLVT medicines' dispensing database. For 21 PMed among prescription opioids, benzodiazepines and z-drugs (BZDR), antidepressants (AD) and anticonvulsants (AC), we estimated the number of users of each PMed, and assessed PMed misuse by a set of proxy indicators for studying this practice: chronic use (use of ≥180 DDD during the study period) of PMed intended for short-term treatments, concomitant use of several PMed, in particular if involving long-term (≥ 30 days) opioid analgesic (OA) use, and doctor shopping (patients consulting several physicians in order to have access to a quantity higher than intended by each prescriber). Data were analysed using descriptive statistics and hypothesis testing, and multivariate logistic regression was used to explore potential factors affecting long-term concomitant treatment of chronic OA with other PMed. PMed use prevalence was 21.7%: 6.6% for OA, 12.7% for benzodiazepines (BZD), 5.3% for AD and 2.8% for AC. BZDR were mainly prescribed in primary care and OA in hospital outpatients. Chronic use of PMed was observed in 25%, especially with sertraline and buprenorphine for opioid use disorder (long-term treatment), and lorazepam (short-term treatment). About 56.6% of OA chronic users were long-term concurrent users with other PMed, mainly BZDR. Risk of abuse was low for BZDR, whilst four opioids had meaningful doctor shopping indicators - fentanyl, opioid use disorder buprenorphine, morphine and hydromorphone. BZD are the main PMed used in ARSLVT, often chronically, especially lorazepam. Prevalence of OA use is low, although with higher risk of misuse than BZDR. Concomitant use of several PMed is frequent.

Exploratory analysis of high-dose corticosteroid therapy on epileptic encephalopathy with spike-and-wave activation in sleep.

This study aims to evaluate the therapeutic efficacy of high-dose corticosteroid therapy in children diagnosed with epileptic encephalopathy with spike-and-wave activation in sleep (EE-SWAS), investigate associated clinical indicators influencing treatment outcomes, and establish a predictive model for recurrence. Children diagnosed with EE-SWAS who received high-dose corticosteroid therapy were categorized into responder group and non-responder group. Data on clinical parameters, electroencephalogram (EEG) features, and serum cytokine levels were collected. Six months post-treatment, the effectively treated children were further stratified into recurrence and non-recurrence groups. Risk factors for poor outcomes following corticosteroid therapy were identified using univariate analysis. Multivariate logistic regression analysis was then employed to determine independent factors influencing the recurrence of corticosteroid therapy, which facilitated the development of a predictive model. The study included 48 children, with 33 cases in the responder group (effective rate = 68.8%) and 15 cases in the non-responder group. The responder group exhibited an older onset age of electrical status epilepticus in sleep (ESES) and higher proportions of combined benzodiazepines (BZDs) use (P < 0.05). Among those responding to corticosteroid therapy, 11 cases experienced a recurrence (recurrence rate = 33.3%), while 22 cases did not. Significant differences were observed between the two groups concerning age of seizure onset, age of ESES onset, seizure frequency, atypical presentations, and concomitant frontal lobe discharges (all P < 0.05). Concomitant frontal lobe discharges and an earlier age of seizure onset were identified as risk factors for ESES recurrence following corticosteroid therapy. The predictive model was formulated as Logit(P) = 2.35 × presence of frontal lobe discharges-0.802 × age of seizure onset + 2.457. The Area Under the Curve (AUC) of Receiver Operating Characteristics (ROC) was 0.93, with sensitivity and specificity at 100% and 77.3%, respectively. High-dose corticosteroid therapy for EE-SWAS exhibited a high effective rate as well as a notable recurrence rate. Onset age of ESES and combined benzodiazepines usage correlated with therapeutic efficacy. Seizure onset age and the presence of frontal lobe discharges may hold predictive value for recurrence following corticosteroid therapy.

The role of the GABAergic system on insomnia.

Sleep is an essential activity for the survival of mammals. Good sleep quality helps promote the performance of daily functions. In contrast, insufficient sleep reduces the efficiency of daily activities, causes various chronic diseases like Alzheimer's disease, and increases the risk of having accidents. The GABAergic system is the primary inhibitory neurotransmitter system in the central nervous system. It transits the gamma-aminobutyric acid (GABA) neurotransmitter via GABAA and GABAB receptors to counterbalance excitatory neurotransmitters, such as glutamate, noradrenaline, serotonin, acetylcholine, orexin, and dopamine, which release and increase arousal activities during sleep. Several studies emphasized that dysfunction of the GABAergic system is related to insomnia, the most prevalent sleep-related disorder. The GABAergic system comprises the GABA neurotransmitter, GABA receptors, GABA synthesis, and degradation. Many studies have demonstrated that GABA levels correlate with sleep quality, suggesting that modulating the GABAergic system may be a promising therapeutic approach for insomnia. In this article, we highlight the significance of sleep, the classification and pathology of insomnia, and the impact of the GABAergic system changes on sleep. In addition, we also review the medications that target the GABAergic systems for insomnia, including benzodiazepines (BZDs), non-BZDs, barbiturates, GABA supplements, and Chinese herbal medicines.

Performance Evaluation of Multi-Drug Rapid Test for Rapid Detection of Multiple Drugs and Drug Metabolites in Human Blood Samples

Objective: The Multi-Drug Rapid Test Cassette, developed by Hangzhou AllTest Biotech Co., Ltd, is a rapid chromatographic immunoassay designed for the qualitative detection of multiple drugs and drug metabolites in human whole blood, serum, or plasma. It aims to simultaneously detect various abused substances, including Amphetamine (AMP), Barbiturates (BAR), Benzodiazepines (BZO), Buprenorphine (BUP), Cocaine (COC), Cannabis (THC), Methadone (MTD), Methamphetamine (MET), 3,4-Methylenedioxymethamphetamine (MDMA), Morphine (MOP/OPI), Propoxyphene (PPX), Tricyclic antidepressants (TCA), Oxycodone (OXY), 2-Ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), Cotinine (COT), Tramadol (TML), Fentanyl (FYL), 3,4-Methylenedioxy pyrovalerone (MDPV), Synthetic cannabinoids(K2), Phencyclidine(PCP), Ketamine(KET), Lysergic acid diethylamide(LSD), 3,4-Methylenedioxyamphetamine(MDA), Acetaminophen(ACE), Ketamine(CAT), 6-Monoacetylmorphine (6-MAM), Zolpidem (ZOL), AB-PINACA (ABP/K3). Therefore, the present research was done to evaluate the diagnostic performance of this test. Material and Method: In this study, the accuracy, precision, and sensitivity of the drug testing methods were assessed. Approximately 100 specimens of each drug, obtained from previous drug screening tests, were tested. The results were compared to confirmatory analysis using GC/MS, and the accuracy of the testing was determined based on the comparative classification results. The evaluation of precision included measuring the consistency of measurements within a single run, between different runs, and among different operators, using the AllTest multi-drug detection tool across three different hospitals and three different batches. To evaluate the sensitivity of the detection method, various concentrations of drugs were added to a pool of whole blood, serum, or plasma without any drugs. The positive and negative results obtained from the testing were analyzed to assess the method’s ability to detect drugs at different concentrations. Results: In this study, we evaluated the performance of the Multi-Drug Rapid Test Cassette developed by Hangzhou AllTest Biotech Co., Ltd. The results demonstrated excellent performance of the test in terms of accuracy, sensitivity, and precision. Conclusion: The Multi-Drug Rapid Test Cassette developed by Hangzhou AllTest Biotech Co., Ltd exhibited reliable detection of multiple drugs and drug metabolites, providing trustworthy results for drug abuse screening. These findings have significant implications for drug control and monitoring, as well as supporting the broad application of this test in clinical and legal settings.

Comparative efficacy of various pharmacologic treatments for alcohol withdrawal syndrome: a systematic review and network meta-analysis.

This study was to compare multiple classes of medications and medication combinations to find alternatives or additives for patients not applicable to benzodiazepines (BZDs). We performed a network meta-analysis to assess the comparative effect of 11 pharmacologic treatments in patients with alcohol withdrawal syndrome. Forty-one studies were included, comprising a total sample size of 4187 participants. The pooled results from the randomized controlled trials showed that there was no significant difference in the Clinical Institute Withdrawal Assessment-Alcohol, revised (CIWA-Ar) reduction with other medications or medication combinations compared to BZDs. Compared to BZDs, the mean difference in ICU length of stay of anticonvulsants + BZDs was -1.71 days (95% CI = -2.82, -0.59). Efficacy rankings from cohort studies showed that anticonvulsant + BZDs were superior to other treatments in reducing CIWA-Ar scores and reducing the length of stay in the ICU. Synthesis results from randomized controlled trials indicate that there are currently no data suggesting that other medications or medication combinations can fully replace BZDs. However, synthetic results from observational studies have shown that BZDs are effective in the context of adjuvant anticonvulsant therapy, particularly with early use of gabapentin in combination with BZDs in the treatment of alcohol withdrawal syndrome, which represents a promising treatment option.

A strategy for the detection of benzodiazepine drugs using low-resolution paper-spray mass spectrometry for harm reduction drug checking.

The ability to detect newly emerging substances is of great importance in reducing harms for people who use drugs. New psychoactive substances including novel benzodiazepines in the illicit drug supply have been linked to high rates of overdose deaths while complicating drug checking as an overdose prevention strategy. Paper-spray mass spectrometry (PS-MS) has emerged as a novel strategy to rapidly detect trace components in street drug samples. While targeted, low-resolution PS-MS methods have proven effective, newly emerging substances are often missed. To address this, a method was applied to low-resolution full-scan PS-MS data to aid in the early detection and identification of novel benzodiazepines in the unregulated drug supply. Using the developed method, true positives rates of 0.89 and 0.75 were achieved for bromazolam and etizolam in street samples obtained in a community drug checking service. The applicability of the method was further demonstrated for a novel benzodiazepine, desalkylgidazepam, that has recently emerged in the illicit drug supply.

A CONSULTANT PHARMACIST INTERVENTION TO DEPRESCRIBE OPIOIDS AND BENZODIAZEPINES FOR OLDER ADULTS IN PRIMARY CARE

Abstract Long-term use of opioids and benzodiazepines (BZDs) by older adults may cause harm. We evaluated the impact of a targeted consultant pharmacist opioid and BZD deprescribing intervention for older adults. We conducted a pragmatic study in which fifteen primary care clinics were randomized to receive standard care (n=7) or a consultant pharmacist service (n=8) to provide targeted medication review and recommendations for deprescribing opioids and BZDs. The primary outcome was opioid and BZD prescribing in the following year, using average daily morphine milligram equivalents (MMEs) and diazepam milligram equivalents (DMEs). We used generalized linear models to evaluate the association of the intervention with average daily MMEs and DMEs, adjusted for medication exposures in the prior year and demographics. Incident falls were examined as a secondary outcome. We included 961 opioid and 1107 BZD users, with 15.6% and 13.6% being prescribed both medications, respectively. Average daily MMEs and DMEs prescribed at baseline were 23.6 and 7.67. Deprescribing recommendations were made for 71% of opioid and BZD users seen in intervention clinics. We observed non-statistically significant reductions in average daily MMEs (Intervention: -2.42 MMEs, Control: -1.02 MMEs, p=0.71) and DMEs (Intervention: -1.0 DMEs, Control: -0.1 DMEs, p=0.06). There was no significant reduction in incident falls. A consultant pharmacist-driven intervention is a feasible approach to deliver targeted deprescribing recommendations, but did not significantly impact medication use or falls. Future studies should explore whether multimodal interventions would be more effective in achieving deprescribing and reducing medication-related harms.

Management strategies for refractory status epilepticus

Refractory status epilepticus (RSE) is defined as the persistence of either clinical or electrographic seizures despite the administration of appropriate doses of an initial benzodiazepine and suitable second-line antiepileptic drugs (AEDs). The Neurocritical Care Society and the American Epilepsy Society have proposed a treatment paradigm for the management of convulsive status epilepticus (CSE). The third-line therapy in refractory CSE may involve general anesthesia using intravenous midazolam, propofol, or other agents, while recent evidence supports the use of ketamine to manage RSE in both adults and children. However, although these treatment strategies are frequently employed in nonconvulsive status epilepticus (NCSE), the efficacy of AEDs and anesthetics in NCSE has not been thoroughly investigated. Recent evidence has demonstrated the safety and efficacy of newer AEDs, including levetiracetam and lacosamide, in the treatment of status epilepticus (SE) and RSE, which also encompasses NCSE. Use of multiple combinations of various intravenous AEDs can also be considered in NCSE before the administration of general anesthesia. In addition, AEDs alone exhibit limited effectiveness in managing SE for new-onset RSE (NORSE) and its subset, febrile infection-related epilepsy syndrome. Therefore, in cases of refractory status, it is imperative to explore treatment options beyond AEDs, including immunotherapy and the incorporation of a ketogenic diet. The present review suggests treatment approaches for RSE based on subgroups, including CSE, NCSE, and NORSE. A discussion of recent clinical studies on AEDs and anesthetics in the management of RSE, as well as proposed treatment methods for NORSE, is also provided.

Synthesis of novel MOF-on-MOF composite as a magnetic sorbent to dispersive micro solid phase extraction of benzodiazepine drugs prior to determination with HPLC-UV

Diazepam and lorazepam are two benzodiazepine drugs widely prescribed as antidepressants and antiepileptics. A straightforward and time-save dispersive micro solid phase extraction method as a sample preparation strategy was developed to extract these drugs in human urine and real water samples prior to their determination by HPLC-UV. A novel sorbent based on growing Co-MOF on Fe-MOF was synthesized and then magnetized using magnetic Fe3O4 nanoparticles and a sol–gel strategy. The sorbent (Fe3O4@SiO2@Co-MOF@Fe-MOF composite) showed the highest extraction efficiency toward diazepam and lorazepam compared to Fe-MOF and Co-MOF@Fe-MOF as sorbents. The effects of various factors on diazepam and lorazepam determination were studied by experimental design, in which a Plackett-Burman design and Box-Behnken design were used for screening the factors and optimizing the significant factors, respectively. Under optimum conditions, the method linearity for the diazepam and lorazepam determination was 0.3–450 and 0.2–400 ng mL−1 with an R2 of 0.9926 and 0.9943, respectively. Proper detection limits of 0.09 and 0.06 ng mL−1 were obtained for the diazepam and lorazepam determination. Also, intra-day and inter-day RSDs (n = 3) were in the range of 3.42–3.75 % and 4.76–5.39 % for the diazepam and lorazepam determination, respectively. The method exhibits a high preconcentration factor of 654.3 and 719.1 for the diazepam and lorazepam determination. Besides, the recoveries and RSDs were evaluated by analysis of tap, river, and well water, and two human urine samples using the method. RSDs were in the range of 3.09–6.80 %, with recoveries between 88.2 and 97.5 % for analysis of spiked real water and urine samples.

Quantitative Opiate, Opioid, and Benzodiazepine Testing by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).

Fatalities due to opioids and other controlled substances continue to increase year over year and maintain an epidemic level nationally. CDC data indicates that drug overdoses killed more than 100,000 Americans in 2021 with synthetic opioids being the main driver of the national crisis (Wide-ranging online data for epidemiologic research (WONDER). Multiple Cause of Death 1999-2020. Centers for Disease Control and Prevention, National Center on Health Statistics. http://wonder.cdc.gov . Accessed 28 Feb 2023, 2021). Response to this crisis includes the development of laboratory testing to support the evolving drug trends. Urine drug testing provides clinicians with objective information to assist in making treatment decisions by identifying the presence of potential drugs of abuse and assessing patient compliance to a controlled substance prescription regimen. In this chapter, we describe a rapid LC-MS/MS method for the simultaneous quantitation of 21 opiate, opioid, and benzodiazepine drugs in less than 4min. The method requires 100uL of urine and includes enzymatic hydrolysis of glucuronide conjugates using β-glucuronidase to provide total drug measurement. Quantitation is accomplished using multiple reaction monitoring (MRM), a seven-point calibration curve, and deuterated internal standards. This method provides a robust and reliable means to measure commonly prescribed opioid (including natural, semi-synthetic, and synthetic) and benzodiazepine drugs in urine.

The association of benzodiazepine and benzodiazepine-related drugs with outcomes after surgery for colorectal cancer

Benzodiazepines increase plasma brain-derived neurotrophic factor (BDNF) level which, in turn, may improve survival in colorectal cancer (CRC) patients. This study aimed to evaluate the associations between benzodiazepine and benzodiazepine-related drugs (BZRD) use and outcomes of patients operated for CRC. This is a retrospective cohort study including patients operated for CRC at Limoges’ University Hospital between 2010 and 2019. Data were collected from two sources: medical records of patients in the digestive, general and endocrine surgery department at Limoges University Hospital and from the Haute-Vienne general cancer registry. Patients were divided into benzodiazepine users and non-users. Outcomes were overall survival (OS) and recurrence-free survival (RFS). Among 504 patients who underwent surgery for CRC, 125 (24.8%) patients were treated with benzodiazepine/BZRD drugs. Users and non-users of benzodiazepine/BZRD showed no statistically significant differences in 5-year OS (45.5 ± 1.9% vs. 46.5 ± 1.1% p = 0.25) and 5-year RFS (41.0 ± 2.1% vs. 39.6 ± 1.3%, p = 0.94), even after adjustment for confounders and propensity score (OS: aHR=1.02, 95%CI: 0.71–1.48; RFS: aHR=1.00, 95%CI: 0.72–1.40). Subgroup analysis on CRC patients with psychiatric disorders revealed that benzodiazepine users had better RFS (aHR=0.58, 95%CI: 0.35–0.96) compared with non-users, particularly, patients with stages III or IV of CRC had better OS (aHR=0.27; 95%CI: 0.12–0.59) and RFS (aHR=0.30, 95%CI: 0.15–0.62). OS and RFS was significantly better in patients taking benzodiazepines classified as anxiolytics, having longer half-life, and producing active metabolites. In conclusion, benzodiazepine use was not associated with outcomes in CRC patients. Nevertheless, in subgroup of patients with psychiatric disorders and advanced CRC stage, benzodiazepine could improve survival.