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Background: Catatonia is a potentially life-threatening condition that is characterized by psychiatric and motor disturbances, such as negativism, hypomotility, bradykinesia, and unusual movements. The diagnosis is based on clinical examination and occurs in both pediatric and adult patients and is associated with an increased mortality. Catatonia is associated with psychiatric illnesses such as schizophrenia, major depression, encephalitis, and bipolar disorder. The physiopathology of catatonia is complex and not fully understood. There is an ongoing debate in the medical community whether catatonia is an independent syndrome, or secondary to other mental illnesses. This case presentation is unique, as there are few reports describing cases of isolated catatonic syndrome in the absence of any other psychiatric or medical condition with a delayed onset caused by recreational drug abuse., Case Presentation: We present the case of a 17-year-old Caucasian athletic girl with no previous contact with child and adolescent psychiatry, nor any previous drug abuse. After recreational intake of drugs, there was a delay of approximately 7 days, before the patient searched care with symptoms that were at a later stage recognized as catatonia. Treatment with a high dose of lorazepam in combination with memantine and lithium resulted in a regression of the symptoms. After 6 weeks the patient could be discharged from the hospital almost fully recovered., Conclusions: An acute onset of psychomotor symptoms without any previous history of mental illnesses must be addressed early as a potential catatonic syndrome. Delayed onset of catatonic symptoms after intake of drugs should not be overlooked, and we here suggest that mephedrone might be capable of inducing delayed catatonia. It is feasible to use memantine as an adjuvant to the treatment of catatonia in adolescents., Competing Interests: Declarations Ethics approval and consent to participate The patient, who had recently turned 18 years old at the time of discharge from Uppsala University Hospital, has signed a written consent regarding this case report. The written consent contains personal data including the patient’s national ID number, which would make it very easy to identify the patient. At this stage we have therefore chosen to not include the consent along with submission of the manuscript. Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests There are no competing interests., (© 2024. The Author(s).)

Background: Benzodiazepines are the preferred treatment for alcohol withdrawal. Phenobarbital is an alternative in the setting of prescriber expertise or benzodiazepine contraindication., Objective: To evaluate the efficacy and safety of a phenobarbital dosing strategy aimed at treating a spectrum of alcohol withdrawal symptoms across various patient populations., Methods: Retrospective review of patients admitted with concerns of alcohol withdrawal between May 2018 and November 2022. Patients were separated into a before-after cohort of lorazepam or phenobarbital. The primary outcome was hospital length of stay (LOS). Secondary outcomes were intensive care unit (ICU) LOS, escalation of respiratory support, increased level of care (LOC), and incidence of delirium tremens and/or seizures., Results: Two hundred and seventy-seven patients received lorazepam and 198 received phenobarbital. Hospital LOS was longer in the phenobarbital cohort compared with the lorazepam cohort (6.9 vs 9.3 days). There was no difference in ICU LOS. Level of care increases were fewer in the phenobarbital cohort (4 events vs 19 events). There were higher rates of non-invasive respiratory interventions in the lorazepam cohort and higher rates of mechanical ventilation in the phenobarbital cohort. Utilization of phenobarbital was attributed to a reduction in delirium tremens and seizures., Conclusion and Relevance: This study is novel because of the broad application of a phenobarbital order set across multiple levels of care and patient admission diagnoses. A risk targeted split load intravenous phenobarbital order set can safely be administered to patients with fewer escalations of care, seizures, delirium tremens, and respiratory care escalation., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: The aim of the study is to describe prepubescent catatonia in very young children, which is poorly documented in the current literature and, as a result, overlooked in medical settings., Methods: We examined a convenience sample of 10 patients at an academic center who were younger than 12 years and met criteria for catatonia. After institutional review board approval, we extracted from the electronic medical records demographic and diagnostic information, comorbidity, developmental history, and laboratory testing. Bush Francis Catatonia Rating Scales at initial presentation and other symptomatology were gathered in addition to treatment received. Fifty percent of patients in this group were seen and diagnosed with catatonia at their presentation in an outpatient clinic, whereas the remaining 50% were diagnosed upon hospitalization, by the psychiatry consultation liaison team., Results: All patients but one was diagnosed with a comorbid condition before the diagnosis of catatonia, including 70% with a previous diagnosis of autism spectrum disorder. Three patients had concurrent anti-N-methyl-D-aspartate receptor encephalitis, and one initially presented with seizures. All patients were treated for catatonia with lorazepam, and two patients additionally received electroconvulsive therapy. Regardless of the presence of early regression invariably associated with an autism spectrum diagnosis, secondary symptoms of regression were noted in each case at the time of diagnosing catatonia., Conclusions: Similar to previous observations in adolescents, prepubescent catatonia seems strongly associated with neurodevelopmental disorders, secondary regression, variability in presentation, and comorbidity with other neurological conditions. Delayed recognition of catatonia can hinder rapid and effective treatment in young children., Competing Interests: The authors have no conflicts of interest or financial disclosures to report., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Catatonia is a neuropsychiatric disorder associated with changes in behavior and affect. In adults, catatonia can respond rapidly to treatment with benzodiazepines as part of the "lorazepam challenge test." The acute effectiveness of benzodiazepine treatment in pediatric catatonia, however, has received less study. This study reports catatonia severity as measured by the Bush Francis Catatonia Rating Scale (BFCRS) in pediatric patients before and after treatment with lorazepam., Methods: Multicenter retrospective cohort study from 1/1/2018 to 6/1/2023 of patients aged 18 and younger with a clinical diagnosis of catatonia and assessment using the BFCRS before and after treatment with lorazepam., Results: Among 54 patients, median age was 16, and 26 (48.1 %) were female. Neurodevelopmental disabilities were present in 24 (44.4 %) of patients. Prior to treatment, patients had a mean BFCRS score of 16.6 ± 6.1, which significantly reduced to 9.5 ± 5.3 following treatment with lorazepam (mean paired difference 7.1; t = 9.0, df = 53, p < 0.001), representing a large effect size (Hedges's g = 1.20; 95 % CI: 0.85 to 1.55). No significant association was found between lorazepam dose or route of administration and clinical response, nor were age, sex, study site, the presence of a neurodevelopmental disorder, the presence of hyperactive catatonic features, or the time between treatment and reassessment associated with post-treatment BFCRS., Conclusions: Lorazepam resulted in a rapid improvement in BFCRS score in pediatric patients, with a large effect size. Further research is needed into optimal dosing and route of administration of the lorazepam challenge test in pediatric patients., Competing Interests: Declaration of competing interest JL receives funding from Harvard Medical School Dupont Warren Fellowship and Livingston Awards, the Rappaport Foundation, and the Foundation for Prader-Willi Research. He has received equity and consulting fees from Revival Therapeutics, Inc. THM receives funding from the National Institute of Mental Health, National Human Genome Research Institute Home, Telefonica Alfa, and Springer Nature. GF has received equity from Revival Therapeutics and fees from intellectual property licensed to Adya Health. JRS receives funding from Roche, Axial Therapeutics, and the National Institute of Child and Human Development. TY, IB and CF declaration of interest: none., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: It is unclear how the evidence from clinical trials best translates into complex clinical settings. The aim of this quality improvement (QI) project was to change prescribing practice for rapid tranquillization in inpatient mental health care services examining the effectiveness of the Plan-Do-Study-Act (PDSA) method., Methods: A prospective QI project was conducted to ensure that intramuscular (IM) diazepam was substituted with IM lorazepam for benzodiazepine rapid tranquillization in inpatient mental health care. We monitored the prescription and administration of medication for rapid tranquillization before (N = 371), during (N = 1130) and after (N = 364) the QI intervention. Seven iterative PDSA cycles with a multiple-component intervention approach were conducted to gradually turn the prescribing practice in the desired direction. Simultaneously, a standard monitoring regimen was introduced to ensure patient safety., Results: Lorazepam administrations gradually replaced diazepam during the intervention period which was sustained post-intervention where lorazepam comprised 96% of benzodiazepine administrations for rapid tranquillization. The mean dose of benzodiazepine administered remained stable from pre (14.40 mg diazepam equivalents) to post (14.61 mg) intervention phase. Close to full compliance (> 80%) with vital signs monitoring was achieved by the end of the observation period., Conclusion: It was possible to increase the quality of treatment of acute agitation in a large inpatient mental health care setting using a stepwise approach based on iterative PDSA cycles and continuous data feedback. This approach might be valuable in other prescribing practice scenarios with feedback from local stakeholders and opinion leaders., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

This review aimed to examine the place of benzodiazepines, specifically lormetazepam, in the treatment of insomnia, including during pregnancy or in patients with psychodermatoses. PubMed was searched for the term "lormetazepam" in association with MeSH terms encompassing anxiety, insomnia/sleep disorders, pregnancy/gestation, and psychodermatoses/skin disorders. English-language articles up to 31 July 2022 were identified. Ad hoc searches for relevant literature were performed at later stages of review development. Multiple randomized, placebo-controlled studies have demonstrated that lormetazepam dose-dependently increases total sleep time, decreases wakefulness over a dosing range of 0.5-2.0 mg, and improves subjective assessments of sleep quality. Lormetazepam is as effective as other benzodiazepines in improving sleep duration and quality, but is better tolerated than the long-acting agents with minimal next-day effects. Benzodiazepines can be used as short-term monotherapy at the lowest effective dose during the second or third trimesters of pregnancy; lormetazepam is also a reasonable choice due to its limited transplacental passage. Insomnia associated with skin disorders or pregnancy can be managed by effective symptom control (especially itching), sleep hygiene, treatment of anxiety/depression, and a short course of hypnotics., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Catatonia is a rare neuropsychiatric condition; it is estimated that around 10% of patients with mood disorders present signs and symptoms of catatonia. A catatonic syndrome is characterised by mutism, negativism, rigidity, and stupor., Case Report: We report the case of a 59-year-old patient with a medical history of bipolar disorder who was admitted to the internal medicine service due to a seizure episode. During hospitalisation, the patient presented significant worsening of her clinical condition, showing marked symptoms of stupor and catatonia. Once the neurological and metabolic etiologies of altered mental status had been ruled out, pharmacological treatment with high doses of lorazepam was started. The patient had a complete clinical remission, and her evolution was favourable without any complications. Electroconvulsive therapy was recommended as a definitive treatment., Conclusions: The diagnosis of catatonia is a challenge for both hospitalists and psychiatrists due to the clinical presentation of catatonia. In reporting this clinical case, we want to emphasise the importance of taking into account the catatonic syndrome in our differential diagnoses in patients with altered mental status., (Copyright © 2022 Asociación Colombiana de Psiquiatría. Published by Elsevier España, S.L.U. All rights reserved.)

Symptoms of catatonia include silence, motionlessness, and postural retention. Although it is important to detect and treat catatonia early, before it becomes severe, postoperative cases have inherent risks that hinder diagnosis and treatment. A 60-year-old man with schizophrenia underwent endoscopic/thoracoscopic esophagectomy and was extubated in the operating room. In the intensive care unit (ICU), he had stiffness in the neck, ankles, and knees, catalepsy during passive knee flexion, mild disturbance of consciousness, mild creatine kinase elevation, and respiratory depression. Intravenous diazepam was administered for diagnosis, and the patient's rapid improvement indicated catatonia. He was intubated and started on lorazepam; tapering produced no recurrence of symptoms. The patient was extubated and transferred to the general ward on postoperative Day 2. Because this patient was extubated in the operating room and was managed postoperatively in the ICU with a full-time doctor, his symptoms were easily recognized and early diagnosis was possible. Thus, we were able to administer drug therapy quickly and adequately and perform forward management that accounted for postoperative risks, thereby achieving a favorable outcome.

Given the rising frequency of drug shortages in hospitals, interdisciplinary collaboration is necessary to manage medications, modify electronic medical records, and evaluate safety outcomes. One such shortage impacted lorazepam injection, a medication commonly used in palliative care to treat anxiety, agitation, and seizures. In anticipation of the lorazepam shortage in the summer of 2022, pharmacy staff collaborated with palliative care physicians to identify alternative treatment recommendations when providers were prohibited from ordering lorazepam injection. Before the shortage, lorazepam was used an average of 95 times per month on the palliative care unit. The overall use of benzodiazepines decreased substantially following the recommendation for the therapeutic alternative, midazolam, during the shortage. Once the shortage ended, use roughly returned to pre-shortage baselines. During this time, there were no patient safety events documented on the palliative care unit. Moreover, no changes to the care experience were reported by patients, family/caregivers, providers, or staff. The collaborative effort between pharmacy and palliative care specialists resulted in alternative treatments for palliative care patients during the drug shortage. This preserved the hospital's supply of lorazepam injection for a patient population with no suitable alternatives while still allowing for management of palliative patients.

Cannabinoid hyperemesis syndrome (CHS), an under-recognized and seemingly paradoxical condition, arises in some adolescents and adults who chronically use cannabis. It presents acutely with intractable nausea, vomiting, and abdominal pain but standard antiemetic therapy leads to improvement for only a minority of patients. Randomized controlled trial evidence in adults indicates the superiority of haloperidol over ondansetron in alleviating the acute symptoms of CHS, but safe and effective treatment for adolescents with the disorder is currently unknown. The successful use of topical capsaicin has also been reported. We report a case series of 6 adolescent patients with CHS who presented to Johns Hopkins All Children's Hospital and were treated with haloperidol, lorazepam, and/or capsaicin. Four patients given 5 mg intravenous (IV) haloperidol and 2 mg IV lorazepam and 1 patient treated with 5 mg IV haloperidol and peri-umbilical topical capsaicin (0.025%) experienced full acute symptomatic relief. One patient, treated only with topical capsaicin, reported improvement of symptoms with some persistent nausea. Haloperidol/lorazepam, haloperidol/capsaicin, and topical capsaicin alone appear safe and effective in adolescents, but larger studies are required to confirm our findings., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Status epilepticus (SE) is a neurological emergency associated with high mortality if not identified and treated promptly. For the emergent treatment of SE, the recommended intravenous (IV) lorazepam dose is 0.1 mg/kg/dose, up to a maximum of 4 mg. It has been shown that lorazepam is commonly under dosed in SE, but there is conflicting data on whether this has a negative impact on patient outcomes. This study assessed any dose less than 4 mg to help identify the effects of under dosing lorazepam in SE., Methods: This was a retrospective cohort study of patients admitted to a quaternary health system between October 1, 2017 and September 30, 2019 that experienced SE and were initially treated with IV lorazepam. Patients were divided into two cohorts, less than 4 mg or 4 mg, based on the initial one-time dose of lorazepam received. The primary outcome was the proportion of patients that progressed to refractory status epilepticus (RSE) that received an initial IV lorazepam dose of 4 mg compared to less than 4 mg for the treatment of SE. Secondary outcomes evaluated include length of stay, mortality, time in SE, number of seizures, cumulative lorazepam dose prior to urgent therapy, number of lorazepam doses prior to urgent therapy, time to urgent therapy, appropriately dosed urgent therapy, and number of antiepileptic drugs given in SE., Results: One hundred twenty patients were included in this study (107 patients received less than 4 mg and 13 patients received 4 mg). All patients included in the study were greater than 40 kg. The primary outcome of progression to RSE was observed in a significantly greater proportion of patients in the less than 4 mg group compared to the 4 mg group (93 [87%] vs. 8 [62%], p = 0.03). There was no difference in hospital or intensive care unit length of stay. However, there was an increased rate of in-hospital mortality in patients who received 4 mg compared to less than 4 mg (5 [39%] vs. 12[11%], p = 0.02)., Discussion: The majority of patients in the study received less than the recommended dose of IV lorazepam for SE. Patients who received less than 4 mg experienced an increased progression to RSE, which supports current guideline recommended dosing. While there was an increased rate of mortality in patients who received 4 mg compared to less than 4 mg, time in SE was prolonged in the patient population and severity of illness was only available for a limited number of patients included., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Despite frequent benzodiazepine use in anxiety disorders, the trajectory and magnitude of benzodiazepine response and the effects of benzodiazepine potency, lipophilicity, and dose on improvement are unknown., Methods: We performed a meta-analysis using weekly symptom severity data from randomized, parallel group, placebo-controlled trials of benzodiazepines in adults with anxiety disorders. Response was modeled for the standardized change in continuous measures of anxiety using a Bayesian hierarchical model. Change in anxiety was evaluated as a function of medication, disorder, time, potency, lipophilicity, and standardized dose and compared among benzodiazepines., Results: Data from 65 trials (73 arms, 7 medications, 7110 patients) were included. In the logarithmic model of response, treatment effects emerged within 1 week of beginning treatment (standardized benzodiazepine-placebo difference = -0.235 ± 0.024, CrI: -0.283 to -0.186, P < .001) and placebo response plateaued at week 4. Doses <6 mg per day (lorazepam equivalents) produced faster and larger improvement than higher doses ( P = .039 for low vs medium dose and P = .005 for high vs medium dose) and less lipophilic benzodiazepines (beta = 0.028 ± 0.013, P = .030) produced a greater response over time. Relative to the reference benzodiazepine (lorazepam), clonazepam (beta = -0.217 ± 0.95, P = .021) had a greater trajectory/magnitude of response (other specific benzodiazepines did not statistically differ from lorazepam)., Conclusions: In adults with anxiety disorders, benzodiazepine-related improvement emerges early, and the trajectory and magnitude of improvement is related to dose and lipophilicity. Lower doses and less lipophilic benzodiazepines produce greater improvement.

Treatment of seizure clusters endeavors to prevent additional seizures and avoid progression to conditions such as prolonged seizures and status epilepticus. Rescue therapies are key components of seizure action plans (SAPs) for individuals with seizure clusters. Three rescue therapies are approved in the United States for the treatment of seizure clusters: diazepam rectal gel, midazolam nasal spray, and diazepam nasal spray. Diazepam rectal gel is an effective rescue therapy for seizure clusters, though adults and adolescents may have social reservations regarding its administration. Intranasal delivery of midazolam or diazepam is a promising alternative to rectal administration because these formulations offer easy, socially acceptable administration exhibit a rapid onset, and allow for the possibility of self-administration. Off-label benzodiazepines, such as orally disintegrating lorazepam and intranasal use of an intravenous (IV) formulation of midazolam via nasal atomizer, are less well characterized regarding bioavailability and tolerability compared with approved agents., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Convulsive status epilepticus is the most severe form of epilepsy and requires urgent treatment. We synthesised the current evidence on first-line treatments for controlling seizures in adults with convulsive status epilepticus before, or at, arrival at hospital., Methods: We conducted a systematic review of randomised controlled trials (RCTs) assessing antiepileptic drugs offered to adults as first-line treatments. Major electronic databases were searched., Results: Four RCTs (1234 adults) were included. None were conducted in the UK and none assessed the use of buccal or intranasal midazolam. Both intravenous lorazepam and intravenous diazepam administered by paramedics were more effective than placebo and, notably, intramuscular midazolam was non-inferior to intravenous lorazepam. Overall, median time to seizure cessation from drug administration varied from 2 to 15 min. Rates of respiratory depression among participants receiving active treatments ranged from 6.4 to 10.6%. Mortality ranged from 2 to 7.6% in active treatment groups and 6.2 to 15.5% in control groups., Conclusions: Intravenous and intramuscular benzodiazepines are safe and effective in this clinical context. Further research is needed to establish the most clinically and cost-effective first-line treatment and preferable mode of administration. Head-to-head trials comparing buccal versus intranasal midazolam versus rectal diazepam would provide useful information to inform the management of the first stage of convulsive status epilepticus in adults, especially when intravenous or intramuscular access is not feasible. Approaches to improve adherence to clinical guidelines on the use of currently available benzodiazepines for the first-line treatment of convulsive status epilepticus should also be considered., (© 2022. The Author(s).)

Study Objectives: The objective of this study was to compare the combination of intramuscular (IM) droperidol/midazolam to haloperidol/lorazepam regarding time to sedation in patients with acute undifferentiated agitation in the emergency department (ED)., Methods: This was a prospective, unblinded observational study in the ED of a university teaching hospital. Subjects with acute undifferentiated agitation refractory to verbal de-escalation were assigned to receive a combination of either haloperidol 5 mg/lorazepam 2 mg or droperidol 5 mg/midazolam 5 mg IM. The primary outcome was the proportion of patients adequately sedated at 10 min defined as ED Sedation Assessment Tool (SAT) score of 0 or less. Secondary outcomes included change in ED SAT score at 5, 15, 30, and 60 min, the need for oxygen supplementation, and the need for airway intervention., Results: A total of 86 patients were enrolled in the study, with 43 patients receiving droperidol/midazolam and 43 patients receiving haloperidol/lorazepam. Ten minutes after receiving medication, 51.2% of patients in the droperidol/midazolam group were adequately sedated compared to 7% of patients in the haloperidol/lorazepam group (OR: 14; 95% CI: 3.7, 52.1). Median time to adequate sedation was 10 min for the droperidol/midazolam group and 30 min for the haloperidol/lorazepam group. Eleven patients (25.6%) in the droperidol/midazolam group received oxygen supplementation compared to four patients (9.3%) in the haloperidol/lorazepam group. No study patients experienced extrapyramidal symptoms or required endotracheal intubation., Conclusion: Intramuscular droperidol/midazolam was superior to intramuscular haloperidol/lorazepam in achieving adequate sedation at 10 min. Patients in the droperidol/midazolam arm may be more likely to receive oxygen supplementation than those in the haloperidol/lorazepam arm., Competing Interests: Declaration of Competing Interest No conflicts of interest to report., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: The acute seizure in childhood is a medical emergency which is usually managed by benzodiazepines used as a first line of therapy. There are no strict guidelines of using intranasal lorazepam in India. Many paediatricians use it in an emergency situation as it is inexpensive, easy to administer and even treatment can be started at home. Very few studies are available to compare efficacy and safety of intravenous lorazepam with intranasal lorazepam in childhood seizure, though both routes have comparable pharmacokinetic profile. Intravenous lorazepam (0.1 mg/kg) is already recommended as a first-line treatment of acute childhood seizures in India. There are very few studies regarding the usefulness of intranasal lorazepam. With this background, we compared intranasal lorazepam with the more widely accepted intravenous lorazepam for control of acute seizure., Aim: To compare effectiveness and safety of intranasal and intravenous lorazepam in acute seizure in children aged 5-12 years., Materials and Methods: This is an analytical observational cross-sectional study involving patients with acute seizure who received lorazepam via either the intravenous or intranasal route. Formulation and dosage of lorazepam were the same in both routes., Results: Distributions of patient groups according to sex, age, and weight were statistically not significant (p=0.42, p=0.391, and p=0.605, respectively). Time to control seizure within 10 min and persistent cessation of seizure activity were similar in both groups. Safety parameters showed no differences statistically., Conclusions: Though intravenous lorazepam is recommended as first-line treatment, intranasal lorazepam may be a good alternative choice in a convulsing child., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Polypharmacy is common among patients taking prescription opioids long-term, and the codispensing of interacting medications may further increase opioid overdose risk. To identify nonopioid medications that may increase opioid overdose risk in this population, we conducted a case-crossover-based screening of electronic claims data from IBM MarketScan and Optum Clinformatics Data Mart spanning 2003 through 2019. Eligible patients were 18 years of age or older and had at least 180 days of continuous enrollment and 90 days of prescription opioid use immediately before an opioid overdose resulting in an emergency room visit or hospitalization. The main analysis quantified the odds ratio (OR) between opioid overdose and each nonopioid medication dispensed in the 90 days immediately before the opioid overdose date after adjustment for prescription opioid dosage and benzodiazepine codispensing. Additional analyses restricted to patients without cancer diagnoses and individuals who used only oxycodone for 90 days immediately before the opioid overdose date. The false discovery rate (FDR) was used to account for multiple testing. We identified 24,866 individuals who experienced opioid overdose. Baclofen (OR 1.56; FDR < 0.01; 95% confidence interval (CI), 1.29 to 1.89), lorazepam (OR 1.53; FDR < 0.01; 95% CI, 1.25 to 1.88), and gabapentin (OR 1.16; FDR = 0.09; 95% CI, 1.04 to 1.28), among other nonopioid medications, were associated with opioid overdose. Similar patterns were observed in noncancer patients and individuals who used only oxycodone. Interventions may focus on prescribing safer alternatives when a potential for interaction exists., (© 2021 The Authors. Clinical Pharmacology & Therapeutics © 2021 American Society for Clinical Pharmacology and Therapeutics.)

Background: Toxicity from antimuscarinic agents precipitates a constellation of signs and symptoms; two of the most significant are agitation and delirium. Benzodiazepines are commonly used for treatment; physostigmine is also effective but is underutilized due to concerns for safety and short duration of action. The objective of this study was to compare lorazepam to physostigmine for the treatment of antimuscarinic delirium and agitation., Methods: This was a blinded, randomized clinical trial in patients presenting for antimuscarinic toxidrome. Inclusion criteria were: ≥10-<18 years old, at least one central and two peripheral antimuscarinic symptoms, delirium and moderate agitation. Subjects were randomized to either (1) lorazepam bolus (0.05 mg/kg) followed by a 4-h normal saline infusion, or (2) physostigmine 0.02 mg/kg bolus followed by a 4-h physostigmine infusion (0.02 mg/kg/h). Primary outcomes were the control of delirium and agitation after bolus and during the infusion., Results: Ten (53%) subjects were enrolled in the lorazepam arm, 9 (47%) in the physostigmine arm. Diphenhydramine was the most common agent ingested (16, 84%). Fewer patients receiving physostigmine had delirium after the initial bolus (44% vs 100%, p  = 0.01) and at the 4th hour of infusion (22% vs 100%, p  < 0.001) compared to patients who received lorazepam. There was a significant decrease in agitation scores in the physostigmine arm compared to the lorazepam arm after the initial bolus (89% vs 30%, p  = 0.02), but no difference at the 4th hour of infusion ( p  > 0.99). There were no seizures, bradycardia, bronchorrhea, bronchospasm, intubation, or cardiac dysrhythmias., Conclusion: Physostigmine was superior to lorazepam in controlling antimuscarinic delirium and agitation after bolus dosing, and control of delirium after a 4-h infusion. There were no serious adverse events in either treatment arm. Physostigmine bolus and infusion should be considered in adolescent patients with significant delirium and agitation from antimuscarinic agents.

Background: Front-loaded diazepam is used to rapidly control agitation in patients with severe alcohol withdrawal syndrome (AWS). Our institution began using front-loaded lorazepam in August 2017 secondary to a nation-wide shortage of intravenous (IV) diazepam. Currently, there are no studies comparing lorazepam to diazepam for frontloading in severe AWS., Method: Retrospective cohort study of all adults presenting to the emergency department with a diagnosis of AWS and prescribed the institution's alcohol withdrawal agitated delirium protocol 8 months pre and post shortage of IV diazepam were eligible inclusion for the study. Of these, 106 patients were front-loaded with diazepam and 70 patients were front-loaded with lorazepam., Results: There was no difference in the mean change in Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised scores 24 h pre and post front-loading in the two groups (-13.9 ± -8.08 vs. -13.1 ± -8.91, p = 0.534). Patients who received front-loaded lorazepam had an increased incidence of ICU-delirium (positive for the Confusion Assessment Method in the ICU: 75% with lorazepam vs. 52.6% with diazepam, p = 0.009) and a higher risk of over-sedation, but this did not reach statistical significance (Richmond Agitation-Sedation Scale score < -1: 32.1% with lorazepam vs. 18.2% with diazepam, p = 0.063)., Conclusion: Front-loaded lorazepam was similar to front-loaded diazepam in controlling AWS symptoms. Lorazepam's delayed onset of action should be considered when determining how quickly repeat doses are administered to avoid the potential for adverse drug events., Competing Interests: Declaration of competing interest None., (Copyright © 2020. Published by Elsevier Inc.)

Objective: We aimed to examine the impact of resumption of home antiseizure drugs alone (ASD-) compared with adjunct administration of scheduled intravenous (IV) lorazepam 2 mg every 6 h (ASD+) following ictal single-photon emission computed tomography (SPECT) injection on the localization value of SPECT studies and treatment-emergent adverse events (TEAEs)., Methods: We conducted a prospective study at Mayo Clinic inpatient epilepsy monitoring unit (EMU) between January 2018 and May 2020 in Jacksonville, Florida. The ASD- and ASD+ groups were compared for concordance of SPECT studies with the epilepsy surgical conference (ESC) consensus or intracranial electroencephalography (icEEG) findings as reference. Treatment-emergent adverse events, obtained from surveys at 24 h and one week postictal SPECT injection, were also compared between both groups., Results: Twenty-two consecutive patients with temporal (eight patients, 36%) and extratemporal (14 patients, 64%) epilepsy were included: 12 ASD+ and 10 ASD-. The two groups were well matched with regard to clinical and ictal SPECT injection characteristics including the occurrence of seizure between ictal and interictal SPECT injections. The localization value of SPECT studies was similar in the two groups. Patients in the ASD+ group reported higher rates of dizziness and excessive sedation at 24 h (p-value = 0.008). Fourteen patients (64%) underwent icEEG monitoring. For the entire cohort, the localization concordance of SPECT analysis by statistical parametric mapping (SPM) was superior to raw ictal SPECT (p-value = 0.003) and subtraction ictal SPECT coregistered to magnetic resonance imaging (MRI) (SISCOM; p-value = 0.021). Eventually, seven patients (31.8%) underwent resective brain surgery of whom four (57.1%) became seizure-free (median follow-up = 22 months)., Conclusions: Our findings suggest that resuming home ASDs without the addition of scheduled IV lorazepam following inpatient ictal SPECT injection is equally efficacious for seizure onset zone (SOZ) localization on SPECT studies, especially SPM. This approach is also associated with fewer transient TEAEs and lower financial cost with no difference in preventing seizure between ictal and interictal SPECT injections., Competing Interests: Declaration of competing interest None to declare., (Published by Elsevier Inc.)

Background/objectives: Repetitive transcranial magnetic stimulation (rTMS) has been established as an effective therapeutic intervention for the treatment of depression. Preliminary data suggest that the efficacy of rTMS is reduced in patients taking benzodiazepines (BZD). Here, we use real-world data from a large sample to investigate the influence of lorazepam on the effectiveness of rTMS., Methods: From a retrospective cohort of clinically depressed patients that were treated with rTMS, we compared 176 patients not taking any BZD with 73 patients taking lorazepam with respect to changes in the Hamilton Depression Rating Scale (HRDS)., Results: Both groups improved during rTMS according to HRDS scores, but the amelioration of symptoms was significantly less pronounced in patients taking lorazepam (18% vs. 38% responders in the non-lorazepam group). We could not see any association of intake regimen of lorazepam with response in rTMS., Conclusion: Our observational study suggests that intake of lorazepam impedes the response to rTMS. The impact of lorazepam and other BZD on rTMS should receive more attention and be further investigated in prospective, hypothesis-based treatment studies to determine causal relationships between medication treatments and outcome. This could lead to specific recommendations for pharmacological treatment for depressed patients undergoing rTMS.

Commercially available Kratom ( Mitragyna speciosa ) is a dietary supplement that has gained popularity in the United States for its psychoactive effects and potential medicative properties as an opioid receptor agonist. Likewise, sudden discontinuation may be accompanied by an opioid-like withdrawal. We present the first case in the literature of the withdrawal manifesting in disturbing obsessive thoughts after the substance was used as an opioid replacement treatment by our patient, as well as the first case where lorazepam is utilized for mitigation of these thoughts.

Study Objective: Alcohol withdrawal is a common emergency department (ED) presentation. Although benzodiazepines reduce symptoms of withdrawal, there is little ED-based evidence to assist clinicians in selecting appropriate pharmacotherapy. We compare lorazepam with diazepam for the management of alcohol withdrawal to assess 1-week ED and hospital-related outcomes., Methods: From January 1, 2015, to December 31, 2018, at 3 urban EDs in Vancouver, Canada, we studied patients with a discharge diagnosis of alcohol withdrawal. We excluded individuals presenting with a seizure or an acute concurrent illness. We performed a structured chart review to ascertain demographics, ED treatments, and outcomes. Patients were stratified according to initial management with lorazepam versus diazepam. The primary outcome was hospital admission, and secondary outcomes included in-ED seizures and 1-week return visits for discharged patients., Results: Of 1,055 patients who presented with acute alcohol withdrawal, 898 were treated with benzodiazepines. Median age was 47 years (interquartile range 37 to 56 years) and 73% were men. Baseline characteristics were similar in the 2 groups. Overall, 69 of 394 patients (17.5%) receiving lorazepam were admitted to the hospital compared with 94 of 504 patients receiving diazepam (18.7%), a difference of 1.2% (95% confidence interval -4.2% to 6.3%). Seven patients (0.7%; 95% confidence interval 0.3% to 1.4%) had an in-ED seizure, but all seizures occurred before receipt of benzodiazepines. Among patients discharged home, 1-week return visits occurred for 78 of 325 (24.0%) who received lorazepam and 94 of 410 (23.2%) who received diazepam, a difference of 0.8% (95% confidence interval -5.3% to 7.1%)., Conclusion: In our sample of ED patients with acute alcohol withdrawal, patients receiving lorazepam had an admission rate similar to that of those receiving diazepam. The few in-ED seizures occurred before medication administration. For discharged patients, the 1-week ED return visit rate of nearly 25% could warrant enhanced follow-up and community support., (Copyright © 2020 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Introduction: Guidelines specify early administration of benzodiazepines (BZD) for the management of convulsive status epilepticus. The distinction between acute convulsive seizure and status epilepticus can be misconstrued resulting in BZD administration prior to a patient meeting criteria of status epilepticus. Early BZD administration may theoretically lead to systemic vital instability. Our study aims to assess if administering lorazepam, for convulsive seizures <5 min, causes vital instability., Methods: This is a retrospective study analyzing patients who presented with a seizure lasting <5 min between 2011 and 2016. Continuous variables of lorazepam receivers versus non- receivers were analyzed using t-test for parametric and Mann-Whitney U test for nonparametric data. Categorical variables were analyzed using Chi-Square Test. Subsequently, subjects were analyzed through univariate and multivariate regression models to determine predictors of vital instability., Results: Out of 1052 subjects initially screened, 165 were included. Of these, 91 (55 %) received lorazepam, and 74 (45 %) did not. Through univariate and multivariate analyses, there was a significantly higher incidence of vital instability (defined as receipt of a vasopressor or intubation) in patients who received lorazepam (OR = 6.76, 95 % CI = 1.48, 30.95) (p = 0.014). This was dose-dependent (p < 0.0001). It was responsible for 22.5 % of the vital instability. Lorazepam administration significantly prolonged the intensive care unit (ICU) length of stay (0 days [IQR 0 - 0] vs [IQR 0-2.3]; p = 0.038)., Conclusion: Our study suggests that lorazepam administration for acute convulsive seizures not meeting convulsive status epilepticus criteria may lead to iatrogenic vital instability and need for ICU admission., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Functional neurological symptom disorder presents with varied neurological signs often as a result of stress. It is usually treated with supportive psychotherapy and occasionally antidepressants. Literature regarding treatment for resistant cases is scarce. We describe on such presentation., Case Presentation: A 40-year-old man who presented with a history of sudden onset dysphonia for 5 days. There were no immediate stressors. Physical examination revealed that he was unable to make movements of the tongue while speaking although power and range of movement were normal. Magnetic resonance imaging and computed tomography of brain and endoscopic examination of oral cavity and larynx did not reveal any organic cause. Functional magnetic resonance imaging imaging was conducted under a language protocol to determine neurophysiological circuits involved in this unique presentation. The patient failed conventional pharmacotherapy and supportive psychotherapy. Thereafter, he underwent lorazepam-assisted interviews where he would be asked to made purposive movements of the tongue and attempt to pronounce basic phonemes. He would converse normally during the lorazepam interviews and made gradual improvements after each session. The patient was able speak clearly after 12 such sessions and continues to maintain well since., Conclusions: We describe a resistant case of functional dysphonia. The patient presented without any stressor and failed conventional treatments. The case demonstrates that Lorazepam can be used effectively in drug-assisted interviews for functional dysphonia. It also provides information regarding functional activity of the brain during a dissociative state., (Copyright © 2019 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Catatonia was first described by Karl Ludwig Kahlbaum in 1874, occurring in association with other psychiatric and medical disorders. However, in the nineteenth century the disorder was incorrectly classified as a subtype of schizophrenia. This misclassification persisted until the publication of DSM-5 in 2013 when important changes were incorporated. Although the etiology is unknown, disrupted gamma-aminobutyric acid has been proposed as the underlying pathophysiological mechanism. Key symptoms can be identified under 3 clinical domains: motor, speech, and behavioral. Benzodiazepines and electroconvulsive therapy are the only known effective treatments. Timely recognition and treatment have important outcome, and sometimes lifesaving, implications., Competing Interests: Disclosure N. Ghaziuddin: Royalties from book, Use of Electroconvulsive Therapy in Children and Adolescents. Publisher: Oxford University Press, 2013. M. Ghaziuddin and L. Andersen do not have any disclosures., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The objective of this study was to develop an in-situ gel containing lorazepam (LZM) loaded nanostructured lipid carriers (NLCs) for direct nose-to-brain delivery in order to increase drug therapeutic efficacy in the treatment of epilepsy. Accordingly, LZM loaded NLCs were formulated using emulsification solvent diffusion and evaporation method; then the effects of the formulation variables on different physicochemical characteristics of NLCs were investigated. Thermosensitive in-situ gels containing LZM-NLCs were prepared using a combination of chitosan and β-glycerol phosphate (β-GP). The anticonvulsant efficacy of LZM-NLCs-Gel was then examined using the pentylenetetrazole (PTZ) model. The optimised NLCs were spherical, showing the particle size of 71.70 ± 5.16 nm and the zeta potential of -20.06 ± 2.70 mV. The pH and gelation time for the chitosan solution with 15% (w/v) β-GP were determined to be 7.12 ± 0.03 and 5.33 ± 0.58 min, respectively. The in-vivo findings showed that compared with the control group and the group that received LZM-Gel, the occurrence of PTZ-induced seizures in the rats was significantly reduced by LZM-NLCs-Gel after intranasal administration. These results, therefore, suggested that the LZM-NLCs-Gel system could have potential applications for brain targeting through nasal route and might increase LZM therapeutic efficacy in the treatment of epilepsy.

Children and adults with Down syndrome may experience unexplained neurodevelopmental regression leading to considerable diagnostic uncertainty as well as morbidity. In this study we describe a series of seven children with Down syndrome presenting with developmental regression, some of whom had lengthy periods of symptomatology and investigation prior to a final diagnosis of catatonia. While catatonia typically presents with immobility, mutism and posturing, these symptoms can often be overlooked if not recognised as catatonic phenomena. Treatment with lorazepam led to improvement in symptoms in all, eventually reversing the catatonia in some children to previous baseline function. Autistic traits were present upon retrospective analysis, a potentially under recognised co-morbidity. It is essential to recognise catatonia in children with Down syndrome, as this is an under-recognised, treatable cause of developmental regression., Competing Interests: Declaration of competing interest The other authors have no conflicts of interest to disclose., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: The purpose of this study was to evaluate the safety and efficacy of a single parenteral dose of phenobarbital in addition to symptom-triggered lorazepam for the acute management of alcohol withdrawal syndrome (AWS)., Methods: This was a retrospective chart review of adult patients who presented to the Emergency Department with moderate or severe symptoms of alcohol withdrawal. Patients were included if they received at least 4 mg of lorazepam through the hospital's Alcohol Withdrawal Order Set on hospital day one. Patients who received a single parenteral dose of phenobarbital on hospital day one were compared to those who did not., Results: Forty patients received phenobarbital and 38 patients received lorazepam only. Median daily lorazepam requirements, disposition, hospital length of stay, and median maximum daily CIWA-Ar scores were not statistically significant different between the groups. Significantly more patients in the phenobarbital group were discharged within three days in comparison to the lorazepam only group (9 patients vs. 2 patients, respectively, p < 0.05). In the lorazepam only group, two patients were intubated, one patient had delirium tremens, and no patients seized. In the phenobarbital group no adverse events were observed., Conclusions: More patients were discharged within three days if they received a single parenteral dose of phenobarbital on hospital day one, in addition to symptom-triggered lorazepam for the acute management of AWS. Emergency Medicine physicians should consider ordering one parenteral phenobarbital dose on hospital day one to patients presenting with AWS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Alcohol withdrawal syndrome (AWS) is a serious complication of abrupt alcohol cessation. Severe AWS can develop into delirium tremens (DT), which is potentially life-threatening. Lorazepam (LOR) and chlordiazepoxide (CDE) are mainstays of therapy for AWS. Current literature lacks studies comparing outcomes between the two drugs for patients who are not in a de-addiction ward specifically for withdrawal treatment. The primary objective of the study was to determine the incidence rate of DT between the groups. Of 2112 patients screened, 142 met inclusion criteria (LOR = 74, CDE = 68). Baseline characteristics were similar between groups. No significant difference in the primary outcome of DT development was observed (7% LOR, 9% CDE; p = 0.76). No significant differences in cumulative doses of scheduled LOR or CDE were observed (LOR 14.6 ± 8 mg, CDE 15.4 ± 12; p = 0.64). However, significant differences were found in the amount of "as needed" (PRN) LOR required for the two groups (LOR 3.2 ± 4 mg, CDE 6.6 ± 13 mg; p = 0.03) and the amount of scheduled plus PRN LOR required (LOR 17.7 ± 10 mg, CDE 21.9 ± 14 mg; p = 0.04). Doses are reported in LOR equivalents. There were no observed differences in duration of treatment (LOR 3.6 ± 1.3 days, CDE 3.9 ± 2.1 days; p = 0.3) or length of stay (LOR 5.28 ± 3.8 days, CDE 4.73 ± 4.2 days p = 0.4). No adverse events related to BZD were noted in either group. Hospital outcomes did not differ between the groups, but patients treated with CDE may require more adjuvant therapy to control symptoms of AWS. Both agents appear equally effective at preventing the development of DT in those patients admitted to general medicine wards., (Copyright © 2019 Elsevier Inc. All rights reserved.)

High-dose benzodiazepine (BZD) abuse is emerging as a substance use disorder (SUD). The aim of the study is to explore the impact of high-dose lormetazepam (LMZ) abuse and the characteristics of patients affected by this SUD in a tertiary referral addiction unit. We have retrospectively evaluated 1112 patients admitted to the Addiction Medicine Unit, Verona University Hospital, Italy for detoxification from high-dose BZD dependence. LMZ was the most common BZD, with an increasing prevalence from January 2003 to June 2018. Socio-demographic (more women; higher age and education) and clinical features (higher daily diazepam dosage equivalent, BZD abuse duration, age of first BZD intake; BZD prescribed more frequently for sleep disorders; less frequent history of other SUDs, previous/active alcohol, previous opioids abuse; more frequent overall major psychiatric diseases and major depression; less-frequent bipolar disorders and other psychoses, personality disorders, and more than one psychiatric disease) of LMZ vs. other BZD abusers significantly differed. 96.7% LMZ abusers took oral solution, while two-thirds of other BZD abusers took tablets. Oral solution, BZD abuse duration and prescription of BZD for sleep disorders increased, while history of other SUDs, previous/active alcohol and active cannabinoids SUD reduced the risk of high-dose LMZ vs. other BZDs abuse. The large prevalence of high-dose LMZ abusers in Italy may be strongly related to the availability and characteristics of oral formulation that may transform the innocuous Dr. Jekyll tablets into an evil Mr. Hyde. Restriction to the market of LMZ oral formulation might reduce the risk of high-dose abuse.

Objectives: The objectives of this study were primarily to assess the efficacy and safety of SM-1 in a circadian challenge model of transient insomnia and secondarily, to assess the contribution of diphenhydramine to the combination., Methods: Randomized, double-blind, placebo-controlled three-way cross-over study with a 5-hr phase advance. Subjects were 39 healthy adults reporting a history of transient insomnia. All treatments (SM-1, SM-1 without diphenhydramine, or placebo) were administered to all subjects in a randomly assigned sequence, with at least 1 week between treatments. The primary endpoint was total sleep time (TST) determined by polysomnography. Secondary endpoints included wakefulness after sleep onset (WASO), latency to persistent sleep, number of awakenings (NAW), subjective TST (sTST) and sleep latency (sSL), TST, and NAW by quarters of the night and sleep quality. Safety endpoints included adverse events, Karolinska Sleepiness Scale digit symbol substitution test, and subject-reported alertness level., Results: SM-1 provided an increase of 126.7 min in TST over placebo (p < .001). WASO, sTST, sleep quality, and sSL also showed significant improvement. Diphenhydramine demonstrated a significant (p = .014) contribution of 43.7 min to TST. SM-1 was well-tolerated with type and frequency of adverse events comparable with placebo, and no residual sleepiness upon awakening after 8 hr., Conclusions: SM-1 provided a robust and statistically significant increase in TST compared with placebo in a circadian model of transient insomnia, without evidence of next-day impairment. Diphenhydramine contributed to the effect., (© 2019 John Wiley & Sons, Ltd.)

Background: Digestive endoscopies must be performed within a safe and comfortable environment. We have previously shown that the quality of intravenous sedation is influenced by preoperative stress., Aim: Our primary objective was to compare the effects of oral lorazepam and placebo on the salivary cortisol response of children undergoing a digestive endoscopy. Secondary objectives were the assessment of procedural pain and comfort as well as the occurrence of adverse events., Methods: Participants were randomized and received either lorazepam, placebo, or no premedication. Saliva was collected upon arrival at the hospital and 1 h following randomization. The sedation protocol included midazolam and fentanyl ± ketamine. Procedural pain was evaluated with the Nurse Assessed Patient Comfort Score (NAPCOMS). Patients completed a postoperative questionnaire. The primary outcome was defined as the proportion of children having a cortisol decrease ≥ 15 nmol/L., Results: 101 participants (54 females) were included. The rate of children having a cortisol decrease ≥ 15 nmol/L was 27.3%, 35.3%, and 19.4% for lorazepam, placebo, and no premedication, respectively (p = 0.356). The median (IQR) NAPCOMS pain score was 3.0 (0-6) for lorazepam, 4.4 (0-6) for placebo, and 3.4 (3-4) for no premedication (p = 0.428). With lorazepam, 75.9% of children reported experiencing a comfortable procedure, compared with 41.9% taking placebo and 34.5% with no premedication (p = 0.013). Transient tachycardia was the most frequent intraoperative adverse event, particularly with lorazepam (62.5%, p = 0.029)., Conclusions: Oral lorazepam had no effect on patients' preoperative stress, as measured by salivary cortisol, but was associated with a higher rate of comfortable procedures., Clinical Trial Registration: Clinicaltrials.gov, Identifier NCT03180632.