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BackgroundDespite 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.MethodsWe 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.ResultsData 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 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).ConclusionsIn 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.

Large nest building behaviour (LNB), as expressed by a subpopulation of laboratory housed deer mice (Peromyscus maniculatus bairdii), is persistent and repetitive. However, the response of LNB to an anxiogenic environment has not yet been investigated. Here, we employed LNB and normal nesting (NNB) expressing mice, subdivided into three drug-exposed groups per cohort, i.e. water (28 days), escitalopram (50 mg/kg/day, 28 days) and lorazepam (2 mg/kg/day; 4 days) to investigate this theme. During the last 4 days of drug exposure, mice were placed inside anxiogenic open field arenas which contained a separate enclosed and dark area for 4 consecutive nights during which open field and/or nest building assessments were performed. We show that LNB behaviour in deer mice is stable, irrespective of the anxiety-related context in which it is assessed, and that LNB mice find an open field arena to be less aversive compared to NNB mice. Escitalopram and lorazepam differentially affected the nesting and open field behaviour of LNB expressing mice, confirming deer mouse LNB as a repetitive behavioural phenotype that is related to a compulsive-like process which is regulated by the serotonergic system.

Background Methamphetamine (M) is a widely used, powerful sympathomimetic drug that produces significant CNS stimulation. Its use is associated with psychiatric disorders, abnormal brain chemistry, and cardiovascular disease. Pre-hospital M use is associated with increased intubation, intensive care unit admission, and hospital length of stay. The purpose of this study was to determine the influence of acute M use on analgesia and sedation requirements in mechanically ventilated trauma patients. Methods This single center retrospective cohort study included injured adult patients (≥16 years) admitted to the trauma intensive care unit (TICU) between 2016 and 2018 who were mechanically ventilated and had a urine drug screen (UDS) completed. The primary outcome was the median sedation and total analgesia administered during the first 48 hours of TICU admission, expressed as propofol, dexmedetomidine, lorazepam, and morphine equivalents. Secondary endpoints included the median Richmond Agitation Sedation Scale (RASS) score, median Critical Pain Observation Tool (CPOT) score, ventilator days, length of stay, in-hospital mortality, and discharge disposition. Results A total of 245 patients were included in the final analysis (53 M+ and 192 M-). The patients were mostly men (78%) and sustained blunt trauma (89%) with a median age of 35 (IQR 26-52) years and median ISS of 11 (IQR 4-24). A M+ UDS was associated with increased morphine requirements, defined as greater than the cohort median of 1.91 mg/kg, during the first 12 hours of admission on the univariable analysis (OR 2.03; 95% CI, 1.07-3.82). There was no difference in median propofol (M+ 30 mcg/kg/min vs. M- 30 mcg/kg/min, p=0.58) or total morphine equivalents (M+ 5.42 mg/kg s. M- 3.89 mg/kg, p=0.30) over 48 hours between M+ and M- groups to achieve similar RASS and CPOT scores. Conclusion To achieve the same level of pain control and depth of sedation, intubated TICU patients with a M+ UDS do not require more analgesia and sedation than patients with a M- UDS during the first 48 hours of admission.

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.

Introduction Phenobarbital has been successfully used in the emergency department (ED) to manage symptoms of alcohol withdrawal, but few studies have reported outcomes for ED patients who receive phenobarbital and are discharged. We compared return encounter rates in discharged ED patients with alcohol withdrawal who were treated with benzodiazepines and phenobarbital. Methods This is a retrospective cohort study conducted at a single academic medical center utilizing chart review of discharged ED patients with alcohol withdrawal from July 1, 2016, to June 30, 2019. Patients were stratified according to ED management with benzodiazepines, phenobarbital, or a combination of both agents. The primary outcome was return ED encounter within three days of the index ED encounter. Multivariate logistic regression identified significant covariates of an ED return encounter. Results Of 470 patients who were discharged with the diagnosis of alcohol withdrawal, 235 were treated with benzodiazepines, 133 with phenobarbital, and 102 with a combination of both. Baseline characteristics were similar among the groups. However, patients who received phenobarbital were provided significantly more lorazepam equivalents compared to patients who received benzodiazepines alone. Treatment with phenobarbital, alone or in combination with benzodiazepines, was associated with significantly lower odds of a return ED visit within three days compared with benzodiazepines alone [AOR 0.45 (95% CI 0.23, 0.88) p = 0.02 and AOR 0.33 (95% CI 0.15, 0.74) p = 0.007]. Conclusions Patients who received phenobarbital for alcohol withdrawal were less likely to return to the ED within three days of the index encounter. Despite similar baseline characteristics, patients who received phenobarbital, with or without benzodiazepines, were provided greater lorazepam equivalents the ED.

In this first cross-sectional MRI study in acute catatonia, we compared the resting state whole-brain, within-network and seed (left precentral gyrus)-to-voxel connectivity, as well as cortical surface complexity between a sample of patients in acute retarded catatonic state (n = 15) diagnosed as per DSM-5 criteria and a demographically matched healthy control sample (n = 15). The patients had comorbid Axis-I psychiatric disorders including schizophrenia spectrum disorders and psychotic mood disorders, but did not have diagnosable neurological disorders. Acute retarded catatonia was characterized by reduced resting state functional connectivity, most robustly within the sensorimotor network; diffuse region of interest (ROI)-ROI hyperconnectivity; and seed-to-voxel hyperconnectivity in the frontoparietal and cerebellar regions. The seed (left precentral gyrus)-to-voxel connectivity was positively correlated to the catatonia motor ratings. The ROI-ROI as well as seed-to-voxel functional hyperconnectivity were noted to be higher in lorazepam responders (n = 9) in comparison to the non-responders (n = 6). The overall Hedges' g effect sizes for these analyses ranged between 0.82 and 3.53, indicating robustness of these results, while the average Dice coefficients from jackknife reliability analyses ranged between 0.6 and 1, indicating fair (inter-regional ROI-ROI connectivity) to perfect (within-sensorimotor network connectivity) reliability of the results. The catatonia sample showed reduced vertex-wise cortical complexity in the right insular cortex and contiguous areas. Thus, we have identified neuroimaging markers of the acute retarded catatonic state that may show an association with treatment response to benzodiazepines. We discuss how these novel findings have important translational implications for understanding the pathophysiology of catatonia as well as for the mechanistic understanding and prediction of treatment response to benzodiazepines.

Medications are available to manage alcohol and drug withdrawal, but they are underutilized. Only a handful, such as methadone, buprenorphine, clonidine, or benzodiazepines (chlordiazepoxide, lorazepam, or diazepam), are prescribed. Our objective was to provide an adjusted, inclusive, critical review of the clinical benefits of medications studied for the management of psychoactive substance withdrawal syndrome. We performed an electronic literature search for randomized controlled trials (RCTs) and systematic reviews of RCTs with or without meta-analysis by free-text searching for pharmacotherapy on drug and alcohol withdrawal in eight databases. Doxepin, citalopram, doxepin, and pregabalin manage dysphoria and anxiety during opioid withdrawal. Gabapentin and atenolol lessen alcohol cravings. Gabapentin improves the sleep difficulties associated with cannabis withdrawal. Melatonin reduces anxiety, irritability, depressed mood, and cravings for nicotine. Doxepin alleviates benzodiazepine withdrawal anxiety and depression. Riluzole reduces amphetamine craving and depression. Modafinil reduces the intensity of cocaine cravings. Controlled trials on caffeine withdrawal were lacking. Buspirone and gabapentin accounted for more than 70% of all the medications studied. No conclusions can be drawn on adverse events because of reporting inconsistencies in the studies reviewed. Substitution therapy seems to be the foremost choice for the treatment of psychoactive substance withdrawal. However, other medications are available but poorly utilized. Practitioners can use the armory of other available medications to manage psychoactive substance withdrawal. Patients can broaden their medication choice. Voltage-gated ion channels are a promising niche to explore.

We present a case of a 14-year-old, previously healthy female, admitted with acute coronavirus disease 2019 infection and new-onset seizures secondary to virus-associated necrotizing disseminated acute leukoencephalopathy. Her symptoms resolved completely with intravenous immunoglobulin and steroids. Pathophysiology and prognosis of neurologic manifestations of coronavirus disease 2019 remain unclear.

The excessive prescription of benzodiazepines is putting more people at risk of dependence on these drugs and is exacerbating the fatal overdose toll of opioids. A rapid and sensitive SERS method has been developed for trace detection of select benzodiazepines in low-dosage suspect counterfeit tablets, capsules, and injectable solutions using two different portable handheld Raman spectrometers equipped with either a 785-nm laser or a 1064-nm laser. A total of 169 samples and blanks were examined using five handheld Raman spectrometers, which provided data set of 729 examinations. The extraction/SERS procedures yielded true positive rates above 90% for alprazolam, diazepam, and midazolam using the 1064-nm device and yielded true positive rates above 95% for alprazolam, clonazepam, diazepam, estazolam, midazolam, and temazepam using the 785-nm device; however, the extraction/SERS procedures yielded true positive rates below 60% for lorazepam and triazolam. The minimum concentration (Cmin ) of the benzodiazepine standards that reproducibly yielded a positive match ranged from 1 to 10 μg/ml using the 1064-nm laser device and from 0.5 to 50 μg/ml using the 785-nm laser device. For the analysis of authentic and suspect counterfeit tablets containing these benzodiazepines, the measured Cmin ranged between 10 and 15 µg per tablet or capsule for 1064-nm laser device and 1-100 µg per tablet or capsule for 785-nm laser device. The developed methods are simple, rapid, and ideal for screening suspect benzodiazepine-containing pharmaceutical products at satellite laboratories located within or near international mail facilities and express courier hubs.

Background: Inhibitory control is a crucial executive function with high relevance to mental and physical well-being. However, there are still unanswered questions regarding its neural mechanisms, including the role of the major inhibitory neurotransmitter, γ-aminobutyric acid (GABA). Aims: This study examined the effects of lorazepam (0.5 mg and 1 mg), a positive allosteric modulator at the GABAA receptor, on response inhibition and interference control. We also explored the heterogeneity of inhibitory control and calculated delta plots to explore whether lorazepam affects the gradual build-up of inhibition and activation over time. Methods: N = 50 healthy participants performed antisaccade, Eriksen flanker and Simon tasks in a within-subjects, placebo-controlled, double-blind randomized design. Results: Lorazepam increased reaction time (RT) and error rates dose dependently in all tasks ( p ⩽ 0.005). In the antisaccade and Simon tasks, lorazepam increased congruency effects for error rate ( p ⩽ 0.029) but not RT ( p ⩾ 0.587). In the Eriksen flanker task, both congruency effects were increased by the drug ( p ⩽ 0.031). Delta plots did not reflect drug-induced changes in inhibition and activation over time. Delta plots for RT in the Simon task were negative-going, as expected, whereas those for the antisaccade and flanker tasks were positive-going. Conclusions: This study provides evidence for GABAergic involvement in performance on response inhibition and interference control tasks. Furthermore, our findings highlight the diversity of the broader construct of inhibitory control while also pointing out similarities between different inhibitory control tasks. In contrast to RT and error rates, the cognitive processes indexed by delta plots may not be sensitive to GABAergic modulation.

Introduction Benzodiazepines contribute to substance use disorder and are often part of polydrug abuse, most frequently with opioids. Although dental opioid prescribing differs significantly between countries, little is known about the patterns of dental benzodiazepine prescribing. The aim of this study is to compare dental prescribing of benzodiazepines among the U.S., England, and Australia in 2013–2018. Methods Population-level data were accessed from national data sets for each country for dental benzodiazepine prescriptions. Outcome measures of dental benzodiazepine prescribing included: (1) prescribing rates by population for each year and (2) the quantity and relative proportion of benzodiazepines by type for each country. The analysis was conducted in 2020. Results Between 2013 and 2018, U.S. dentists prescribed 23 times more than English dentists and 7 times more than Australian dentists by population. During the study period, the rate of dental benzodiazepine prescribing decreased in England and the U.S. but increased in Australia. Despite these trends, U.S. dental prescribing rates remained 28 times more than English dentists and 6 times more than Australian dentists in 2018 (U.S., 3.10 prescriptions/1,000 population; England, 0.11 prescriptions/1,000 population; Australia, 0.50 prescriptions/1,000 population). U.S. dentists prescribed a wider variety of benzodiazepines than English and Australian dentists. Diazepam was most commonly prescribed in all countries. In the U.S., triazolam, lorazepam, and alprazolam were next most commonly prescribed. Temazepam was next most frequent in England and Australia. Conclusions Significant variation in benzodiazepine prescribing rates and types were seen among the countries. To improve patient safety, further investigation into the appropriate use and choices of benzodiazepines in dentistry is needed.

The Japanese Pharmacopoeia (JP) is an official normative publication that is referred to, for establishing the authenticity and properties and maintaining the quality of pharmaceutics in Japan. Partial amendments are periodically made to these guidelines to keep up with the progress of science and technology, and the international harmonization is revised every 5 years. Thus, "Internationalization of the JP" is one of the more important issues to address for the revision of the JP. For example, the incorporation of the test methods that have been used in other pharmacopeias, such as the United States Pharmacopeia (USP) and the European Pharmacopoeia (EP), into the JP is a useful approach. In light of this, we have recently reported changes in test methods in the 17th JP, "Establishment of a quantitative test method for clonidine hydrochloride from using a potentiometric titration method to using HPLC". As a part of our ongoing research to change test methods for internationalization, we selected lorazepam. Lorazepam is analyzed using a potentiometric titration method as listed in the 17th JP; however, both the USP and EP use HPLC for quantitative analysis of this drug. In this study, we synthesized the related impurities of lorazepam listed in the USP and the EP and determined their purities using quantitative NMR. The separation conditions of these compounds, including lorazepam, were examined using HPLC and simultaneous analyses were performed. In addition, lorazepam extracted from the tablets was analyzed using conditions similar to those used for the analysis of the related impurities.

Background Catatonia is an often underdiagnosed diagnosis in the pediatric population that carries substantial morbidity and mortality. Early recognition of catatonia is important, especially whenit presents with autonomic abnormalities to ensure timely initiation of treatment. Treatment of catatonia is well established, especially the use of GABAergic agents such as benzodiazepines. Although the use of high potency cannabis has been associated with multiple neuropsychiatric sequelae, the relationship between vaporized cannabis use and catatonia has not been previously described. Case Presentations We report two cases of malignant catatonia in adolescent males with psychiatric histories significant for trauma and depression, and a recent history of vaporized marijuana use. These adolescents presented to the pediatric emergency room with classic symptoms of catatonia including psychomotor and behavioral disturbances. Both patients had evidence of autonomic dysfunction including hypertension, tachycardia, and mydriasis, and in one case, even evidence of cardiac ischemia. Laboratory and imaging workups for both patients were otherwise unremarkable. Both patients had resolution of symptoms following the administration of lorazepam. Conclusions These cases represent the first reported instances of pediatric malignant catatonia secondary to vaporized cannabis use. Given the increasing popularity of vaporized cannabis use among adolescents, malignant catatonia should be on the differential in a pediatric patient presenting with psychomotor disturbances and autonomic instability. Further research is needed to quantify the risk of catatonia secondary to vaporized cannabis use.

BACKGROUND: Few studies have examined how the use of rescue medications could be used to inform on the efficacy of interventions in delirium clinical trials. The objective of this study was to determine the association among rescue medication use, Richmond Agitation-Sedation Scale (RASS), and perceived comfort by the nurses and caregivers. METHODS: This was a pre-planned secondary analysis of a double-blind, randomized clinical trial comparing the use of a single dose of lorazepam plus haloperidol versus placebo plus haloperidol in patients with agitated delirium. Rescue medications were considered the gold standard for this analysis. The optimal cutoff for RASS analysis was calculated by using general linear regression models and determining the area of the curve and using the top left approach. We used 2 × 2 tables to examine the association between rescue medication use and perceived comfort. RESULTS: Fifty-eight patients received the study medications and 52 (89%) completed the 8-h observation period. There were 26 (50%) patients in each arm. The lorazepam/haloperidol arm required fewer rescue doses (4/26 (15%)) vs. 16/26 (62%), p = 0.004). Patients with a greater initial RASS reduction required fewer rescue doses. The cutoff value for RASS improvement was 4 points, area under the curve (AUC) 0.64 (95% CI 0.49–0.79) for those who required no rescue doses, and 3 points, AUC 0.74 (95% CI 0.52–0.96) for those who required more than one rescue dose. CONCLUSIONS: Rescue medication use was responsive to change and associated with both RASS scores and perceived patient comfort by the nurse and caregiver.

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.

Although guidelines recommend specific benzodiazepine doses for the treatment of generalized convulsive status epilepticus (GCSE), underdosing appears to be common. The purpose of this investigation was to assess benzodiazepine dosing strategies for the initial management of GCSE in patients presenting to the Emergency Department (ED).This was a retrospective review of adult patients who received benzodiazepines in the ED for treatment of GCSE. Characteristics of those achieving seizure cessation following initial benzodiazepine therapy were assessed.222 patients presented to the ED and received 403 doses of benzodiazepines, of which 1.5% conformed with recommendations. First-line therapy was successful in 86.8% of patients with an average dose of 1.6 mg (0.02 mg/kg). No difference in dosing was noted between those experiencing early cessation and those that did not (p = 0.132). Patients experiencing early cessation were significantly less likely to receive further doses, be intubated, or be admitted to the intensive care unit (ICU) or hospital (p 0.05 for all comparisons). Those that received early antiepileptic drug therapy were significantly less likely to receive additional benzodiazepine doses, be intubated, or be admitted to the ICU or hospital (p 0.05 for all comparisons).According to guideline recommendations, there was consistent underdosing of benzodiazepines noted in both prehospital and ED settings. Early seizure cessation and the early receipt of an antiepileptic drug were found to be associated with multiple significant clinical outcomes. Future investigations should explore optimal dosing strategies for benzodiazepines as well as the impact of early antiepileptic drug administration.

Clinicians often encounter agitated patients, and current treatment options include benzodiazepines and antipsychotics. Ketamine rapidly induces dissociation, maintains cardiovascular stability, spontaneous respirations, and airway reflexes. There are no prospective, randomized studies comparing ketamine to other agents in the initial management of acute agitation in the Emergency Department (ED).Determine the efficacy and safety of ketamine compared to parenteral haloperidol plus lorazepam for initial control of acute agitation.This study was a prospective, single-institution, randomized, open-label, real world, standard of care pilot study. Adult patients with combative agitation were randomized to ketamine (4 mg/kg IM or 1 mg/kg IV) or haloperidol/lorazepam (haloperidol 5-10 mg IM or IV + lorazepam 1-2 mg IM or IV). The primary outcome was sedation within 5 min, and secondary outcomes included sedation within 15 min, time to sedation, and safety.Ninety three patients were enrolled from January 15, 2018 to October 10, 2018. Significantly more patients who received ketamine compared to haloperidol/lorazepam were sedated within 5 min (22% vs 0%, p = 0.001) and 15 min (66% vs 7%, p 0.001). The median time to sedation in patients who received ketamine compared to haloperidol/lorazepam was 15 vs 36 min respectively (p 0.001). Patients who received ketamine experienced a significant, but transient tachycardia (p = 0.01) and hypertension (p = 0.01).In patients with combative agitation, ketamine was significantly more effective than haloperidol/lorazepam for initial control of acute agitation, and was not associated with any significant adverse effects.

Scopolamine is an alkaloid which acts as competitive antagonists to acetylcholine at central and peripheral muscarinic receptors. We report the case of a 41-year-old male convict with a 27-year history of cannabis abuse who suddenly died in the bed of his cell after having smoked buscopan® tablets. Since both abuse of substances and recent physical assaults had been reported, we opted for a comprehensive approach (post-mortem computed tomography CT (PMCT), full forensic autopsy, and toxicology testing) to determine which was the cause of the death. Virtopsy found significant cerebral edema and lungs edema that were confirmed at the autopsy and at the histopathological examination. Scopolamine was detected in peripheral blood at the toxic concentration of 14 ng/mL in blood and at 263 ng/mL in urine, and scopolamine butyl bromide at 17 ng/mL in blood and 90 ng/mL in urine. Quetiapine, mirtazapine, lorazepam, diazepam, and metabolites and valproate were also detected (at therapeutic concentrations). Inmates, especially when they have a history of drug abuse, are at risk to use any substance they can find for recreational purposes. In prisons, active surveillance on the management and assumption of prescribed drugs could avoid fatal acute intoxication.

Purpose: To describe the use of ketamine in an adult patient in aborting a cyclic vomiting syndrome (CVS) episode. Summary: A 40-year-old man with a history of CVS was admitted after several days of nausea and vomiting. He was given parenteral doses of lorazepam and ondansetron but was unable to remain emesis-free. Ketamine was recommended by Gastroenterology as a therapeutic option after exhausting all first- and second-line agents. Ketamine is a noncompetitive N-methyl-D-aspartate receptor antagonist that is widely used for its analgesic and sedative effects. While there is some data to support its use in CVS, most of the published literature has been limited to the Emergency Department setting and no specific therapeutic dose has been established. We will review our institution’s experience with low dose ketamine in an adult patient with a CVS episode that is refractory to first-line agents. Conclusion: In the case described, ketamine at a low sub-anesthetic dose successfully aborted a CVS episode with no appreciable side effects. As much of ketamine’s full effects remain relatively unknown, additional studies are needed to determine optimal strategies for ketamine use in patients with a CVS episode.

BACKGROUND/OBJECTIVES Psychotropic and opioid medications are routinely prescribed for symptom management in hospice, but national estimates of prescribing are lacking. Changes in Medicare hospice payment in 2014 provide the first opportunity to examine psychotropic and opioid prescribing among hospice beneficiaries, and the factors associated with use of specific medication classes. DESIGN Cross-sectional analysis of a 20% sample of traditional and managed Medicare with Part D enrolled in hospice, 2014-2016. SETTING Beneficiaries enrolled in the Medicare hospice benefit. PARTICIPANTS Medicare beneficiaries ≥65 newly enrolled in hospice between July 1, 2014 and December 31, 2016 (N = 554,022). MAIN OUTCOME Prevalence of psychotropic and opioid medication prescribing by class and factors associated with prescribing. RESULTS 70.3% of hospice beneficiaries were prescribed a psychotropic and 63.3% were prescribed an opioid. The most common psychotropic classes prescribed were: benzodiazepines (60.6%), antipsychotics (38.3%), antidepressants (18.4%), and antiepileptics (10.2%). Lorazepam (56.4%), morphine (52.8%), and haloperidol (28.6%) were received by the most beneficiaries. Prevalence of any psychotropic and opioid prescription was highest among beneficiaries who were female (76.7%), non-Hispanic white (76.6%), and those with cancer (78.9%). Compared to white beneficiaries, non-Hispanic black beneficiaries were less likely to receive nearly every class of medication, with significantly lower odds of receiving opioids (64.1% vs 57.9%; AOR 0.75, 95% CI 0.72-0.77) and benzodiazepines (61.6% vs 52.2%; AOR 0.66, 95% CI 0.64-0.68). Differences were seen across hospice diagnosis; those with cancer were more likely to receive opioids, benzodiazepines, and antipsychotics but less likely to receive antidepressants and antiepileptics. CONCLUSIONS Psychotropic and opioid medications are frequently prescribed in hospice. Observed variations in prescribing across race and ethnicity may reflect disparities in prescribing as well as patient preferences for care. Further work is important to understand factors driving prescribing given limited studies surrounding medication prescribing in hospice.

Background In this quality improvement project, we set out to study the effectiveness and feasibility of using music as an adjunct or replacement for pharmacologic agitation management on an inpatient psychiatric unit. We hypothesized music intervention would not only assist in de-escalation/calming of agitated patients, but also reduce overall administration of PRN medications on the unit. Method The project included 172 volunteer participants over 6 months: Three months without music available and 3 months with a music de-escalation option. During the latter period, patients were given the option of selecting a preferred music genre and provided with wireless headphones for up to 30 min. The number of as needed (PRN) medications administered for agitation and anxiety (including oral, sublingual, and intramuscular routes) was compiled from raw data using pharmacy records. Patients and nurses were provided with self-report surveys regarding the music intervention. Results The average weekly PRN medication administrations decreased significantly during the 3 months with music for both haloperidol (8.46 [+/− 1.79, p p p p p p Conclusion Music may play a significant role in reducing the utilization of PRN agitation medications on acute inpatient psychiatric units. More studies are needed to expand on these findings and explore the effect of PRN music on other therapeutic outcomes. Trial registration Protocol registration NCT04514432, retrospectively registered on 08/13/2020.

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.

Objective: To determine the diagnostic accuracy of immunoassays in drug screening as required in emergency for the rapid diagnosis of drug intoxication in travel related crimes. Study Design: Diagnostic accuracy study. Place and Duration of Study: department of Chemical Pathology and Endocrinology, Armed Forces Institute ofPathology, Rawalpindi Pakistan, from Jul 2017 to Jun 2018. Methodology: Sealed urine specimens of 77 patients with history of suspected intoxication in drugs facilitatedstreet crimes, received for toxicology screening were included in the study. All the specimens were analysed,initially on immunoassay (index test) and then on Triple Quadrupole Liquid chromatography–Mass spectrometry (reference standard). Benzodiazepine being the main class of drugs involved in travel related crimes, diagnostic accuracy of immunoassay technique was assessed for these by calculating its sensitivity, specificity, positive predictive value and negative predictive value. Results: Victims were predominantly males and public transportation was the most common mode of transport. The most commonly used drug was Lorazepam. Immunoassay failed to detect few cases who were shown to be intoxicated with benzodiazepines by liquid-chromatography tandem mass spectrometry. The false negative rate was 4.9%. Only one false positive case was observed. The accuracy was calculated to be 94.8% with sensitivity of 95.08% and specificity of 93.7%. Conclusion: Immunoassay was found reliable for rapid testing in drug facilitated intoxication cases. Howevercritical decision making should be done cautiously keeping in mind the limitations associated with thesescreening procedures.

Background Lithium can cause not only acute neurotoxicity but also chronic and persistent neurotoxicity known as syndrome of irreversible lithium-effectuated neurotoxicity (SILENT). The combined use of lithium and antipsychotics increases the possibility of SILENT. Neuroleptic malignant syndrome (NMS) is a reversible, idiosyncratic, and potentially life-threatening reaction, which is usually caused by antipsychotics and other agents, such as mood stabilizers (eg, lithium and metoclopramide). Neuroleptic malignant syndrome is characterized by hyperpyrexia, muscle rigidity, and altered mental status. We describe a case of SILENT combined with NMS in this case report. Case report A 46-year-old man who had been treated with lithium for bipolar II disorder since 2008 was prescribed lorazepam, lithium, and aripiprazole at his last outpatient visit. The patient experienced financial difficulties (bankruptcy) and suffered severe emotional stress. Subsequently, he overused lorazepam, lithium, and aripiprazole. Two days after the overdose, he experienced a high fever, confused mental status, and rhabdomyolysis and was diagnosed with NMS. However, even after resolution of NMS-related symptoms, quadriplegia, visual field defects, ataxia, and severe dysarthria persisted. A positron emission tomography-computed tomography brain scan showed decreased 15F-fludeoxyglucose uptake in bilateral primary motor cortices and in the thalamus, midbrain, and cerebellum. Brain magnetic resonance imaging diffusion tensor imaging and diffusion tensor tractography of the subcortical tracts revealed structural disruptions, especially in the corticospinal tract, dentatorubrothalamic tract, and optic radiation, which seemed to be correlated with the clinical symptoms of the patient. Conclusion This case suggests that the clinical use of diffusion tensor tractography could be helpful to explain the clinical features in the case of SILENT combined with NMS.

Objective To describe a case of a patient who developed psychosis after ingestion of Vertigoheel for treatment of dizziness. Case Summary A 28-year-old male with no psychiatric history presented with 5 days of worsening depression and psychosis. He denied current use of prescription medications, alcohol, or illicit substances. Approximately 2 weeks prior, while visiting family in Germany, he developed dizziness. A provider in Germany prescribed Vertigoheel, 1 tablet to be taken every hour until symptom improvement. This did not improve his dizziness but did cause him to feel as if he were “in a dream.” He stopped taking the medication after 2 days but continued to feel amotivated with decreased appetite and insomnia. Several days later, he developed ego-dystonic auditory hallucinations. He returned to the United States; was admitted to an inpatient psychiatric unit for 4 days; and given olanzapine 5 mg at bedtime, lorazepam 1 mg every evening, and melatonin 6 mg every evening. He experienced gradual improvement in symptoms and was discharged with olanzapine 5 mg daily and outpatient follow-up. Discussion Vertigoheel is a homeopathic preparation containing ambra grisea, Cocculus indicus, Conium maculatum, and petroleum. Psychosis was not reported in any of the randomized controlled trials evaluating the use of Vertigoheel for treatment of vertigo. A literature search revealed no published reports of psychosis as a result of administration of any components of Vertigoheel. Conclusion A possible causal relationship was observed between the homeopathic supplement Vertigoheel and an acute episode of psychosis in a young male patient with no comorbidities.

Purpose Benzodiazepines (BZDs) are a mainstay of treatment of catatonia with response rates of 60 to 80%, but there is virtually no data regarding the relative efficacy of different agents. We report a patient with catatonia who responded incompletely to lorazepam but much more definitively to clonazepam. Procedures Single case report. Findings A 74 year old man with recurrent catatonia had responded only partially to lorazepam and to a number of other interventions. He was ultimately treated with clonazepam monotherapy and exhibited a much more robust response. Conclusions In this patient, clonazepam may have proved more effective than lorazepam due to its higher affinity for the BZD binding site of the GABAA receptor or possibly due to its longer half life or intrinsic serotonergic activity. It may be reasonable to consider clonazepam in a patient whose response to other BZDs has been incomplete, but this remains to be confirmed in controlled studies.

Despite a lack of evidence of benefit, the compounded product ABH gel (lorazepam, diphenhydramine, and haloperidol) continues to be prescribed for individuals in hospice and palliative care settings for the treatment of nausea and vomiting and terminal delirium. More effective and reliable pharmacological and nonpharmacological strategies exist for the treatment of these conditions in the palliative care and hospice settings. We discuss the pharmacokinetic and clinical evidence for the individual components of ABH gel, as well as the compounded product, and attempt to understand the mechanism of effect that some purport to see, as well as why the compound continues to enjoy such a cult following. Truly, the continued use of ABH gel makes for a pricey placebo and delays the treatment of end-of-life symptoms with modalities that work.

Introduction Delirium and catatonia are two representations of acute brain dysfunction that can occur in medically ill patients. It has become increasingly evident that delirium and catatonia can co-occur in the setting of medical illnesses. Delirium and catatonia have been separately described as neuropsychiatric sequelae of Coronavirus Disease 2019 (COVID-19) infection; however, to the best of our knowledge the co-occurrence of delirium and catatonia in the setting of COVID-19 has not been previously reported. Case We describe a case of concurrent delirium and catatonia in a 70-year-old woman with multiple medical comorbidities but with no prior psychiatric history, who was hospitalized with COVID-19 pneumonia. Her symptoms of both delirium and catatonia improved with administration of low-dose lorazepam. Discussion We highlight the importance of recognizing catatonia in medically ill patients and the overlap between and co-occurrence of delirium and catatonia in this population. We explore how the conditions imposed by COVID-19 illness and its unique pathophysiology predispose patients to the development of both delirium and catatonia, as well as the challenges imposed by traditionally different approaches to treatment of these two conditions. Conclusion Delirium and catatonia can co-occur in the context of acute COVID-19 illness. Features specific to COVID-19, both pathophysiological and environmental, create a unique set of conditions, which predispose patients to co-occurring delirium and catatonia. Delirium and co-occurring catatonia may improve with administration of low-dose lorazepam in selected patients.

This study aimed at better understanding the neurochemistry underlying transcranial magnetic stimulation (TMS) and magnetic resonance spectroscopy (MRS) measurements as it pertains to GABAergic activity following administration of allosteric GABAA receptor agonist lorazepam. Seventeen healthy adults (8 females, 26.0 ± 5.4 years old) participated in a double-blind, crossover, placebo-controlled study, where participants underwent TMS and MRS two hours after drug intake (placebo or lorazepam; 2.5 mg). Neuronavigated TMS measures reflecting cortical inhibition and excitation were obtained in the left primary motor cortex. Sensorimotor cortex and occipital cortex MRS data were acquired using a 3T scanner with a MEGA-PRESS sequence, allowing water-referenced [GABA] and [Glx] (glutamate + glutamine) quantification. Lorazepam administration decreased occipital [GABA], decreased motor cortex excitability and increased GABAA-receptor mediated motor cortex inhibition (short intracortical inhibition (SICI)). Lorazepam intake did not modulate sensorimotor [GABA] and TMS measures of intra-cortical facilitation, long-interval cortical inhibition, cortical silent period, and resting motor threshold. Furthermore, higher sensorimotor [GABA] was associated with higher cortical inhibition (SICI) following lorazepam administration, suggesting that baseline sensorimotor [GABA] may be valuable in predicting pharmacological or neuromodulatory treatment response. Finally, the differential effects of lorazepam on MRS and TMS measures, with respect to GABA, support the idea that TMS measures of cortical inhibition reflect synaptic GABAergic phasic inhibitory activity while MRS reflects extrasynaptic GABA.

Objective Report on the first known successful use of ECT for treatment of catatonia in a patient with hypoxic-ischemic brain injury. Background Catatonia is a psychomotor disorder characterized by difficulty initiating or inhibiting volitional behavior. Catatonia is likely underdiagnosed in medically ill patients, whose features may be misinterpreted as delirium or static brain injury-related deficits. While catatonia itself is rarely described after hypoxic-ischemic brain injury, its features are commonly reported in the context of delayed post-hypoxic leukoencephalopathy. To date, there are no reports of successful use of ECT for catatonia in this population. Methods Case Report. 32-year-old man with opioid and cocaine use disorders suffered hypoxic-ischemic brain injury after heroin overdose. He recovered well though reported depressive symptoms. Seven months later, he developed progressive mutism, rigidity, stupor, catalepsy, and dysautonomia consistent with catatonia, unspecified. MRI at that time did not show leukoencephalopathy. Results Twenty-four months after initial injury, lorazepam trial for suspected catatonia produced dramatic improvement but he required increasing doses to maintain effect. Right unilateral ECT was initiated for benzodiazepine-resistant catatonia and the patient received 12 treatments during an inpatient admission with complete resolution of catatonia. He reported no adverse effects. Catatonic symptoms re-emerged after discharge, and he received 21 outpatient ECT treatments (9 right unilateral and 12 bilateral) with overall improvement in catatonia. Conclusions The following factors may underlie the successful use of ECT for treatment of catatonia in this patient with hypoxic-ischemic brain injury: mood symptoms prior to onset of catatonia; initial response to lorazepam; absence of neuroimaging evidence of leukoencephalopathy; and longer length of time between the hypoxic-ischemic brain injury and initiation of ECT. Despite literature suggesting ECT can be detrimental after hypoxic-ischemic brain injury, stringent case selection criteria may allow for safe and effective use of ECT for catatonia in these patients.

Background: Granisetron is a popular antiemetic medication used in the emergency department to control nausea and vomiting with an excellent side effect profile among adults and pediatric, in both healthy and oncology patients. Case Presentation: Our patient received granisetron for nausea and vomiting then developed torsional nystagmus, asymmetrical abnormal muscle contractions, and electrocardiography showed QTc prolongation 487 ms. The patient did improve after IV lorazepam and magnesium sulphate administration. Conclusion: QTc prolongation increases the risk of developing Torsades de Pointes and sudden death. Extrapyramidal syndrome caused by granisetron is rare and should not be confused with seizure. Both are significant effects associated with 5-HT3 antagonists administration to be aware of and if they occurred, should be managed in a timely fashion.

Background: Status epileptics are classically defined as seizures that are continuous for 30 minutes or longer or repetitive seizures between which the patient does not regain consciousness. This study reports a case of a boy with a 2-hour seizure. Case Presentation: We present the case of a 7-year-old boy, who is known to have tuberous sclerosis (TSC2 gene mutation). On the day of presentation, the seizure had started with aura (epigastric pain with weakness in the face), then started to seize in a form left focal jerky movement with generalization associated with rolling up of the eyes, and lasted for 5 minutes; it was aborted clinically by lorazepam 0.1 mg/kg IV. However, the electroencephalography (EEG) showed subclinical seizure. The patient received a loading dose of phenytoin, 20 mg/kg IV, with no changes in the EEG; then Keppra (three doses) with a total of 40 mg/kg IV was given, but subclinical seizure still persisted. The patient was given one dose of Ketamine IV of 1 mg/kg, which resulted in complete cessation of the seizure activity within 3 minutes after injection, which was confirmed by prolonged EEG monitoring. The total duration of the seizure was 2 hours. Conclusion: Ketamine can be considered as a third-line drug in refractory status epilepticus.

Electroconvulsive therapy (ECT) may be considered for treatment of severe, treatment-resistant, and emergent depression associated with MDD or bipolar disorder. Patients with epilepsy usually take medications that raise the seizure threshold, which poses challenges during ECT. We report a 66-year-old male with epilepsy taking levetiracetam extended-release (XR), lorazepam, and zonisamide requiring ECT for severe MDD. After literature review, the XR form of levetiracetam was changed to higher doses of the immediate-release (IR) formulation, and zonisamide was discontinued 2 days prior to ECT in the hospital and was resumed when the patient underwent outpatient continuation ECT. The patient was treated to remission after receiving 8 acute bilateral ECT treatments before being transitioned to continuation ECT. We provide a brief review of medication management of antiepileptic drugs and other medications that increase the seizure threshold during ECT. To our knowledge, this is the first reported case describing the management of levetiracetam, lorazepam, and zonisamide concomitantly during ECT. Our case suggests that utilizing the IR formulation of levetiracetam, administering the evening dose early the day prior to the procedure, and temporarily discontinuing zonisamide prior to bilateral ECT is effective for the treatment of severe MDD while maintaining seizure prophylaxis.

Since the 1960s, benzodiazepines have been a clinical mainstay, utilized for sedation, anxiety, and withdrawal states. Between 1996 and 2013 alone, benzodiazepine prescriptions increased annually by 2.5%. Rather than risk symptoms of withdrawal such as muscle pain and severe cardiomyopathy, patients must be properly informed about how to taper their medications. A 75-year-old female with a history of anxiety, hypertension, lupus, and degenerative disc disease presented with palpitations, mid-sternal chest pain, diaphoresis, and progressive shortness of breath. The patient was found to have elevated troponins (peak troponin of 1.45) and EKG showed sinus rhythm and ST segment abnormalities. The patient stated that her chest pain started 24 hours ago, 48 hours after she had stopped taking lorazepam which she had been taking for the past 50 years for anxiety. Her PCP gave her a plan to taper down the dose of lorazepam safely, but the patient opted to stop “cold turkey.” Due to the patient’s typical chest pain and elevating troponin level, ACS protocol was initiated. Initial echocardiogram showed an ejection fraction of 35-40% with hypokinesis of the anterioseptal wall with impaired left ventricular diastolic filling. The cardiology team performed a catheterization which showed minimal coronary artery disease and no significant stenosis in the left anterior descending artery. Within the next few days, the patient’s chest pain resolved and her troponins were negative. The medical team concluded that the physical stress from withdrawing from benzodiazepine caused the patient to go into Takotsubo Cardiomyopathy. This case illustrates the risks involved with benzodiazepine in an era of polypharmacy. More importantly, this case illustrates the strong need to taper benzodiazepines properly. Because this patient had taken a benzodiazepine for 50 years, the tapering should have been as slow as possible. The result was Takotsubo cardiomyopathy.

Although seizures are common in prehospital settings, standardized emergency medical services (EMS) treatment algorithms do not exist nationally. We examined nationwide variability in status epilepticus treatment by analyzing 33 publicly available statewide EMS protocols. All adult protocols recommend intravenous benzodiazepines (midazolam, n = 33; lorazepam, n = 23; diazepam, n = 24), 30 recommend intramuscular benzodiazepines (midazolam, n = 30; lorazepam, n = 8; diazepam, n = 3), and 27 recommend intranasal benzodiazepines (midazolam, n = 27; lorazepam, n = 3); pediatric protocols also frequently recommend rectal diazepam (n = 14). Recommended dosages vary widely, and first- and second-line agents are designated in only 18 and 2 states, respectively. Given this degree of variability, standardized national EMS guidelines are needed. ANN NEUROL 2021;89:604-609.

SUMMARYEstablishing an evidence base for the clinical management of catatonia is made difficult by the heterogeneous nature of the condition and the limited understanding of its pathophysiology. Benzodiazepines are a mainstay of treatment. The Cochrane review discussed identified only one eligible study (17 participants with catatonia who received either lorazepam or oxazepam), which found no difference on the single outcome measure (a 50% improvement on a visual analogue scale). This commentary discusses the findings in more detail, and considers what constitutes high-quality evidence for the acute treatment of catatonia, why there is such a paucity of randomised controlled trials (RCTs) on the topic and whether RCTs are both feasible and appropriate for the condition.

Pharmacological agents are analyzed, in respect of which it is advisable to develop dosage forms for inhalation use as medical means of protection at the prehospital stage of medical evacuation in case of damage by emergency-hazardous chemicals. It was found that the inhalation intake of hazardous chemicals, especially with a pronounced pulmonotoxic, irritating and generally poisonous effect, is highly likely to develop post-intoxication complications associated with damage to the lung parenchyma, and death. For the therapy of such intoxications, it is advisable to administrate drugs in a dosage form for inhalation administration, which have several advantages: high bioavailability, rapid onset of effect, and severity of local action in various parts of tracheobronchial tree. The data of experimental and clinical studies of the effectiveness of drugs belonging to various pharmacological groups allow us to recommend for the further development of inhaled forms of means of prevention and treatment of toxic pulmonary edema (fluticasone, roflumilast, rolipram). Bronchodilators and donors of sulfhydryl groups (ipratropium bromide, tiotropium bromide, atropine sulfate, fenoterol, salbutamol, formoterol, unitiol dimercaprol) are referred to means of correction of respiratory disorders of various etiologies. Diazepam, midazolam, clonazepam, lorazepam are considered to be the most likely anticonvulsants from the enzodiazepine-class suitable for inhalation. Acetylcysteine, hydroxycobalamin can be used to combat hypoxia. The principal possibility of inhalation application of bioscavengers (acetylcholinesterase, butyrylcholinesterase) for the treatment of cholinopositive symptoms of toxic genesis is shown. Existing methods and means of delivery allow the use of these drugs at the prehospital stage of medical evacuation as part of single dose metered powder inhalers.

Introduction: The objective of this study was to study the prescribing pattern of antiepileptic medications in patients with epilepsy in a tertiary care hospital. Materials and Methods: This was an observational study, conducted in psychiatry outpatient department (OPD) of Bapuji attached to Jagadguru Jayadeva Murugarajendra medical college and CG Hospital, Davangere. Patients demographic details, clinical diagnosis, type of epilepsy, type of AED used, drug dose and frequency of 100 outpatients who attended the psychiatry OPD was recorded. Results: A total of 100 prescriptions were analysed with more number of males (62%) than females (38%). Epilepsy was more commonly seen in the patients of age group of 20-40 years (52%) and GTCS was diagnosed in 79% of the patients followed by partial seizures and other types. Majority of them received monotherapy (67%) with most commonly prescribed AED phenobarbitone (28%) followed by phenytoin (16%), levetiracetam (12%), carbamazepine (8%), lorazepam (2%) and ethosuximide (1%). 33% of the patients received combined therapy, most commonly used two drug combination was phenobarbitone with phenytoin and three drug combination was with phenobarbitone, phenytoin and carbamazepine. 19 patients reported adverse events, most common were related to CNS. Conclusion: In our study, majority of the patients were males with age group 20-40 yrs and most commonly used drugs were conventional AEDs as monotherapy with phenobarbitone, phenytoin and levetiracetam. Keywords: Epilepsy, Anti Epileptic Drug (AED), Monotherapy, Combined therapy, Prescribing pattern.

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.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.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%,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.

To reduce potentially inappropriate medications, the FORTA (Fit fOR The Aged) concept classifies drugs in terms of their suitability for geriatric patients with different labels, namely A (indispensable), B (beneficial), C (questionable), and D (avoid). The aims of our study were to assess the medication appropriateness in PD inpatients applying the FORTA list and drug-drug interaction software, further to assess the adequacy of FORTA list for patients with PD. We retrospectively collected demographic data, comorbidities, laboratory values, and the medication from the discharge letters of 123 geriatric inpatients with PD at the university hospital of Hannover Medical School. Patients suffered on average from 8.2 comorbidities. The majority of the medication was labeled A (60.6% of PD-specific and 40.9% of other medication) or B (22.3% of PD-specific and 26.9% of other medication). Administered drugs labeled with D were amantadine, clozapine, oxazepam, lorazepam, amitriptyline, and clonidine. Overall, 545 interactions were identified, thereof 11.9% severe interactions, and 1.7% contraindicated combinations. 81.3% of patients had at least one moderate or severe interaction. The FORTA list gives rational recommendations for PD-specific and other medication, especially for general practitioners. Considering the demographic characteristics and the common multimorbidity of geriatric PD patients, this study underlines the importance of awareness, education, and preventive interventions to increase drug safety.

Background Silexan is a lavender essential oil with established anxiolytic and calming efficacy. Here we asked whether there is a potential for abuse in human patients. Methods We carried out a phase I abuse liability single-center, double-blind, 5-way crossover study in healthy users of recreational central nervous system depressants. They received single oral doses of 80 mg (therapeutic dose) and 640 mg Silexan, 2 mg and 4 mg lorazepam (active control) and placebo in randomized order, with 4- to 14-day washout periods between treatments. Pharmacodynamic measures included validated visual analogue scales assessing positive, negative, and sedative drug effects and balance of effects; a short form of the Addiction Research Center Inventory; and a drug similarity assessment. The primary outcome measure was the individual maximum value on the drug liking visual analogue scale during 24 hours post-dose. Results Forty participants were randomized and 34 were evaluable for pharmacodynamic outcomes. In intraindividual head-to-head comparisons of the drug liking visual analogue scale maximum value, both doses of Silexan were rated similar to placebo whereas differences were observed between Silexan and lorazepam and between placebo and lorazepam (P Conclusions Silexan did not exhibit any abuse potential in a standard abuse potential detection screen study and is unlikely to be recreationally abused.

BACKGROUND The rapidity with which a medication can be delivered to the systemic circulation and then into the brain always play a significant role in reducing the mortality and morbidity. We wanted to determine and compare the efficacy of intranasal midazolam with that of intravenous lorazepam in the control of acute onset seizures and side effects. METHODS This is an open labelled randomized control trial conducted in the Emergency Department of KIMS Hospital, which is a multi-specialty tertiary care centre in south Kerala, India, among children with acute seizure between 6 months and 15 years of age. They received intranasal midazolam or intravenous lorazepam. RESULTS 65.2 % (15) of the children in whom intranasal midazolam was given, seizures were controlled within 5 minutes from ER presentation, whereas in lorazepam group, only 34.8 % (8) children ceased to seizure within 5 minutes. P value was 0.039. CONCLUSIONS The overall time to cessation of seizure after arrival at hospital was faster with intranasal midazolam than intravenous lorazepam. No untoward side effects were noticed. KEYWORDS Acute Seizure in Children, Intranasal Midazolam, Lorazepam, Randomized Trial

A 20-year-old woman with no prior psychiatric and medical history presented with acute autobiographical memory loss and a psychogenic tremor. Her laboratory and imaging work-up revealed no infectious, inflammatory, or other organic etiologies. A lorazepam infusion-assisted interview successfully facilitated recovery of memories and elucidated precipitating events. We discuss the utility of drug-assisted interviews and the safety of benzodiazepine infusions for dissociative amnesia.

Background The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as one of the biggest health threats of our generation. A significant portion of patients are presenting with delirium and neuropsychiatric sequelae of the disease. Unique examination findings and responses to treatment have been identified. Objective In this article, we seek to provide pharmacologic and treatment recommendations specific to delirium in patients with COVID-19. Methods We performed a literature search reviewing the neuropsychiatric complications and treatments in prior coronavirus epidemics including Middle Eastern respiratory syndrome and severe acute respiratory syndrome coronaviruses, as well as the emerging literature regarding COVID-19. We also convened a work group of consultation-liaison psychiatrists actively managing patients with COVID-19 in our hospital. Finally, we synthesized these findings to provide preliminary pharmacologic recommendations for treating delirium in these patients. Results Delirium is frequently found in patients who test positive for COVID-19, even in the absence of respiratory symptoms. There appears to be a higher rate of agitation, myoclonus, abulia, and alogia. No data are currently available on the treatment of delirium in patients with COVID-19. Extrapolating from general delirium treatment, Middle Eastern respiratory syndrome/severe acute respiratory syndrome case reports, and our experience, preliminary recommendations for pharmacologic management have been assembled. Conclusions COVID-19 is associated with neuropsychiatric symptoms. Low-potency neuroleptics and alpha-2 adrenergic agents may be especially useful in this setting. Further research into the pathophysiology of COVID-19 will be key in developing more targeted treatment guidelines.