The Neuroprotective Action of Resveratrol Against Cognitive Impairments Induced by Lorazepam in Male Rats.

INTRODUCTION/AIM: The study examines how chronic resveratrol administration affects behavioral and neurochemical changes caused by Lorazepam (LZP), a classical anti-anxiety medicine associated with neurodegenerative and neurological problems. METHOD: Forty male rats were placed into four groups: a control group receiving 1% Tween 80, the LZP group receiving 2 mg/kg/day, the Resveratrol group receiving 50 mg/kg/day, and the LZP plus resveratrol group receiving the same doses of LZP and Resveratrol. Oral therapy was given daily for 6 weeks. The animals were euthanized after open field and Y maze behavioral tests. In specific brain regions, neurochemical analyses were performed on GABA, glutamic acid, monoamines (norepinephrine, dopamine, and serotonin) and their metabolites, DNA fragmentation (8-hydroxy-2-deoxyguanosine or 8-HdG), brain-derived neurotrophic factor (BDNF), and Ca-ATPase. RESULTS: Resveratrol therapy improved GABA, glutamic acid, monoamines, and their metabolites in the cerebral cortex, hippocampus, and striatum. Additionally, it reduced DNA fragmentation (8- HdG) and counteracted LZP-induced Ca-ATPase downregulation at a significant level (p < 0.05). Resveratrol also reversed LZP-induced behavioral changes in the Y maze and open field tests. CONCLUSION: Resveratrol has anxiolytic-like actions like benzodiazepines and neuroprotective capabilities against LZP-induced adverse effects.

Acute Catatonia Following a Cerebellar Stroke: A Case Report.

Catatonia can present with a wide spectrum of psychomotor symptoms and should be considered in the differential diagnosis of hospitalized patients with speech and motor difficulties. Catatonia is defined as the presence of three or more of the following: catalepsy, waxy flexibility, stupor, agitation, mutism, negativism, posturing, mannerisms, stereotypies, grimacing, echolalia, and echopraxia. In this case, a 72-year-old black woman was admitted with difficulty with speech and ambulation and found to have a cerebellar stroke on a brain MRI. However, her symptoms of variable rigidity, mutism, and marked psychomotor slowing were not attributable to the small left-sided cerebellar infarction on imaging. A dramatic response to a lorazepam challenge confirmed a diagnosis of acute catatonia secondary to a medical condition.

Effects of lorazepam on saccadic eye movements - evidence from prosaccade and free viewing tasks.

RATIONALE: Peak velocities of saccadic eye movements are reduced after benzodiazepine administration. Even though this is an established effect, past research has only examined it in horizontal prosaccade tasks. OBJECTIVES: The spectrum of saccadic eye movements, however, is much larger. Therefore, we aimed to make a first attempt at filling this research gap by testing benzodiazepine effects on saccades under different experimental task conditions. METHODS: 1 mg lorazepam or placebo was administered (within-subjects, double-blind, in randomised order) to n = 30 healthy adults. Participants performed an extended version of the prosaccade task, including vertical saccade directions and different stimulus eccentricities, as well as a free viewing task. RESULTS: Results from the prosaccade task confirmed established effects of benzodiazepines as well as saccade direction on saccadic parameters but additionally showed that the drug effect on peak velocity was independent of saccade direction. Remarkably, in the free viewing task peak velocities as well as other saccade parameters were unaffected by lorazepam. Furthermore, exploration patterns during free viewing did not change under lorazepam. CONCLUSIONS: Overall, our findings further consolidate the peak velocity of prosaccades as a biomarker of sedation. Additionally, we suggest that sedative effects of low doses of benzodiazepines may be compensated in tasks that more closely resemble natural eye movement behaviour, possibly due to the lack of time constraints or via neurophysiological processes related to volition.

The effectiveness of the lorazepam challenge test in pediatric catatonia: A multisite retrospective cohort study.

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.

Pharmacologic management of adolescent catatonia: A dual-case series.

Introduction: Catatonia is a syndrome characterized by psychomotor and behavioral disturbances and is associated with a substantially increased mortality risk in adolescent patients. There is a dearth of published literature describing treatment strategies for pediatric patients with catatonia. This dual-case series will describe the treatment course of 2 adolescent patients with catatonia at our pediatric inpatient psychiatric facility. Case Series: This case series presents 2 adolescent patients (a 17-year-old male and a 16-year-old female) who initially presented with worsening agitation and paranoia, later developing catatonia. Both patients required long durations of hospitalization and were treated with high-dose lorazepam before requiring the addition of electroconvulsive therapy (ECT). Discussion: Treatment of pediatric patients with catatonia creates a significant burden on patients, families, and the healthcare system. Treatment with high-dose benzodiazepines is high risk, while ECT is both difficult to access and comes with its own risks. Both patients discussed are transitional age, meaning they will soon be young adults who will continue to require high-level psychiatric care. Psychiatric pharmacists have a large role to play in ensuring safe medication management for these complex patients. Conclusions: This case series of 2 adolescent patients with catatonia demonstrates marginal reduction in symptoms with high-dose lorazepam in conjunction with ECT, with minimal side effects. This case series adds to the limited available literature regarding treatment of catatonia in pediatric patients and highlights the need for further study into effective treatment alternatives.

Ziprasidone population pharmacokinetics and co-medication effects in Chinese patients.

Ziprasidone is widely used in the treatment of psychiatric disorders. Despite its prevalence, there is a notable lack of population pharmacokinetics (PPK) studies on ziprasidone in serum, both domestically and internationally. This study aimed to comprehensively investigate the various factors influencing the PPK characteristics of Ziprasidone, thereby providing a scientific basis for personalized treatment strategies in clinical settings. This is a retrospective study. A non-linear mixed-effects modeling method was used for data analysis, with the ziprasidone PPK model established using the Phoenix NLME 8.1 software. Model evaluation employed goodness-of-fit plots, visual predictive checks, and Bootstrap methods to ensure reliability and accuracy. To further validate the model's applicability, data from an additional 30 patients meeting the same inclusion criteria but not included in the final model were collected for external validation. Simulations were performed to explore the personalized dosage regimens. This retrospective analysis collected 547 drug concentration data points from 185 psychiatric disorder patients, along with related medical records. The data included detailed demographic information (such as age, gender, weight), dosing regimens, laboratory test results, and concomitant medication details. In the final model, Ka was fixed at 0.5 h-1 based on literature, and the population typical values for ziprasidone clearance (CL) and volume of distribution (V) were 18.74 L/h and 110.24 L, respectively. Co-administration of lorazepam and valproic acid significantly influenced the clearance of ziprasidone. Moreover, the model evaluation indicated good stability and predictive accuracy. A simple to use dosage regimen table was derived based on the results of simulations. This study successfully established and validated a PPK model for ziprasidone in Chinese patients with psychiatric disorders. The model provides a scientific reference for individualized dosing of ziprasidone and holds the potential to optimize treatment strategies, thereby enhancing therapeutic efficacy and safety.

Acupuncture for reducing the south to reinforce the north on executive function and sleep structure in patients with chronic insomnia disorder of heart-kidney disharmony. / æ³»å—è¡¥åŒ—æ³•é’ˆåˆºå¯¹å¿ƒè‚¾ä¸äº¤åž‹æ ¢æ€§å¤±çœ éšœç¢æ‚£è€ æ‰§è¡ŒåŠŸèƒ½åŠç¡çœ ç»“æž„çš„å½±å“.

OBJECTIVES: To observe the efficacy of acupuncture for reducing the south to reinforce the north on executive function, sleep structure and sleep quality in patients with chronic insomnia disorder of heart-kidney disharmony. METHODS: A total of 100 patients with chronic insomnia disorder of heart-kidney disharmony were randomized into an acupuncture group (50 cases, 1 case dropped out) and a western medication group (50 cases, 2 cases dropped out). Acupuncture for reducing the south to reinforce the north was applied at Baihui (GV 20) and bilateral Shenmen (HT 7), Sanyinjiao (SP 6), Shenmai (BL 62), Zhaohai (KI 6), Xinshu (BL 15), Shenshu (BL 23) in the acupuncture group, once a day, 5 days a week. Lorazepam tablet was given orally in the western medication group, 0.5-1 mg a time, once a day. Both groups were treated for 4 weeks. The Stroop color-word test (SCWT) indexes (the time consuming and the correct number of card A, B, C and the Stroop interference effect [SIE]), sleep structure indexes (total sleep time [TST], sleep latency [SL], wake after sleep onset [WASO], sleep efficiency [SE], non-rapid eye movement period 1 [N1], non-rapid eye movement period 2 [N2], non-rapid eye movement period 3 [N3], rapid eye movement period [REM]) and Pittsburgh sleep quality index (PSQI) score were observed before and after treatment in the two groups. RESULTS: After treatment, the time consuming of card B and C, the time consuming and the correct number of SIE, SL, WASO, N1, N2, as well as the sub-item scores and total score of PSQI were decreased (P<0.05, P<0.01), the correct number of card A, B and C, TST, SE, N3 and REM were increased (P<0.01) compared with those before treatment in the acupuncture group; the time consuming of card C and SIE, the correct number of card A and SIE, TST, SE, REM were increased (P<0.05, P<0.01), SL, WASO, N1, as well as the sub-item scores of sleep quality, sleep latency, sleep duration, sleep efficiency, daytime function and total score of PSQI were decreased (P<0.01) compared with those before treatment in the western medication group. After treatment, in the acupuncture group, the time consuming of card C, the time consuming and the correct number of SIE, N1, N2, as well as the sub-item scores of sleep quality, sleep dysfunction, daytime function and total score of PSQI were lower than those in the western medication group (P<0.01), the correct number of card B and C, N3, REM were higher than those in the western medication group (P<0.01). CONCLUSIONS: Acupuncture for reducing the south to reinforce the north can improve the executive function of patients with chronic insomnia disorder of heart-kidney disharmony, adjust the sleep structure, and improve the night sleep quality and daytime body function.

Influence of GABAA and GABAB receptor activation on auditory sensory gating and its association with anxiety in healthy volunteers.

BACKGROUND: Dysfunctional sensory gating in anxiety disorders, indexed by the failure to inhibit the P50 event-related potential (ERP) to repeated stimuli, has been linked to deficits in the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). AIMS/METHODS: This study, conducted in 30 healthy volunteers, examined the acute effects of GABAA (lorazepam: 1 mg) and GABAB receptor (baclofen: 10 mg) agonists on P50 measures of auditory sensory gating within a paired-stimulus (S1-S2) paradigm and assessed changes in gating in relation to self-ratings of anxiety. RESULTS: Compared to placebo, lorazepam reduced ERP indices of sensory gating by attenuating response to S1. Although not directly impacting P50 inhibition, baclofen-induced changes in gating (relative to placebo) were negatively correlated with trait but not state anxiety. CONCLUSIONS: These preliminary findings support the involvement of GABA in sensory gating and tentatively suggest a role for GABAB receptor signaling in anxiety-associated gating dysregulation.

Neuropsychiatric Effects Associated with Opioid-Based Management for Palliative Care Patients.

PURPOSE OF REVIEW: The abundance of opioids administered in the palliative care setting that was once considered a standard of care is at present necessitating that providers evaluate patients for unintentional and deleterious symptomology related to aberrant opioid use and addiction. Polypharmacy with opioids is dynamic in affecting patients neurologically, and increased amounts of prescriptions have had inimical effects, not only for the individual, but also for their families and healthcare providers. The purpose of this review is to widen the perspective of opioid consequences and bring awareness to the numerous neuropsychiatric effects associated with the most commonly prescribed opioids for patients receiving palliative care. RECENT FINDINGS: Numerous clinical and research studies have found evidence in support for increased incidence of opioid usage and abuse as well as undesirable neurological outcomes. The most common and concerning effects of opioid usage in this setting are delirium and problematic drug-related behavioral changes such as deceitful behavior towards family and physicians, anger outbursts, overtaking of medications, and early prescription refill requests. Other neuropsychiatric effects detailed by recent studies include drug-seeking behavior, tolerance, dependence, addictive disorder, anxiety, substance use disorder, emotional distress, continuation of opioids to avoid opioid withdrawal syndrome, depression, and suicidal ideation. Opioid usage has detrimental and confounding effects that have been overlooked for many years by palliative care providers and patients receiving palliative care. It is necessary, even lifesaving, to be cognizant of potential neuropsychiatric effects that opioids can have on an individual, especially for those under palliative care. By having an increased understanding and awareness of potential opioid neuropsychiatric effects, patient quality of life can be improved, healthcare system costs can be decreased, and patient outcomes can be met and exceeded.

Catatonia and melancholia interface: exploring a new paradigm for evaluation and treatment. A case series and literature review.

Background: Catatonia has been increasingly associated with mood disorders and is recognized as a specifier in the DSM-5 and DSM-5-TR. The DSM-5-TR recognizes melancholia as a specifier for depressive episodes in major depressive disorder and bipolar disorder. It is characterized by severe anhedonia, lack of reactivity, excessive or delusional guilt, and significant vegetative symptoms. As the conceptualization of melancholia expanded beyond its mood components to include psychomotor disturbances, its overlap with psychomotor symptoms or catatonia becomes evident. This overlap was also described in Kahlbaum's original literature, where he describes the transition between states of melancholia, mania, and catatonia. Method: Case summary of six patients with major depressive disorder or depressed phase of bipolar disorder who were admitted for severe depression, anhedonia, intense anxiety, psychomotor agitation or retardation, indecisiveness, perseveration, and vegetative symptoms such as poor sleep, appetite, and significant weight loss. Results: All patients demonstrated rapid and complete resolution of their mood and psychomotor symptoms, indecisiveness, perseveration, as well as psychosis shortly after administration of lorazepam, with recurrence of the above symptoms upon lorazepam discontinuation and resolution upon resumption, in an on-and-off manner. Conclusion: The present study argues for a closer relationship between melancholia and catatonia based on our case series, historical review, overlap in phenomenology, and response to treatment. We propose provisional [Mahgoub] criteria for patients with severe depression and melancholia. The role of GABA agonists, such as lorazepam, can be explored as an option for patients with treatment-resistant depression who meet these criteria for melancholia. Limitations: Absence of a standardized, systematic assessment tool and a small sample size.

Effectiveness and Safety of Intravenous Medications for the Management of Acute Disturbance (Agitation and Other Escalating Behaviors): A Systematic Review of Prospective Interventional Studies.

Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available management options include de-escalation techniques and rapid tranquilization, mostly via parenteral formulations of medication. While the intramuscular route has been extensively studied in a range of clinical settings, the same cannot be said for intravenous (IV); this is despite potential benefits, including rapid absorption and complete bioavailability. This systematic review analyzed existing evidence for effectiveness and safety of IV medication for management of acute disturbances. It followed a preregistered protocol (PROSPERO identification CRD42020216456) and is reported following the guidelines set by Preferred Reporting Items for Systematic Review and Meta-Analysis. APA PsycINFO, MEDLINE, and EMBASE databases were searched for eligible interventional studies up until May 30th, 2023. Data analysis was limited to narrative synthesis since primary outcome measures varied significantly. Results showed mixed but positive results for the effectiveness of IV dexmedetomidine, lorazepam, droperidol, and olanzapine. Evidence was more limited for IV haloperidol, ketamine, midazolam, chlorpromazine, and valproate. There was no eligible data on the use of IV clonazepam, clonidine, diazepam, diphenhydramine, propranolol, ziprasidone, fluphenazine, carbamazepine, or promethazine. Most studies reported favorable adverse event profiles, though they are unlikely to have been sufficiently powered to pick up rare serious events. In most cases, evidence was of low or mixed quality, accentuating the need for further standardized, large-scale, multi-arm randomized controlled trials with homogeneous outcome measures. Overall, this review suggests that IV medications may offer an effective alternative parenteral route of administration in acute disturbance, particularly in general hospital settings.

Lorazepam in catatonia - Past, present and future of a clinical success story.

The effect of lorazepam in the treatment of catatonia is outstanding and almost immediate. Clinicians are familiar with its effects: mute patients can speak again, akinetic patients can move again and patients with negativism can eat and drink again within usually a short duration of about 10 min to 1-2 h. Fear is often gone after lorazepam administration. While not always effective, the introduction of lorazepam into clinical practice represented a breakthrough and was often life-saving for many patients suffering from catatonia. It is rare to observe such rapid therapeutic effects in other domains of psychiatry. In this narrative review we will briefly look at the past, present and future of lorazepam in the treatment of catatonia. It is gratifying to reflect on the fact that clinicians using the age-old medical practice of observation and empirical treatment succeeded in advancing the management of catatonia 40 years ago. The present evidence shows that the clinical effect of lorazepam in catatonia treatment is excellent and more or less immediate although it remains to be explicitly tested against other substances such as diazepam, zolpidem, clozapine, quetiapine, amantadine, memantine, valproate and dantrolene in randomized clinical trials. In addition, future studies need to answer the question how long lorazepam should be given to patients with catatonia, months or even years? This narrative review promotes the rapid use of lorazepam in the treatment of acute catatonic patients and stipulates further scientific examination of its often impressive clinical effects.

A Comparison of Injectable Diazepam and Lorazepam in the Goal-Directed Management of Severe Alcohol Withdrawal.

BACKGROUND: Benzodiazepines are the gold standard for treatment of alcohol withdrawal, yet the selection of a preferred benzodiazepine is limited due to a lack of comparative studies. OBJECTIVES: The primary objective of this study was to compare the efficacy and safety of injectable lorazepam (LZP) and diazepam (DZP) in the treatment of severe alcohol withdrawal syndrome (AWS). METHODS: Retrospective cohort study of adult patients admitted to an intensive care unit with a primary diagnosis of AWS. Subjects who received at least 12 LZP equivalent units (LEU) of injectable DZP or LZP within 24 hours of initiation of the severe AWS protocol were included. The primary outcome was time with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scores at goal over the first 24 hours of treatment. RESULTS: A total of 191 patients were included (DZP n = 89, LZP n = 102). Time with CIWA-Ar scores at goal during the first 24 hours was similar between groups (DZP 12 hours [interquartile range, IQR, = 9-15] vs LZP 14 hours [IQR = 10-17]), P = 0.06). At 24 hours, LEU requirement was similar (DZP 40 [IQR = 22-78] vs LZP 32 [IQR = 18-56], P = 0.05). Drug cost at 24 hours was higher in the DZP group ($204.6 [IQR = 112.53-398.97] vs $8 [IQR = 4.5-14], P < 0.01). CONCLUSION AND RELEVANCE: DZP or LZP are equally efficacious for the treatment of severe AWS. LZP may be preferred due to cost but both medications can be used interchangeably based on availability.

Evaluation of the sedative effect of sublingual lorazepam versus placebo in patients underwent endoscopy: a double-blind, randomized controlled clinical trial.

Background: Digestive endoscopy (DE) is uncomfortable for most patients. Lorazepam is a potent benzodiazepine with anxiolytic and sedative effects. Objective: This study aims to determine the sedative effect of sublingual lorazepam versus placebo as a premedication in patients who underwent DE. Design: This is a mono-center, double-blind, and randomized controlled trial. Methods: A lorazepam sublingual tablet was made by researchers and physical tests were done on it, then the double-blind placebo-controlled trial was done to investigate the efficacy of 2 mg sublingually administered lorazepam as a premedication for endoscopy. Lorazepam or a placebo tablet was administered sublingually 30 min before the endoscopy. The patients, nurses, and physicians were blinded to the patient group. The depth of sedation was evaluated according to the American Society of Anesthesiology. Results: In all, 116 patients were randomly assigned to take either lorazepam (n = 58) or a placebo (n = 58). The results of physical properties tests were acceptable according to United States Pharmacopeia. There were no statistical differences between groups regarding age and gender. In the lorazepam group, 75.8% of patients showed mild sedation, and 24.2% of patients showed no sedation. All of the patients in the placebo had no sedation (p = 0.001). Time of procedure (p < 0.001), intraoperative O2 saturation (p < 0.001), intraoperative heart rate (p < 0.001), and intraoperative blood pressure (p < 0.001) were significantly lower in the lorazepam group. No significant or dangerous side effects were observed except a bit of giddiness and dizziness. Conclusion: The results of this study showed that prescription of sublingual lorazepam 25-30 min before endoscopy provided mild sedation. Registration: IRCT201611039014N130 (05/11/2016); https://en.irct.ir/trial/9568.

Revisión de la utilización de la prueba con lorazepam como evaluación diagnóstica de catatonía / Review of the utilization of the lorazepam test as a diagnostic evaluation of catatonia

La catatonía es un síndrome neuropsiquiátrico que se presenta con una serie heterogénea de signos y síntomas psicomotores, afectivos, conductuales y autonómicos. Es una manifestación inespecífica de ciertos trastornos mentales, metabólicos, inmunológicos, endocrinológicos, infecciosos y neurológicos, y es fundamental establecer estrategias de diagnóstico precoz para implementar medidas terapéuticas eficaces y oportunas. El objetivo de esta revisión sistematizada es evaluar la utilidad de la prueba de lorazepam como estrategia diagnóstica en individuos con catatonía. Se utilizó los buscadores Cochrane, Lilacs, Scielo, Pubmed y Scopus. Los artículos seleccionados son ensayos clínicos y cohortes prospectivos, en los cuales se analizó la forma de diagnóstico de catatonía, la utilización y protocolo de la prueba de lorazepam y las medidas de respuesta. La búsqueda inicial determinó 87 artículos; aplicando los criterios de inclusión y exclusión se culminó en la elección de 8 artículos. La identificación de la catatonía presenta dificultades y su diagnóstico es variable, lo cual genera limitaciones en cuanto a intervenciones precoces. Existe una heterogeneidad de evaluaciones y de estrategias, pero la bibliografía es sugerente en cuanto a la utilización de lorazepam como evaluación confirmatoria y tratamiento inicial de la catatonía. La prueba de lorazepam forma parte de un protocolo de manejo, y puede ser un paso en la toma de decisiones para que individuos con catatonía reciban una intervención oportuna. Se concluye que la prueba de lorazepam es una técnica accesible y replicable, con resultados prometedores para su eventual implementación, pero se necesita nuevos estudios que involucren su aplicación estandarizada.

Catatonia is a neuropsychiatric syndrome characterized by a heterogeneous range of psychomotor, affective, behavioral, and autonomic signs and symptoms. It is a nonspecific manifestation of certain mental, metabolic, immunological, endocrinological, infectious, and neurological disorders. Therefore, it is essential to establish early diagnostic strategies to implement effective and timely therapeutic measures. This review aims to evaluate the utility of the Lorazepam Challenge Test as a diagnostic strategy in individuals with catatonia. A review was conducted using search engines such as Cochrane, Lilacs, Scielo, Pubmed, and Scopus. The initial search yielded 87 articles, and after applying inclusion and exclusion criteria, 8 articles were selected. The selected articles are clinical trials and prospective cohorts, where catatonia diagnosis, the use and protocol of the Lorazepam Challenge Test, and response measures were analyzed. Identifying catatonia is challenging, and its diagnosis varies, leading to limitations in early interventions. There is a heterogeneity of evaluations and strategies, but the literature suggests the use of lorazepam as a confirmatory evaluation and initial treatment for catatonia. The Lorazepam Challenge Test is part of a management protocol and can be a decision-making step for individuals with catatonia to receive timely intervention. It is concluded that The Lorazepam Challenge Test is an accessible and replicable technique with promising results for potential implementation, requiring further studies involving its standardized application.

A case of comorbidity of schizophrenic catatonia and chronic intestinal pseudo-obstruction Successfully managed with lorazepam.

It is challenging to manage schizophrenic catatonia and comorbid chronic intestinal pseudo-obstruction (CIPO). The pathology of catatonia is unclear. There are few reports or research on this issue. In this case, we present a middle-aged woman diagnosed with schizophrenia with catatonic features and comorbid CIPO. In the treatment process, modified electroconvulsive therapy (mECT) improved her stupor and CIPO partially. Lorazepam alleviated her stupor and CIPO completely. It is the first report describing complete remission with lorazepam in patient suffering from comorbid schizophrenic catatonia and CIPO, which may benefit the exploration of pathophysiology and treatment of comorbidity of schizophrenia with catatonia and CIPO.

Using Interdisciplinary Teams to Mitigate the Effects of Drug Shortages in Palliative Care: The Case of Lorazepam Injection.

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.

Percutaneous absorption and Skin accumulation of Lorazepam-Diphenhydramine- Haloperidol Carbopol gel in Porcine Ear Skin.

This study presents the formulation and evaluation of an ABH Carbopol gel containing lorazepam (Ativan®), diphenhydramine hydrochloride (Benadryl®), and haloperidol (Haldol®) for treating chemotherapy-induced nausea and vomiting (CINV) in hospice patients. ABH PLO gel is widely used for this purpose due to its low cost and presumed efficacy. However, previous studies, including one conducted by the authors, have reported insufficient drug absorption from the ABH PLO gel. Here we hypothesized that the ABH Carbopol gel would provide superior percutaneous absorption of the drugs. ABH Carbopol gel was characterized for pH, viscosity, thermal properties, and infrared spectroscopy. The percutaneous absorption and skin retention of the gel was evaluated across porcine ear skin using Franz diffusion cells, and the drug concentrations were determined by high-performance liquid chromatography. The pH of the ABH Carbopol gel was found to be 6.80 ± 0.33, and the retention time of diphenhydramine, haloperidol, and lorazepam were 4.73, 7.11, and 18.69 minutes, respectively. The thermogram of the ABH Carbopol gel indicates the drugs were present in the dissolved state. Based on the flux data, the estimated steady-state concentration (Css) of diphenhydramine, haloperidol, and lorazepam were found to be 44.64 ng/ml, 2.58 ng/ml, and 20.1 ng/ml, respectively. These values were significantly higher than those obtained from the ABH PLO gel. In conclusion, the ABH Carbopol gel provides a promising alternative to the ABH PLO gel for treating CINV in hospice patients. Further studies are required to validate these findings in clinical settings.

Improving the pharmacotherapeutic treatment of agitation associated with bipolar disorder.

INTRODUCTION: Agitation is commonly encountered in people with bipolar disorder, particularly when experiencing a manic episode. The number of approved pharmacological agents to manage acute episodes of agitation in this population is limited. AREAS COVERED: A search was conducted using the US National Library of Medicine PubMed.gov resource for English-language papers of clinical trials and reviews/meta-analyses, using the text words 'bipolar disorder' AND 'agitation,' as well as any papers with both two text words in the title, without any date restrictions. EXPERT OPINION: Existing pharmacologic options approved by regulatory authorities for the treatment of acute episodes of agitation associated with bipolar disorder have similar degrees of efficacy but differ in their tolerability profiles and ease of use, giving clinicians an opportunity to individualize treatment. The goal is to treat mild-moderate agitation before it evolves into severe agitation, encouraging noninvasive pharmacologic treatment options. Inhaled loxapine and sublingual dexmedetomidine are newer options with rapid onset of action and may be preferable for patients willing to cooperate with treatment.