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Background: Busulfan at high doses has been associated with a risk of seizures. Phenytoin has been used traditionally as anti-seizure prophylaxis, and benzodiazepines and levetiracetam have been introduced more recently, providing data from retrospective series. The main purpose of this study was to evaluate the effectiveness of oral clonazepam as anti-seizure prophylaxis in adult patients receiving high doses of intravenous busulfan as part of the conditioning regimen for hematopoietic stem cell transplantation. The secondary objectives were to determine the feasibility of this regimen and to analyze the adverse events associated with the use of clonazepam. Methods: This prospective, single-center study included 64 adult patients who received conditioning regimens with high doses of intravenous busulfan and anti-seizure prophylaxis with oral clonazepam, at a dose of 1 mg/8 h, from 12 h before starting treatment with busulfan until 48 h after ending administration. Results: The effectiveness of the prophylaxis was 100%, with no episodes of seizures during busulfan treatment or in the 72 h afterwards. Treatment was feasible, and oral scheduled administration was completed in all patients. Adverse events that could be associated with clonazepam included the onset of somnolence, dizziness, and confusion, mostly mild. Conclusion: The oral clonazepam regimen described in this study has been prospectively shown to be an effective, feasible anti-seizure prophylaxis option with manageable toxicity. [ABSTRACT FROM AUTHOR]

BACKGROUND: Post natal adaptation syndrome is well reported but early presentation of neurological symptoms severe enough to warrant detailed neurological work up is rare. Our aim was to evaluate and describe abnormal early neurological symptoms in infants following in-utero exposure to a varying combination of selective serotonin uptake inhibitor medication and other psychotropic medications, with negative seizure work-up. METHOD: Descriptive case series of infant exposed to selective serotonin uptake inhibitor medication and other psychotropic medications, presenting with early neurologic signs and symptoms within the first 24 hours of life concerning for seizures, who underwent an extensive neurologic evaluation. RESULTS: Five infants met criteria. Infant #1 : 39-weeks gestational age (GA), with escitalopram, clonazepam, gabapentin, methadone exposure, presented with generalized hypertonia and intermittent back-arching. #2 : 40-weeks GA with escitalopram and hydroxyzine exposure, with bilateral arm stiffening and sucking mouth movements. #3 : 34-weeks GA with fluoxetine, quetiapine and clonazepam exposure, presented with decerebrate posturing. #4 : 38-weeks GA with fluoxetine, clonazepam, clonidine, quetiapine and gabapentin exposure, presented with asynchronous tremoring of all extremities. #5 : 35-weeks GA with citalopram, quetiapine exposure, presented with increased tone and posturing of upper extremities. Electroencephalogram was negative for seizures in all infants. CONCLUSION: In-utero exposure to selective serotonin uptake inhibitor medication, especially in combination with other psychotropic medications, may be associated with significant abnormal neurological symptoms, which may not represent true seizures. [ABSTRACT FROM AUTHOR]

Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative condition. This report presents the largest published case series on the condition. The palliative care symptom burden and management of these patients is considered. Early advanced care planning and goals of care discussions are necessary. [ABSTRACT FROM AUTHOR]

Background/Objectives: The treatment of tics and psychiatric comorbidities is crucial when they affect the patient's well-being and relationships. However, the optimal pharmacological treatment (PT) tailored to each patient's phenotype remains unclear. The primary objective of this study is to describe the clinical characteristics and treatment received for tics and psychiatric comorbidities in our cohort of children and adult patients with tic disorders. Additionally, a further aim was to quantify the severity of tics, comorbidities and overall severity, and the overall clinical changes observed during the follow-up. Methods: Retrospective descriptive study of patients with tic disorders under follow-up at our Tic Functional Unit from January 2022 to March 2024. Two independent neurologists retrospectively applied the Clinical Global Impression of Change (CGI-C) and the Clinical Global Impression of Severity (CGI-S) scales at baseline and at last assessment. Results: A total of 36 individuals were included (63.8% males, median age = 18 years, IQR 19): 94.4% with Tourette syndrome (TS), 2.8% with chronic tic disorder (CTD), and 2.8% with provisional tic disorder (PTD). A total of 86% had at least one psychiatric comorbidity, the most common being obsessive–compulsive symptomatology (OCS) (52%), anxiety (52%), and attention deficit hyperactivity disorder (ADHD) (35%). At last assessment, 26 patients (72.2%) were on undergoing PT for tics and 3 were receiving additional botulinum toxin. The most used medication for tics were aripiprazole (46.2%) and clonazepam (46.2%), and for psychiatric comorbidities, SSRIs (42.9%), methylphenidate (19%), and benzodiazepines (57.1%). Overall improvement according to the CGI-C scale was mild (CGI-C 3). Children and adolescents showed greater improvement than adults (CGI-C 2 vs. 3; p = 0.005). Aripiprazole and clonazepam produced similar outcomes in reducing CGI-C. Conclusions: We observed a favorable clinical course in patients treated with aripiprazole and clonazepam, which appear to be better than that obtained with other treatments. We consider that clonazepam may be useful as a first-line monotherapy and as an adjuvant for both tics and comorbidities in selected cases. [ABSTRACT FROM AUTHOR]

Abstract Background Busulfan at high doses has been associated with a risk of seizures. Phenytoin has been used traditionally as anti-seizure prophylaxis, and benzodiazepines and levetiracetam have been introduced more recently, providing data from retrospective series. The main purpose of this study was to evaluate the effectiveness of oral clonazepam as anti-seizure prophylaxis in adult patients receiving high doses of intravenous busulfan as part of the conditioning regimen for hematopoietic stem cell transplantation. The secondary objectives were to determine the feasibility of this regimen and to analyze the adverse events associated with the use of clonazepam. Methods This prospective, single-center study included 64 adult patients who received conditioning regimens with high doses of intravenous busulfan and anti-seizure prophylaxis with oral clonazepam, at a dose of 1 mg/8 h, from 12 h before starting treatment with busulfan until 48 h after ending administration. Results The effectiveness of the prophylaxis was 100%, with no episodes of seizures during busulfan treatment or in the 72 h afterwards. Treatment was feasible, and oral scheduled administration was completed in all patients. Adverse events that could be associated with clonazepam included the onset of somnolence, dizziness, and confusion, mostly mild. Conclusion The oral clonazepam regimen described in this study has been prospectively shown to be an effective, feasible anti-seizure prophylaxis option with manageable toxicity.

Objective To investigate the clinical and nerve electrophysiological features of patients with propriospinal myoclonus (PSM), and to improve the understanding of this disease. Methods A retrospective analysis was performed for the medical records of five patients with PSM who were treated at Electroencephalogram Monitoring Center of our hospital from July 2019 to September 2021. Their clinical and nerve electrophysiological features were summarized, and they were followed up to observe the efficacy of drug treatment. Results All fivepatients met the diagnostic criteria for PSM, among whom there were three male patients and two female patients, with involuntary myoclonus of the body as the main symptom. The age of onset of PSM ranged from 28 to 50 years. There were three patients with idiopathic PSM and two with secondary PSM. All five patients underwent video electroencephalography (V-EEG) and electromyography examinations, and no abnormal discharges were observed du-ring the ictal period, while only electromyographic artifacts were observed. Myoelectricity mainly originated from the abdomen and the trunk, with a conduction velocity of 1.4-13.7 m/s and a burst duration of 100-1 000 ms. Medications such as clonazepam could effectively reduce myoclonic seizuresin PSM patients. Conclusion Understanding the clinical and nerve electrophysiological features of PSM is the key to its diagnosis. V-EEG is an important basis for the differential diagnosis of PSM, characterized by the absence of abnormal discharges during the ictal period and the presence of myoclonic electromyographic bursts on electromyography. Clonazepam has a good therapeutic effect on the symptoms of PSM.

AIMS: Although clonazepam (CLO) and melatonin (MLT) are the most frequently used treatments for REM sleep behavior disorder, the polysomnographic features associated with their use are little known. The aim of this study was to evaluate polysomnographic and clinical parameters of patients with idiopathic/isolated REM sleep behavior disorder (iRBD) treated chronically with CLO, sustained-release MLT, alone or in combination, and in a group of drug-free iRBD patients. METHODS: A total of 96 patients were enrolled: 43 drug-free, 21 with CLO (0.5-2 mg), 20 with sustained-release MLT (1-4 mg), and 12 taking a combination of them (same doses). Clinical variables and polysomnography were collected. RESULTS: Although clinical improvement was reported in all groups, MLT impacted sleep architecture more than the other treatments, with significant and large increase in N3 stage, moderate reduction in N2 and REM sleep, and moderate increase in REM latency. CLO moderately increased the percentage of both REM sleep and especially N2, while reducing N1 and wakefulness. Patients treated with both CLO and MLT did not show major changes in sleep architecture. CONCLUSION: These results suggest that the administration of MLT or CLO impacts (positively) on sleep parameters of iRBD patients. However, there is a need to better stratify patients, in order to treat them in a targeted manner, depending on the patients individual sleep architecture and expected differential effects of these agents.

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Background and Aims: Antipsychotic drugs are critical in managing psychosis but they also carry risks when misused, leading to toxicity. Case Presentation: A patient overdosed on olanzapine, resulting in anticholinergic toxidrome with symptoms like tachycardia and altered mental status. Immediate recognition and management of antipsychotic toxicity-induced toxidromes in emergency settings are crucial. Treatment strategy includes maintaining airway, breathing and circulation along with decontamination. There is no specific antidote. Conclusion: This case underscores the need for emergency physicians to remain vigilant and proactive in identifying and addressing such toxicity by identification of toxidromes to prevent complications and missed diagnosis in emergency department. [ABSTRACT FROM AUTHOR]

Clonazolam is a designer triazolobenzodiazepine first synthesized in 1971 and is primarily used for its anxiolytic and sedative effects. It became a drug of misuse in 2012 and is known for its high potency and long duration of effect. Previous studies of nitrobenzodiazepines, such as nitrazepam, clonazepam, and flunitrazepam, as well as their metabolites, have demonstrated that bacterial species native to the gastrointestinal tract and active during postmortem (PM) decomposition are capable of affecting positivity and compound-to-metabolite ratios. Further studies have not been performed with clonazolam; however, it possesses the nitro functional group necessary for this biotransformation. To understand whether clonazolam may be similarly affected, PM cases (n  = 288) and driving under the influence of drugs (DUID, n  = 54) cases, positive for 8-aminoclonazolam reported by NMS Laboratories from 2020 to 2023, were selected for inclusion in this study. Concentrations of clonazolam and 8-aminoclonazolam were evaluated, and concurrent identification of parent drugs and their metabolites occurred less frequently in PM cases (n  = 1, 0.30% of cases) than in DUID cases (n  = 21, 38% of cases). The clonazolam concentration in one PM case was 13 ng/mL. In DUID cases, the median clonazolam concentration was 4.0 ng/mL and ranged from 2.0 to 10 ng/mL. 8-Aminoclonazolam had median concentrations of 13 and 19 ng/mL, with ranges 2.0–580 and 2.8–59 ng/mL for PM and DUID cases, respectively. Due to the ever-changing landscape of the designer benzodiazepine market, in vitro studies of PM microbial biotransformation of clonazolam are unavailable. The data reported herein provide valuable information in the absence of such studies and represent an alternative method of investigating this phenomenon as a potential cause of parent nitrobenzodiazepine to metabolite conversion. [ABSTRACT FROM AUTHOR]

Background: Anxiety refers to the pathological persistence and intensification of emotional responses to danger, affecting health from psychological and physical aspects. Serotonin is an important neurotransmitter involved in the onset of anxiety. Methods and Results: To explore the biological changes in the formation of anxiety in crustaceans under the regulation of serotonin, we applied the open field-like test method for assessing anxiety states of larval Portunus trituberculatus, a highly aggressive crustacean species with a more simple neural structure compared with rodents and mammals. Compared with the control group, serotonin treatment resulted in a significant decrease in the time spent by the larvae in the central zone, suggesting anxiety-like behavior. Clonazepam treatment reversed this result and provided further evidence that the behavior of larval P. trituberculatus displayed anxiety. Moreover, a non-targeted metabolomic analysis found a significant alteration in the metabolites involved in tryptophan metabolism pathways associated with anxiety, including L-kynurenine, N-acetyl serotonin, and serotonin. These metabolites are involved in the serotonin pathway, the kynurenine pathway, and other pathways that affect anxiety through tryptophan metabolism. There were no significant differences in tryptophan metabolism levels between the control and clonazepam treatment groups. Conclusions: Our results demonstrate the possible existence of anxiety-like behavior in the larvae of P. trituberculatus from two perspectives. Being a species with a simpler neural structure than that of mammals, the larvae of P. trituberculatus offer a convenient model for studying the mechanisms of anxiety in crustaceans. [ABSTRACT FROM AUTHOR]

Clonazepam causes sedation and psychomotor impairment in people. Due to similarities between people and swine in response to benzodiazepines, clonazepam may represent a viable option to produce mild‐to‐moderate tranquillization in pigs. The objective of this study was to determine the pharmacokinetic profile of a single oral dose (0.5 mg/kg) of clonazepam in eight healthy, growing commercial cross pigs. Serial plasma samples were collected at baseline and up to 96 h after administration. Plasma concentrations were quantified using reverse‐phase high‐performance liquid chromatography, and compartment models were fit to time–concentration data. A one‐compartment first‐order model best fits the data. Maximum plasma concentration was 99.5 ng/mL, and time to maximum concentration was 3.4 h. Elimination half‐life was 7.3 h, mean residence time 7.4 h, and apparent volume of distribution 5.7 L/kg. Achieved plasma concentrations exceeded those associated with psychomotor impairment in people although pharmacodynamic effects have not been investigated in pigs. A simulated oral regimen consisting of 0.35 mg/kg administered every 8 h to pigs would achieve plasma concentrations above 32 ng/mL which are shown to produce psychomotor impairment in people. Further studies to test the clinical efficacy of these dosages in commercial and miniature pigs are warranted. [ABSTRACT FROM AUTHOR]

ABSTRACT: Existing data suggest that clozapine has lesser propensity of developing akathisia as compared to first general antipsychotics. Clozapine is mostly used in patients with treatment-resistant schizophrenia, which is a second-generation antipsychotic. Akathisia is one of the rare side effects of clozapine. A 34-year-old woman with a 7-year history of schizophrenia exhibited positive and negative symptoms, initially treated with haloperidol and clonazepam. Despite relief in positive symptoms, she experienced recurring cycles of symptom exacerbation upon discontinuing medication. Because of poor compliance, she was admitted and started on clozapine, reaching 150 mg/day. Although showing symptom improvement, she developed clozapine-induced akathisia, characterized by restlessness and limb movements. Propranolol and a gradual reduction in clozapine alleviated akathisia, supplemented by lorazepam. The Barnes Akathisia Rating Scale dropped to 0 after three weeks. This case highlights the challenges of managing schizophrenia and the importance of tailored medication strategies. The use of clozapine should be customized based on each patient's needs to prevent clozapine-induced akathisia. [ABSTRACT FROM AUTHOR]

[Display omitted] • Investigates the impact of clonazepam on Megaselia scalaris larval development for PMI estimation. • Utilizes the S9 fraction to assess the effect on larval growth of Phase I and II metabolites. • Megaselia scalaris larvae exposed to clonazepam show accelerated development. • Findings suggest potential accuracy implications for PMI estimation in forensic cases. Fly colonization patterns and development are crucial in estimating the post-mortem interval (PMI) of decomposing corpses. Understanding the potential effects of xenobiotics on species development in cadaveric entomofauna is essential for accurate PMI estimation, given their presence in decomposing bodies. Benzodiazepines, commonly prescribed for their anxiolytic, hypnotic, and muscle relaxant effects, are of forensic interest due to their potential for abuse, dependence, intoxication, and overdose-related deaths. This study aimed to explore the effect of clonazepam and its metabolites on Megaselia scalaris , a species commonly used to estimate PMI, the alteration of which could impact the accuracy of said estimation. The S9 biotransformation fraction, an in vitro model consisting of an array of metabolic enzymes, was used to generate phase I and II metabolites for evaluating their effect on M. scalaris development, representing an innovative approach to this type of study. Megaselia scalaris larvae were reared in synthetic growth media under controlled conditions. The study compared different groups: control, clonazepam, and clonazepam with S9 fraction. Larvae were measured daily to determine growth rate, and clonazepam concentrations were analyzed using HPLC-DAD. Results showed that larvae grown in media containing clonazepam or clonazepam with S9 fraction developed faster than control larvae, reaching their pupal stage earlier. Growth rates were also altered in treated groups. In conclusion, the presence of clonazepam and its metabolites accelerated the life cycle of M. scalaris , potentially impacting the accuracy of PMI estimation. These findings underscore the importance of considering xenobiotics in forensic entomological studies for precise post-mortem interval determination. [ABSTRACT FROM AUTHOR]

Transport intoxication in the form of body stuffing, a dangerous practice involving the ingestion or insertion of psychoactive substances into the body to evade detection during drug trafficking, represents a major medical problem that requires immediate attention in the emergency department. Unlike body packing, where substances are encapsulated and swallowed for later extraction, body stuffing involves direct ingestion without wrapping, which greatly increases the risk of serious intoxication and even death. Benzodiazepines, due to their high demand on the black market, are among the most common drugs used in body stuffing. The management of this type of poisoning in the emergency department presents a significant clinical challenge due to the variability in clinical presentation, which can range from drowsiness and confusion to respiratory depression and coma.Rapid and accurate assessment is critical for effective management.The initial focus is on patient stabilization and life support as needed, which may include administration of naloxone to reverse opioid effects, mechanical ventilation for respiratory depression, and management of seizures if they occur.An appropriate approach in the emergency department is crucial to improve the prognosis and quality of life of patients affected by this type of poisoning. Timely intervention and expert management can prevent serious complications and even death. We present the case of a patient with benzodiazepine intoxication with an atypical presentation due to clonazepam transport with bradycardia and its management in an institution in Bogotá-Colombia.

West Nile virus is a mosquito-borne illness that usually presents as asymptomatic or with a viral syndrome, and normally is treated with supportive care or immunotherapy. However, some patients can develop neurologic symptoms of viral meningoencephalitis. This article describes a patient who developed opsomyoclonus, a rare complication of West Nile virus meningoencephalitis. She was treated with immunotherapy with no resolution of her symptoms. Symptom improvement occurred with subsequent treatment with clonazepam and dexamethasone. [ABSTRACT FROM AUTHOR]

Abstract Burning mouth syndrome (BMS) is characterized by burning sensations in the oral region without corresponding abnormalities and is often accompanied by uncomfortable sensations. Herein, we present cases of BMS in which the remaining uncomfortable sensations improved with perospirone augmentation with clonazepam. Case 1: A 61‐year‐old man complained of a burning pain in his tongue, a sensation of dryness and discomfort as if his tongue was sticking to a palatal plate. With the diagnosis of BMS, psychopharmacotherapy was initiated with amitriptyline. At the dose of amitriptyline 50 mg, the pain lessened but uncomfortable sensations persisted. Further attempts to alleviate symptoms by combining aripiprazole with amitriptyline, aripiprazole with mirtazapine, or aripiprazole with clonazepam were limited; however, nearly all symptoms were relieved by a combination of perospirone 8.0 mg with clonazepam 1.5 mg. Case 2: A 51‐year‐old woman complained of a burning sensation along with oral dryness and crumb‐like feeling on her tongue. She was diagnosed with BMS and began treatment with amitriptyline. Her burning sensation improved at the dose of 25 mg, but uncomfortable sensations persisted. Augmentation of amitriptyline with aripiprazole, aripiprazole either with valproate, mirtazapine, or clonazepam failed to produce a significant improvement. However, a regimen of perospirone 6.0 mg and clonazepam 1.5 mg relieved the crumb‐like sensation and pain and culminated in a stabilized condition. The reported cases suggested that multiple approaches targeting the dopaminergic circuit in basal ganglia involving the serotoninergic and GABA systems, through the administration of perospirone with clonazepam is an effective adjunctive treatment for the remaining uncomfortable sensations in patients with BMS.

INTRODUCTION: This guideline establishes clinical practice recommendations for the management of rapid eye movement sleep behavior disorder (RBD) in adults. METHODS: The American Academy of Sleep Medicine (AASM) commissioned a task force of experts in sleep medicine to develop recommendations and assign strengths based on a systematic review of the literature and an assessment of the evidence using Grading of Recommendations, Assessment, Development and Evaluation methodology. The task force provided a summary of the relevant literature and the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations that support the recommendations. The AASM Board of Directors approved the final recommendations. GOOD PRACTICE STATEMENT: The following good practice statement is based on expert consensus, and its implementation is necessary for the appropriate and effective management of patients with RBD: It is critically important to help patients maintain a safe sleeping environment to prevent potentially injurious nocturnal behaviors. In particular, the removal of bedside weapons, or objects that could inflict injury if thrown or wielded against a bed partner, is of paramount importance. Sharp furniture like nightstands should be moved away or their edges and headboard should be padded. To reduce the risk of injurious falls, a soft carpet, rug, or mat should be placed next to the bed. Patients with severe, uncontrolled RBD should be recommended to sleep separately from their partners, or at the minimum, to place a pillow between themselves and their partners. RECOMMENDATIONS: The following recommendations, with medications listed in alphabetical order, are a guide for clinicians in choosing a specific treatment for RBD in adults. Each recommendation statement is assigned a strength (strong or conditional). A strong recommendation (ie, We recommend…) is one that clinicians should follow under most circumstances. A conditional recommendation (ie, We suggest…) is one that requires that the clinician use clinical knowledge and experience and strongly consider the patients values and preferences to determine the best course of action. UNLABELLED: Adult patients with isolated RBD. UNLABELLED: 1. The AASM suggests that clinicians use clonazepam (vs no treatment) for the treatment of isolated RBD in adults. (CONDITIONAL). UNLABELLED: 2. * The AASM suggests that clinicians use immediate-release melatonin (vs no treatment) for the treatment of isolated RBD in adults. (CONDITIONAL). UNLABELLED: 3. * The AASM suggests that clinicians use pramipexole (vs no treatment) for the treatment of isolated RBD in adults. (CONDITIONAL). UNLABELLED: 4. The AASM suggests that clinicians use transdermal rivastigmine (vs no treatment) for the treatment of isolated RBD in adults with mild cognitive impairment. (CONDITIONAL). UNLABELLED: Adult patients with secondary RBD due to medical condition. UNLABELLED: 5. * The AASM suggests that clinicians use clonazepam (vs no treatment) for the treatment of secondary RBD due to medical condition in adults. (CONDITIONAL). UNLABELLED: 6. * The AASM suggests that clinicians use immediate-release melatonin (vs no treatment) for the treatment of secondary RBD due to medical condition in adults. (CONDITIONAL). UNLABELLED: 7. The AASM suggests that clinicians use transdermal rivastigmine (vs no treatment) for the treatment of secondary RBD due to medical condition (Parkinson disease) in adults. (CONDITIONAL). UNLABELLED: 8. * The AASM suggests that clinicians not use deep brain stimulation (DBS; vs no treatment) for the treatment of secondary RBD due to medical condition in adults. (CONDITIONAL). UNLABELLED: Adult patients with drug-induced RBD. UNLABELLED: 9. * The AASM suggests that clinicians use drug discontinuation (vs drug continuation) for the treatment of drug-induced RBD in adults. (CONDITIONAL). UNLABELLED: * The Recommendations section of this paper includes remarks that provide additional context to guide clinicians with implementation of this recommendation. CITATION: Howell M, Avidan AY, Foldvary-Schaefer N, et al. Management of REM sleep behavior disorder: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2023;19(4):759-768.

The global concern over water pollution caused by contaminants of emerging concern has been the subject of several studies due to the complexity of treatment. Here, the synthesis of a graphene oxide-based magnetic material (GO@Fe3O4) produced according to a modified Hummers' method followed by a hydrothermal reaction was proposed; then, its application as a photocatalyst in clonazepam photo-Fenton degradation was investigated. Several characterization analyses were performed to analyze the structure, functionalization and magnetic properties of the composite. A 23 factorial design was used for the optimization procedure to investigate the effect of [H2O2], GO@Fe3O4 dose and pH on clonazepam degradation. Adsorption experiments demonstrated that GO@Fe3O4 could not adsorb clonazepam. Photo-Fenton kinetics showed that total degradation of clonazepam was achieved within 5 min, and the experimental data were better fitted to the PFO model. A comparative study of clonazepam degradation by different processes highlighted that the heterogeneous photo-Fenton process was more efficient than homogeneous processes. The radical scavenging test showed that O 2 · - was the main active free radical in the degradation reaction, followed by hydroxyl radicals (•OH) and holes (h+) in the valence layer; accordingly, a mechanism of degradation was proposed to describe the process. [ABSTRACT FROM AUTHOR]

Background and Aims: High-pressure liquid chromatography (HPLC) data on the effects of various chromatographic conditions on the retention behaviour of three different psychotropic drugs; clonazepam, diazepam, and oxazepam) were considered for simulation using a machine learning approach. Methods: For the simulation of selected psychoactive compounds using HPLC, different machine learning techniques were used in this study: adaptive neuro-fuzzy inference system, multilayer perceptron, Hammerstein-Weiner model, and a traditional linear model in the form of stepwise linear regression. Four evaluation criteria were used to assess the effectiveness of the models: coefficient of determination, root mean squared error, mean squared error, and correlation coefficient. Results: The results show that machine learning approaches, especially multilayer perceptions, are more reliable than classical linear models with an average coefficient of determination value of 0.98 in both calibration and validation phases. Conclusion: The performance results also demonstrate that these models can be improved using additional approaches, such as hybrid models, ensemble machine learning, evolving algorithms, and optimisation techniques. [ABSTRACT FROM AUTHOR]

Aim: To compare the efficacy of intravenous clonazepam (CLZ) for the initial management of convulsive status epilepticus (CSE) in children as a function of the first‐line in‐hospital dose used. Method: This monocentric retrospective study included children who received a first dose of CLZ for CSE at Montpellier University Hospital, France, between January 2016 and June 2019. Data from medical records (clinical, treatment, course) were collected and compared as a function of the first CLZ dose used. Results: Among the 310 children treated for CSE, 105 received at least one CLZ dose (median age 3 years; quartile 1–quartile 3 [Q1–Q3] = 1 years 2 months–6 years 6 months). Among these 105 patients, 24 (22%) received a dose less than 0.03 mg/kg (low dose) and 69 (65%) received a dose of at least 0.03 mg/kg (high dose). Seizure cessation rate was not different between the low‐ and high‐dose groups (62.5% vs 76%; odds ratio 0.53, 95% confidence interval [CI] 0.19–1.44, p = 0.29). The administration of a second dose of CLZ was more frequent in the low‐ than the high‐dose group (37.5% vs 16%; odds ratio 3.2, 95% CI 1.1–9.1, p = 0.04). Interpretation: Our study did not find any difference in seizure termination rate as a function of CLZ dose in children with CSE. However, a second CLZ dose was more frequently needed in the group receiving low (less than 0.03 mg/kg) CLZ. [ABSTRACT FROM AUTHOR]

Background: Tracheostomy ventilation in motor neurone disease is an uncommon life-sustaining treatment. Best practice is having a plan for ventilation withdrawal, but the literature to guide practice is limited. Case reports have documented standard doses of opioids and benzodiazepines used for sedation in such cases. Case: A 49-year-old man was diagnosed with motor neurone disease in 2016. He commenced tracheostomy ventilation in 2018. In 2022 and 2023, planning was undertaken, at the patient's request, for withdrawal of tracheostomy ventilation at home, when he was no longer able to communicate with technology. Case planning: Planning included Bispectral Index monitoring prior to cessation of ventilation, ensuring this only occurred when deep sedation was achieved. After ventilation withdrawal in 2023, a retrospective review of medications given and his level of sedation on monitoring was undertaken, with family consent. Outcome: Ventilation withdrawal was initiated after deep sedation was achieved, 6 h after commencing subcutaneous infusions of morphine, midazolam, clonazepam and phenobarbital. Lessons: Doses required to achieve acceptable sedation exceeded literature reports. Achieving deep sedation was a longer than expected process. Conclusion: More research using an objective measure of sedation is required, as clinical assessment of sedation in this context is compromised. [ABSTRACT FROM AUTHOR]

The article focuses on a case of Painful Legs and Moving Toes Syndrome (PLMT) that initially resembled somatic symptom disorder. Topics include the clinical characteristics of PLMT, diagnostic challenges due to its rarity and varied symptomatology, and the differential diagnosis process involving neurophysiological studies to distinguish it from other conditions.

Despite the necessity of the study of therapeutic drug monitoring of clonazepam (CLZ), there are only a few fast detection methods available for determining CLZ in biological media. This study aims to develop a cost‐effective and ratiometric probe for the quantification of CLZ in plasma samples. Fluorescent polydopamine nanoparticles were produced through a self‐polymerization process at a pH of 8.5. Rhodamine B molecules were employed as a fluorescent reference material, emitting stable fluorescence in the visible range. The fabricated probe exhibited a specific detection capability for CLZ. The fluorescence emission of the probe was enhanced in two concentration ranges: from 50 ng/mL to 1.0 μg/mL and from 1.0 to 15.0 μg/mL with a lower limit of quantification of 50 ng/mL, indicating the sensitivity of the probe for detecting CLZ plasma levels. The accuracy of the probe is favorable which could be recommended for CLZ monitoring in the biological media. Furthermore, this probe is highly specific towards CLZ in the presence of various interfering agents which is mainly caused by its ratiometric nature. The developed platform showed high reliability in quantifying CLZ concentrations in patients' plasma samples. Hence, the fabricated probe could be recommended as a reliable method for the routine detection of CLZ in clinical settings. [ABSTRACT FROM AUTHOR]

The article discusses research which investigated physician approaches to the pharmacologic dystonia treatment in people with cerebral palsy. The study surveyed physician approaches regarding medications for dystonia in CP including baclofen, trihexyphenidyl, gabapentin, carbidopa/levodopa, clonazepam, diazepam, clonidine, tetrabenazine, clobazam and cannabidiol. It described physician's prescribing practices and choice of medications for dystonia.

The article focuses on hereditary hyperekplexia (HPX), a rare disorder characterized by exaggerated startle response and generalized muscle stiffness, often presenting in infancy. It discusses the standard treatment with clonazepam and explores the novel use of trihexyphenidyl to alleviate persistent generalized stiffness episodes in patients unresponsive to clonazepam.

Background: Hypertrophic olivary degeneration (HOD) is a unique type of neuronal degeneration presenting as hypertrophy, in contrast to atrophy as seen in most cases. It presents with classical characteristic clinical features due to involvement of dentate-rubral-olivary pathway, also described as triangle of Guillain and Mollaret formed in midbrain, pons and cerebellum. It can be idiopathic or secondary to infarction, bleeding, tumours, trauma or demyelination. However, the mechanism is still unclear. Herein, we present a case of HOD that had developed after post-traumatic pontine and midbrain haemorrhagic contusion. Case presentation: A young male patient presented with progressively increasing tremors of both hands, inability to walk and multiple cranial nerve palsy. Magnetic resonance imaging demonstrated bilateral inferior olivary nucleus enlargement and signal changes seen as T2 and T2-FLAIR hyperintensities and non-enhancing T1 iso-intensities. Based on these features, diagnosis of HOD was made. Patient was kept on conservative management and his condition improved. Conclusions: Hypertrophic olivary degeneration is a unique neuronal degeneration with typical clinical manifestations and distinct imaging features. Proper and early recognition and multidisciplinary treatment approach can result in the best outcomes for the patient. [ABSTRACT FROM AUTHOR]

Sleep-related eating disorder (SRED) is a non-REM parasomnia with potentially significant negative effects on general health (dangerous activities during night eating episodes, obesity, or metabolic syndrome, for example). Although the history of SRED encompasses more than six decades, public awareness and even the awareness of the mental health specialists of this disorder is very limited, a phenomenon that hinders the development of research in this field. Therefore, a systematic review based on PRISMA 2020 guidelines explored the available evidence for SRED found in four electronic databases (PubMed, Cochrane Collaboration, Google Scholar, and Clarivate/Web of Science). A number of 94 primary and secondary reports were retrieved, investigating aspects regarding the risk factors, epidemiology, clinical data and differential diagnosis, epidemiology, structured evaluation, and treatment of SRED. Based on the results of these reports, Z-drugs, but also certain benzodiazepines, antidepressants, antipsychotics, and psychostimulants may trigger the onset of SRED. Psychiatric and neurologic disorders have also been associated with SRED, either as risk factors or comorbid conditions. Cerebral glucose metabolism dysfunctions, neurotransmitter dysfunctions, and genetic factors have been invoked as pathogenetic contributors. Structured assessment of SRED is possible, but there is a dearth of instruments dedicated to this purpose. Data on the prevalence and treatment of SRED exist, but good-quality epidemiological studies and clinical trials are still missing. In conclusion, future research is expected to address the shortcomings of SRED exploration by creating the conditions for better quality and larger group clinical research. The need for such investigation is granted by the importance of this pathology and its negative functional consequences. [ABSTRACT FROM AUTHOR]

There is a lack of objective indicators to evaluate the treatment effect of burning mouth syndrome, a neuropathic pain of unknown causes. Therefore, this study aimed to evaluate potential salivary biomarkers by analyzing saliva before and after clonazepam treatment in patients with burning mouth syndrome. Saliva was collected from 23 patients with burning mouth syndrome before and 4 weeks after the topical administration of clonazepam. Patients were classified as responders (pain relief of 50% or more, n = 10) or non-responders (n = 13) based on pain relief after treatment. Clinical examination data of responders and non-responders were compared using Mann-Whitney U test and Fisher's exact test. Changes in the level of salivary biomarkers (salivary α-amylase, cortisol, calmodulin, α-enolase and interleukin-18) were evaluated before and after treatment using Wilcoxon signed-rank sum test, and their association with treatment response was examined using Fisher's exact test. The salivary biomarker levels showed no significant differences between the responders and non-responders. However, the change in salivary α-amylase activity after treatment revealed a significant difference between the two groups (p = 0.039). Although not all patients showed the same pattern, there was a difference in the alteration of salivary α-amylase activity before and after treatment between responders and non-responders. Further study is required to clarify whether there is a causal relationship between salivary α-amylase activity and treatment response. However, considering that salivary α-amylase activity is related to orofacial pain and psychological stress, this suggests the potential use of salivary α-amylase as a biomarker for burning mouth syndrome. [ABSTRACT FROM AUTHOR]

Burning mouth syndrome (BMS) is characterized by burning sensations in the oral region without corresponding abnormalities and is often accompanied by uncomfortable sensations. Herein, we present cases of BMS in which the remaining uncomfortable sensations improved with perospirone augmentation with clonazepam. Case 1: A 61‐year‐old man complained of a burning pain in his tongue, a sensation of dryness and discomfort as if his tongue was sticking to a palatal plate. With the diagnosis of BMS, psychopharmacotherapy was initiated with amitriptyline. At the dose of amitriptyline 50 mg, the pain lessened but uncomfortable sensations persisted. Further attempts to alleviate symptoms by combining aripiprazole with amitriptyline, aripiprazole with mirtazapine, or aripiprazole with clonazepam were limited; however, nearly all symptoms were relieved by a combination of perospirone 8.0 mg with clonazepam 1.5 mg. Case 2: A 51‐year‐old woman complained of a burning sensation along with oral dryness and crumb‐like feeling on her tongue. She was diagnosed with BMS and began treatment with amitriptyline. Her burning sensation improved at the dose of 25 mg, but uncomfortable sensations persisted. Augmentation of amitriptyline with aripiprazole, aripiprazole either with valproate, mirtazapine, or clonazepam failed to produce a significant improvement. However, a regimen of perospirone 6.0 mg and clonazepam 1.5 mg relieved the crumb‐like sensation and pain and culminated in a stabilized condition. The reported cases suggested that multiple approaches targeting the dopaminergic circuit in basal ganglia involving the serotoninergic and GABA systems, through the administration of perospirone with clonazepam is an effective adjunctive treatment for the remaining uncomfortable sensations in patients with BMS. This is the first report introduced cases of BMS where patients' remained discomfort was ameliorated by perospirone augmentation with clonazepam, which approaches multiply to dopaminergic circuit in basal ganglia involving serotoninergic and GABA system. It may be as effective adjunctive treatment for the remaining uncomfortable sensations in the patients with BMS. [ABSTRACT FROM AUTHOR]

In this study, a new chemical modifier based on copper nitrate hydroxide-containing mesoporous silica decorated with a C3N4 framework (MSN/C3N4/CNH) was developed to design a modified sensor for the determination of clonazepam (CZP). The resulting composite was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), energy-dispersive X-ray spectroscopy (EDS), simultaneous thermal analysis (STA), Brunauer-Emmett-Teller (BET) and Barrett Joyner–Halenda (BJH) analyses. The fabricated electrochemical sensor which was designed with a new modified glassy carbon electrode (GCE) for CZP analysis, exhibits outstanding electrocatalytic activities toward the reduction of CZP. The results showed that significant sensitivity compared to existing methods improved with an excellent detection limit of 2.50 nmol L−1 for the CZP detection, and the modified electrode has high activity toward the oxidation and reduction of CZP, with an oxidation peak around 0.32 V, and a lower reduction peak around −0.78 V; at pH = 7.0. The effect of experimental and instrumental factors on the electrochemical sensor response was examined, and the cyclic voltammetric results confirmed the 4H+/4e− process in the electrochemical studies. Moreover, in differential pulse voltammetry, the reduction peak current was proportional toward the CZP concentration from 0.82 to 76.90 μmol L−1, at optimum conditions. The modified electrode showed good reproducibility, and repeatability with relative standard deviation values of 2.7% and 1.2%, respectively. The proposed method can be applied as a simple, selective, and precise method to determine CZP drug in real samples, with satisfactory results.

The article describes the case of a 34-year-old man with a four-day history of fever and abnormal behavior in the form of irritability, easily being annoyed, and restlessness. A diagnosis of febrile encephalopathy was made and tests were performed to identify the cause. He received antibiotics, atenolol, pantoprazole, and clonazepam but did not improve his condition and he became drowsy and less communicative. The patient met the criteria for serotonin syndrome and responded to cyproheptadine.

Key Clinical Message: Clonazepam has some evidence in the treatment of tardive dyskinesia. It can be used as an alternative treatment option in situations where vesicular monoamine transporter 2 inhibitors are not available or when it is not feasible to use them. [ABSTRACT FROM AUTHOR]

Objective: Burning mouth syndrome (BMS) is a chronic pain disorder characterized by intraoral burning or dysaesthetic sensation, with the absence of any identifiable lesions. Numerous treatments for BMS have been investigated, though without conclusive results. An analysis was conducted of the efficacy of treatment with a low-level diode laser and clonazepam in patients with BMS, and a study was carried out on the levels of different salivary biomarkers before and after treatment. Material and methods: A randomized, single-blind clinical trial was carried out involving 89 patients divided into the following groups: group 1 (laser, The Helbo® Theralite Laser 3D Pocket Probe + clonazepam) (n = 20), group 2 (sham laser placebo) (n = 19), group 3 (laser) (n = 21) and group 4 (clonazepam) (n = 18). Symptom intensity was scored based on a visual analogue scale (VAS). Sialometry was performed before and after treatment, and the Xerostomia Inventory, Oral Health Impact Profile-14 (OHIP-14) and Mini-Nutritional Assessment (MNA) questionnaires were administered. The following markers were measured in saliva samples: interleukins (IL2, IL4, IL5, IL6, IL7, IL8, IL1β, IL10, IL12, IL13, IL17, IL21 and IL23), proteins (MIP-3α, MIP-1α and MIP-1β), GM-CSF, interferon gamma (IFNγ), interferon-inducible T-cell alpha chemoattractant (ITAC), fractalkine and tumor necrosis factor α (TNFα). Results: A significant decrease in the VAS scores was observed after treatment in group 1 (laser + clonazepam) (p = 0.029) and group 3 (laser) (p = 0.005). In turn, group 3 (laser) showed a decrease in the salivary concentration of fractalkine (p = 0.025); interleukins IL12 (p = 0.048), IL17 (p = 0.020), IL21 (p = 0.008), IL7 (p = 0.001) and IL8 (p = 0.007); proteins MIP1α (p = 0.048) and MIP1β (p = 0.047); and TNFα (p = 0.047) versus baseline. Following treatment, group 1 (laser + clonazepam) showed significant differences in IL21 (p = 0.045) and IL7 (p = 0.009) versus baseline, while group 4 (clonazepam) showed significant differences in IL13 (p = 0.036), IL2 (p = 0.020) and IL4 (p = 0.001). No significant differences were recorded in group 2 (sham laser placebo). Conclusions: The low-level diode laser is a good treatment option in BMS, resulting in a decrease in patient symptoms and in salivary biomarkers. However, standardization of the intervention protocols and laser intensity parameters is needed in order to draw more firm conclusions. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is a rare neurodegenerative disorder with a distinct phenotype, including involuntary movements, cognitive decline, and behavioral disturbances. Sleep disorder include insomnia, increased sleep onset latency, decrease in total sleep time with frequent nocturnal awakenings and excessive daytime sleepiness. Increased sleep motor activities and abnormal nocturnal agitation have been increasingly recognized as an important component affecting negatively the sleep quality. Here, we report a case of an intensification of diurnal choreic movement during the night, notably during REM-sleep in a patient with manifest HD. This case highlights the diversity of nocturnal sleep motor disorders encountered in HD. [ABSTRACT FROM AUTHOR]

Background: The goal of the present study was to compare the efect of clonazepam tablets with Noma syrup (lettuce leaf extract) on the insomnia severity in hemodialysis patients. Methods: This randomized controlled clinical trial study was carried out with 95 eligible patients that were included in 2 groups: intervention (n = 46) and control (n = 49). Noma syrup (20 mL) was prescribed to the intervention group half an hour before going to sleep every night, and 0.5 mg of clonazepam tablets was also given to the control group half an hour before going to bed for 2 weeks. The insomnia severity index (ISI) was completed by both groups before and 2 weeks afer the intervention. Results: The insomnia severity in the noma syrup and control groups before the intervention was 8 ± 1.77 and .20.81 ± 1.86, respectively (P = .009). But the postintervention insomnia severity in the Noma and clonazepam groups was 17.45 ± 4.13 and 16.46 ± 3.01, which was not signifcant (P = .184). The analysis of the preintervention insomnia severity index did not reveal a signifcant relationship among the studied groups in relation to the postintervention sleep scores. Conclusion: According to the results, Noma syrup and clonazepam tablets were equally eficient in treating the insomnia of hemodialysis patients. [ABSTRACT FROM AUTHOR]

Objectives: The impact of benzodiazepine use on mortality in patients with chronic non‐cancer pain (CNCP) has not been identified. We aimed to examine the factors associated with benzodiazepine use among patients with CNCP and examine whether long‐term benzodiazepine usage is associated with mortality in patients with CNCP. Methods: This study was conducted using data from the National Health Insurance Service database of South Korea. We selected 2.5% of all adult patients diagnosed with musculoskeletal diseases (MSD) in South Korea from 2010 to 2019 using a stratified random sampling technique and included them in the analysis as patients with CNCP. The risk of 10‐year all‐cause mortality in patients with CNCP was investigated using the 2010 cohort of patients with CNCP. Results: The proportion of the study population that used benzodiazepine during the 10‐year study period was 2.1% (390,683/18,770,234). Multivariable logistic regression showed that old age; increased Charlson comorbidity index (CCI); opioid, gabapentin or pregabalin, paracetamol, non‐steroidal anti‐inflammatory drugs, and Z‐drugs usage; and underlying psychiatric comorbidities were associated with increased benzodiazepine use. In addition, benzodiazepine use was associated with increased 10‐year all‐cause mortality (adjusted hazard ratio: 1.03, 95% confidence interval: 1.01, 1.06; p < 0.001). Conclusions: Benzodiazepine was prescribed to 2.1% of the patients with CNCP in South Korea from 2010 to 2019. Old age, increased CCI, underlying psychiatric comorbidities, and use of certain drugs are associated with increased use of benzodiazepines. In addition, benzodiazepine use is associated with 10‐year all‐cause mortality in patients with CNCP. [ABSTRACT FROM AUTHOR]

Stiff person syndrome (SPS) is a disease characterized by rigidity in the extremities, axial muscles, and abdominal muscles, severe and painful spasms, and accompanying gait disturbances. Stiff person syndrome is most common in adults between the ages of 20 to 50 and in female sex. The most frequently reported antibody in patients with SPS is antibodies developed against glutamic acid decarboxylase enzyme. In this article, two SPS cases from different age groups who presented with gait disturbance and painful spasms and were found to have glutamic acid decarboxylase antibody positivity were reported with clinical and electrophysiological findings in the light of the literature. As in our cases, SPS should be considered in the differential diagnosis of patients of all age presenting with muscle stiffness and spasms, specifically those that increase with stimulus. [ABSTRACT FROM AUTHOR]

Objectives: On 11 March 2020, the World Health Organization (WHO) announced the detection of a new virus epidemic in Wuhan, China. Many studies have shown that the SARS-CoV-2 virus can cause mental disorders, such as anxiety, depression, and bipolar disorder. Here, we presented a case without a history of psychiatric illness. After contracting... [ABSTRACT FROM AUTHOR]