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The initial treatment in convulsive status epilepticus in China: A multi-center observational study.Epilepsy Research Nov 2023To investigate the initial treatment of patients with convulsive status epilepticus (CSE) in a resource-limited region of China, and to discuss the difference of... (Observational Study)
Observational Study
OBJECTIVE
To investigate the initial treatment of patients with convulsive status epilepticus (CSE) in a resource-limited region of China, and to discuss the difference of in-hospital outcomes and economic costs between those with guideline-recommended initial treatment and those without.
METHODS
In this retrospective study, we screened adult patients discharged with the diagnosis of CSE in four centers in west China. Individuals with different exposure to the initial drug were divided into benzodiazepine (BDZ) and non-BDZ group for outcome comparison. The primary outcomes were seizure control, and the ratio of patients who developed refractory SE. The secondary outcomes included in-hospital mortality, the modified Rankin Scale (mRS) score at discharge, in-hospital respiratory support rate, length, and cost of the stay.
RESULTS
Three-hundred and thirteen patients (127, 40.6% were women) with CSE were included. The median age was 43 (range 16-92). There were 152 (48.6%) patients initially treated with BDZ. Among the 36 who received midazolam as initial treatment, twenty-six received an insufficient dose. The other 116 (76.3%) patients in the BDZ group chose diazepam as initial treatment. Fifteen of them (12.9%) were treated underdose. In the non-BDZ group (161, 51.4%), antiseizure medications (ASMs) and/or coma-induced drugs were used as initial treatment. Among those initially administrated ASMs, intramuscular phenobarbital (38,37.6%) and valproate (46, 52.3%) were most frequently seen. There was a significant difference in the time latency to initial treatment and etiology between BDZ and non-BDZ group. The non-BDZ group reported a higher cessation rate after initial treatment compared to the BDZ group (P = 0.012). No significant difference in other primary and secondary outcomes.
SIGNIFICANCE
Non-adherence and underdosing of the initial treatment of SE were common in China. However, the non-BDZ group showed a better seizure control rate. The effect came from early aggressive medication, that is, the combination of ASMs and anesthesia. Non-BDZ group was not inferior to BDZs in terms of seizure control, the occurrence of in-hospital death, and poor outcome at discharge. More robust evidence is needed in developing settings when choosing the initial treatment.
Topics: Adult; Humans; Female; Male; Anticonvulsants; Retrospective Studies; Hospital Mortality; Status Epilepticus; Seizures; China
PubMed: 37864968
DOI: 10.1016/j.eplepsyres.2023.107245 -
Frontiers in Cellular Neuroscience 2023The rapid relief of depressive symptoms is a major medical requirement for effective treatments for major depressive disorder (MDD). A decrease in neuroactive steroids...
The rapid relief of depressive symptoms is a major medical requirement for effective treatments for major depressive disorder (MDD). A decrease in neuroactive steroids contributes to the pathophysiological mechanisms associated with the neurological symptoms of MDD. Zuranolone (SAGE-217), a neuroactive steroid that acts as a positive allosteric modulator of synaptic and extrasynaptic δ-subunit-containing GABA receptors, has shown rapid-onset, clinically effective antidepressant action in patients with MDD or postpartum depression (PPD). Benzodiazepines, on the other hand, act as positive allosteric modulators of synaptic GABA receptors but are not approved for the treatment of patients with MDD. It remains unclear how differences in molecular mechanisms contribute to the alleviation of depressive symptoms and the regulation of associated neuronal activity. Focusing on the antidepressant-like effects and neuronal activity of the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC), we conducted a head-to-head comparison study of the neuroactive steroid allopregnanolone and the benzodiazepine diazepam using a mouse social defeat stress (SDS) model. Allopregnanolone but not diazepam exhibited antidepressant-like effects in a social interaction test in SDS mice. This antidepressant-like effect of allopregnanolone was abolished in extrasynaptic GABA receptor δ-subunit knockout mice (δko mice) subjected to the same SDS protocol. Regarding the neurophysiological mechanism associated with these antidepressant-like effects, allopregnanolone but not diazepam increased theta oscillation in the BLA of SDS mice. This increase did not occur in δko mice. Consistent with this, allopregnanolone potentiated tonic inhibition in BLA interneurons via δ-subunit-containing extrasynaptic GABA receptors. Theta oscillation in the mPFC of SDS mice was also increased by allopregnanolone but not by diazepam. Finally, allopregnanolone but not diazepam increased frontal theta activity in electroencephalography recordings in naïve and SDS mice. Neuronal network alterations associated with MDD showed decreased frontal theta and beta activity in depressed SDS mice. These results demonstrated that, unlike benzodiazepines, neuroactive steroids increased theta oscillation in the BLA and mPFC through the activation of δ-subunit-containing GABA receptors, and this change was associated with antidepressant-like effects in the SDS model. Our findings support the notion that the distinctive mechanism of neuroactive steroids may contribute to the rapid antidepressant effects in MDD.
PubMed: 38259500
DOI: 10.3389/fncel.2023.1274459 -
Addiction (Abingdon, England) Oct 2023The aim of this study was to present the first nation-wide, systematic, repeated assessment of doctor-shopping (i.e. visiting multiple physicians to be prescribed the...
AIMS
The aim of this study was to present the first nation-wide, systematic, repeated assessment of doctor-shopping (i.e. visiting multiple physicians to be prescribed the same drug) during 10 years for more than 200 psychoactive prescription drugs in the 67 million inhabitants in France.
DESIGN
This was a nation-wide, repeated cross-sectional study.
SETTING AND PARTICIPANTS
Data are from the French National Health Data System in 2010, 2015 and 2019 for 214 psychoactive prescription drugs (i.e. anaesthetics, analgesics, antiepileptics, anti-Parkinson drugs, psycholeptics, psychoanaleptics, other nervous system drugs and antihistamines for systemic use).
MEASUREMENTS
The detection and quantification of doctor-shopping relied upon an algorithm that detects overlapping prescriptions from repeated visits to different physicians. We used two doctor-shopping indicators aggregated at population level for each drug dispensed to more than 5000 patients: (i) the quantity doctor-shopped, expressed in defined daily doses (DDD), which measures the total quantity doctor-shopped by the study population for a given drug; and (ii) the proportion doctor-shopped, expressed as a percentage, which standardizes the quantity doctor-shopped according to the use level of the drug.
FINDINGS
The analyses included approximately 200 million dispensings to approximately 30 million patients each year. Opioids (e.g. buprenorphine, methadone, morphine, oxycodone and fentanyl), benzodiazepines and non-benzodiazepine hypnotics (Z-drugs) (e.g. diazepam, oxazepam, zolpidem and clonazepam) had the highest proportions doctor-shopped during the study period. In most cases, the proportion and the quantity doctor-shopped increased for opioids and decreased for benzodiazepines and Z-drugs. Pregabalin had the sharpest increase in the proportion doctor-shopped (from 0.28 to 1.40%), in parallel with a sharp increase in the quantity doctor-shopped (+843%, from 0.7 to 6.6 DDD/100 000 inhabitants/day). Oxycodone had the sharpest increase in the quantity doctor-shopped (+1000%, from 0.1 to 1.1 DDD/100 000 inhabitants/day), in parallel with a sharp increase in the proportion doctor-shopped (from 0.71 to 1.41%). Detailed results for all drugs during the study period can be explored interactively at: https://soeiro.gitlab.io/megadose/.
CONCLUSIONS
In France, doctor-shopping occurs for many drugs from many pharmacological classes, and mainly involves opioid maintenance drugs, some opioids analgesics, some benzodiazepines and Z-drugs and pregabalin.
Topics: Prescription Drug Misuse; Prescription Drugs; Cross-Sectional Studies; Psychotropic Drugs; France; Humans; Office Visits
PubMed: 37203878
DOI: 10.1111/add.16261 -
Advances in Clinical and Experimental... Nov 2023Epilepsy is a severe neurological disease that results from excessive and/or synchronized neuronal activity in the brain, and oxidative stress plays a role in its...
BACKGROUND
Epilepsy is a severe neurological disease that results from excessive and/or synchronized neuronal activity in the brain, and oxidative stress plays a role in its pathogenesis. Taxifolin is a flavonoid that exhibits antioxidant activity.
OBJECTIVES
To investigate the effects of taxifolin on caffeine-induced epileptic seizures in rats and reveal the role of antioxidant activity in antiepileptic therapy.
MATERIAL AND METHODS
Forty rats were divided into 4 groups (n = 6/group): caffeine 300 mg/kg group (CG), taxifolin 50 mg/kg + caffeine 300 mg/kg group (TCG), 2 mg/kg diazepam + 300 mg/kg caffeine group (DCG), and a healthy group (HG). Taxifolin was given to the TCG, and diazepam was given to the DCG orally. One hour later, caffeine was injected intraperitoneally into the CG, TCG and DCG rats. The time between the caffeine injection and the contractions (the latency period) was determined. Animals were euthanized 1 h after caffeine injection, and brain tissues were biochemically examined for oxidants and antioxidants.
RESULTS
Taxifolin and diazepam prolonged the latency period to a similar extent (p = 0.549), while taxifolin was more successful in preventing mortality. Taxifolin suppressed the caffeine-induced increase in myeloperoxidase, total oxidant status and oxidative stress index, and decreased total glutathione, superoxide dismutase and total antioxidant status more effectively than diazepam (p < 0.05).
CONCLUSIONS
We showed the relationship between antioxidant activity and epilepsy treatment, and demonstrated that taxifolin may be useful for treating epilepsy.
PubMed: 37962257
DOI: 10.17219/acem/172448 -
PloS One 2024Pulmonary fibrosis caused by lung injury is accompanied by varying degrees of inflammation, and diazepam can reduce the levels of inflammatory factors. Therefore, the...
BACKGROUND AND OBJECTIVE
Pulmonary fibrosis caused by lung injury is accompanied by varying degrees of inflammation, and diazepam can reduce the levels of inflammatory factors. Therefore, the purpose of this study was to determine whether diazepam can inhibit inflammation and ameliorate pulmonary fibrosis by regulating the let-7a-5p/myeloid differentiation factor 88 (MYD88) axis.
METHODS
Lipopolysaccharide (LPS) was used to induce cell pyroptosis in an animal model of pulmonary fibrosis. After treatment with diazepam, changes in cell proliferation and apoptosis were observed, and the occurrence of inflammation and pulmonary fibrosis in the mice was detected.
RESULTS
The results showed that LPS can successfully induce cell pyroptosis and inflammatory responses and cause lung fibrosis in mice. Diazepam inhibits the expression of pyroptosis-related factors and inflammatory factors; moreover, it attenuates the occurrence of pulmonary fibrosis in mice. Mechanistically, diazepam can upregulate the expression of let-7a-5p, inhibit the expression of MYD88, and reduce inflammation and inhibit pulmonary fibrosis by regulating the let-7a-5p/MYD88 axis.
CONCLUSION
Our findings indicated that diazepam can inhibit LPS-induced pyroptosis and inflammatory responses and alleviate pulmonary fibrosis in mice by regulating the let-7a-5p/MYD88 axis.
Topics: Animals; Pyroptosis; Lipopolysaccharides; Mice; Diazepam; Pulmonary Fibrosis; Myeloid Differentiation Factor 88; MicroRNAs; Inflammation; Male; Mice, Inbred C57BL; Disease Models, Animal; Signal Transduction
PubMed: 38875245
DOI: 10.1371/journal.pone.0305409 -
Journal of Ethnopharmacology Jan 2024Rosemary (Rosmarinus officinalis L.) has been widely used as a traditional remedy for insomnia, depression and anxiety in China and Western countries. Modern...
ETHNOPHARMACOLOGICAL RELEVANCE
Rosemary (Rosmarinus officinalis L.) has been widely used as a traditional remedy for insomnia, depression and anxiety in China and Western countries. Modern pharmacological studies have shown that rosemary has important applications in neurological disorders. However, the mechanism of action of rosemary hydrosol in the treatment of insomnia is not known.
AIMS OF THE STUDY
Insomnia is closely linked to anxiety and depression, and its pathogenesis is related to biology, psychology, and sociology. Rosemary is a natural plant that has been used to treat insomnia and depression and has good biological activity, but its material basis and mechanism for the treatment of insomnia are not clear. Here, we report on the role of aqueous extracts of rosemary in the treatment of insomnia.
MATERIALS AND METHODS
The study was based on network pharmacology, using a combination of RNA-sequencing, "quantity-effect" weighting coefficients, and pharmacodynamic experiments. DL-4-chlorophenylalanine (PCPA) was intraperitoneally injected into SD rats to replicate the insomnia model with a blank, model, diazepam, and rosemary hydrosol low-, medium-, and high-dose groups were set up for the experiment. The key pathways in the treatment of insomnia with rosemary hydrosol were analyzed by molecular docking, open field assay, ELISA, western-Blot, Rt-PCR, and immunohistochemical assay.
RESULTS
Rosemary hydrosol was analyzed by GC-MS to identify 19 components. 1579 differential genes were obtained by RNA-Seq analysis, 533 targets for rosemary hydrosol and 2705 targets for insomnia, and 29 key targets were obtained by intersection. The KEGG results were ranked by "quantity-effect" weighting coefficients, resulting in serotonergic synapse was the key pathway for the treatment of insomnia with rosemary hydrosol. Molecular docking results showed that 1,7,7-trimethylbicyclo[2.2.1] heptan-2-one, 3-methyl-4-isopropylphenol, caryophyllene, and citronellol of rosemary hydrosol acted synergistically to achieve a therapeutic effect on insomnia. Caryophyllene acts on the HTR1A target by upregulating 5-HT1AR, leading to increased 5-HT release, and upregulation of ADCY5, cAMP, PKA and GABAA at serotonergic synapses; citronellol upregulated ADCY5 and 1,7,7-trimethylbicyclo[2.2.1] heptan-2-one, and 3-methyl-4-isopropylphenol up-regulated GABAA to improve insomnia symptoms. In open-field experiments, ELISA kits (5-HT, GABA, and DA), Western-blotting, Rt-PCR and immunohistochemical assay experiments, insomnia rats in the low-, medium- and high-dose groups of rosemary hydrosol showed different degrees of improvement compared with the model group.
CONCLUSIONS
It was shown that rosemary hydrosol may exert its therapeutic effects on insomnia through serotonergic synapses by combining RNA-Seq, "quantity-effect" weighting coefficients network pharmacology and pharmacodynamic experiments. We have provided a preliminary theoretical study for the development of rosemary hydrosol additive into a beverage for the treatment of insomnia, but it needs to be studied in depth. This study was conducted in rats and the results have limitations and may not apply to humans.
Topics: Humans; Rats; Animals; Plant Extracts; Rosmarinus; Molecular Docking Simulation; Serotonin; Sleep Initiation and Maintenance Disorders; Rats, Sprague-Dawley
PubMed: 37532071
DOI: 10.1016/j.jep.2023.116984 -
Frontiers in Veterinary Science 2023Emergency seizure disorders such as status epilepticus and cluster seizures are unlikely to cease spontaneously while prolonged seizure activity become progressively...
BACKGROUND
Emergency seizure disorders such as status epilepticus and cluster seizures are unlikely to cease spontaneously while prolonged seizure activity become progressively more resistant to treatment. Early administration of rescue medication in canine epileptic patients, in particular benzodiazepines, at seizure onset by the owners can be life-saving and brain protecting. Clinical studies in dogs evaluating the use of rescue medication in hospital environment exist, however, the owner perspective has not been assessed to date.
HYPOTHESIS OR OBJECTIVES
To evaluate the use of rescue medication in dogs with seizure emergencies by the owner at home.
METHOD
Observational study based on online surveys of owners of dogs with emergency seizure disorders.
RESULTS
The questionnaire was answered by 1,563 dog owners, of which 761 provided complete and accurate answers suitable for analysis. Of these, 71% administered diazepam, 19% midazolam, 6% levetiracetam, 3% lorazepam, and 4% more than one rescue or other medication. Overall, the success rates based on owners' perspective for intranasal midazolam and rectal diazepam were 97 and 63%, respectively. Owners reported a compliance level of 95 and 66% for intranasal midazolam and rectal diazepam administration, respectively.
CONCLUSIONS AND CLINICAL IMPORTANCE
Even though rectal diazepam was the most used rescue medication in this survey population, intranasal midazolam was perceived by the owners as a better option regarding effectiveness, time to seizure cessation and owner compliance.
PubMed: 37850066
DOI: 10.3389/fvets.2023.1278618 -
Zhongguo Yi Xue Ke Xue Yuan Xue Bao.... Oct 2023Objective To explore the inhibitory effects and mechanisms of benzodiazepines on (Hp).Methods The Hp international standard strain ATCC43504 was treated with...
Objective To explore the inhibitory effects and mechanisms of benzodiazepines on (Hp).Methods The Hp international standard strain ATCC43504 was treated with benzodiazepines diazepam,midazolam,and remimazolam,respectively.The treatments with amoxicillin and clarithromycin were taken as the positive controls,and that with water for injection as the negative control.The inhibition zone of each drug was measured by the disk diffusion method.The minimum inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of each drug against Hp were determined.Hp suspension was configured and treated with diazepam and midazolam,respectively.The bacterial suspension without drug added was used as the control group.The concentration of K in each bacterial suspension was measured by an automatic biochemical analyzer before drug intervention(T)and 1(T),2(T),3(T),4(T),5(T),6(T),and 7 h(T)after intervention.Hp urease was extracted and treated with 1/2 MIC diazepam,1 MIC diazepam,2 MIC diazepam,1/2 MIC midazolam,1 MIC midazolam,2 MIC midazolam,1 mg/ml acetohydroxamic acid,and water for injection,respectively.The time required for the rise from pH 6.8 to pH 7.7 in each group was determined by the phenol red coloring method.Results The inhibition zones of diazepam,midazolam,remimazolam,amoxicillin,clarithromycin,and water for injection against Hp were 52.3,42.7,6.0,72.3,60.8,and 6.0 mm,respectively.Diazepam and midazolam showed the MIC of 12.5 μg/ml and 25.0 μg/ml and the MBC of 25 μg/ml and 50 μg/ml,respectively,to Hp.The concentrations of K in the diazepam,midazolam,and control groups increased during T-T compared with those at T(all <0.01).The concentration of K in diazepam and midazolam groups during T-T was higher than that in the control group(all <0.01).The time of inhibiting urease activity in the 1/2 MIC diazepam,1 MIC diazepam,2 MIC diazepam,1/2 MIC midazolam,1 MIC midazolam,and 2 MIC midazolam groups was(39.86±5.11),(36.52±6.65),(38.58±4.83),(39.25±6.19),(36.36±4.61),and(35.81±6.18)min,respectively,which were shorter than that in the acetohydroxamic acid group(all <0.01)and had no significance differences from that in the water for injection group(all >0.05).Conclusion Diazepam and midazolam exerted inhibitory effects on Hp,which may be related to the cleavage of Hp cells rather than inhibiting urease.
Topics: Midazolam; Helicobacter pylori; Urease; Clarithromycin; Benzodiazepines; Diazepam; Amoxicillin; Water; Anti-Bacterial Agents
PubMed: 37927020
DOI: 10.3881/j.issn.1000-503X.15651 -
Cureus Jul 2023Background Dementia is an age-related gradual loss of memory that is progressive in nature. Presently, the most common cause of dementia is Alzheimer's disease (AD),...
Background Dementia is an age-related gradual loss of memory that is progressive in nature. Presently, the most common cause of dementia is Alzheimer's disease (AD), which is treated with donepezil, an anticholinesterase. But it only provides short-term symptomatic improvement. Liraglutide, which is an anti-diabetic drug, stimulates the anti-apoptotic pathway of nerve damage, which helps in regenerating nerve cells; so, it may help in dementia cases. Therefore, this study aimed to explore the effect of liraglutide on learning and memory and to compare its effect with donepezil in diazepam-induced amnesic albino rats. Methodology Twenty healthy male Albino rats weighing 150-200 grams were taken and divided into four groups: A, B, C, and D. Group A rats were normal rats, whereas the rats in groups B, C, and D were made amnesic by the intraperitoneal (i.p.) administration of 0.1 mg per kg of diazepam. Immediately after producing amnesia, group B rats received normal saline, group C received liraglutide, and group D received donepezil through the intraperitoneal route as test drugs. Group A rats received only normal saline. The amnesic effect was measured by the escape latency period, which was measured by using a Morris Water Maize (MWM) instrument. Escape latency is the time (in seconds) to locate the platform from the starting point. The amnesic effect is shown by an increase in escape latency and the anti-amnesic effect by a decrease in escape latency. Escape latency was recorded at 0 hr, 1 hr, 2 hr, 3 hr, and 4 hr after test drug administration. Results Group B rats showed an increase in escape latency, which shows the amnesic effect of diazepam. When group C and group D amnesic rats were treated with liraglutide and donepezil, respectively, a one-hour after-treatment increase in escape latency was seen but after two hours, both groups showed a decrease in escape latency, which indicates the anti-amnesic effect of both drugs. When groups C and D were compared, and the post-hoc highly significant difference (HSD) test was used, there was no significant difference between the two drugs, although the liraglutide-treated group (C) showed a lower anti-amnesic effect. However, group C showed a significant effect as compared to group B rats (p-value <0.05), which indicates the anti-amnesic property of liraglutide as compared to normal saline. Conclusion Liraglutide shows an anti-amnesic property. Since it works by a mechanism different from donepezil, it can be used as add-on therapy with donepezil in dementia patients.
PubMed: 37551235
DOI: 10.7759/cureus.41495 -
Alcohol and Alcoholism (Oxford,... Sep 2023Baclofen may reduce the symptoms of alcohol withdrawal, as an alternative or as an adjuvant for benzodiazepines, but the available data are insufficient to support... (Randomized Controlled Trial)
Randomized Controlled Trial
Baclofen may reduce the symptoms of alcohol withdrawal, as an alternative or as an adjuvant for benzodiazepines, but the available data are insufficient to support baclofen-assisted alcohol withdrawal. This study investigated the need for diazepam during acute alcohol withdrawal in patients receiving baclofen. In a single-blind, dose-dependent randomized controlled trial with three study arms, 63 patients with alcohol use disorder, starting in-patient benzodiazepine-assisted alcohol detoxification, were randomly assigned to receive placebo (n = 18), baclofen 30 mg/day (N = 20), or baclofen 60 mg/day (N = 25) for 7 days. Diazepam was provided as needed based on the withdrawal symptoms stated by Clinical Institute Withdrawal Assessment for Alcohol-revised. The primary outcome measure was the number of patients in need of diazepam during alcohol detoxification. Secondary outcome measure included the between-group difference in the amount of diazepam needed during alcohol detoxification. Using baclofen 60 mg/day, 32% of patients needed additional diazepam compared to 35% on baclofen 30 mg/day and compared to 72% on placebo (P = .013). The median total amount of diazepam needed was significantly lower in patients receiving baclofen 60 mg/day (0 ± 10 mg diazepam) and baclofen 30 mg/day (0 ± 10 mg diazepam) compared to placebo (10 ± 43 mg diazepam; P = .017). Adverse events were comparable between patients on baclofen and placebo. Baclofen can reduce the withdrawal symptoms during alcohol detoxification. Baclofen was well tolerated and may be considered for the management of alcohol withdrawal syndrome, especially useful in situations where benzodiazepines should be withheld, such as patients with liver impairment.
Topics: Humans; Alcoholism; Diazepam; Baclofen; Substance Withdrawal Syndrome; Single-Blind Method; Benzodiazepines; Double-Blind Method
PubMed: 37526038
DOI: 10.1093/alcalc/agad050