-
Revista Brasileira de Epidemiologia =... 2023To describe the profile of dispensation of mental health drugs by analyzing trends in use before and during the COVID-19 pandemic within the Unified Health System...
OBJECTIVE
To describe the profile of dispensation of mental health drugs by analyzing trends in use before and during the COVID-19 pandemic within the Unified Health System (Sistema Único de Saúde [SUS]).
METHODS
Pharmacoepidemiological study based on the retrospective analysis of records regarding the dispensation of psychotropic medicines in the SUS database in the state of Minas Gerais between 2018 and 2021, considering the periods before (2018-2019) and during the COVID-19 pandemic (2020-2021). A database with the records of dispensation of municipalities was created, and the consistency of releases was verified using the Analysis of Variance (ANOVA) test. Medicine consumption was measured in a defined daily dose (DDD) per 1,000 inhabitants/day for SUS, and the difference between periods was evaluated using Student's t-test.
RESULTS
During the COVID-19 pandemic, there was an increase in the consumption of psychotropic drugs in SUS-MG. The most consumed medicines were fluoxetine hydrochloride, diazepam and phenobarbital sodium (DDD=5.89; 3.42; 2.49) in the Basic Pharmaceutical Services Component(CBAF), and olanzapine, risperidone and quetiapine hemifumarate (DDD=0.80; 0.47; 0.38) in the Specialized Pharmaceutical Services Component (CEAF). The highest percentage increase in consumption was attributed to clonazepam (75.37%) and lithium carbonate (35.35%), in CBAF, and levetiracetam (3,000.00%) and memantine hydrochloride (340.0%) in CEAF.
CONCLUSION
The change in the psychotropic drug dispensation profile during the COVID-19 pandemic highlights the need to produce more studies to complete, confirm or rule out this profile and monitor the use of psychotropic drugs by the population in the post-pandemic context.
Topics: Humans; Pandemics; Brazil; Retrospective Studies; COVID-19; Psychotropic Drugs
PubMed: 38088718
DOI: 10.1590/1980-549720230059 -
The Canadian Journal of Hospital... 2023Neonatal abstinence syndrome (NAS) is a collection of symptoms that neonates may experience following antenatal exposure to substances that induce withdrawal. Optimal...
BACKGROUND
Neonatal abstinence syndrome (NAS) is a collection of symptoms that neonates may experience following antenatal exposure to substances that induce withdrawal. Optimal management remains unknown, and there is variation in management and outcomes.
OBJECTIVES
To describe the management, length of hospitalization, and adverse events in near-term and full-term neonates with NAS for whom treatment (pharmacotherapy and/or supportive care) was initiated in the neonatal intensive care unit (NICU).
METHODS
A chart review was conducted of neonates admitted to the NICU of Surrey Memorial Hospital, Surrey, British Columbia, who received treatment for NAS between September 1, 2016, and September 1, 2021.
RESULTS
A total of 48 neonates met the inclusion criteria. Opioids represented the most frequent type of antenatal exposure. Polysubstance exposures occurred in 45 (94%) of the neonates. Morphine was given to 29 (60%) of the neonates, and phenobarbital to 6 (13%); 5 of these neonates received both medications. The average duration of morphine treatment was 14 days, and the average length of hospitalization (all patients) was 16 days. All of the neonates experienced adverse events; in particular, 9 (30%) of the 30 who received pharmacotherapy were too sedated to feed, compared with 0% of the 18 with no pharmacotherapy.
CONCLUSIONS
The common finding of polysubstance antenatal exposure, involving predominantly opioids, was associated with scheduled morphine pharmacotherapy for the majority of patients, prolonged hospitalization, and frequent adverse events. Pharmacotherapy for NAS was associated with levels of sedation that interfered with feeding in neonates.
PubMed: 37409149
DOI: 10.4212/cjhp.3381 -
Frontiers in Medicine 2023Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, potentially life-threatening syndromes characterized by the development of necrotic...
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, potentially life-threatening syndromes characterized by the development of necrotic epidermal and mucosal lesions. The most common etiologic cause of SJS/TEN is drug-induced mechanisms. The group of drugs with high potential risk includes sulfonamides, anticonvulsants, non-steroidal anti-inflammatory drugs (NSAIDs), allopurinol, phenobarbital, etc. There is no gold standard treatment algorithm for SJS/TEN. In medical practice, systemic glucocorticosteroids (sGCS), intravenous immunoglobulin (IVIG), plasmapheresis, and cyclosporine are used empirically and in various combinations. Recently published studies have demonstrated the efficacy of TNF-α inhibitors as a promising approach in SJS/TEN, including cases resistant to high-dose sGCS, with etanercept and infliximab being the most commonly used drugs. In a large multicenter study by Zhang J et al. (XXXX), 242 patients treated with etanercept, sGCS, or a combination of both had lower mortality compared to the control group. A shorter skin healing time was documented compared to sGCS monotherapy, thus reducing the risk of secondary infections. The published data show a high efficacy with THF-α inhibitor blockade, but the safety of TNF-α inhibitors in patients with SJS/TEN is still questionable due to the paucity of available information. As all clinical research data should be accumulated to provide reliable evidence that the use of TNF-α inhibitors may be beneficial in SJS/TEN, we report a case of etoricoxib-associated SJS with progression to TEN in a 50-year-old woman who was refractory to high-dose sGCS therapy.
PubMed: 37554504
DOI: 10.3389/fmed.2023.1210026 -
Iranian Journal of Child Neurology 2023Indicatively, phenobarbital can impair thyroid function in adults and children. The present research aims to evaluate the thyroid hormone levels in preterm neonates who...
OBJECTIVES
Indicatively, phenobarbital can impair thyroid function in adults and children. The present research aims to evaluate the thyroid hormone levels in preterm neonates who had received phenobarbital treatment.
MATERIALS &METHODS
This study was conducted on preterm neonates who weighed less or equal to 2500 g when phenobarbital was prescribed for treatment in the first 15 days of life. TSH and total T4 measurements were performed before and three months after initiation of phenobarbital.
RESULTS
In this study, the sum of preterm neonates stood at 94, of which 53 were girls, with a mean birth weight of 2004.41 ± 315.41g. Weight of 8.5% were under 1500 g. The mean gestational age was estimated at 33.64 ± 2.01 weeks. Mean T4 levels were 12.24 ± 1.96 and 12.07 ± 1.95 (p=0.334), and mean TSH levels were 5.34 ± 2.14 and5.15 ± 2.15 (p=0.376) before and after prescribing phenobarbital, respectively. The same results were compared based on sex, gestational age, birth weight, and height for T4 and TSH and T4 based on head circumference. The only significant difference was TSH in preterm infants with head circumference <32 cm before and after prescribing phenobarbital (p=0.030).
CONCLUSION
In preterm newborns that had less than 2500 g birth weight, phenobarbital did not significantly alter the serum thyroid hormone levels.
PubMed: 38074926
DOI: 10.22037/ijcn.v17i4.42583 -
Healthcare (Basel, Switzerland) Apr 2024The primary aim of this study was to conduct a comparative analysis of the safety and efficacy of levetiracetam (LEV) and phenobarbital (PB) as first-line treatments for...
OBJECTIVES AND AIM
The primary aim of this study was to conduct a comparative analysis of the safety and efficacy of levetiracetam (LEV) and phenobarbital (PB) as first-line treatments for neonatal seizure management. This study was designed to measure and compare the incidence of adverse effects and to determine the discharge and mortality rates associated with the use of these antiseizure medications (ASMs). Through this comparison, this research sought to provide insights to optimise care for neonates experiencing seizures.
MATERIALS AND METHODS
This retrospective cohort study evaluated 104 neonates treated for seizures at Zeynep Kamil Hospital from 2015 to 2020 after excluding those on non-PB/LEV antiseizure medications. Seizures were characterised using electroencephalogram (EEG) and categorised according to aetiology and frequency. Treatment efficacy was gauged by seizure cessation, as confirmed using EEG. Adverse effects and demographic data were recorded. Statistical analyses were conducted using SPSS, employing the Shapiro-Wilk, independent -test, Mann-Whitney U test, and chi-square test, with a significance threshold of < 0.05.
RESULTS
Overall, 104 neonates treated with first-line ASM were evaluated for efficacy; PB was administered in 68.26% of the cases, while LEV was utilised in 31.74%. The total complete response rate was 40.38%, with no significant difference between the PB and LEV groups ( = 0.309). The incidence rate ratios (IRRs) demonstrated that seizure frequency profoundly influenced treatment effectiveness, with IRRs of 2.09 for rare seizures, 3.25 for frequent seizures, and 4.01 for status epilepticus, indicating a higher treatment response rate with increasing seizure frequency. For second-line treatment, among a subset of 62 patients, PB had a slight, non-significant advantage over LEV, with an odds ratio of 1.09, suggesting a marginally better response to LEV. Adverse events were significantly more frequent in the PB group, affecting 19 of 67 neonates (28.36%), compared to only 2 of 71 neonates (2.82%) in the LEV group ( < 0.001). No significant difference was observed in the discharge rates between the two groups (PB, 67.61%; LEV, 75.76%; = 0.674). Interestingly, the mortality rate was significantly higher in the LEV group (45.45%) than that in the PB group (22.54%; = 0.045).
CONCLUSION
This study underscores LEV's superior safety profile over PB in neonatal seizure management, evidenced by a significantly lower rate of adverse events. PB seems to be more effective in the second-line treatment of neonatal seizures. Despite the lack of significant differences in the discharge rates, the higher mortality rate associated with LEV warrants further investigation. These findings advocate the cautious selection of antiepileptic drugs in neonatal care, with a preference for LEV based on its safety profile.
PubMed: 38610222
DOI: 10.3390/healthcare12070800 -
RSC Advances Mar 2024An innovative molecularly imprinted polymer membrane (MIPM) was prepared with polyvinylidene difluoride (PVDF) as the support, phenytoin (PHT) as the single template,...
Fabrication of a surface molecularly imprinted polymer membrane based on a single template and its application in the separation and extraction of phenytoin, phenobarbital and lamotrigine.
An innovative molecularly imprinted polymer membrane (MIPM) was prepared with polyvinylidene difluoride (PVDF) as the support, phenytoin (PHT) as the single template, methacrylic acid as the functional monomer, ethylene glycol dimethacrylate as the cross-linking reagent, azobisisobutyronitrile as the initiator, and acetonitrile-dimethylformamide (1 : 1.5, v/v) as the porogen. These materials were characterized scanning electron microscopy, Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller measurements and X-ray photoelectron spectroscopy. Their adsorption performances were evaluated through a series of experiments including isothermal adsorption, kinetic adsorption, selective adsorption, adsorption-desorption, reusability, and preparation reproducibility. Additionally, the application was explored by investigating the extraction recovery of MIPMs towards PHT, phenobarbital (PHB) and lamotrigine (LTG) in different matrices including methanol, normal saline (NS), phosphate buffer solution (PBS) and plasma. The results showed that MIPMs with rough and porous surfaces were successfully constructed, which offered good preparation reproducibility, reusability and selectivity. The adsorption capacities of MIPMs towards PHT, PHB and LTG were 2.312, 2.485 and 2.303 mg g, respectively, while their corresponding imprinting factors were 8.538, 12.122 and 4.562, respectively. The adsorption equilibrium of MIPMs was achieved within 20 min at room temperature without stirring or ultrasonication. The extraction recoveries of MIPMs for PHT, PHB or LTG in methanol, NS and PBS were more than 80% with an RSD% value of less than 3.64. In the case of plasma, the extraction recovery of MIPMs for PHT and PHB was more than 80% with an RSD% value of less than 2.41, while that of MIPMs for LTG was more than 65% with an RSD% value of less than 0.99. All the results indicated that the preparation method for MIPMs was simple, stable, and reliable, and the prepared MIPMs possessed excellent properties to meet the extraction application of PHT, PHB and LTG in different matrices.
PubMed: 38469200
DOI: 10.1039/d4ra00294f -
Basic and Clinical Neuroscience 2023Drug-resistant epilepsy is an unmet medical condition that impacts 30% of epileptic patients. Numerous antiseizure drugs have already been developed but they provide...
INTRODUCTION
Drug-resistant epilepsy is an unmet medical condition that impacts 30% of epileptic patients. Numerous antiseizure drugs have already been developed but they provide only symptomatic relief and do not target the underlying pathogenesis. Preclinical models provide opportunities to gain insights into obscure mechanisms of drug-resistant epilepsy. Current animal models possess lacunae that need rectification and validation to discover novel antiepileptic drugs. The present study aims to validate 3 different doses of phenobarbital at 2 different periods.
METHODS
Pentylenetetrazole was given at a sub-convulsive dose (30 mg/kg/day/intraperitoneal [IP]) for 28 days to develop kindling in male Wistar rats. Further, kindled rats were divided into the following four groups: Pentylenetetrazole control, pentylenetetrazole and phenobarbital (20 mg/kg), pentylenetetrazole and phenobarbital 40 mg/kg, and pentylenetetrazole and phenobarbital (60 mg/kg). They were assessed on days 14 and 28 post-kindling. Seizure scoring, oxidative stress, phenobarbital plasma levels, and histopathology of hippocampal neurons were analyzed.
RESULTS
The results showed that the combination of pentylenetetrazole and phenobarbital (40 and 60 mg/kg) remarkably decreased seizure score, elucidated higher antioxidant effect, and prevented neuronal injury on day 14, whereas increased seizure score, oxidative stress, and neuronal death was observed with chronic administration of pentylenetetrazole and phenobarbital in kindled rats at day 28. Moreover, phenobarbital levels in blood were significantly increased at day 28 of phenobarbital treatment compared to day 14.
CONCLUSION
The adapted protocol with phenobarbital 40 mg/kg dose could be of great potential in screening antiseizure drugs in refractory epilepsy.
PubMed: 38628829
DOI: 10.32598/bcn.2022.3904.1 -
Revista Paulista de Pediatria : Orgao... 2023To analyze the prevalence of off-label and unlicensed prescriptions for a population of neonates admitted to the Neonatal Intensive Care Unit in a hospital in southern... (Observational Study)
Observational Study
OBJECTIVE
To analyze the prevalence of off-label and unlicensed prescriptions for a population of neonates admitted to the Neonatal Intensive Care Unit in a hospital in southern Santa Catarina.
METHODS
Observational study with a cross-sectional design. All neonates admitted to the Intensive Care Unit during the period from March 2020 to March 2021 were included. Data collection was performed through a questionnaire made by the authors and the classification of drugs based on the Electronic Drug Description (Bulário Eletrônico) of the Brazilian Health Regulatory Agency and Drug Dex-Micromedex.
RESULTS
Data from 296 neonates were evaluated. The prevalence was 50,7% for prescribing off-label medications and 37,2% for unlicensed medications. The use of drugs was higher in preterm neonates, with low birth weight, 1st minute Apgar between 6-8, 5th minute Apgar between 7-8, and in need of invasive procedures. The most used off-label drugs were ampicillin, gentamicin and fentanyl (92.6, 92.0 and 26.6%, respectively), whereas the most used unlicensed drugs were caffeine, phenobarbital and bromopride (78.1, 16.3 and 10.9%, respectively).
CONCLUSIONS
This study showed a large percentage of prescriptions made in the off-label (50.7%) and unlicensed (37.2%) form in the Neonatal Intensive Care Unit, corroborating the worrying world scenario. The most exposed neonates were precisely the most vulnerable ones and, among the most commonly prescribed medications, ampicillin and gentamicin stood out in off-label form and caffeine in unlicensed form.
Topics: Infant, Newborn; Humans; Caffeine; Cross-Sectional Studies; Off-Label Use; Intensive Care Units, Neonatal; Ampicillin; Gentamicins
PubMed: 37729244
DOI: 10.1590/1984-0462/2024/42/2023023 -
Frontiers in Pharmacology 2024Phenobarbital (PB) and levetiracetam (LEV) are the first-line therapies for neonates with diagnosed seizures, however, a growing body of evidence shows that these drugs...
Phenobarbital (PB) and levetiracetam (LEV) are the first-line therapies for neonates with diagnosed seizures, however, a growing body of evidence shows that these drugs given during critical developmental windows trigger lasting molecular changes in the brain. While the targets and mechanism of action of these drugs are well understood-what is not known is how these drugs alter the transcriptomic landscape, and therefore molecular profile/gene expression during these critical windows of neurodevelopment. PB is associated with a range of neurotoxic effects in developing animals, from cell death to altered synaptic development to lasting behavioral impairment. LEV does not produce these effects. Here we evaluated the effects of PB and Lev on the hippocampal transcriptome by RNA sequencing. Neonatal rat pups were given a single dose of PB, Lev or vehicle and sacrificed 72 h later-at time at which drug is expected to be cleared. We found PB induces broad changes in the transcriptomic profile (124 differentially expressed transcripts), as compared to relatively small changes in LEV-treated animals (15 transcripts). PB exposure decreased GABAergic and oligodendrocyte markers and , and increased the marker of activated microglia, and the astrocyte- associated gene . These data are consistent with the existing literature showing developmental neurotoxicity associated with PB, but not LEV. The widespread change in gene expression after PB, which affected transcripts reflective of multiple cell types, may provide a link between acute drug administration and lasting drug toxicity.
PubMed: 38606173
DOI: 10.3389/fphar.2024.1340691 -
Neurological Research and Practice Jan 2024Status epilepticus in pregnancy (SEP) is rare and life-threatening for both mother and fetus. There are well-established guidelines for the management of women with...
BACKGROUND
Status epilepticus in pregnancy (SEP) is rare and life-threatening for both mother and fetus. There are well-established guidelines for the management of women with epilepsy during pregnancy; however, there is little evidence guiding the management of SEP, leading to uncertainty among treating physicians. Therefore, this survey aims to investigate the real-world practices of physicians treating SEP to explore management approaches for improvements in care.
METHODS
An anonymous, electronic survey was created and distributed to neurointensivists and neurologists between September and December 2021.
RESULTS
One hundred physicians initiated the survey and 95 completed it in full: 87 (87%, 87/100) identified neurology as their primary specialty, 31 had subspecialty training in neurocritical care, and 48 had subspecialty training in epilepsy and/or clinical neurophysiology. Over half of the survey respondents (67%, 67/100) reported having participated in the management of SEP, with 48.9% (49/98) having done so in the past year. Most survey respondents (73%, 73/100) reported that their management approach to SEP is different than that of non-pregnant patients. Survey respondents were more likely to involve epilepsy consultants when treating SEP (58.5%, 58/99) and the vast majority involved Obstetrics/Maternal Fetal Medicine consultants (90.8%, 89/98). Survey respondents showed a clear preference for levetiracetam (89.7%, 87/97) in the treatment of benzodiazepine refractory status epilepticus followed by lacosamide (61%, 60/98) if an additional second line agent was needed. Valproate and phenobarbital were unlikely to be used. There was less agreement for the management of refractory and super-refractory SEP.
CONCLUSIONS
Levetiracetam is the most frequently used anti-seizure medication (ASM) for benzodiazepine-refractory SEP. Survey participants tended to manage SEP differently than in non-pregnant patients including greater involvement of interdisciplinary teams as well as avoidance of ASMs associated with known teratogenicity.
PubMed: 38233889
DOI: 10.1186/s42466-023-00295-z