Phenobarbital Group Research Articles

The protective role of oleuropein against diethylnitrosamine and phenobarbital induced damage in rats

Abstract Objective Liver cancer is amongst the most lethal cancers worldwide. Diethylnitrosamine (DEN) and phenobarbital (PB) are common agents that form reactive oxygen species (ROS). Oleuropein (OLE) has efficient biological properties and used as a therapeutic agent. In this study, we aimed at investigating OLE against DEN + PB induced liver damage. Methods Adult Sprague-Dawley rats were divided into 5 groups (n = 10): Control, DEN, DEN + PB, DEN + PB + OLE and OLE. DEN, DEN + PB, DEN + PB + OLE groups were administered a single dose of 150 mg/kg DEN. After two weeks, DEN + PB and DEN + PB + OLE groups received 500 ppm of PB. 10 mg/kg/day of OLE was orally administered to DEN + PB + OLE and OLE groups. Biochemical and histopathological changes evaluated after the 8 weeks study. Results DEN and PB application with OLE treatment resulted significant differences, alone or combined. Although there was a significant difference among the groups in terms of liver GSH and MDA levels and CAT activities, there was no significant difference among the groups in SOD activity. In the liver sections of the DEN, DEN + PB and OLE groups, increase in some histopathological findings and TUNEL positive cells were increased compared to the control group. Conclusion OLE can be used as a protector against the effects of carcinogens causing liver damage.

Efficacy of phenobarbital and sodium valproate in treating convulsive epilepsy in rural northeast China

PurposePhenobarbital and sodium valproate are broad spectrum and inexpensive antiepileptic drugs that are used to treat convulsive epilepsy. We examined the therapeutic effects of phenobarbital and sodium valproate in patients with convulsive epilepsy in the rural northeast China, and discuss our efforts to ensure patients’ compliance. MethodsPatients with convulsive epilepsy were screened by trained township health center doctors. Patients in the phenobarbital group were enrolled between January 2011 and December 2012, and followed up until December 2017. Patients in the sodium valproate group were enrolled between January 2011 and December 2017, and followed up for 1 year. Efficacy of phenobarbital or sodium valproate was assessed by the reduction in seizure frequency. ResultsA total of 1200 patients were diagnosed by screening and rechecking, of which 925 patients received phenobarbital and 275 received sodium valproate. In the phenobarbital group, 528 patients were followed up for ≥60 months, and the efficacy rates of reduction of seizure frequency by at least 75% was in the fifth year. In the sodium valproate treatment group, 228 patients were followed up for 12 months, and the reduction of seizure frequency by at least 75% was 60.4%. 444 patients (37%) did not complete the study. Dizziness (27%) was a common adverse event in phenobarbital group. In the sodium valproate group, gastrointestinal complaints (27.3%) was a common adverse event. ConclusionPhenobarbital and sodium valproate were proven to be efficacious in treating convulsive epilepsy in rural northeast China. The patients’ compliance still needs to be improved.

Efficacy of phenobarbital for benign convulsions with mild gastroenteritis: A randomized, placebo-controlled trial

ObjectiveThis study was performed to evaluate the efficacy and safety of intravenous phenobarbital (PB) for benign convulsions with mild gastroenteritis (CwG). MethodsA randomized, single-blind, placebo-controlled trial involving patients with CwG was conducted at the Japanese Red Cross Society Himeji Hospital. Patients with CwG who had experienced two or more seizures were eligible. Patients were excluded if any anticonvulsant was used before enrollment. Patients who were allocated to the PB group were administered 10 mg/kg of PB intravenously. Patients who were allocated to the placebo group were administered 20 ml of normal saline. ResultsFrom April 2016 to October 2018, 13 of 24 patients with CwG were randomized (PB group, n = 7; placebo group, n = 6; age, 1–3 years). Five of six patients in the placebo group had seizures after administration of placebo. However, patients in the PB group had no seizures after administration of PB, with a significant difference in efficacy between the two groups (P = 0.005). Five patients who had seizures after administration of normal saline were administered 10 mg/kg of PB, and no patients had a seizure thereafter. No significant differences were found in heart rate, blood pressure, or saturation of percutaneous oxygen between the two groups. ConclusionThis is the first randomized controlled trial to evaluate the efficacy of an anticonvulsant for CwG. Intravenous PB at 10 mg/kg is effective and well tolerated for CwG.

Stereological examination of curcumin’s effects on hippocampal damage caused by the anti-epileptic drugs phenobarbital and valproic acid in the developing rat brain

The anti-epileptic drugs phenobarbital and valproic acid have an extremely strong negative effect on cognitive processes such as learning and memory in the developing brain. We examined whether or not curcumin has protective effects on neuronal injury caused by these drugs in the developing rat brain. Young male Wistar rats were studied in two groups, a 7 days old and a 14 days old group (35 rats in each). Both groups were then divided into 7 sub-groups as the control, curcumin, dimethylsulfoxide, phenobarbital, valproic acid, phenobarbital + curcumin, and valproic acid + curcumin groups (n = 5 in each group). At 24 h after the intraperitoneal injection of the compounds, the rats were sacrificed, and the hippocampal tissue was subjected to stereological analysis with the optical fractionation method. Total numbers of neurons in the hippocampus of the 7 days old and 14 days old rats were calculated. It was found that treatment with phenobarbital resulted in a loss of 43% of the neurons, and valproic acid induced a loss of 57% of the neurons in the 7 days old rats. Curcumin prevented this loss significantly with only 19% in the phenobarbital group and 41% in the valproic acid group. In the 14 days old rat groups, phenobarbital was found to reduce the number of neurons by 30%, and valproic acid reduced it by 38%. Curcumin treatment limited neuronal loss to 3% in the phenobarbital + curcumin group and 10% in the valproic acid + curcumin group. These data strongly indicate that curcumin is a protective agent and prevents hippocampal neuronal damage induced by phenobarbital and valproic acid treatment.

Single dose phenobarbital in addition to symptom-triggered lorazepam in alcohol withdrawal

ObjectiveThe purpose of this study was to evaluate the safety and efficacy of a single parenteral dose of phenobarbital in addition to symptom-triggered lorazepam for the acute management of alcohol withdrawal syndrome (AWS). MethodsThis was a retrospective chart review of adult patients who presented to the Emergency Department with moderate or severe symptoms of alcohol withdrawal. Patients were included if they received at least 4 mg of lorazepam through the hospital's Alcohol Withdrawal Order Set on hospital day one. Patients who received a single parenteral dose of phenobarbital on hospital day one were compared to those who did not. ResultsForty patients received phenobarbital and 38 patients received lorazepam only. Median daily lorazepam requirements, disposition, hospital length of stay, and median maximum daily CIWA-Ar scores were not statistically significant different between the groups. Significantly more patients in the phenobarbital group were discharged within three days in comparison to the lorazepam only group (9 patients vs. 2 patients, respectively, p < 0.05). In the lorazepam only group, two patients were intubated, one patient had delirium tremens, and no patients seized. In the phenobarbital group no adverse events were observed. ConclusionsMore patients were discharged within three days if they received a single parenteral dose of phenobarbital on hospital day one, in addition to symptom-triggered lorazepam for the acute management of AWS. Emergency Medicine physicians should consider ordering one parenteral phenobarbital dose on hospital day one to patients presenting with AWS.

The effects on the endocrine system under hepatotoxicity induction by phenobarbital and di(2-ethylhexyl)phthalate in intact juvenile male rats

Phenobarbital (PB) and Di (2-ethylhexyl) phthalate (DEHP), an anti-epileptic drug and a plasticizer used in flexible polyvinylchloride formulations, respectively, are well-known typical hepatotoxicants. This study investigated the effects of PB (100 mg/kg/day) or DEHP (500 mg/kg/day) on the endocrine system in intact juvenile/peripubertal male rats exposed for 31 days beginning on postnatal day 23. Slight hormone level changes, histopathological changes in thyroid gland or induction of UDP-glucuronosyltransferase in liver were observed in both the PB and DEHP groups. One of the assumed mechanisms inducing thyroid effects is predictable to be secondary changes based on the enhancement in thyroid hormone metabolism via the induction of hepatic microsomal enzymes. No reproductive system-related changes in organ weights, histopathology, and sexual maturation were observed in both groups. Lower testosterone level was observed in the PB group. CYP2B and CYP3A, which are involved in testosterone metabolism, were induced in liver of the PB group. There was no change of 17β-hydroxysteroid dehydrogenase activity in testis of both groups. Lower testosterone level in the PB-treated male rats was attributed to an indirect, hepatotoxicity-associated effect on the reproductive system and not to direct effects on testis such as the antiandrogenic activity and the inhibition of steroidogenesis. These results did not indicate that PB or DEHP exposure affects the endocrine system directly.

Cost-Effectiveness Analysis of Topiramate versus Phenobarbital in the Treatment of Children with Febrile Seizure.

Febrile seizure is common disorder in childhood, with a prevalence of 2% to 5%. There are many drugs for treatment of this disease; however, the most common prescribed medication in Iran is phenobarbital that is cheap, but it has many side effects. We aimed to compare the cost-effectiveness of topiramate versus phenobarbital in patients with febrile seizure in the south of Iran. This econometric cost-effectiveness and cost-utility study were conducted on 91 patients with febrile seizure to assess two strategies of oral drug therapy including phenobarbital and topiramate in 2016-2017. Of all, 51 patients were treated with phenobarbital and 40 patients received topiramate. We followed up the patients for six months, using a randomized and single-blinded approach. A decision tree model was used. The outcomes of the model included febrile seizure and utility. The study was conducted from the perspective of the community; therefore, direct and indirect costs were included in the study. Excel and Tree Age software (2011) were used to analyze the results. Topiramate was cheaper and more effective than phenobarbital. In patients in the phenobarbital and topiramate groups, the mean costs were $740 and $674 per PPP, utility scores were 0.72 and 0.82, and febrile seizure without side effects were 0.3 and 0.6, respectively. Moreover, one-way sensitivity analysis confirmed the robustness of the results of the study. Topiramate in patients with febrile seizure is a fully cost-effective and cost-efficient strategy suggested as a better alternative for children with febrile seizure.

Treatment of Alcohol Withdrawal Syndrome: Phenobarbital vs CIWA-Ar Protocol.

Benzodiazepine-based therapy for alcohol withdrawal is associated with agitation and respiratory depression. Treatment can be complicated by a need for adjunctive therapy to control these symptoms and in patients requiring mechanical ventilation. Strong evidence for the effectiveness of alternative treatment modalities is lacking, despite the availability of promising pharmacological agents such as phenobarbital. To compare the standard of care for the treatment of alcohol withdrawal-a symptom-triggered benzodiazepine protocol used in conjunction with the revised Clinical Institute Withdrawal Assessment of Alcohol (CIWA-Ar) scale-with a phenobarbital protocol. Retrospective cohort study conducted from January 2016 through June 2017 at a 42-bed medical intensive care unit in a private teaching hospital in Nashville, Tennessee. The primary outcome was intensive care unit length of stay. Secondary outcomes included hospital length of stay, incidence of invasive mechanical ventilation, and use of adjunctive pharmacotherapy. Patients who received phenobarbital had significantly shorter stays in the intensive care unit than did those who received therapy based on the CIWA-Ar scale (mean [SD], 2.4 [1.5] vs 4.4 [3.9] days; P < .001). Those who received phenobarbital also had significantly shorter hospital stays (4.3 [3.4] vs 6.9 [6.6] days; P = .004). The incidence of invasive mechanical ventilation was lower in the phenobarbital group (1 [2%] vs 14 [23%] patients; P < .001), as was use of adjunctive agents for symptom control, including dexmedetomidine (4 [7%] vs 17 [28%] patients; P = .002). A phenobarbital protocol for the treatment of alcohol withdrawal is an effective alternative to the standard-of-care protocol of symptom-triggered benzodiazepine therapy.

Effects of Dendrobium huoshanense on expressions and activities of hepatic microsomal cytochrome P450s in mice

This study was carried out to investigate the effect of oral administration of Dendrobium huoshanense on the expressions and activities of hepatic microsomal cytochrome P450s in mice, and to provide a reference for the evaluation of drug-drug interactions between D. huoshanense and clinical drugs. The C57BL/6 mice were randomly divided into blank control group, D. huoshanense low dose group (crude drug 1.25 g·kg⁻¹), D. huoshanense high dose group (crude drug 7.5 g·kg⁻¹), and phenobarbital positive control group (0.08 g·kg⁻¹). Each group was intragastrically administered with drugs for 2 weeks. The mice were sacrificed and their liver microsomes were prepared. The expressions of major subtypes of P450 enzyme were determined by Western blot and the probe drugs were used to detect the enzyme activities of P450 subtypes with protein expression changes. Western blot analysis showed that the protein expressions of CYP1A1, CYP1A2 and CYP2B in liver tissues were up-regulated in D. huoshanense-treated group. In vitro enzyme activity tests showed that there were no significant difference in metabolism of 7-ethoxyresorufin (a probe drug for CYP1A1) and bupropion (a probe drug for CYP2B) between D. huoshanense group and control group. The metabolism of phenacetin (a probe drug for CYP1A2) showed a statistical difference in rate Vmax, and it was significantly increased by approximately 20% in D. huoshanense group as compared with the blank control group, and the clearance CLint in treated group was also increased by about 32%. Therefore, oral administration of D. huoshanense had no effects on the activities of most hepatic P450 enzymes in mice, with no drug-drug interaction related to the P450 enzyme system in most clinical drugs theoretically. However, oral administration of D. huoshanense may accelerate the metabolism of CYP1A2-catalyzed drugs, which needs to be considered in clinical practice.

Comparison of phenobarbital-adjunct versus benzodiazepine-only approach for alcohol withdrawal syndrome in the ED

ObjectivesTo compare a phenobarbital-adjunct versus benzodiazepine-only approach for the management of alcohol withdrawal syndrome in the emergency department (ED) with regard to the need for intensive care unit (ICU) admission, severity of symptoms on ED discharge, and complications. MethodsThis was a retrospective cohort study conducted in two academic EDs in the United States. Adult patients seen in the ED with a diagnosis of alcohol withdrawal syndrome were included. Patients were categorized into two groups based on whether phenobarbital was administered in the ED: 1) phenobarbital group (with or without benzodiazepines) or 2) non-phenobarbital group. The primary outcome measure was the need for ICU admission. Secondary outcomes included Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scores at ED discharge, and complications. Complications were a composite of death, need for intubation, hypotension or vasopressor use, seizures, and hospital acquired pneumonia. ResultsThe study cohort included 209 patients (phenobarbital = 97, non-phenobarbital = 112). The mean (standard deviation) age was 49 (12) years and 85% (n = 178) were male. A similar proportion of patients in the phenobarbital (14%, n = 14) and non-phenobarbital (11%, n = 12) groups required ICU admission (p = 0.529). The median CIWA-Ar score on ED discharge was 7 (IQR 4–12) points in the phenobarbital group and 7 (IQR 4–14) points in the non-phenobarbital group (p = 0.752). The occurrence of complications was also similar in the phenobarbital (9%, n = 9) and non-phenobarbital groups (11%, n = 10). ConclusionAdjunctive phenobarbital use in the ED for alcohol withdrawal syndrome did not result in decreased ICU admission, severity of symptoms, or complications.

Randomized Controlled Trial between Levetiracetam and Phenobarbital in the Treatment of Neonatal Seizure due to Perinatal Asphyxia

Background: Seizure occurs more frequently in neonatal period and incidence of seizure is 50%-68% in perinatal asphyxia. At present phenobarbital is the drug of choice for treating neonatal seizure, which has some adverse effects on neurodevelopment status. Levetiracetam is a novel antiepileptic agent well-tolerated and effective in focal, generalized and neonatal seizure as well and lacks the adverse effects like phenobarbital. The present study was undertaken to compare the safety and efficacy of levetiracetam to phenobarbital in the treatment of neonatal seizure due to perinatal asphyxia.Methodology: This interventional study (Randomized Controlled Trial) was conducted in Department of Neonatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka and Dhaka Medical College Hospital, Dhaka, Bangladesh from 1st January’ 2014 to 30th June’ 2015. Intravenous levetiracetam injection, 50 mg/kg loading followed by 10 mg/kg 8 hourly maintenance was used and phenobarbital intravenous 20-40 mg/kg loading and 2.5 mg/kg/dose 12 hourly maintenance was given as per institutional protocol.Results: Sixty-nine term asphyxiated neonates (intention to treat population) provided analyzable data. Seizure control was found significantly higher (p = 0.011) higher in levetiracetam group in comparison to phenobarbital group (71% vs 40%). Need for more than one drug was significantly lower in levetiracetan group (p=0.011). Adverse effects were found significantly (p=0.001) lower in levetiracetam group (9% vs 43%). No serious adverse effect was observed in any group and most common adverse effect was somnolence in both group followed by irritability. Restlessness, sedation and shallow breathing were found only in phenobarbital group.Conclusion: Levetiracetam is more effective and safe in comparison to phenobarbital in the treatment of neonatal seizure due to perinatal asphyxia.Bangladesh J Child Health 2018; VOL 42 (2) :67-72

The effect of antiepileptic drugs on thyroid hormonal function: valproic acid and phenobarbital.

The aim of this study was to evaluate the thyroid function alterations in a group of epileptic children taking antiepileptic drugs. The study included a total of 183 pediatric epilepsy patients, aged 15months-16years, comprising 114 patients treated with valproic acid, 69 patients treated with phenobarbital, and 151 age-matched healthy volunteers as the control group. Serum levels of thyroid hormones were measured before the beginning of the antiepileptic therapy and after 12months of treatment. Thyroid-stimulating hormone levels were significantly higher in the 12th month of phenobarbital and valproic acid treatment. The level of free triiodothyronine before treatment was higher in epileptic patients than in the control group. Subclinical hypothyroidism at month 12 was determined in 15.2% of the valproic acid group and in 2.9% of the phenobarbital group. When compared with the pre-treatment values, there was a statistically significant difference in the incidence of subclinical hypothyroid in the valproic acid group and no significant difference in the phenobarbital group. Symptomatic hypothyroidism was not detected. It was concluded that the thyroid functions of patients using valproic acid and phenobarbital for a long time should be regularly monitored.

Neonatal phenobarbital exposure disrupts GABAergic synaptic maturation in rat CA1 neurons.

Phenobarbital is the most commonly utilized drug for the treatment of neonatal seizures. The use of phenobarbital continues despite growing evidence that it exerts suboptimal seizure control and is associated with long-term alterations in brain structure, function, and behavior. Alterations following neonatal phenobarbital exposure include acute induction of neuronal apoptosis, disruption of synaptic development in the striatum, and a host of behavioral deficits. These behavioral deficits include those in learning and memory mediated by the hippocampus. However, the synaptic changes caused by acute exposure to phenobarbital that lead to lasting effects on brain function and behavior remain understudied. Postnatal day (P)7 rat pups were treated with phenobarbital (75mg/kg) or saline. On P13-14 or P29-37, acute slices were prepared and whole-cell patch-clamp recordings were made from CA1 pyramidal neurons. At P14 we found an increase in miniature inhibitory postsynaptic current (mIPSC) frequency in the phenobarbital-exposed as compared to the saline-exposed group. In addition to this change in mIPSC frequency, the phenobarbital group displayed larger bicuculline-sensitive tonic currents, decreased capacitance and membrane time constant, and a surprising persistence of giant depolarizing potentials. At P29+, the frequency of mIPSCs in the saline-exposed group had increased significantly from the frequency at P14, typical of normal synaptic development; at this age the phenobarbital-exposed group displayed a lower mIPSC frequency than did the control group. Spontaneous inhibitory postsynaptic current (sIPSC) frequency was unaffected at either P14 or P29+. These neurophysiological alterations following phenobarbital exposure provide a potential mechanism by which acute phenobarbital exposure can have a long-lasting impact on brain development and behavior.

Comparison of the Effect of Phenobarbital versus Sodium Valproate in Management of Children with Status Epilepticus.

Acute prolonged seizure is the most common neurological emergency in children. This research was conducted to compare the effect of intravenous phenobarbital and Sodium valproate in control of seizure in children with status epilepticus, referred to emergency ward from Mar to Nov 2013. In this randomized clinical trial, registered with the code number IRCT2015051722300N1, 80 children aged 6 months to 10 years with prolonged seizure and with no response to one dose of diazepam (0.2 mg/kg) administered through IV injection during the five min were selected. Children were randomly divided into two groups, intervention, and control through permutation blocks. In intervention group, intravenous Sodium valproate (20 mg/kg) and in control group, intravenous phenobarbital (20 mg/kg) were prescribed. Data such as age, gender, history of previous seizure, seizure type, and recovery time after receiving drug was recorded in the form. Data analysis was done through descriptive statistics, Chi-square and Independent t- test. Two groups were the same in terms of age and gender and had no statistically significant difference, but they were different in terms of seizure type. In valproate group, 18 patients (45%) and in phenobarbital group, 32 patients (80%) had positive response to the treatment and the chi-square test showed the significant difference. With regards to this point that in phenobarbital group, patients had more rapid response to drug in comparison with patients in Sodium valproate group, phenobarbital is a suitable and effective drug for controlling of seizure in children.

Evaluation of the Effects of Extracorporeal Membrane Oxygenation on Antiepileptic Drug Serum Concentrations in Pediatric Patients.

Patients supported on extracorporeal membrane oxygenation (ECMO) have an increased incidence of seizures. Phenobarbital (PB) and fosphenytoin (fos-PHT) are common antiepileptic drugs (AEDs) used to manage seizures in the pediatric population; however, it is unknown what effect ECMO has on the serum concentrations of AEDs. The purpose of this study is to evaluate the effect of ECMO on AED serum concentrations. A retrospective, matched-cohort study was performed in patients younger than 18 years who received ECMO and were treated with intravenous (IV) PB or fos-PHT at Texas Children's Hospital between 2004 and 2014. Patients receiving IV AED therapy and ECMO were matched, based on age, sex, and weight, with patients receiving IV AED therapy without ECMO. The 24-hour cumulative AED dose, serum concentrations, number of doses per serum concentration drawn ratio, volume of distribution, therapeutic serum concentrations, and time to therapeutic serum concentration were compared between both groups. The fos-PHT and PB groups were analyzed in all patients and in neonates only. Fourteen patients met inclusion criteria. The fos-PHT neonatal (20.1 vs 11.3 mg/kg/day, p = 0.044), PB composite (33.9 vs 21.6 mg/kg/day, p = 0.012), and PB neonatal (40.3 vs 20 mg/kg/day, p = 0.04) had larger 24-hour cumulative doses compared with non-ECMO patients. Lower serum concentrations were observed in the PB composite ECMO group (19.1 vs 35.4 mg/L, p < 0.001) and the PB neonatal ECMO group (20.5 vs 27.8 mg/L, p = 0.01) compared with non-ECMO patients. Pediatric patients receiving PB on ECMO and neonatal patients receiving fos-PHT on ECMO required larger doses, and in pediatric patients achieved lower serum concentrations, suggesting the necessity for alternative dosing strategies in these populations.

Patient Outcomes Associated With Phenobarbital Use With or Without Benzodiazepines for Alcohol Withdrawal Syndrome: A Systematic Review.

Purpose: Benzodiazepines are the drug of choice for alcohol withdrawal syndrome (AWS); however, phenobarbital is an alternative agent used with or without concomitant benzodiazepine therapy. In this systematic review, we evaluate patient outcomes with phenobarbital for AWS. Methods: Medline, Cochrane Library, and Scopus were searched from 1950 through February 2017 for controlled trials and observational studies using ["phenobarbital" or "barbiturate"] and ["alcohol withdrawal" or "delirium tremens."] Risk of bias was assessed using tools recommended by National Heart, Lung, and Blood Institute. Results: From 294 nonduplicative articles, 4 controlled trials and 5 observational studies (n = 720) for AWS of any severity were included. Studies were of good quality (n = 2), fair (n = 4), and poor (n = 3). In 6 studies describing phenobarbital without concomitant benzodiazepine therapy, phenobarbital decreased AWS symptoms (P < .00001) and displayed similar rates of treatment failure versus comparator therapies (38% vs 29%). A study with 2 cohorts showed similar rates of intensive care unit (ICU) admission (phenobarbital: 16% and 9% vs benzodiazepine: 14%) and hospital length of stay (phenobarbital: 5.85 and 5.30 days vs benzodiazepine: 6.64 days). In 4 studies describing phenobarbital with concomitant benzodiazepine therapy, phenobarbital groups had similar ICU admission rates (8% vs 25%), decreased mechanical ventilation (21.9% vs 47.3%), decreased benzodiazepine requirements by 50% to 90%, and similar ICU and hospital lengths of stay and AWS symptom resolution versus comparator groups. Adverse effects with phenobarbital, including dizziness and drowsiness, rarely occurred. Conclusion: Phenobarbital, with or without concomitant benzodiazepines, may provide similar or improved outcomes when compared with alternative therapies, including benzodiazepines alone.

Phenobarbital or potassium bromide as an add-on antiepileptic drug for the management of canine idiopathic epilepsy refractory to imepitoin

Imepitoin has recently been approved in Europe for the management of dogs with idiopathic epilepsy. Currently, there is no evidence-based information available on the efficacy of antiepileptic drugs used as additions to the therapeutic regimen in dogs with idiopathic epilepsy that are not well controlled with imepitoin. The goal of this study was to evaluate the efficacy of phenobarbital or potassium bromide (KBr) as add-on antiepileptic drugs for controlling dogs refractory to a maximum dose of imepitoin (30 mg/kg twice daily). The study was performed as a prospective, randomised, controlled clinical trial. The efficacy of phenobarbital and KBr was evaluated by comparing monthly seizure frequency (MSF), monthly seizure day frequency (MSDF), the presence of cluster seizures during a retrospective 2-month period with a prospective follow-up of 6 months, and the overall responder rate.Twenty-seven dogs were included in the study, 14 dogs in the phenobarbital group and 13 dogs in the KBr group. Both median MSF and MSDF decreased in the phenobarbital group (both P = 0.001) and in the KBr group (P = 0.004 and P = 0.003, respectively). Overall, the number of dogs with cluster seizures decreased (P = 0.0005). The responder rate was 79% vs. 69% in the phenobarbital and KBr groups, respectively. We conclude that phenobarbital or KBr add-on treatment decreases median MSF and MSDF in epileptic dogs refractory to a maximum dose of imepitoin. Combination therapy was generally well tolerated and resulted in an improvement in seizure management in the majority of the dogs.

Levetiracetam in the management of feline audiogenic reflex seizures: a randomised, controlled, open-label study.

Objectives Currently, there are no published randomised, controlled veterinary trials evaluating the efficacy of antiepileptic medication in the treatment of myoclonic seizures. Myoclonic seizures are a hallmark of feline audiogenic seizures (FARS). Methods This prospective, randomised, open-label trial compared the efficacy and tolerability of levetiracetam (20-25 mg/kg q8h) with phenobarbital (3-5 mg/kg q12h) in cats with suspected FARS that experienced myoclonic seizures. Cats were included that had ⩾12 myoclonic seizure days during a prospective 12 week baseline period. This was followed by a 4 week titration phase (until a therapeutic serum concentration of phenobarbital was achieved) and a 12 week treatment phase. Results Fifty-seven cats completed the study: 28 in the levetiracetam group and 29 in the phenobarbital group. A reduction of ⩾50% in the number of myoclonic seizure days was seen in 100% of patients in the levetiracetam group and in 3% of patients in the phenobarbital group ( P <0.001) during the treatment period. Levetiracetam-treated cats had higher freedom from myoclonic seizures (50.0% vs 0%; P <0.001) during the treatment period. The most common adverse events were lethargy, inappetence and ataxia, with no difference in incidence between levetiracetam and phenobarbital. Adverse events were mild and transient with levetiracetam but persistent with phenobarbital. Conclusions and relevance These results suggest that levetiracetam is an effective and well tolerated treatment for cats with myoclonic seizures and is more effective than phenobarbital. Whether it will prevent the occurrence of generalised tonic-clonic seizures and other forebrain signs if used early in the course of FARS is not yet clear.

The random and comparative study on therapeutic effect and safety between Levetiracetam and Phenobarbital administration for neonatal seizures

Objective To randomly compare the therapeutic effect and safety between Levetiracetam (LEV) and Phenobarbital (PB) in the treatment of neonatal seizures. Methods A total of 61 infants with acute convulsion were randomly divided into 2 groups: LEV group(n=30) and PB group (n=31) during January 2013 to December 2014 in Urumqi Children's Hospital.All neonates received routine management including etiology treatment and adverse drug reaction monitoring.In the LEV group, subjects received oral formulation of LEV with initial loading dose 30 mg/kg, followed by 15 mg/kg twice a day.If the seizures were not controlled completely, PB treatment was added until seizures were completed controlled.If seizures were controlled quickly, the dose of PB was gradually reduced and LEV was used as monotherapy.The subjects in PB group received intramuscular or intravenous injection of PB with 10 mg/kg as the first dose, then 5 mg/(kg·d) oral PB was administered, if seizures were not controlled, LEV treatment was added, then dose of PB was gradually reduced until seizures were controlled completely, and then patients were switched to LEV monotherapy gradually. The drug adverse reactions were observed. Results (1) After LEV or PB monotherapy, 66.7%(20/30 cases) and 54.8%(17/31 cases) of the subjects obtained sustainable seizure free respectively.Although, there was a higher control ratio in LEV group, but no significant difference was observed between the 2 groups (P>0.05). (2) LEV group (16/30 cases, 53.33%) had higher rapid seizure control ratio with seizure controlled within 24 h after first dosage administration than that of PB group(8/31 cases, 25.80%), and there was significant difference (χ2=4.841, P=0.028). Further more, if adding the cases who had to change to use another comparative one (LEV or PB) due to their seizures failure control with the first one treated, LEV group (21/44 cases, 47.72%)still had higher rapid seizure control ratio in total patients than that of PB group(10/41 cases, 24.39%), and there was significant difference (χ2=4.988, P=0.026). (3) Eight cases who changed to LEV after PB as the first treatment drug failed obtained sustainable seizure free.(4) One case in PB group with transient urinary retention was observed but the symptom disappeared 36 h after PB withdrawal, and no significant drug adverse reaction was observed in LEV group. Conclusion LEV is more rapid and safe for seizure control of neonates than PB. Key words: Levetiracetam; Phenobarbital; Seizure; Infant, newborn

Intermittent Diazepam versus Continuous Phenobarbital to Prevent Recurrence of Febrile Seizures: A Randomized Controlled Trial.

Febrile seizure is the most common neurologic problem in children between 3 months to 5 years old. Two to five percent of children aged less than five yr old will experience it at least one time. This type of seizure is age dependent and its recurrence rate is about 33% overalls and 50% in children less than one yr old. The prophylactic treatment is still controversial, so we conducted a randomized controlled clinical trial to find out the effectiveness of continuous phenobarbital versus intermittent diazepam for febrile seizure. This clinical trial was conducted in the Department of Pediatric Neurology, Babol University of Medical Sciences, Babol, Iran between March 2008 and October 2010. All children from 6 month to 5 yr old referred to Amirkola Children's Hospital, Babol, Iran were enrolled in the study. Children with febrile seizure that had indication for prophylaxis but did not receive any prophylaxis previously were enrolled in the study. For prophylactic anti convulsion therapy, patients were divided randomly in two groups. One group received continuous phenobarbital and another treated with intermittent diazepam whenever the children experienced an episode of febrile illness for up to one year after their last convulsion. Of all 145 studied cases, the recurrent rate in children under prophylaxis with diazepam was 11/71 and in phenobarbital group was 17/74. There was no significant difference in the recurrence rate in both groups. There was no significant difference in the effectiveness of phenobarbital and diazepam in prevention of recurrent in febrile seizure and we think that in respect of lower complication rate in diazepam administration, it cloud be better choice than phenobarbital.