Doses Of Phenobarbital Research Articles

P03-363 - Minding the levels: about a clinical case with neuropsychiatric manifestations

Introduction and aimsPsychiatry makes use of a wide range of medications, such as anti-epileptic drugs in the treatment of affective disorders, impulsive behavior or epilepsy. The authors aim to present a particular clinical presentation in order to reinforce the awareness of the side effects of our prescriptions.Case report54 year-old man, epileptic, medicated with Sodium Valproate (VPA) and Phenobarbital, admitted to our hospital due to insomnia, irritability and aggressiveness with two weeks of duration. Early evaluations showed disorientation, slow and poor speech, and prejudice ideas towards his family. Disequilibrium, asterixis and slurred speech imposed evaluation by Neurology. Analytic evaluations demonstrated high phenobarbital and ammonia levels. Both anti-epileptics were slowly withdrawn, with clinical resolution.DiscussionVPA may be associated with elevation of ammonia levels, and eventually with encephalopathy without evidence of liver failure. There is a wide range of clinical presentations of hyperammonemic encephalopathy ranging from decreased level of consciousness, irritability, agitation, focal neurological deficits, cognitive slowing, vomiting, drowsiness, and lethargy. On the other hand, high doses of phenobarbital may have similar presentations which could be potentiated by VPA.ConclusionThere was a good correlation between the fall in serum ammonia levels, clinical improvement, and anti-epileptics withdrawal, suggesting the implication of medication in this clinical picture. The case illustrates the need to check ammonia and anti-epileptic levels, and to consider this diagnosis in patients taking VPA and Phenobarbital who present with new neuropsychiatric manifestations.

Phenobarbital for Long-Term Management of Marked Hyperbilirubinemia.

Abstract 5089 Gilbert's syndrome (GS) is associated with a mild chronic unconjugated hyperbilirubinemia, due to partial deficiency of bilirubin uridine diphosphate glucuronyl transferase (UDPGT). Phenobarbital is a known inducer of hepatic UDPGT and has been used in hyperbilirubinemia of newborns. It has also been used as a test for support of the diagnosis of GS. However, because hyperbilirubinemia of GS is mild and harmless, phenobarbital is not used for treatment of hyperbilirubinemia in adults. I report a case of a 46-year-old woman who, because of having chronic hereditary hemolytic anemia and GS, had marked hyperbilirubinemia with psychosocial problems, as the result of her hyperbilirubinemia and her skin color, which responded well to chronic phenobarbital treatment. Case report- CH was diagnosed to have hereditary high phosphatidylcholine hemolytic anemia (HHPCHA) at the age of 23. She was seen again at the age of 30 because of very high serum ferritin and iron saturation which seemed disproportionally high for the degree of her mild hemolytic anemia (51Cr RBC survival T½ of 16.5 days). Further investigation revealed that she had hereditary hemochromatosis due to homozygosity for H63D HFE gene. She was started on phlebotomies initially weekly and later on every 2-3 months to control her iron overload. During the follow-up it was noted that her serum unconjugated bilirubin (SUB) was persistently much higher than is expected from her mild hemolytic anemia (up to 288 μmol/L). Since she had no abnormality of liver function tests, I suspected that she also has Gilbert's syndrome. In September 2008 her blood was sent for genetic testing which showed that she has an additional TA repeat [(TA)7/(TA)7], confirming the diagnosis of GS. On January 21, 2009 when her SUB was 149 μmol/L, she expressed concern that her friends and coworkers keep making fun of her, because of the orange color of her face and sclera. She was started on phenobarbital 30 mg daily for a month and then 60 mg daily. This therapy rapidly brought her bilirubin down and changed the color of her face to normal, making her very happy. Her SUB on February 20, March 20 and June 30, 2009 were 103, 63 and 37 μmol/L, respectively. Conclusion Gilbert's syndrome is a common hereditary disorder that can aggravate hyperbilirubinemia of chronic hemolytic anemia. However, this association is often unrecognized, because many physicians attribute the hyperbilirubinemia to hemolysis and do not look for associated GS. In chronic hemolytic anemias, if hyperbilirubinemia is more than expected, the possibility of an associated GS should be considered. If such association exists, small daily doses of phenobarbital can markedly reduce this hyperbilirubinemia and improve the psychosocial effects of hyperbilirubinemia. Furthermore, marked reduction of bilirubin, following the therapeutic trial of Phenobarbital, will confirm the association of GS with hemolytic anemia. Disclosures No relevant conflicts of interest to declare.

Successful Use of Dexmedetomidine for Sedation in a 24-Week Gestational Age Neonate

To describe a case of dexmedetomidine use for sedation in a 24-week gestational age premature neonate. A 9-day-old, 24-week gestational age male neonate on high-frequency oscillatory mechanical ventilation was experiencing severe agitation refractory to high-dose intravenous narcotics and benzodiazepines. Since the infant's respiratory stability was reliant on adequate sedation, he was given dexmedetomidine after several days of suboptimal response to escalation of standard agents. Treatment prior to dexmedetomidine included continuous-infusion fentanyl 10 microg/kg/h, intravenous lorazepam 0.6 mg/kg every 4 hours, intermittent doses of both lorazepam and midazolam as needed, and a single bolus dose of phenobarbital. The patient calmed markedly during the dexmedetomidine loading dose infusion and remained adequately sedated while the drug was continued. The dexmedetomidine infusion allowed weaning of mechanical ventilation settings and eventual extubation of the infant, as well as rapid tapering of other sedative medications. The maximum dexmedetomidine infusion rate was 0.7 microg/kg/h, and total duration of therapy was 19 days. No significant adverse effects were directly attributed to dexmedetomidine use during this time. Dexmedetomidine is a novel alpha(2)-agonist approved for short-term sedation in mechanically ventilated adults. Data describing its use in pediatric and neonatal patients continue to emerge. The prolonged use of dexmedetomidine in very-low-birth-weight neonates has not been described in the literature. Dexmedetomidine was an effective sedative and analgesic in a 24-week gestational age neonate treated for refractory agitation while on mechanical ventilation. Based on its documented efficacy for pain and sedation and its favorable adverse effect profile, dexmedetomidine warrants further study as first-line or adjunct therapy with narcotics for sedation in ventilated newborns.

Reversible Coma Associated With Prolonged High-Dose Phenobarbital Therapy in Bilateral Sturge-Weber Syndrome

High-dose phenobarbital therapy is an effective treatment for refractory status epilepticus in children. The advantages of this therapy include milder adverse effects without limits for maximal phenobarbital levels or doses during the initial phase of treatment. However, little is known about the safety of continuing the treatment. We describe an infant with intractable epilepsy associated with bilateral Sturge-Weber syndrome who became comatose after 1(2/3) months of high-dose phenobarbital treatment. The patient regained consciousness as serum phenobarbital concentration decreased to below 40 microg/mL. The progression and recovery were also documented by electroencephalogram and brainstem auditory evoked potentials. The present case suggests that prolonged high-dose phenobarbital therapy may cause cerebral and brainstem dysfunction in patients with severe cerebrovascular diseases. The underlying baseline metabolic and perfusion deficit related to the disease can precipitate the neurological complication during long-term high-dose phenobarbital therapy.

2-Methyl-6-phenylethynyl-pyridine (MPEP), a non-competitive mGluR5 antagonist, differentially affects the anticonvulsant activity of four conventional antiepileptic drugs against amygdala-kindled seizures in rats

2-Methyl-6-phenylethynyl-pyridine (MPEP), a selective noncompetitive mGluR5 antagonist, influences the action of conventional antiepileptic drugs in amygdala-kindled seizures in rats. MPEP alone (up to 40mg/kg) did not affect any seizure parameter. Moreover, the common treatment of MPEP with either carbamazepine or phenytoin (administered at subeffective doses) did not result in any anticonvulsant action in kindled rats. However, when combined with subprotective doses of valproate or phenobarbital, MPEP significantly shortened seizure and afterdischarge durations. Importantly, combinations of MPEP with the two antiepileptics did not have the adverse effects of impaired motor performance or long-term memory in rats. Our data indicate that MPEPmay positively interact with some conventional antiepileptic drugs in the amygdala-kindling model of complex partial seizures.

Targeting Prostaglandin E2 EP1 Receptors Prevents Seizure-Associated P-glycoprotein Up-Regulation

Up-regulation of the blood-brain barrier efflux transporter P-glycoprotein in central nervous system disorders results in restricted brain access and limited efficacy of therapeutic drugs. In epilepsies, seizure activity strongly triggers expression of P-glycoprotein. Here, we identified the prostaglandin E2 receptor, EP1, as a key factor in the signaling pathway that mediates seizure-induced up-regulation of P-glycoprotein at the blood-brain barrier. In the rat pilocarpine model, status epilepticus significantly increased P-glycoprotein expression by 92 to 197% in the hippocampal hilus and granule cell layer as well as the piriform cortex. The EP1 receptor antagonist 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-3-(4-pyridinyl)propyl]hydrazide hydrochloride (SC-51089) abolished seizure-induced P-glycoprotein up-regulation and retained its expression at the control level. The control of P-glycoprotein expression despite prolonged seizure activity suggests that EP1 receptor antagonism will also improve antiepileptic drug efficacy. Preliminary evidence for this concept has been obtained using a massive kindling paradigm during which animals received a subchronic SC-51089 treatment. After withdrawal of the EP1 receptor antagonist, a low dose of the P-glycoprotein substrate phenobarbital resulted in an anticonvulsant effect in this pretreated group, whereas the same dosage of phenobarbital did not exert a significant effect in the respective control group. In conclusion, our data demonstrate that EP1 is a key signaling factor in the regulatory pathway that drives P-glycoprotein up-regulation during seizures. These findings suggest new intriguing possibilities to prevent and interrupt P-glycoprotein overexpression in epilepsy. Future studies are necessary to further evaluate the appropriateness of the strategy to enhance the efficacy of antiepileptic drugs.

Levetiracetam as monotherapy for seizures in a neonate with acute lymphoblastic leukemia

Congenital acute lymphoblastic leukemia (ALL) is a relatively rare disorder that is characterized by frequent central nervous system involvement that may increase the risk for seizures. Appropriate choice of anticonvulsant therapy with respect to ongoing oncologic treatment is not established in this age group. We report the case of a neonate with ALL who was successfully treated for seizures with levetiracetam monotherapy. This full-term boy did well until 3 days of age when he had an episode of left extremity jerking (07/06/07). Computed tomography of the head demonstrated extensive multifocal intraparenchymal hemorrhages. Initial EEG demonstrated multifocal epileptiform activity. Patient was loaded with Phenobarbital at 20 mg/kg. Complete blood count revealed leukocytosis (78 × 103/mm 3). Peripheral blood smear contained blastocytes and DNA analysis confirmed B-cell ALL. A second focal seizure was reported on the same day and he was re-loaded with Phenobarbital. Maintenance dosing of Phenobarbital was initiated and no further seizures were noted. A repeat EEG on 7/10/07 remained abnormal with excessive multifocal sharp waves. Continuation of anticonvulsant therapy was recommended. Given concern for interaction between Phenobarbital and planned chemotherapy regimen, oncology requested a non-enzyme inducing anticonvulsant. Phenobarbital was subsequently weaned and Levetiracetam monotherapy initiated at 40 mg/kg/day (07/10/2007). Currently, the patient is seizure free at 8 months of age on Levetiracetam monotherapy. The use of Levetiracetam as monotherapy in neonates has not been formally evaluated and experience is limited. We report the successful use of levetiracetam monotherapy after Phenobarbital load in a neonate with leukemia and localization-related epilepsy.

Multiple organ toxicity, including hypochromic anemia, following repeated dose oral administration of phenobarbital (PB) in rats

A 4-week repeated dose oral toxicity study of phenobarbital (PB) sodium was conducted in F344 rats of both sexes at PB doses of 0.8, 8, and 80 mg/kg/day to fully elucidate its general toxicity including hematological changes. Both sexes in the 80 mg/kg/day group showed staggering gait, lacrimation, and/or sedation, which were more evident in the early stage of treatment. The body weight gain and food consumption were greater in these animals than in controls. Hematology revealed a significant reduction in the hematocrit (Ht), hemoglobin concentration (Hb), and erythrocyte count (RBC) in both sexes at 80 mg/kg/day, which was accompanied by a decrease in the cell mean Hb (CHCM) in mature erythrocytes with an increase in unsaturated iron binding capacity. Female rats also showed reduction in the CHCM in reticulocytes, content of hemoglobin per reticulocyte, and transferrin saturation. PB prolonged the activated partial thromboplastin time and inversely increased the platelet count with no evidence of platelet activation. Well-known toxic effects of PB on the liver and thyroid were observed in a dose-dependent manner, along with altered lipid, glucose, and electrolyte metabolism. The serum levels of PB increased dose-dependently, when examined in females received 8 and 80 mg/kg/day on day 1 and 28; there were no difference in C(max) and AUC(0-24) values between day 1 and day 28. These results indicated that PB has the potential to elicit multiple organ toxicity including an effect on the hematopoietic system. The hematological analysis provided evidence for hypochromic anemia, plausibly caused by the impairment of iron utility.

Measurement of the lowest dosage of phenobarbital that can produce drug discrimination in rats

Accurate measurement of the threshold dosage of phenobarbital that can produce drug discrimination (DD) may improve our understanding of the mechanisms and properties of such discrimination. This study aimed to compare three methods for determining the threshold dosage for phenobarbital (D) versus no-drug (N) DD. Rats learned a D versus N DD in two-lever operant training chambers. A titration scheme was employed to increase or decrease dosage at the end of each 18-day block of sessions depending on whether the rat had achieved criterion accuracy during the sessions just completed. Three criterion rules were employed, all based on average percent drug lever responses during initial links of the last six D and six N sessions of a block. The criteria were: D% > 66 and N% < 33; D% > 50, and N% < 50; (D% - N%) > 33. Two squads of rats were trained, one immediately after the other. All rats discriminated drug versus no drug. In most rats, dosage decreased to low levels and then oscillated near the minimum level required to maintain criterion performance. The lowest discriminated dosage significantly differed under the three criterion rules. The squad that was trained second may have benefited by partially duplicating the lever choices of the previous squad. The lowest discriminated dosage is influenced by the criterion of discriminative control that is employed and is higher than the absolute threshold at which discrimination entirely disappears. Threshold estimations closer to absolute threshold can be obtained when criteria are employed that are more permissive of errors and that allow rats to maintain lever preferences.

Index of Suspicion in the Nursery

After an uncomplicated pregnancy, a term female infant is delivered vaginally to a healthy 29-year-old primigravida whose serology test results are within normal parameters. Apgar scores are 8 and 9 at 1 at 5 minutes, respectively. Shortly after delivery, a “blueberry muffin” rash is noted on the infant. Her initial complete blood count shows a white blood cell (WBC) count of 70.0×103/mcL (70.0×109/L) with 74% blasts on the peripheral smear. The patient is admitted to the neonatal intensive care unit for further evaluation. Physical examination on admission reveals an infant who is breathing comfortably on room air, has a birthweight of 3,220 g, and exhibits no dysmorphic features. The liver edge is palpable, and a purpuric petechial rash involves the trunk, extremities, face, and lower lip. Multiple 1- to 2-cm palpable purple nodules are nonblanching and nontender, resembling a blueberry muffin. The remainder of the examination findings are unremarkable. Laboratory investigation reveals a repeat elevated WBC count of 70.0×103/mcL (70.0×109/L) with 14% blasts, platelet count of 50×103/mcL (50×109/L), uric acid of 7.8 mg/dL (464.0 mcmol/L), lactate dehydrogenase of 1,974 international units/L (normal, <400 international units/L), prothrombin time of 30 seconds, and International Normalized Ratio (INR) of 2.8. Further laboratory tests aid in the diagnosis. A 3-week-old male presents to the pediatrician's office for routine follow-up after discharge from the neonatal intensive care unit. He was born at term via emergent cesarean section for late decelerations and decreased fetal movement. He displayed apnea at birth and was placed on a ventilator for suspected meconium aspiration syndrome. Intravenous antibiotics also were initiated for possible sepsis. On the second postnatal day, the infant demonstrated brief clonic posturing of his upper extremities, which was treated with one dose of phenobarbital. He had …

Serum triglyceride concentration in dogs with epilepsy treated with phenobarbital or with phenobarbital and bromide

To compare serum triglyceride concentrations obtained after food had been withheld (i.e., fasting concentrations) in dogs with epilepsy that had been treated long term (> or = 3 months) with phenobarbital or with phenobarbital and potassium bromide with concentrations in healthy control dogs. Cross-sectional study. 57 epileptic dogs that had been treated with phenobarbital (n=28) or with phenobarbital and bromide (29) and 57 healthy, untreated control dogs matched on the basis of age, breed, sex, neuter status, and body condition score. Blood samples were collected after food had been withheld for at least 12 hours, and serum biochemical and lipid concentrations were determined. Oral fat tolerance tests were performed in 15 control dogs and 9 dogs with epilepsy treated with phenobarbital alone. 19 of the 57 (33%) epileptic dogs had fasting serum triglyceride concentrations greater than the upper reference limit. Nine (16%) dogs had a history of pancreatitis, and 5 of the 9 had high fasting serum triglyceride concentrations at the time of the study. A significant relationship was found between body condition score and fasting serum triglyceride concentration in all dogs, but serum triglyceride concentration was not significantly associated with phenobarbital dosage or serum phenobarbital concentration. Results suggested that dogs treated long term with phenobarbital or with phenobarbital and bromide may develop hypertriglyceridemia. Fasting serum triglyceride concentration should be periodically monitored in dogs treated with phenobarbital because hypertriglyceridemia is a risk factor for pancreatitis.

Effects of urine pH modification on pharmacokinetics of phenobarbital in healthy dogs

Although pH modification is one of the effective strategies for dissolving or preventing uroliths, little is known about its effects on the pharmacokinetics of phenobarbital in dogs. Five spayed, female Beagles were fed with a twice-daily diet that included potassium citrate and ammonium chloride for urine alkalinization and acidification, respectively. After a stabilizing period of 7 days, a single clinical dose of phenobarbital (3 mg/kg) was orally administered, and time-course changes in its serum and urine concentrations were determined by high-performance liquid chromatography. Total amounts of unchanged phenobarbital excreted into urine for 216 h were decreased by urine acidification and increased by urine alkalinization. The elimination half-life of serum phenobarbital in dogs with urine alkalinization was shortened and Cl(R) increased when compared with dogs with urine acidification. Other pharmacokinetic parameters, including C(max), T(max), AUC(0-216), Cl/F, and A(e0-216) were not changed by modification of the urine pH. These results suggest that the pH of urine is likely to be a determinant of the pharmacokinetics, especially urine excretion rate, of a clinical dose of oral phenobarbital. It is possible that the serum concentration of phenobarbital might be altered when a pH modifying-diet is administered for the purpose of dissolving or preventing uroliths.

Pharmacokinetics of zonisamide and drug interaction with phenobarbital in dogs

The purposes of the present study were to elucidate the pharmacokinetics of zonisamide, determine the presence of a drug interaction with phenobarbital, and evaluate how long any interaction lasted after discontinuation of phenobarbital in dogs. Five dogs received zonisamide (5 mg/kg, p.o. and i.v.) before and during repeated oral administration of phenobarbital (5 mg/kg, bid, for 30-35 days). Zonisamide (5 mg/kg, p.o.) was also administered 8, 10, and 12 weeks after discontinuation of phenobarbital. Blood was sampled until 24 h after each zonisamide administration and serum concentrations of zonisamide were determined. Repeated phenobarbital decreased the maximum serum concentration, area under the serum concentration vs. time curve, apparent elimination half-life, and bioavailability of zonisamide. Total clearance increased. Time to maximum serum concentration and volume distribution were not changed. The maximum serum concentration and area under the serum concentration vs. time curve of zonisamide continued to be low until 10 weeks after the discontinuation of phenobarbital. They were restored to the same serum concentration as before phenobarbital administration 12 weeks after the discontinuation of phenobarbital. These data suggested that repeated administration of a clinical dose of phenobarbital enhanced the clearance of zonisamide and the enhanced clearance lasted at least 10 weeks after the discontinuation of phenobarbital. Caution may be necessary when zonisamide is given with phenobarbital and when antiepileptic therapy is changed from phenobarbital to zonisamide.

Animal Behavior Case of the Month

Animal Behavior Case of the Month

Laserakupunktur als Therapie bei ausgeprägter Unruhe: – bei einem ehemaligen Frühgeborenen der 28. Schwangerschaftswoche

Background As pediatricians, we often experience agitated infants worrying their parents by crying for hours on end. Frequently, these infants are troubled by colics, but ever so often, no organic reason for such agitated behavior can be found. Prenatal as well as birth-related traumatization can lead to angst and emotional shock, thereby hindering the flow of qi in the body. Preterm babies can suffer a traumatization by the sudden birth and a sense of being “forced into the world” too early. The baby described in this case study was a preterm after 28 weeks with a very difficult postnatal period and extreme periods of agitation and crying. No objective reason for these “crying-fits” could be determined. Objective To evaluate a diagnose using the criteria of Traditional Chinese Medicine, and then treat the baby accordingly, using laser acupuncture. Method Heart rate monitoring over the 14 days before and during laser therapy. Discussion Laser acupuncture treatment made the child calmer. The baby was able to relax and sleep more frequently. During the time of treatment, the mean heart rate dropped over more then ten beats per minute. Unfortunately, laser therapy could not be continued after the baby's discharge from the hospital. To improve parent-child-interaction, we decided to treat the child with a daily low dose of Phenobarbital.

Delayed Postoperative Agitation in a Child After Preoperative Midazolam

We present a case report of a 5-year-old boy who had severe agitation after PACU discharge after midazolam premedication for minor otologic surgery. He was treated over several hours in the emergency department with several doses of midazolam and phenobarbital, without resolution of the agitation. Finally, a single dose of flumazenil (0.2 mg) effectively reversed the child's agitation. The incidence and potential mechanisms for postoperative agitation are discussed, with a focus on the potential for midazolam-induced behavioral reactions. This information has nursing implications for postoperative discharge instructions and follow-up.

EEG wavelet analyses of the striatum– substantia nigra pars reticulata– superior colliculus circuitry: Audiogenic seizures and anticonvulsant drug administration in Wistar audiogenic rats (War strain)

The importance of the substantia nigra pars reticulata (SNPr), striatum (STR) and superior colicullus (SC) in the blockade of experimental seizures is well known. But, in audiogenic seizures (brainstem tonic-clonic seizures), the anticonvulsant activity of these nuclei is still controversial. In the present study we aimed to analyze the STR–SNPr–CS circuitry in the audiogenic seizures of Wistar audiogenic rat (WAR). Behavioral and electroencephalographic (EEG) data were collected from WARs under no treatment or injection with systemic (phenobarbital) or intracerebral (intranigral) drugs (muscimol and phenobarbital). The main EEG frequency oscillation of STR, SNPr and SC seen before, during and after audiogenic seizures or during seizure protection, was determinated with wavelet spectral analyses. This method allows the association between behavior and EEG (video-EEG). Audiogenic seizures last only for half a minute in average, suggesting that the interruptions of seizures are probably not due to exhaustion. Systemic phenobarbital caused an acute and dose-dependent behavioral and EEGraphic anticonvulsant effect both in WARs. The dose of phenobarbital 15 mg/kg protected animals almost completely, without side effects such as ataxia and sedation. In our data, this endogenous “natural” seizure blockade (or termination) seems to be similar to the “forced” seizure abolition, like the one caused by a systemic non-ataxic phenobarbital dose, because in both cases an intense decrease in the EEG main frequency oscillation can be seen in SNPr and SC. Intranigral phenobarbital or muscimol did not protect animals, and actually induced an increase in the main EEG frequency oscillation in SC. The main finding of the present study is that, in contrast to what is well believed about the incapacity to control audiogenic seizures by the striato-nigro-tectal circuitry, we collected here evidences that these nuclei are involved in the ability to block these seizures. However, the striato-nigro-tectal circuitry in WARs, a genetically developed strain, seems to have different functional mechanisms when compared with normal rats.

Effects of therapeutic and toxic phenobarbital doses on brain tissue caspase 3-activity in the neonatal rat

Effects of therapeutic and toxic phenobarbital doses on brain tissue caspase 3-activity in the neonatal rat

Antiepileptic treatment against clustered seizures in benign partial epilepsy in infancy

We performed detailed review of clinical course of clustered seizures in patients with benign partial epilepsy in infancy in order to determine the optimal treatment during the acute period. We retrospectively investigated the details of antiepileptic treatment for clustered seizures in 20 patients with benign partial epilepsy in infancy. The temporal course of seizures and the use of antiepileptic drugs were investigated in each patient. Drugs were judged as effective when seizure cessation was achieved after administration of the drug. As the first drug, diazepam/bromazepam was effective in 14% and phenobarbital in 60%. As the second drug, diazepam/bromazepam was effective in 13% and phenobarbital in 40%. As the third drug, phenobarbital was effective in 56%. The efficacy rate of the first dose of phenobarbital was relatively higher than that of diazepam/bromazepam. Persistence of seizures after treatment was relatively shorter and the number of seizures after treatment was relatively smaller in patients treated with PB as the first 2 drugs. In conclusion, the efficacy of diazepam/bromazepam or phenobarbital was insufficient for the cessation of clustered seizures in benign partial epilepsy in infancy.

Evaluation of the efficacy of phenobarbital in treatment of epilepsy in rural areas: study of 2455 patients in rural China

To evaluate the efficacy of phenobarbital in treatment of patients with convulsive forms of epilepsy in rural areas and to develop a suitable relevant model for rural China. A demonstration protocol was conducted in the rural areas of 8 counties from 6 provinces and municipality in China, Heilongjiang, Ningxia, Henan, Jiangsu, Shanxi, and Shanghai from December 2001 to June 2004. Epidemiological investigation of the prevalence and treatment gap of epilepsy was carried out. Patients with convulsive forms of epilepsy thus screened underwent treatment of phenobarbital. Physicians of township hospitals received short-term training to be in charge of the treatment and regular follow-up of the patients. A total of 2455 patients with generalized tonic-clonic seizures in these 6 rural areas were screened and entered the treatment group. 347 patients (26.2%) had been seizure-free during the period of these 2 years, 415 patients (31.3%) had their seizure frequencies decreased by > 75% as compared with those during the period of 6 months before treatment, and the conditions of 26.1% of the patients did not change or even became worse. About 26.1% of the patients had mild side effects, 3.7% had moderate side effects, and only 0.3% had severe side effects when the dosage of phenobarbital in the first 3 months was increased. 597 patients (24.3%) withdrew from the treatment group because of various reasons. This protocol was suitable to the rural areas of China. The trained physicians are capable of fulfilling the task to treat the patients with epilepsy. Phenobarbital is an effective drug for most patients with convulsive seizures and has no severe side effect.