Received Sodium Valproate Research Articles

Medical treatment of an\xa0unusual cerebral hydatid disease

BackgroundHydatid disease is a worldwide zoonosis produced by the larval stage of cestodes of the Echinococcus genus. Hydatid disease primarily involves the liver and lungs. The brain is involved in less than 2% of cases. Surgery has long been the only choice for the treatment, but chemotherapy has been successfully replaced surgery in some special cases.Case presentationWe report a rare hydatid disease case which presented with multiple lesions in right frontal lobe, an uncommon site, and in the liver and lungs. A 28-year-old woman presented with 6 months history of recurrent convulsion. Cranial magnetic resonance imaging found multiple lesions in right frontal lobe, so she was hospitalized for surgical treatment and received sodium valproate by oral for controlling epilepsy. Before the operation, other lesions were found in the liver and lungs by computerized tomography scan. There were multiple pulmonary nodules near the pleura and large cyst in the liver. The pathology of liver showed that it may be a hydatid disease. Then, positive serum antibodies for echinococcus antigen further confirmed our diagnosis. Since her central nerve system was involved, she received four pills (800 mg, about 17 mg/kg/day) albendazole treatment for 18 months without operation. Her symptoms abated and a follow-up magnetic resonance imaging showed that the lesion had obviously diminished after treatment. She was recurrence free 2 years after we stopped albendazole treatment.ConclusionsThis case reveals an uncommon pattern of intracranial hydatid disease. Albendazole can be beneficial for some inoperable cerebral hydatid disease patients.

A Study of The Effect of Prenatal Exposure to Valproic Acid on The Cerebellum of Albino Rat’s Offspring and The Possible Protective Role of Folic Acid

ABSTRACTAbstract: Valproic acid (VPA) is used as an anticonvulsant for the treatment of epilepsy. It is also used as one of the mood stabilizing agents in patients with anxiety disorder and as a prophylactic treatment of migraine. The need for anticonvulsant prophylaxis in women of childbearing period is essential since convulsive seizures are considered harmful to the developing embryo. Exposure to VPA during the first trimester of pregnancy was found to be associated with increased risks of several congenital malformations and also in utero exposure to VPA in rats caused cerebellar anomalies.Folic acid (vitamin B9) is essential for the DNA synthesis and certain biological reactions. Adequate folate intake helped in protection against congenital malformations including neural tube defects.Aim of the work: To investigate the effect of prenatal exposure to valproic acid on the cerebellum of albino rat’s offspring and to clarify the possible protective role of folic acid.Material and Methods: Twenty four pregnant albino rats were divided into four groups, six rats each. Group (A); a control group. Group (B); rats received sodium valproate (400 mg/Kg. B.W) starting on gestational day 13 daily till the end of pregnancy by oral gavage. Group (C); rats received folic acid (4 mg/Kg. B.W) starting from first day of pregnancy daily till the end of pregnancy by oral gavage. Group (D); rats received folic acid as in group (C) concomitantly with sodium valproate as in group (B) by oral gavage. At the end of the experiment, six male pups from each group were sacrificed on the postnatal day 14. The cerebella were extracted and processed for light microscopic examination using HE the molecular layer, the Purkinje cell layer and the granular layer. The molecular layer appeared pale with few stellate cells and basket cells. The Purkinje cell layer consisted of Purkinje cells arranged in single row with their oval or flask shaped cell bodies, pale central nuclei and apical cytoplasmic cones. The granular layer consisted of deeply stained rounded small granule cells. This general architecture of the cerebellar cortex was greatly affected in group (B) and an external granular layer was detected on the cerebellar surface in some sections. The Purkinje cells appeared degenerated with pyknotic nuclei and the number of apparently normal cells was statistically decreased compared to control. The number of Bergmann cells was statistically significantly increased. Some granule cells were degenerated with pyknotic nuclei. Also astrocytes showed a strong positive reaction to GFAP with statistically significantly high percentage area compared to the control group. Examination of group (D) showed apparently normal arrangement of layers, Purkinje cells restored their normal flask shaped appearance and arranged in single row with Bergmann glia inbetween. Also astrocytes gave a mild positive reaction to GFAP similar to control group.Conclusion: Valproic acid (VPA) had degenerative structural effect on the cerebellar cortex if administered during pregnancy. VPA should be administered at the least effective dose and that folic acid co-administration is highly recommended to reduce its toxic effect.

Bifid epiglottis, high-arched palate, and mental disorder in a patient with Pallister-Hall syndrome.

Bifid epiglottis, high-arched palate, and mental disorder in a patient with Pallister-Hall syndrome.

Combined effect of sodium valproate and ascorbic acid on pentylenetetrazole-induced seizures in mice

Epilepsy is one of the most frequent neurological afflictions characterized by excessive temporary neuronal discharges resulting in convulsion. The pathophysiology is still not fully understood. Even though oxidative stress has been implicated as one of the mechanisms, yet the management of convulsions do not take into cognizance the important role played by antioxidants. The aim of the study was to assess the combined effect of sodium valproate (conventional antiepileptic drug) and ascorbic acid (potent antioxidant) in pentylenetetrazole (PTZ) induced seizures. Thirty mice were divided into six groups of five each (n=5). Group 1 served as control and administered normal saline 1ml/kg, group 2 received sodium valproate 200mg/kg, groups 3 and 4 were administered ascorbic acid (vitamin C) 100mg/kg and 300mg/kg, groups 5 and 6 were administered ascorbic acid (vitamin C) 100mg/kg and 300mg/kg respectively, in combination with sodium valproate 200mg/kg, 15 and 30 minutes prior to intra-peritoneal injection of PTZ (65 mg/kg). Seizure latency and duration were determined. The results showed that ascorbic acid alone has no effect on the seizure parameters. Sodium valproate 200mg had protective effect on PTZ-induced seizures. Combination of 300 mg/kg ascorbic acid with 200 mg/kg sodium valproate had a significant (p<0.05) synergistic and marked protective effect, as indicated by increase in the latency of seizure and reduction in seizure duration as compared to the control. Anti-oxidant vitamin C is recommended as co-treatment with sodium valproate in the management of seizures. Keywords: Pentylenetetrazole, sodium valproate, ascorbic acid, seizures

PROTECTIVE EFFECT OF LEMONGRASS (CYMBOPOGON CITRATUS) AND VITAMIN E ON SODIUM VALPROATE INDUCED TESTICULAR TOXICITY IN RATS

Abstract The present study was carried to investigate the effect of extract and powder of Cymbopogon citrates and vitamin E on the sexual hormonal profiles against testicular toxicity of sodium valproate of normal male rats. The forty two mature male albino rats were divided into seven groups every group of 6 rats. The group control received fed on basal diet, whereas the other five groups received sodium valproate (positive group) the other four groups received Vit. E orally at a dose of (200 mg/kg b.wt./day), Lemongrass powder (100 mg/kg/diet/day), Lemongrass extract (10 ml/kg/b.wt/rat/day), vitamin E with lemongrass powder and vitamin E with lemongrass extract, for a period of 6 weeks, caused a significant increase in serum HDL-c, testosterone, serum follicle stimulating hormone level (FSH) ,luteinizing hormone (LH), total antioxidants , superoxide dismutase and glutathion levels compared to positive control group. Effect on in serum total cholesterol, triglycerides, LDL-c, sexual organs weight (testis, prostate, and seminal vesicles), malondialdehyde were also determined, and was found to be significantly lower in all the administered groups when compared with sodium valproate group. Findings in this study showed that lemongrass powder and extract combination with vitamin E has a potent protective effect against sodium valproate-induced testicular injury in rats. It also did not exert oxidative damage to the sexual organs and the various hormonal profiles as well as its relative safety and possible use to protect from sodium valproate side effects. Keywords: Cymbopogon citrates - Sodium valproate - Phenolic compounds - Seminal vesicles - Testicular toxicity.

Efficacy of Sodium Valproate and Olanzapine in treating bipolar affective disorder 'mania' at a tertiary care hospital in Nepal: A comparative study

Background and Objectives: Bipolar affective disorder, mania is the mood of an abnormally elevated arousal energy level or a state of heightened overall activation with enhanced affective expression together with lability of affect. The objective of the study was to compare the efficacy of sodium valproate and olanzapine in bipolar affective disorder, mania patients at a tertiary care hospital in NepalMaterial and Methods: A randomized observational prospective open label study was conducted for one and half year at College of Medical Sciences-Teaching Hospital (CMS-TH), Bharatpur, Nepal in the Psychiatry Department. Sixty patients diagnosed with bipolar affective disorder, mania were enrolled. 30 patients received sodium valproate and 30 patients received olanzapine. Patients were monitored and evaluated on baseline (day 0), day 7 and day 30 and compared to the baseline for the severity of illness using the 11-item Young Mania Rating Scale (YMRS).Results: The mean baseline YMRS score for all cases on sodium valproate (n=30) on day 0 was 38.87 ± 3.73, while it was reduced to 13.90 ± 1.95 (p &lt; 0.001) on day 30. Similarly, the mean baseline YMRS score for all cases on olanzapine (n=30) on day 0was 40.83 ± 6.50, while it was reduced to 14.47 ± 2.83 (p &lt; 0.001) on day 30.The mean decrease in YMRS score by sodium valproate was 64.24% and by olanzapine was 64.56%.Conclusion: Treatment with sodium valproate and olanzapine significantly improves the mean mania ratings score and there is no statistically significant difference in efficacy of both the drugs in patients diagnosed with bipolar affective disorder, mania.Janaki Medical College Journal of Medical Sciences (2016) Vol. 4(1): 27-35

Sodium Valproate Induced Alopecia: A Case Series.

Drug induced alopecia may range from a barely detectable shedding to an irreversible baldness. Alopecia associated with valproate is a dose-dependent and reversible side effect. We hereby report, three cases of alopecia that occurred in patients who received sodium valproate for various neurological conditions. In all three cases, long term exposure of valproate therapy led to the development of alopecia which eventually resolved after dose reduction or discontinuation. The Naranjo's causality assessment scale indicated valproate as the probable cause of the alopecia in all our patients.

Effect of Ginseng (Panax ginseng) against Testicular Toxicity Induced by Sodium Valproate in Male Rats

The aim of this experimental study was to investigate the effects of ginseng powder, extract, L-carnitine and their combination against sodium valproate induced testicular toxicity in rats, the reproductive performance of male rats with respect to semen parameters, male sex hormones and the testicular antioxidant system. A total of forty two mature male albino rats were divided into six groups of seven rats. The control group received saline, whereas the other five groups received sodium valproate the firs represented positive group, after that four groups received ginseng (100 mg/kg. diet), ginseng extract (10 mg/kg. B wt /rat), L-carnitine (150 mg/kg Bwt/rat /day) or a combination of both ginseng and L-carnitine via a stomach tube daily respectively for one month. At the end of the treatment period, rats were sacrificed, weights of sexual organ recorded and their sperm characteristics count, antioxidant enzyme factors levels (reduced glutathione, malondialdehyde, superoxide dismutase and total antioxidant capacity) and sex hormone levels (testosterone, Follicle stimulating hormone (FSH) and luteinizing hormone (LH) were analyzed. Results showed that the four experimental treatments improved lipid parameters, liver function, sperm parameters, antioxidant enzyme activity and testosterone hormone levels; the most pronounced positive effects were observed in the group that received a combination of both ginseng and L-carnitine. Therefore, the administration of a combination of ginseng and L-carnitine may be beneficial for improving male sexual performance.

Recurrent febrile encephalopathy: A presentation form of glutaric aciduria type 1

A 22-month-old male child presented with recurrent febrile encephalopathy with regression of developmental milestones from 6-month of age. He had upper limb dystonia and startle response for which he received sodium valproate. He had compensated metabolic acidosis. Cranial magnetic resonance imaging revealed widening of the Sylvian fissure, fronto-temporal atrophy and T2 hyperintensity in globus pallidus, putamen and cerebellum. His urinary glutaryl carnitine was high (3.17 μ mol/L) and free urine carnitine low (6.63 μ mol/L). Glutaric aciduria should be considered in children with recurrent febrile encephalopathy and in them valproate should be avoided. Characteristic magnetic resonance imaging feature is helpful.

Acute anticonvulsant activity of fluoxetine in wistar albino rats by maximum electroshock induced seizure

A seizure is paroxysmal event due to abnormal, excessive, hypersynchronous discharges from an aggregate of central nervous system neurons. Epilepsy describes a condition in which a person has recurrent seizures due to a chronic or underlying process. The objective of this study was to evaluate anti-convulsant effect of Fluoxetine by Maximum Electroshock induced Seizure in Wistar albino rats. Wistar albino rats of either sex weighing 150-200 gms were randomly divided into five groups containing five animals in each group. All the drug preparations were administered intra-peritoneally. Group 1 received 0.5 ml/100 gm of Propylene Glycol and served as a control. Group 2 received Sodium Valproate 300 mg/kg and served as standard. Group three, four and five received Fluoxetine 10, 20 and 30 mg/kg respectively. After an interval of 30 minutes they were subjected to Maximal electroshock (MES) stimulation of 150mA for 0.2 seconds through trans-auricular electrodes by using technoelectroconvulsiometer. The duration of different parameters was noted. Statistical method was One way ANOVA was used for multiple group comparisons followed by post- hoc Tukey‟s test for group wise comparisons. Group 4 and 5 which received Fluoxetine 20 and 30 mg/kg significant anticonvulsant action when compared to control group with respect to reduction in time taken for like fore limb flexion, hind limb extension, clonus and stupor. Our study reveals that Fluoxetine elicited an effective protection against MES seizures in Wistar albino rats in the dose of 20 and 30 mg/kg.

New blisters in a patient treated for Stevens-Johnson syndrome/toxic epidermal necrolysis

Conflict of interest: none declared. A 26‐year‐old woman presented with a fever, oral and genital mucositis, purulent conjunctivitis, and a generalized blistering rash covering 15% of her body surface area, typical of Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) overlap (SCORTEN score1). On histological examination of a skin biopsy, a subepidermal blister with overlying full‐thickness epidermal necrosis was seen, consistent with SJS/TEN. Direct immunofluorescence studies were negative. The patient had been receiving sodium valproate for epilepsy since the age of 11 years. Lamotrigine had been introduced 8 weeks before her presentation to us to improve seizure control, and her symptoms had developed 4 weeks after the dose was doubled. The patient was admitted to the intensive care unit for supportive care. Lamotrigine and sodium valproate were discontinued, and methylprednisolone (1.5 g over 3 days) was started. By day 7, the patient was systemically well and afebrile, the blisters were re‐epithelializing, and her mucositis had improved; however, new asymptomatic blisters appeared on previously nonblistered skin on her limbs and trunk. There were no new macular or targetoid lesions.

Rapid clozapine dose titration and concomitant sodium valproate increase the risk of myocarditis with clozapine: A case–control study

BackgroundDespite the implementation of cardiac monitoring guidelines, clozapine-induced myocarditis continues to cause deaths in Australia, and the risk is a barrier to prescription of this effective drug for the treatment of schizophrenia. This study was designed to identify clinical and phenotypic risk factors for clozapine-induced myocarditis. MethodPossible cases of clozapine related myocarditis occurring between June 1993 and November 2009 and a comparative group of controls taking clozapine for at least 45days without cardiac disease were documented from the patients' medical records. Results105 cases, with time to onset of 10–33days, and 296 controls were included in the study. In multivariate analysis, the risk of myocarditis increased by 26% for each additional 250mg of clozapine administered in the first nine days of clozapine titration (odds ratio 1.26; 95% confidence interval 1.02–1.55; p=0.03) and concomitant sodium valproate more than doubled the risk (2.59; 1.51–4.42; 0.001). Further, each successive decade in age was associated with a 31% increase in risk (1.31; 1.07–1.60; 0.009).Nevertheless, 33 cases received less than 920mg of clozapine during the first nine days of dose titration, did not take sodium valproate and were aged less than 40years; and nine control patients received sodium valproate and more than 920mg of clozapine in the first nine days without developing myocarditis. ConclusionsClozapine should be initiated by slow dose titration and sodium valproate is best avoided, if clinically feasible, during this period. All patients commencing clozapine should be monitored for myocarditis up to Day 28.

Methylphenidate-Induced Acute Orofacial and Extremity Dyskinesia

Methylphenidate is a short-acting stimulant. In this article, the authors report a 7-year-old male patient who presented with orofacial and limb dyskinesia after his first dose of methylphenidate treatment for a diagnosis of attention-deficit/hyperactivity disorder; he was also receiving sodium valproate treatment for epilepsy. Orofacial dyskinesia appeared 5 hours after methylphenidate administration, persisted for 10 hours, and had completely resolved within 2 days. Although limb dyskinesia after methylphenidate is a commonly reported side effect, to the authors' knowledge this is only the second reported case to develop both orofacial and limb dyskinesia in the acute period after the first dose of methylphenidate. This case is reported to emphasize the potential side effects of methylphenidate, individual differences in drug sensitivities, and drug-receptor interactions via different mechanisms.

A clinical trial of the effect of St. John’s wort on migraine headaches in patients receiving sodium valproate

St John’s wort (Hypericum perfortum) a medicinal plant used for depression has been shown to increase the levels of brain serotonin, which may also influence migraine headache. This study was designed to evaluate the effect of H. perforatum on the frequency and intensity of migraine headaches in patients. In a clinical trial, 100 patients aged 15 to 45 years, with migraine headaches were randomly assigned to two study groups. The trial was conducted in four phases of 45 days. In the pretreatment phase, patients were drug free. In the first treatment phase, both patient groups received sodium valproate (200 mg/tablet), twice daily. In the second phase, patients in study group 1 continued to use sodium valproate and patients in study group 2 received tablets of H. perforatum thrice daily in addition to sodium valproate. In the third phase of study, patients were medicated identically to the first phase of the trial. Patients were free to take indometacin 25 mg capsules as a rescue medication for migraine throughout. Co-administration of H. perforatum coated tablets with sodium valproate in the second trial phase reduced (P=0.04) the intensity of migraine attacks and evoked a more marked decline in their frequency. Therefore, H. perforatum might be beneficial in migraineurs. Key words: St. John's wort, migraine headache, sodium valproate.

Valproate in acute mania: is our practice evidence based?

This audit was conducted on acute psychiatric in-patient wards with the aim of establishing if valproate prescribing in acute mania followed evidence-based guidelines with particular emphasis on formulations used and whether accelerated valproate dosing was employed. Case notes from 43 (42 percent male) patients admitted with mania and subsequently discharged on valproate were reviewed. Valproate formulation, weight measurement (necessary for dose-calculation in accelerated dosing), initial valproate dose and increments, serum valproate monitoring and other prescribed psychotropic agents were noted. Most (95 percent) patients received sodium valproate (epilim chrono/generic), the remaining received valproate semi-sodium (depakote). All but one patient received antipsychotic medication in combination. Weight was recorded in only four (9 percent) patients. The mean valproate daily dose after the first week was 1,027mg (sd = 408). It took 29 (sd = 42) days to reach the maximum daily dose (1,426 mg sd = 467) from valproate initiation. Serum levels were monitored in 34 (79 percent) cases, but the mean period between valproate initiation to the first serum level test was 38 (sd = 47) days. A significant positive correlation was found between days taken to reach maximum dose and hospital stay (Spearman's rho = 0.41, n = 43, p = 0.006, two-tailed). Accelerated valproate dosing was not common practice, which may have resulted in suboptimal efficacy, probably leading to combination treatment. This study highlights the need for adequate initial dosing and dose increments when treating manic patients and suggests current practice is not evidence-based. Local prescribing policy and national guidelines' influence on practice are discussed.

Prophylactic Effects of Melatonin on Sodium Valproate-Induced Neural Tube Defects and Skeletal Malformations in Rat Embryos

Problem statement: Some reports showed the teratogenic effects of sodium valproate can be prevented by application of antioxidant drugs and stimulation of the maternal immune system. Therefore, in this study, the prophylactic effect of melatonin on teratogenic effects of sodium valproate was compared. Approach: This study was performed on 31 pregnant rats that were divided into five groups. Control group received normal saline and test groups received sodium valproate (300 mg kg−1), sodium valproate (300 mg kg−1) plus melatonin (5 mg kg−1) and sodium valproate (300 mg kg−1) plus melatonin (10 mg kg−1) and melatonin (10 mg kg−1), intraperitonealy at 8-9th days of gestation, respectively. Fetuses were collected at 20th day of gestation and after determination of weight and length; they were stained by Alizarin red-Alcian blue method. Results: Cleft palate, spina bifida and exencephaly incidence were 17.70, 20 and 20% in fetuses of rats that received only sodium valproate. Cleft palate, spina bifida and exencephaly incidence were 4.16, 8.33 and 8.33% range in group which received sodium valproate plus melatonin (5 mg kg−1), respectively. However, Cleft palate, spina bifida and excencaphaly incidence were 4/76, 0 and 0% in group which received sodium valproate plus melatonin (10 mg kg−1), respectively. The mean of weight and length of animals’ fetuses that received melatonin were significantly greater than those received only sodium valproate. Conclusion: It is concluded that melatonin with dose of 10 mg kg−1 had significantly more prophylactic effect than melatonin with dose of 5 mg kg−1 on incidence of sodium valproate-induced skeletal malformations.

Effect of sodium valproate on midazolam distribution.

The displacement of midazolam, a new water-soluble, short acting benzodiazepine, from its plasma binding sites by sodium valproate, has been studied in man. An increase of its free fraction (ranging from 2.71 to 5.35%) in plasma from epileptic patients receiving sodium valproate was observed. A similar situation was created in rabbits by pretreatment with sodium valproate (600 mg kg-1 day-1) and posterior hypnosis with midazolam. Due to the interaction, sodium valproate-pretreated rabbits showed an increase in midazolam brain levels (130.91 micrograms g-1 in cortex vs 84.55 micrograms g-1 in control animals). Therefore, it seems likely that displacement of midazolam by sodium valproate in epileptic patients could lead to an increase of the midazolam response.

The Effect of Anticonvulsant Drugs (Phenobarbital and Valproic Acid) on the Serum Level of Cholesterol, Triglyceride, Lipoprotein and Liver Enzymes in Convulsive Children

Objective on the effect of various antiepileptic drugs on serum lipids show contradictory results. We aimed to find the effect of Phenobarbital and Sodium Valproate monotherapy on serum lipid profile and liver function tests in epileptic children. Materials & Methods This cohort study was conducted in Amirkola Children Hospital. One hundred and ten children with epilepsy were included in this study. Children with hepatic or renal disease, those receiving medications which could alter liver function tests or serum lipid profile were excluded from the study. Patients were allocated into two groups. The first group, including 63 patients, received Phenobarbital and the second group, including 47 patients, received Sodium Valproate, both in divided doses. A venous blood sample was collected after overnight fasting to evaluate serum triglyceride, total cholesterol, LDL, HDL, and liver function tests. Data was analyzed with SPSS version 17. Results receiving Phenobarbital, total cholesterol, LDL, HDL, ALP, SGOT and SGPT increased significantly after treatment, but TG level showed no significant changes. In children receiving Sodium Valproate, HDL, ALP, SGOT, SGPT significantly increased after treatment but there were no statistically significant changes in total cholesterol, LDL and TG. In our study, the plasma levels of LPa elevated significantly after treatment with Phenobarbital and Sodium Valproate (P Value=0.0001). This increase was more significant in patients receiving Sodium Valproate. Conclusion results suggested a need for monitoring serum total cholesterol, HDL, LDL, and TG levels in patients receiving Phenobarbital and Valproic Acid.

Sodium valproate for prevention of early posttraumatic seizures

Objective To assess the preventive effect of sodium valproate on early posttraumatic seizures in traumatic brain injury (TBI) patients. Methods The retrospective study was based on 159 patients with TBI treated at Department of Neurosurgery, Nanjing General Hospital of Nanjing Command enrolled between January 1, 2008 and December 31, 2009. The inhospital section of the retrospectively collected database includes information on age, sex, initial Glasgow Coma Score (GCS), results of CT scanning, operation, usage of sodium valproate, seizures in the first week after injury and outcome. Results Seven patients (4.4%) showed early post-traumatic seizures. Although the incidence was zero in patients who received sodium valproate treatment, the difference between the treatment and control groups was not statistically significant. Of the 87 severe TBI patients (GCS 3–8), 6 patients in the control group (6.9%) suffered from early seizures during the first week after TBI and no patient who received preventive therapy suffered from seizures. The difference between the treatment and the control groups was still not statistically significant. Of the 72 mild and moderate TBI patients (GCS 9–15), only 1 patient in the control group suffered from seizures and no patient in the treatment group suffered. Conclusion Although the results suggest that the study is not sufficiently powerful to detect a clinically important difference in the seizure rates between the treatment and control groups, sodium valproate is effective in decreasing the risk of early posttraumatic seizures in severe TBI patients. Further prospective studies are recommended.

A Randomized Trial of Propranolol versus Sodium Valproate for the Prophylaxis of Migraine in Pediatric Patients

Migraine is the most common of the paroxysmal disorders to affect the brain in the pediatric population. Both propranolol and sodium valproate (valproic acid) have been advocated as prophylactic agents for childhood migraine. To compare the efficacy and tolerability of propranolol and sodium valproate in the prevention of migraine in the pediatric population. Sixty-three children (aged 5-15 years) with migraine without aura, as defined by the 2004 International Headache Society (IHS) criteria, were included in this prospective, double-blind clinical trial and were randomly assigned to two groups. Group A (n = 32 patients) received propranolol 3 mg/kg/day and group B (n = 31 patients) received sodium valproate 30 mg/kg/day, with at least 6 months of follow up. The propranolol dosage was adjusted to 2 mg/kg/day and the sodium valproate dosage to 15 mg/kg/day, after the first follow-up visit. Participants were evaluated by using a detailed questionnaire that asked about the features of headaches and general health characteristics. The study endpoints were successful treatment for a 4- to 6-month period; 3 months of a persistent unsuccessful or incomplete response to treatment; intolerable side effects; and/or patient non-adherence. All data were analyzed longitudinally by comparing baseline data with data from each follow-up. A total of 60 patients completed the full headache prophylaxis period. The baseline headache frequency was reduced by more than 50% in 83% of propranolol recipients and in 63% of sodium valproate recipients (statistically not significant); the overall reduction of baseline headache frequency per month was better in group A (p = 0.044). The mean headache frequency per month was reduced from 13.86 +/- 2.11 to 4.23 +/- 3.24 in group A, and from 13.23 +/- 2.43 to 5.83 +/- 4.04 in group B; the difference between the two groups was statistically significant (p < 0.01). The mean headache duration per week was decreased from 9.9 +/- 7.4 hours to 3.2 +/- 5.9 hours in group A, and from 9.1 +/- 6.9 hours to 3.7 +/- 5.0 hours in group B; although there was no statistically significant difference between propranolol and sodium valproate, headache duration was markedly improved with each drug (p < 0.002). Reduction of headache severity by at least one grade was seen in 64% of patients in group A and in 56% in group B, and complete cessation of headache attacks occurred in 14% of patients in group A and 10% in group B (not significant). Minor side effects appeared to be fairly well tolerated by patients in both groups, with no significant difference in side effects between the two groups. This prospective study supports the efficacy of propranolol and sodium valproate as prophylaxis for pediatric migraine without aura, based on IHS criteria. There were no significant differences between these two drugs in all evaluated parameters except for the mean headache frequency per month, which was lower with propranolol than with sodium valproate.