Sodium Valproate Group Research Articles

Risperidone versus risperidone plus sodium valproate for treatment of bipolar disorders: a randomized, double-blind clinical-trial.

Objective:This study compared the efficacy of risperidone monotherapy with risperidone plus valproate in bipolar I disorder, manic phase. Some studies showed the efficacy of risperidone monotherapy in the treatment of bipolar disorder, so we examined this effectiveness in this clinical-trial study.Method:This 7-week, randomized, single-blind study included 48 bipolar I inpatients manic phase without psychotic features divided in risperidone group (n = 23) and risperidone plus sodium valproate group (n = 25). According to clinical symptoms, 3 categories: complete remission, partial remission and no remission were mentioned in weekly follow-up. Remission rate compared with survival analysis.Results:The results showed a significant difference in remission rate between risperidone monotherapy and risperidone plus sodium valproate at the 1st, 2nd and the 3rd week (p = 0.012, 0.023, 0.027 respectively), It means the remission rate in risperidone plus valproate group was higher in the first three weeks, but at the end of the seventh week, the difference was not statistically significant. There was no significant difference between the two groups in the development of adverse effects.Conclusions:Risperidone can be effective and well tolerated in both acute manic episodes of bipolar mood disorders.

The efficacy of intravenous sodium valproate and phenytoin as the first-line treatment in status epilepticus: a comparison study

BackgroundStatus epilepticus (SE) is a serious neurological condition and requires prompt treatment. Sodium valproate has been used to treat SE successfully but its role as the first-line antiepileptic drug (AED) is still controversial. This study evaluated the efficacy of intravenous sodium valproate to determine if it is non-inferior to intravenous phenytoin in SE treatment.MethodsPatients diagnosed as SE during 2003–2010 who were of an age of more than 15 years and received either intravenous sodium valproate or intravenous phenytoin as the first-line treatment were enrolled. Clinical characteristics and outcomes of SE were recorded and analyzed. The differences of outcomes between sodium valproate and phenytoin group were determined by descriptive statistics.ResultsDuring the study period, there were 37 and 17 SE patients who received intravenous phenytoin and intravenous sodium valproate as the first-line treatment, respectively. All patients received diazepam 10 mg intravenously as a rescue medication before starting the antiepileptic agents if uncontrolled except one patient in the sodium valproate group. There were no significant differences between the phenytoin and sodium valproate groups in all outcome variables including numbers of patients with clinically-controlled seizures, non-dependent patients, time to seizure control, and duration of hospitalization, and death. No serious cardiovasculars event such as hypotension occurred in either group.ConclusionIntravenous sodium valproate is non-inferior to intravenous phenytoin as the first-line treatment in SE with no significant cardiovascular compromises.

A comparsion study on the social functions promotion of different medicine treatment strategies on the patients with treatment-resistant depression

Objective To evaluate the effectiveness of different medicine treatment strategies on the social functions promotion on the patients with treatment-resistant depression (TRD). Methods 375 Patients with TRD were randomly grouped into 8 groups, and each group was received 8 weeks different treatment for paroxetine,venlafaxine, mirtazapine, paroxetine plus risperidone, paroxetine plus sodium valproate, paroxetine plus buspirone, paroxetine plus trazodone,or paroxetine plus thyroxine, respectively. The efficacy and social functions were evaluated with HAMD-17, SDSS and SF-36. Results There were significant difference in SDSS scores between 8th week and the baseline( P＜0.01 ) , and for social functions factor scores of SF-36 there was significant difference between 4th ,8th week and the baseline in each groups( P＜0.01 ). There were significant difference in social functions factor scores of SF-36 and subtracting scores between 4th and 8th week in all groups except group paroxetine and group venlafaxine(P ＜ 0.05 or P ＜ 0.01 ). There were significant difference in SDSS subtracting scores at 8th week among 8 groups( paroxetine plus risperidone group 7.05 ± 6.39, mirtazapine group 6.53 ± 4.75, paroxetine plusthyroxine group 5.14 ± 4.94, paroxetine group 5.13 ± 4.94 ,paroxetine plus trazodone group 5.00 ± 4.94, paroxetine plus sodium valproate group 4.60 ± 4.09, venlafaxine group 4.57 ± 4.18, paroxetine plus buspirone group 4.24 ± 4.95 ) ( Z = 2.076, P ＜ 0.05 ), between group paroxetine plus risperidone and group venlafaxine , group paroxetine plus sodium valproate, group paroxetine plus buspirone,as group mirtazapine and group paroxetine plus buspirone(P＜ 0.05 ), respectively. The influencing factors on improving social functions are the severity, improvement of depressive symptoms and latest onset time. Conclusions These 8 treatment strategies all can promote social functions on the patients with TRD. But the intensity and chronological order of improvement werent the same among 8 groups. The influencing factors on improving social functions are the severity, improvement of depressive symptoms and latest onset time. Key words: Treatment-resistant depression; Medicine treatment strategies; Social functions

CHANGING IN THYROID FUNCTION TEST IN CHILDREN UNDERWENT ANTIEPILEPTIC THERAPY

Objective To determine the changes in thyroid function tests in children who underwent antiepileptic therapy in Shahid Beheshti Hospital, Kashan, in 2008. Materials & Methods This analytical-observational study was carried out in a cohort fashion without an external control group (self controlled) on 45 children with new onset epilepsy who had not been previously treated with antiepileptic medications. Three subjects were excluded from the study because of presenting clinical symptoms of hypothyroidism. Plasma levels of TSH, T3, FT3, T4 and FT4 hormones were measured and compared at baseline and 3 and 6 months after treatment. Results The results of Mann-Whitney statistical analysis suggested that the increase in the plasma level of TSH was significant only in the Sodium Valproate group. The plasma level of T3 significantly decreased 3 and 6 months after treatment in the Phenobarbital group while the plasma level of FT3 significantly decreased only in the Sodium Valproate group. The decrease in T4 plasma level was significant in all groups (Carbamazepine group, Sodium Valproate group and Phenobarbital group) 3 and 6 months after the onset of treatment but the decreasing in FT4 plasma level was only significant in the Carbamazepine group 6 months after the commencement of treatment. Conclusion Phenobarbital had the least effect on thyroid hormones. Considering the effect of such medications on thyroid function tests, it seems necessary to check the plasma levels of hormones periodically after beginning the treatment.

Liposomalization of hydroxyphenyl fluorescein as a reagent for detecting highly reactive oxygen species

It has been shown that lifestyle-related diseases and aging are related to reactive oxygen species (ROS), and many studies have reported on the direct detection of ROS. The topical fluorescence reagent 2,7-dichlorodihydrofluorescein (DCDHF) is used to measure oxidation. However, there are problems regarding its stability, and its similar sensitivity to ROS cannot be easily distinguished. In this study, we used hydroxyphenyl fluorescein (HPF), which is a novel fluorescence probe with high stability against light that undergoes specific reactions with highly ROS (hROS). We examined the specificity for hROS of HPF solution and liposomal HPF in different reactions. HPF containing high cholesterol liposomes (HC-H-lipo) maintained its ability to tolerate light scattering energy, dependent on the turbidity of this solution, but DCDHF did not. In the reaction with hydroxyl radicals, the fluorescein concentration in HC-H-lipo was increased compared with that in HPF solution. In contrast, in the reaction with peroxynitrite, HC-H-lipo was inhibited. It was confirmed that HC-H-lipo that reacted specifically with hydroxyl radicals was able to distinguishably detect hydroxyl radicals. It was regarded to be useful as an examination kit. Tissue disorder induced by sodium valproate (SV) was one of the prepared murine disease models. The reactivity ratio of HC-H-lipo with serum to that of HPF solution was markedly different between the normal group (30%) and SV group (70%). In conclusion, HC-H-lipo cannot only simply and directly detect ROS but can also selectively detect ROS type. This nanocarrier is expected to be used as a novel diagnosis method.

Cinnarizine in refractory migraine prophylaxis: efficacy and tolerability. A comparison with sodium valproate

This was a double-blind clinical trial designed to assess the efficacy and safety of the cinnarizine (CIN) in patients with migraine who were refractory to propranolol and tricyclic antidepressants in comparison with sodium valproate (SV) to investigate whether CIN could be at least as effective as SV. A total of 125 patients were treated in a treatment period of 12 weeks. All patients had at least one intake of trial medication and 2-week post baseline efficacy observation which all were included in the ITT analysis. Of the 125 subjects treated, 46 discontinued prematurely: 25 from the CIN and 21 from the SV group. The main reasons for premature discontinuation were: lost to follow up (25/46, 63.2%), insufficient response (16/46, 20%), and adverse events (5/46, 12.8%). No statistically significant inter-group differences in the number of discontinuation was observed (p > 0.05). In both groups, number of attacks, intensity, and duration of attacks significantly decreased (p < 0.05). No statistically significant inter-group differences were observed regarding the mean number of attacks, duration, and intensity of migraine attacks for any of the time intervals analysed, except for the mean reduction of third and fourth visits intensity from baseline which were significantly different in two groups (p < 0.05), with the CIN group showing more reduction. Analysis of the number of responders showed that in the CIN group 61.2% subjects were responders, and 63.8% in the SV group. No statistically significant differences between the treatment groups were found for any of the secondary parameters. Overall 26 subjects reported one or more adverse events during the study period: 13 subjects in each group. Five subjects discontinued prematurely due to adverse events; two in the CIN group with significant weight gain, and 3 in the SV group with significant weight gain and severe tremor. These results suggest that CIN is an effective and safe prophylactic agent even in severe migraine headache.

Early effect of sodium valproate and carbamazepine monotherapy on homocysteine metabolism in children with epilepsy

Plasma total homocysteine (p-tHcy), serum folate (s-F), serum vitamin B-12 (s-B12) and plasma pyridoxal-5′-phosphate (p-PLP) were measured in epileptic children before and after a 20-week period of sodium valproate (group A, n = 32) and carbamazepine (group B, n = 20) monotherapy. P-tHcy significantly increased in both groups, s-F and s-B12 significantly increased in group A, while s-F and p-PLP significantly decreased in group B. Our study showed an early effect of antiepileptic drug treatment on homocysteine metabolism.

Evaluation of therapeutic project on acute tetramethylene disulphotetramine poisoning and effect on intelligence in children

To evaluate four therapeutic measures on acute tetramethylene disulphotetramine (TETS) poisoning and the effects of it on intelligence of children. All 86 patients of acute TETS poisoning were randomly divided into 4 groups (the control group, sodium valproate group, sodium dimercaptopropane sulfonate group and the hemoperfusion group). The therapeutic effects were observed after the arranged treatment was administrated. According to age, residence, sex, education and domestic economy, 30 children were matched by 1:1 with children of TETS poisoning. The termination time of seizure, doses of diazepam, mental symptoms and the continual time of mental symptoms were not significantly different among these three groups. After hemoperfusion, the seizure of patients was terminated or the frequency was obviously decreased, but the level of TETS in blood was not reduced. The average scores of full intelligence quotient (FIQ), the verbal intelligence quotient (VIQ) and the performance intelligence quotient (PIQ) of children in poisoning group were 9.1, 8.8 and 7.7 less than the controls. The average scores of FIQ of children with bad state were 15 less than the controls. Therapeutic effects of sodium valproate and sodium dimercaptopropane sulfonate on acute TETS poisoning should be not better than using diazepam and sodium phenobarbital. Therapeutic effects of hemoperfusion on TETS poisoning is good. TETS poisoning should have a great influence on intelligence of children.

Efficacy Of Monotherapy With Carbamazepine And Valproic Acid In Patients With Bronchial Asthma: Is Asthma A Neurological Disease?

Antiasthmatic activity of carbamazepine and sodium valproate was investigated in 28 patients (open-label trial) with moderate and severe bronchial asthma. Stable and complete remission was achieved in 10 patients of the carbamazepine group (n=14), and in 11 patients of the sodium valproate group (n=14). A follow-up study showed high and stable antiasthmatic efficacy of carbamazepine or sodium valproate monotherapy. Based on the high efficacy of these anticonvulsants in patients with bronchial asthma we suppose that bronchial asthma can be considered as mainly neurogenic paroxysmal and inflammatory disease.

A Comparative Study of the Relative Effects of Anticonvulsant Drugs and Dietary Folate on the Red Cell Folate Status of Patients with Epilepsy

In a survey of the red cell folate status of 200 patients with epilepsy, compared to 72 controls, we found that median red cell folate levels were reduced significantly in patients treated with phenytoin (p less than 0.01) or carbamazepine (p less than 0.001) alone. Patients taking more than one drug had reduced levels also (p less than 0.001), but in patients treated with sodium valproate alone there was no significant decrease in red cell folate levels compared to controls. Twenty-two per cent of patients in the group taking more than one drug had reduced levels of red cell folate compared with 17 per cent of those taking carbamazepine alone, 13 per cent of those taking phenytoin only, and 9 per cent of those taking sodium valproate only. Dietary folate intake was significantly reduced in all the patient groups compared with controls (p less than 0.001 for the carbamazepine and phenytoin groups, p less than 0.01 for the polypharmacy and sodium valproate groups); a significant correlation between red cell folate levels and dietary folate was not established. Significant negative relationships were established between carbamazepine dose (r = -0.35, p less than 0.01) or serum level (r = -0.27, p less than 0.05) and red cell folate level in patients on one drug only. The correlation between dose or serum level of phenytoin and red cell folate level was also negative but did not reach significance. Our findings show that all anticonvulsant drugs interfere with folate metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Teratogenesis of calcium valproate in rabbits.

The calcium salt of valproic acid (Valontin) has been proposed for use in the treatment of absence, myoclonic, and tonic clonic seizures of the primarily generalized type. The present study was conducted to determine the teratogenic potential of calcium valproate in rabbits. Groups of 20 Dutch-belted rabbits were given oral doses of 50, 150, or 350 mg/kg on days 6-18 of gestation. A reference group was given 350 mg/kg sodium valproate and control groups were untreated or given vehicle alone. Animals were observed daily and body weights were recorded on gestation days 0, 6, 13, 18, and 30. Litter and fetal parameters were evaluated following uterotomies on day 30. No drug-related clinical signs or deaths occurred. Postimplantation loss and the incidence of malformed vertebrae and ribs, rudimentary or absent pollices, and extra vertebrae and ribs were increased at 350 mg/kg with both calcium and sodium salts of valproic acid. At the 150-mg/kg dose level, calcium valproate markedly increased the incidence of supernumerary ribs. No teratogenic or embryotoxic effects were seen with calcium valproate at 50 mg/kg. These data indicate that the sodium and calcium salts of valproic acid exhibit teratogenic potential in rabbits.

A Comparative Study of the Relative Influence of Different Anticonvulsant Drugs, UV Exposure and Diet on Vitamin D and Calcium Metabolism in Out-Patients with Epilepsy

The biochemical parameters associated with vitamin D metabolism, calcium, 25-hydroxy-vitamin D (25OHD) and alkaline phosphatase levels were assessed in 226 out-patients with epilepsy. Patients were grouped depending on the drug treatment; carbamazepine, phenytoin, phenobarbitone and sodium valproate used alone as monotherapy and a combination of these drugs as polytherapy. The most severe alterations occurred in the polytherapy group. Hypocalcaemia was more severe in the phenobarbitone monotherapy group than the carbamazepine or the phenytoin groups. No patient on sodium valproate monotherapy had subnormal levels of calcium (less than 2.1 mmol/l). 25OHD levels were similarly reduced in the carbamazepine, phenytoin and the phenobarbitone groups with no reduction in the sodium valproate group. Significant elevations in alkaline phosphatase levels were evident in all patient groups except the sodium valproate group. This study confirms biochemical evidence for anticonvulsant osteomalacia when the enzyme-inducing drugs are used, the degree of severity depending on the drug regimen.

Alterations in transient visual-evoked potentials induced by clonazepam and sodium valproate.

The transient visual-evoked potentials (VEP), recorded in patients suffering from generalized epilepsy, can be characterized by a duplication of the negative peak with a latency of 70-100 ms, a strong increase in amplitude of the negative peak between 80 and 130 ms and the development of a high amplitude slow negative wave following the primary complex. In this study we have investigated to which degree these changes are influenced by the intravenous administration of clonazepam and sodium valproate. Therefore, VEPs were registered in 30 patients, suffering from generalized epilepsy, just before and immediately after the intravenous injection of 0.4-0.8 mg clonazepam and further at 15, 30 and 16 min thereafter. The same procedure was applied on 10 patients treated with an intravenous injection of 400 mg sodium valproate. In both groups we found more or less a reduction in number and degree of the mentioned VEP changes. The improvement was associated with a strong decrease in amplitude of the VEP components in the group treated with clonazepam but was not seen in the sodium valproate group.

Correlation between plasma carbamazepine-10,11-epoxide concentration and drug side-effects in children with epilepsy.

Ninety children with epilepsy were treated with carbamazepine (CBZ) alone or with other anticonvulsant drugs. Side-effects were noted in 14 patients. When 25 patients treated with CBZ alone (group 1) were compared with 27 on CBZ and sodium valproate (group 2) and with 38 on CBZ and one or more other anticonvulsants (group 3), the incidence of side-effects was two in group 1 (of whom one patient had a toxic plasma level of CBZ), but 12 in groups 2 and 3 combined. In all but three of the 14 patients with side-effects, plasma levels of CBZ were within the 'therapeutic range'. A significant difference was found between the carbamazepine-10,11-epoxide (CBZ-10,11-EPOX) levels in plasma and CBZ-10,11-EPOX/CBZ ratio in patients with and without side-effects. For five patients on CBZ and other drugs, changes in treatment resulted in changes in side-effects, and also in CBZ-10,11-EPOX levels. Three of these patients showed an interaction between CBZ and sodium valproate, with a correlation between plasma CBZ-10,11-EPOX and side-effects when either drug was introduced or withdrawn, the plasma levels of CBZ itself and of sodium valproate being within the 'therapeutic range'.

Sodium Valproate in the Treatment of the Alcohol Withdrawal Syndrome

The value of sodium valproate in the management of patients during withdrawal from alcohol dependence has been assessed. Alcoholic inpatients were randomly allocated to two groups - one treated with sodium valproate and the other acting as a control. All patients received multivitamins and fluid and electrolyte replacement, and some received chlormethiazole or other tranquillisers. Treatment with sodium valproate (1200 mg daily) was continued for one week. The occurrence of seizures and other withdrawal symptoms (tremulousness, nausea, sweating, disorientation) were noted daily. Forty-nine episodes of withdrawal have been included in the trial - 22 in the sodium valproate group and 27 in the control group. Five patients, all in the control group, had seizures. Other withdrawal symptoms disappeared more quickly in the sodium valproate group even though fewer patients were receiving chlormethiazole.