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Gamma-aminobutyric acid-induced ion transport changes in the retinal pigment epithelium are described. Valproate acts as an inhibitor of gamma-aminobutyric acid transaminase. The purpose of this study was to investigate whether early visual impairment is related to valproate in patients with and without visual symptoms. Thirty-two patients, presenting with a history of seizures currently being treated with valproate, were included in the study. A complete clinical neuroophthalmologic examination was performed, including electroretinogram and visual field test. The electroretinogram parameters of epileptic patients were compared with those of 28 age- and sex-matched healthy volunteers. There was no significant difference in ERG parameters between the two groups. The visual field and visual acuity of all patients were within normal limits. When valproate is not used in conjunction with other antiepileptic drugs and serum levels are within therapeutic levels, it does not cause electrophysiologically detectable retinal dysfunction or any functional defect in visual perception that can be determined clinically.
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A collaborative study was conducted to determine useful and sensitive rat sperm motion parameters in a CellSoft Series 4000 semen analyzer to detect the effects of compounds on sperm motion. The effects on the sperm motion parameters were investigated using alpha-chlorohydrin, boric acid, ethinylestradiol, ethyl methanesulfonate, nitrazepam, nitrobenzene, ornidazole, sulfasalazine or valproic acid which are well known to induce reproductive or testicular toxicities. All compounds used in this study decreased percentage of motile sperm (% motile). Curvilinear velocity (VCL), maximum and mean amplitude of lateral head displacement (ALH max and ALH mean) were decreased by treatment with all compounds except for valproic acid. Treatment with alpha-chlorohydrin, ornidazole or sulfasalazine under mid-dosage regimens decreased only these parameters. Beat cross frequency (BCF) was increased by treatment with sulfasalazine. There were some treatments which caused either decreased or increased changes irrespective of dosage regimen in linearity, average radius, percentage of circular-swimming sperm out of motile sperm (circular/motile) and percentage of circular-swimming sperm out of all sperm (circular/all). Based on these results, we concluded that % motile, VCL, ALH max and ALH mean are considered useful and sensitive parameters for evaluating the effects of compounds on sperm motion. A parameter of BCF can be useful to detect the effects of specific compounds on sperm motion. Linearity, average radius, circular/motile and circular/all are not considered useful or sensitive indicators to detect the effects of compounds on sperm motion.
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Fenproporex (Fen) is converted in vivo into amphetamine, which is used to induce mania-like behaviors in animals. In the present study, we intend to present a new animal model of mania. In order to prove through face, construct, and predictive validities, we evaluated behavioral parameters (locomotor activity, stereotypy activity, and fecal boli amount) and brain energy metabolism (enzymes citrate synthase; malate dehydrogenase; succinate dehydrogenase; complexes I, II, II-III, and IV of the mitochondrial respiratory chain; and creatine kinase) in rats submitted to acute and chronic administration of fenproporex, treated with lithium (Li) and valproate (VPA). The administration of Fen increased locomotor activity and decreased the activity of Krebs cycle enzymes, mitochondrial respiratory chain complexes, and creatine kinase, in most brain structures evaluated. In addition, treatment with mood stabilizers prevented and reversed this effect. Our results are consistent with the literature that demonstrates behavioral changes and mitochondrial dysfunction caused by psychostimulants. These findings suggest that chronic administration of Fen may be a potential animal model of mania.
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Limitations of this study include a relatively small sample size and uncertain generalizability beyond treatment trials.
A propensity score-matched cohort study was conducted of Veterans Health Administration patients (n=21,194/treatment) initiating lithium or valproate from 1999-2008.
Bipolar disorders (BD) are characterized by episodes of mania and depression. There is evidence that states of psychiatric disorders impact on neurotransmitters, endocrine system and membrane transport and, therefore, it is possible that specific phases of BD differentially influence the pharmacokinetics of some drugs. The aim of the present study was to investigate the drug-disease interaction between sodium valproate, one of the major drugs used in the treatment of bipolar disorder, and acute versus maintenance states of manic episodes.
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A substantial portion of the morbidity associated with rapid-cycling bipolar disorder (RCBD) stems from refractory depression. This study assessed the antidepressant effects of lamotrigine as compared with placebo when used as add-on therapy for rapid-cycling bipolar depression non-responsive to the combination of lithium plus divalproex.
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A retrospective cohort based on medical records of both in- and out-patient with bipolar I disorder (DSM-IV-TR) seen at Srinagarind Hospital between January 1, 2009 and December 31, 2010 was done. A recurrence was observed if the patient had fulfilled the remission criteria and valproate was the maintenance drug. Survival analysis and Cox regression analysis were used to analyze the data.
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Slightly more patients on TPM dropped out. Neuropsychological data at all three test periods were available for 62 patients. At the end of maintenance, effects of TPM and VPA were comparable, except for two variables (Symbol Digit Modalities Test and Controlled Oral Word Association Test), in which TPM had greater negative effects relative to VPA. The statistical differences appeared to be due in large part to a small subset of patients who were more negatively affected by TPM. Cognitive effects of TPM relative to VPA were greater at the end of titration than at the end of maintenance.
This study evaluated the protective effect of ellagic acid on sodium valproate-induced sperm abnormalities in male Wistar rats. A total of 30 rats were grouped into five groups, each having 6 animals. Vehicle, sodium valproate (400 mg/kg) and ellagic acid (10, 25, 50 mg/kg) were given orally from day 1 to day 7, and ellagic acid was continued for 3 more days. On day fourteen, animals were sacrificed and the different parameters were recorded. There was a significant decrease in the sperm count and sperm motility after the exposure to sodium valproate. The percentage of abnormal sperms increased in a dose-dependent manner. The histopathological examination revealed that sodium valproate had caused degeneration and desquamation of germinal cells in the epithelium and also showed a decrease in the Johnsen's scoring. Ellagic acid provided partial protection at the doses of 10 and 25 mg/kg and complete protection at 50 mg/kg, against sodium valproate induced testicular and spermatozoal damage.
To study the clinical characteristics of patients with game-induced seizures in the Chinese population.