SEARCH · PubMed Health

Results for “Valproate”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 397 records · Page 22Linked to original sources

PubMed2002

Carbamazepine and valproate in the maintenance treatment of bipolar disorder.

BACKGROUND: Carbamazepine and valproate are used in the treatment of acute bipolar mania and as maintenance treatments for bipolar disorder. We reviewed the available data from randomized clinical trials of these agents in bipolar disorder to assess their efficacy and tolerability in the maintenance phase of illness management. DATA SOURCES: We conducted a MEDLINE search augmented by a manual search of bibliographies, textbooks, and abstracts from recent scientific meetings to identify studies of carbamazepine and valproate in the maintenance treatment of bipolar disorder. DATA SYNTHESIS: Although a paucity of data exists from randomized, placebo-controlled trials, carbamazepine and valproate appear to prevent relapse as monotherapy in patients with bipolar disorder. Preliminary evidence of predictors of response to each respective agent has been identified. Combinations of carbamazepine and lithium and of valproate and olanzapine may have greater efficacy than monotherapy. CONCLUSION: Although carbamazepine and valproate have been less well studied in maintenance treatment than lithium, each agent appears to have efficacy in this phase of illness management. However, for many patients, combination therapy may provide better long-term prevention of illness relapse and recurrence.

Anticonvulsants↗

PubMedDate not supplied

Enhancement of circulatory antioxidants by alpha-ketoglutarate during sodium valproate treatment in Wistar rats.

The effects of alpha-ketoglutarate (alpha-KG) on sodium valproate-induced hyperammonemia and hepatotoxicity were studied in biochemical experiments in rats. The levels of ammonia, urea, serum transaminases, hydroperoxides and thiobarbituric acid reactive substances were significantly increased in sodium valproate-treated rats. These levels were significantly decreased in alpha-KG- and sodium valproate-treated rats. Further, non-enzymatic (vitamins C and E) and enzymatic (superoxide dismutase and catalase) antioxidants were significantly decreased in sodium valproate-treated rats and were increased in alpha-KG- and sodium valproate-treated rats. These biochemical alterations during alpha-KG treatment could be due to (i) its ability to act as an ubiquitous collector of amino groups in body tissues, (ii) the participation of alpha-KG in the non-enzymatic oxidative decarboxylation in the hydrogen peroxide decomposition process and (iii) enhancing the proper metabolism of fats which could suppress oxygen radical generation and, thus, prevent the lipid peroxidative damages in rats.

Animals↗

PubMed1992

Effect of sodium valproate on the open-field behavior of rats.

1. It has been reported that sodium valproate induces a morphine-like withdrawal syndrome in rats. The effects of acute or chronic treatment with sodium valproate on rat behavior was studied in the open-field test. 2. Acute sodium valproate (320 mg/kg, intraperitoneally) decreases the frequency of, and the time spent in grooming even when not modifying locomotion, rearing or defecation (N = 15), either 15 or 60 min after an acute treatment. This effect was not modified (N = 10) by concomitant administration of morphine (2 mg/kg) or naloxone (1 mg/kg). 3. Interruption of prolonged (30 days) valproate treatment with increasing doses of 40 to 320 mg/kg, by gavage, twice daily (N = 10) did not modify rat behavior in the open-field, from the first to the fourteenth day of the test. 4. We conclude that the decreased novelty-induced grooming does not depend on the opioid system and may be related to an anti-anxiety effect of valproate.

Animals↗

PubMed1992

Suppression of experimental barbiturate and phenytoin withdrawal syndrome using valproate sodium.

A neuropharmacological study was performed to investigate the effect of valproate sodium (VS) used to suppress the barbiturate and phenytoin withdrawal syndrome induced experimentally in 1152 male Wistar rats. Valproate sodium was administered by mouth according to the following protocol: initial bolus dose of 400 mg/kg b.w. followed eight hours later by the first maintaining dose of 50 mg/kg b.w. This was given every 12 hours for five days. VS plasma levels were determined by gas chromatography. The therapeutic effect of valproate sodium was assessed by the seizure reactivity of the experimental and the control animals to an electroshock (50 mA/0.1 sec.). The results strongly indicate that valproate sodium inhibits the experimentally induced barbiturate and phenytoin withdrawal syndrome without causing drug dependance. It is suggested that some of the valproate sodium metabolites possess antiwithdrawal effect.

Animals↗

PubMed2003

The history of valproate in clinical neuroscience.

The scientific and medical history of valproic acid is relatively long, compared with other frequently used psychopharmacologic agents. Valproic acid was used as an organic solvent in research laboratories for eight decades, until the fortuitous observation of action against pentylenetetrazol-induced convulsions in rodents. Early clinical experience emphasized therapy of absence seizures in primary generalized epilepsies. During two decades of controlled trials in partial-onset and generalized-onset seizures and myoclonus, valproate was established as the prototypical broad-spectrum antiepileptic drug. Anecdotal observations in patients with both epilepsy and migraine headaches who were started on valproate led to prospective, randomized trials that established antimigraine efficacy. Early observations suggested antimanic actions; more than a decade later, controlled clinical trials established significant efficacy of valproate in mania. Antiproliferative effects of valproate were unexpectedly noted during mechanistic studies; two decades later a maintenance adjunctive or chemopreventive role in oncology is being defined. While pharmacokinetic studies appear definitive, completion of comprehensive pharmacodynamic investigations of valproate's biochemical actions and clinical utility is yet to be achieved.

Anticonvulsants↗

PubMed2004

The relationship between treatment with valproate, lamotrigine, and topiramate and the prognosis of the idiopathic generalised epilepsies.

OBJECTIVE: To examine a large population with idiopathic generalised epilepsy (IGE), and estimate the overall remission rates for the IGEs and subsyndromes in a clinic based sample. Remission rates on valproate, lamotrigine, topiramate, and combinations of these antiepileptic drugs were estimated and factors predicting outcome examined. METHODS: All patients with IGE were identified from a computerised database and EEG records at large adult and paediatric epilepsy clinics. Data were recorded retrospectively on demographics and clinical information, seizure types and syndrome diagnosis, antiepileptic drug treatment details, and remission rates. RESULTS: 54.3% of 962 patients had achieved a one year period of remission; this was most likely with valproate monotherapy (52.1%), with lower rates for lamotrigine and topiramate (16.7% and 34.6%, respectively). The combination of valproate and lamotrigine achieved a remission rate of 15.3%. The factor most predictive of a response to a particular antiepileptic drug regimen was the rank order in which it was given. Relapse rate was high (79.9%) after antiepileptic drug withdrawal in remission, particularly with juvenile myoclonic epilepsy (93.6%). CONCLUSIONS: Valproate may be the most effective antiepileptic drug in the treatment of the IGEs. Combination therapy should be initiated if an adequate trial of valproate monotherapy is not effective, rather than switching to alternative monotherapy. Antiepileptic drug treatment needs to be lifelong in many adult patients with IGE.

Adolescent↗

PubMed2003

Schizophrenia and valproate.

Valproate (the active moiety of both valproic acid and divalproex sodium) is commonly used as an adjunctive agent for the treatment of schizophrenia. Among the anticonvulsants, valproate is the most extensively studied in patients with schizophrenia. Theoretical underpinnings for valproate in schizophrenia include its effect on voltage-gated ion channels and on the g-aminobutyric acid (GABA) system, thus modulating mesolimbic dopaminergic activity. Case reports, retrospective studies, and randomized clinical trials support the use of valproate combined with antipsychotics in managing schizophrenia. A recently completed 28-day, double-blind, randomized clinical trial of 249 patients with schizophrenia demonstrated faster improvement in psychopathology with a combination therapy of divalproex and risperidone or olanzapine, compared to monotherapy with risperidone or olanzapine. Additional research is needed to assess the utility of valproate in specialized populations such as those with treatment-refractory schizophrenia or agitation in schizophrenia. Regarding the latter, positive double-blind, randomized clinical trials have already been conducted in patients with borderline personality disorder, dementia, and with disruptive adolescents. It is anticipated that future research will focus on the new extended-release formulation of divalproex that can be administered on a once-daily basis.

Affect↗

PubMed2004

Effect of sodium valproate on neuromagnetic responses to chromatic flicker: implication for photosensitivity.

The effect of oral administration of sodium valproate in normal subjects was evaluated using whole-scalp magnetoencephalography, with results compared to the effect of sodium valproate in photosensitive children. Neuromagnetic responses to 10 Hz equiluminant red-green and red-blue flicker were measured before and after 5 days of sodium valproate administration. For the red-green flicker, relative power spectra at the stimulus frequency (10 Hz) were attenuated with medication in most brain regions. However, for the red-blue flicker, the 10-Hz power in the occipital region was enhanced with medication, while it was reduced in other regions. These results qualitatively resembled those in photosensitive children. The present findings suggest that (1) combinational chromatic sensitivity can be a critical factor for cortical excitability, that (2) the effect of sodium valproate is qualitatively similar in normal and photosensitive subjects, and that (3) the effect of sodium valproate on cortical excitability is not simply to suppress the stimulus-synchronized occipital activity, but rather to inhibit the spread of cortical activity from the occipital region to other regions.

Adolescent↗

PubMed2006

The effect of valproate on silent period and corticomotor excitability.

OBJECTIVE: To investigate, by transcranial magnetic stimulation, the effects of valproate on silent period and corticomotor excitability. METHODS: thirty patients with generalized epilepsy were studied at baseline, and re-examined 4 (S1) and 25 (S2) weeks after the administration of valproate (mean dose: 1040 +/- 284 mg). Transcranial magnetic stimulation was performed with a figure of eight coil (recording, first dorsal interosseous). Threshold was measured at 1% steps. Silent period was measured using a recently described protocol. Briefly, silent periods were elicited at 5% increments from 0 to 100% maximum stimulus intensity. At each stimulus intensity, 4 silent periods were obtained and the average value of silent period duration was used to construct a stimulus/response curve of stimulus intensity versus silent period. The resulting curves were then fitted to a Boltzman function and were statistically compared. The motor-evoked potential recruitment curve was constructed under active conditions and analyzed in a similar way. RESULTS: Valproate increased threshold from 36.5 +/- 5.99% at baseline to 41.02 +/- 7.84% at S1 (p < 0.0001, paired t-test). The maximum value of the silent period curve decreased from 257.5 +/- 3.9 ms at baseline to 230.3 +/- 3.9 ms at S1 (p < 0.0001, F-test and AIC) while the other best-fit values (V(50), slope, threshold) were not significantly affected. Regarding the motor-evoked potential recruitment curve, the maximum value decreased significantly post-drug (from 0.449 +/- 0.007 to 0.392 +/- 0.009, p < 0.01, F-test and AIC test), whereas the rest of the best-fit values remained unaffected. CONCLUSION: In patients with idiopathic generalized epilepsy, valproate increases threshold and reduces the maximum values of the silent period curve and the motor-evoked potential recruitment curve. These findings probably reflect valproate's effects on voltage-dependent Na(+) channels, as well as an activation of GABA(A) receptors.

Adolescent↗

PubMed1991

Correlates of antimanic response to valproate.

Seventeen patients with acute mania were treated with the antiepileptic agent valproate under placebo-controlled, double-blind conditions for 7 to 21 days. No other psychotropics were allowed, except for lorazepam, up to 4 mg per day, as needed for agitation or insomnia for the first 10 study days only. Of the 17 patients, 12 (71%) showed some response, ranging from a 30 percent to a 100 percent decrease in scores on the Young Mania Rating Scale (MRS). The remaining 5 patients displayed no response to valproate treatment, with increases on the MRS of 3 percent to 13 percent. Compared with nonresponders, responders had an older age of onset and a shorter duration of illness and displayed a higher average serum valproate concentration on Study Days 3 through 6, but not on Study Day 15 or at termination. Degree of valproate response was greater for those patients with more severe sleep disruption at baseline. However, the majority of factors assessed, including a history of rapid cycling and high levels of dysphoria, were not associated with response to valproate.

Acute Disease↗

PubMed1989

Sodium valproate interactions with the HPNS: EEG and behavioral observations.

A new baboon model was used to investigate the therapuetic effect of sodium valproate on the high pressure neurologic syndrome (HPNS). A hyperbaric chamber was used to achieve environmental pressures of 61 ATA, over a 5-h period. Eight animals underwent two compressions, a control and a valproate-treated compression (half the animals had valproate on the first compression). Mild signs of HPNS (e.g., paw and limb tremor) were first observed at approximately 20 ATA. More severe signs (e.g., whole body tremor, myoclonus, and vomiting) were observed above 40 ATA. Sodium valproate was administered during the compression phase and for 2 wk previously. It was effective at the higher pressures above 41 ATA in reducing the severity of the signs of HPNS. The major effect of pressure on the EEG was to increase alpha and theta wave amplitude in a linear manner. Alpha wave amplitude was reduced by sodium valproate.

Animals↗

PubMedDate not supplied

[Lithium valproate: its neuropharmacological spectrum and effect on transmitter amino acid content of the brain of rats].

The authors studied lithium valproate synthesized at the Institute of Pharmacology, Academy of Medical Sciences of the USSR, and compared it with sodium valproate (depakin, France). It was discovered that like sodium valproate, lithium valproate has a marked anticonvulsant activity, being also effective in experimental seizures induced by bicucullin, exerts a moderate sedative action (potentiation of sodium thiopental and hexenal anesthesia), and a distinct tranquilizing effect in experimental outward inhibition of the conditioned active avoidance response. At the same time the presence in the molecule of lithium ions led to a change in the neurochemical profile of valproate, manifested by an increase in the rat brain content of GABA and glutamate.

Amino Acids↗

PubMed1983

Hepatotoxicity of sodium valproate.

Repeated clinical and biochemical evaluations of liver function were performed on 60 patients taking sodium valproate. No clinical evidence of liver disease was found. Biochemical abnormalities were frequently found, but they were far more common in patients treated with multiple anticonvulsants than in patients on valproate alone. A control group of patients taking phenytoin or carbamazepine monotherapy also had a high incidence of biochemical abnormalities. A group of patients started on valproate therapy 6 years previously was followed up. No evidence of liver disease was found in this group. It was concluded that biochemical abnormalities of liver function in patients receiving valproate are not progressive, and in many cases relate to the intake of other drugs. The finding of abnormal liver function tests is not necessarily an indication for ceasing valproate.

Adolescent↗

PubMed1982

Stability of valproate sodium syrup in various unit dose containers.

The stability of valproate sodium syrup repackaged in three types of unit dose containers was studied. Two-millimeter samples of commercial valproate sodium syrup 250 mg/5 ml (of valproic acid) were packaged in polypropylene oral syringes, glass oral syringes, and glass vials (126 of each type). These were stored at 4, 25, or 60 degrees C and assayed for valproic acid concentration using gas chromatography at 0, 5, 10, 20, 30, 90, and 180 days. Polypropylene syringes that were stored for 180 days at 4 and 25 degrees C were rinsed and put in chloroform 50 ml; valproic acid concentration was determined daily for 12 days. Valproate sodium syrup repackaged in glass oral syringes and glass vials retained 95% of valproic acid label claim after storage at 4 and 25 degrees C for 180 days, while valproate sodium syrup repackaged in polypropylene oral syringes did not retain 90% of label claim after storage for 20 days at 4 or 25 degrees C. All samples stored at 60 degrees C had greater loss than those stored at lower temperatures. An average of 86% of the drug lost from the polypropylene syringes was recovered in 12 days during the desorption experiment (range 80-92%). Repackaging valproate sodium syrup in unit dose glass vials or glass syringes resulted in retention of 95% of valproic acid label claim after storage for 180 days at 4 and 25 degrees C. Repackaging of this drug product in polypropylene oral syringes is not recommended.

Adsorption↗

PubMed1995

An open trial of valproate in borderline personality disorder.

BACKGROUND: Target symptoms in pharmacotherapy of borderline personality disorder include mood instability, anxiety, and impulsivity. Valproate appears useful for the treatment of these target symptoms in several disorders, and carbamazepine has been found effective for such symptoms in borderline personality disorder. We therefore conducted a preliminary open-label trial of valproate in borderline personality disorder. METHOD: Eleven patients who met DSM-III-R criteria for borderline personality disorder were entered into an 8-week study of valproate. Exclusion criteria included current major depression or major medical disorder. All patients were in psychotherapy at least once a week for a minimum of 8 weeks prior to starting medication. Valproate was increased as tolerated to reach blood levels of 50 to 100 micrograms/mL. Clinician- and self-rated scales were completed each week. RESULTS: Three patients did not complete the study. Of completers, 4 of 8 patients were responders ("much less" or "less") on clinician-rated change scores for overall pathology and for mood. Three of 8 patients were responders on change scores for anxiety, anger, impulsivity, and rejection sensitivity. There was a significant (p = .03) decrease in total Symptom Checklist-90 scores between the start and end of the trial. On the Overt Aggression Scale (Modified), total other-directed assault did not significantly decrease, but there was a significant (p = .02) decrease in global subjective irritability. CONCLUSION: Valproate led to overall improvement in 50% of a small sample of borderline personality disorder patients who completed an 8-week open trial. The medication was modestly helpful for mood and irritability as well as for anxiety, anger, rejection sensitivity, and impulsivity, but specific therapeutic effects varied from patient to patient. More extensive controlled trials of anticonvulsants for impulsive personality disorders are warranted.

Adult↗

PubMed1994

Neurologic factors predict a favorable valproate response in bipolar and schizoaffective disorders.

The hypothesis that neurologic factors influence the response to valproate (divalproex sodium) in bipolar and schizoaffective disorders was tested. In 115 predominantly lithium-refractory inpatients, neurologic findings were recorded, and blind raters assessed valproate response from the medical record. Patients with a seizure history were much more likely to have a robust response to valproate (70%), when compared with patients without such history (34.6%). History of head injury and abnormal electroencephalographic findings also tended to be more common in those patients with good response. Overall, the group of patients with any neurologic abnormality exhibited a significantly higher rate of good response to valproate (43.6%) than did the neurologically normal group (24.3%). Bipolar or schizoaffective patients with abnormal neurologic features may represent a distinct subtype of illness and appear to be good candidates for valproate therapy.

Bipolar Disorder↗

PubMedDate not supplied

[The action of sodium valproate in central pain syndromes].

A model of acute spinal and phantom pain syndromes caused by the formation of an abnormally increased excitation generator (AIEG) in the system of dorsal horns of the spine was used to study the effects of sodium valproate when used chronically in the phantom pain syndrome, when given in a single dose in the acute pain syndrome and when applied to the spine with disinhibitors inducing the pain syndrome. It was shown that during chronic administration sodium valproate produced a stress-preventive action, but failed to affect pain sensation and to prevent the development of the pain syndrome. When used in the acute pain syndrome, sodium valproate had a marked analgesic effect, and when applied to the spine it substantially reduced the manifestations of the pain syndrome. The action of sodium valproate on the AIEG can be accounted for by the higher GABA level that results in the hyperpolarization of neurons which are a part of AIEG. When the latter is formed and operates in acute and chronic pain syndromes there are differences in the functional activity of the neurochemical structures responsible for the realization of pain reaction components. This is suggested by varying effects of sodium valproate on pain sensation during acute and chronic experiments.

Acute Disease↗

PubMed1993

Valproate oral loading in the treatment of acute mania.

BACKGROUND: Evidence from earlier studies suggests that the antimanic activity of valproate becomes most pronounced within 1 to 4 days of achieving serum concentrations of 50 mg/L or greater. We conducted a prospective study to assess the onset of antimanic activity of oral loading dosages of valproate administered to achieve serum concentrations above 50 mg/L within 24 hours. METHOD: Nineteen patients with bipolar disorder, manic phase, received divalproex sodium 20 mg/kg/day in divided dosages for 5 days, without other psychotropic agents except lorazepam up to 4 mg/day. Serum valproate concentrations were measured after 1 and 4 days of treatment. Improvement was measured daily by a blind rater using the Young Mania Rating Scale (MRS). RESULTS: Serum valproate concentrations greater than 50 mg/L were reached in all 15 patients completing the study. Ten (53%) of the 19 patients who received at least one complete loading dose displayed a significant (greater than 50%) reduction in MRS scores by study termination. These responders displayed the greatest percent change in MRS scores over the first 3 days of treatment. Side effects were minimal. CONCLUSION: Valproate can be safely administered by oral loading and may produce rapid onset of antimanic response in some patients.

Acute Disease↗