When was depakote approved

Study 2: The second study enrolled adult patients who met Research Diagnostic Criteria for manic disorder and who were hospitalized for acute mania. Study 2 also included a lithium group. Baseline scores and change from baseline in the Week 3 endpoint were significantly better in the Depakote treatment arm versus both placebo and lithium.

The FDA approval of Depakote for reducing the incidence of complex partial seizures CPS that occur in isolation or in association with other seizure types was established in two controlled trials.

In one, multi-clinic, placebo controlled study employing an add-on design adjunctive therapy , patients who continued to suffer eight or more CPS per 8 weeks during an 8 week period of monotherapy with doses of either carbamazepine or phenytoin sufficient to assure plasma concentrations within the "therapeutic range" were randomized to receive, in addition to their original antiepilepsy drug AED , either Depakote or placebo.

Randomized patients were to be followed for a total of 16 weeks. The reduction of CPS from baseline was statistically significantly greater for valproate than placebo. The study compared the incidence of CPS among patients randomized to either a high or low dose treatment arm. Patients qualified for entry into the randomized comparison phase of this study only if 1 they continued to experience 2 or more CPS per 4 weeks during an 8 to 12 week long period of monotherapy with adequate doses of an AED i.

Patients entering the randomized phase were then brought to their assigned target dose, gradually tapered off their concomitant AED and followed for an interval as long as 22 weeks.

The reduction from baseline was statistically significantly greater for high dose than low dose at 8 weeks. If the total daily dose exceeds mg, it should be given in divided doses. The recommended starting dose is mg twice daily. The FDA approval of Depakote for was based on the results of two multicenter, randomized, double-blind, placebo-controlled clinical trials.

Both studies employed identical designs and recruited patients with a history of migraine with or without aura of at least 6 months in duration who were experiencing at least 2 migraine headaches a month during the 3 months prior to enrollment. Patients with cluster headaches were excluded. In each study following a 4-week single-blind placebo baseline period, patients were randomized, under double blind conditions, to Depakote or placebo for a week treatment phase, comprised of a 4-week dose titration period followed by an 8-week maintenance period.

Treatment outcome was assessed on the basis of 4-week migraine headache rates during the treatment phase. In the first study, a total of patients were randomized Depakote to placebo. Ninety patients completed the 8-week maintenance period. Drug dose titration, using mg tablets, was individualized at the investigator's discretion. The mean 4-week migraine headache rate during the treatment phase was 5. These rates were significantly different.

The treatments were given in two divided doses BID. One hundred thirty seven patients completed the 8-week maintenance period. The initial dose was mg daily. The mean 4-week migraine headache rates during the treatment phase, adjusted for differences in baseline rates, were 4.

Depakote Sprinkle Capsules are administered orally. Depakote Sprinkle Capsules may be swallowed whole or the contents may be sprinkled on soft food. Please see above for clinical trial information. Depakote ER is an extended-release product intended for once-a-day oral administration. Depakote ER tablets should be swallowed whole and should not be crushed or chewed. The effectiveness of Depakote ER for the treatment of acute mania is based in part on studies establishing the effectiveness of Depakote divalproex sodium delayed release tablets for this indication.

The study was designed to evaluate the safety and efficacy of Depakote ER in the treatment of bipolar I disorder, manic or mixed type, in adults. Adult male and female patients who had a current DSM-IV TR primary diagnosis of bipolar I disorder, manic or mixed type, and who were hospitalized for acute mania, were enrolled into this study.

The results of a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial demonstrated the effectiveness of Depakote ER in the prophylactic treatment of migraine headache. This trial recruited patients with a history of migraine headaches with or without aura occurring on average twice or more a month for the preceding three months. Patients with cluster or chronic daily headaches were excluded.

Patients initiated treatment on mg once daily for one week, and were then increased to 1, mg once daily with an option to permanently decrease the dose back to mg once daily during the second week of treatment if intolerance occurred. Antimanic and prophylactic activity was demonstrated for valpromide, a primary amide of valproic acid Lambert et al.

The preliminary studies conducted by Lambert were not repeated outside France and it was only much later that the efficacy of derivatives of valproic acid in bipolar disorders was demonstrated in studies undertaken in Germany with sodium valproate Enrich and Von Zerssen, , and then in the USA with divalproate in the last decade. The majority of controlled studies were performed with divalproate and demonstrated the efficacy of this drug in monotherapy during manic episodes Pope et al.

The results of the study by Bowden and the findings of other open studies suggest a wider spectrum of activity for divalproate than for lithium with a good efficacy profile in subtypes of mania in which the effects of lithium are mediocre: dysphoric mania, rapid cycling mania and forms of mania secondary to organic brain disease.

The prospective studies by Puzynski and Klosiewicz and by Lambert and Venaud demonstrated the prophylactic activity of valpromide, with slightly greater efficacy being noted against manic episodes than against depressive episodes. The study by Bowden et al. The field of bipolar disorders currently appears much wider and more heterogeneous than has long been held.

Current therapeutic strategy is dominated by thymoregulators.