The therapeutic range in epilepsy is commonly considered to be 50 to 100 µg/mL of total valproate, although some patients may be controlled with lower or higher plasma concentrations.

Mania:

In placebo-controlled clinical trials of acute mania, patients were dosed to clinical response with trough plasma concentrations between 50 and 125 µg/mL (See DOSAGE AND ADMINISTRATION).

Clinical Trials

Mania

The effectiveness of DEPAKOTE for the treatment of acute mania was demonstrated in two 3-week, placebo controlled, parallel group studies.

(1) Study 1: The first study enrolled adult patients who met DSM-III-R criteria for Bipolar Disorder and who were hospitalized for acute mania. In addition, they had a history of failing to respond to or not tolerating previous lithium carbonate treatment. DEPAKOTE was initiated at a dose of 250 mg tid and adjusted to achieve serum valproate concentrations in a range of 50-100 µg/mL by day 7. Mean DEPAKOTE doses for completers in this study were 1118, 1525, and 2402 mg/day at days 7, 14, and 21, respectively. Patients were assessed on the Young Mania Rating Scale (YMRS; score ranges from 0-60), an augmented Brief Psychiatric Rating Scale (BPRS-A), and the Global Assessment Scale (GAS). Baseline scores and change from baseline in the week 3 endpoint (last-observation-carry-forward) analysis were as follows:

Study 1

DEPAKOTE was statistically significantly superior to placebo on all three measures of outcome.

(2) Study 2: The second study enrolled adult patients who met Research Diagnostic Criteria for manic disorder and who were hospitalized for acute mania. DEPAKOTE was initiated at a dose of 250 mg tid and adjusted within a dose range of 750-2500 mg/day to achieve serum valproate concentrations in a range of 40-150 µg/mL. Mean DEPAKOTE doses for completers in this study were 1116, 1683, and 2006 mg/day at days 7, 14, and 21, respectively. Study 2 also included a lithium group for which lithium doses for completers were 1312, 1869, and 1984 mg/day at days 7, 14, and 21, respectively. Patients were assessed on the Manic Rating Scale (MRS; score ranges from 11-63), and the primary outcome measures were the total MRS score, and scores for two subscales of the MRS, i.e., the Manic Syndrome Scale (MSS) and the Behavior and Ideation Scale (BIS). Baseline scores and change from baseline in the week 3 endpoint (last-observation-carry-forward) analysis were as follows:

Study 2

Figure 1
Percentage of Patients Achieving = 30% Reduction in Symptom Score From Baseline

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