Rapid oral loading of extended release divalproex in patients with acute mania

Oral loading with the delayed release formulation of divalproex sodium is widely used for the treatment of patients with acute mania and produces rapid attainment of therapeutic serum levels. Recently, an extended release formulation of divalproex sodium (divalproex ER) was approved for treatment of migraine headaches. This formulation may be a useful treatment option for patients with acute mania.

A retrospective review of medical records was conducted on 14 inpatients with acute mania whose treatment included initiation of divalproex ER at a dose of 30 mg kg(-1) day(-1) in a single dose. Doses, serum levels and side effects associated with this treatment were recorded from the medical records of these patients.

The average dose of divalproex ER was 2034 mg day(-1) (range, 1500-3000 mg day(-1)). Two of the 14 patients (14%) had documented side effects, none of which were severe. The average level obtained on day 3 after initiation of divalproex ER treatment was 93.2 mug ml(-1) (range, 47-136 mug ml(-1)), and in all but three patients valproate levels at this time point were within the therapeutic range of 50-125 mug ml(-1). In no case was divalproex ER discontinued due to a perceived lack of efficacy.

The results suggest that divalproex ER can be safely administered by oral loading in inpatients with acute mania and that using a standard loading protocol can result in therapeutic serum levels in most patients in 3 days or less.