Depakote Loading Protocol for Mania

The Depakote loading protocol below has demonstrated superior efficacy for the rapid reduction of manic symptoms compared to standard Depakote titrations in an inpatient setting. For acute mania, we still recommend combination therapy with an antipsychotic.

Labs:
1.    Prior to beginning Depakote loading, obtain platelet counts and LFTs
2.    Obtain Depakote levels on days 3, 5, and 10 with target level of 90 to 100 pg/mL

Contraindications:
1.    Severe liver disease
2.    Pancreatitis
3.    Pregnancy
4.    Urea cycle disorder
5.    Proven allergy to valproic acid, valproate, or divalproex (Depakote)

Depakote loading:
1.    30 mg/kg of Depakote on days 1 and 2 in divided doses
2.    Then 20 mg/kg of Depakote on days 3 through 10 in divided doses
3.    Then adjust at MD's discretion

Source: Hirschfeld et al: The safety and early efficacy of oral-loaded divalproex versus standard- titration divalproex, lithium, olanzapine, and placebo in the treatment of acute mania associated with bipolar disorder. J Clin Psychiatry. 2003 Jul;64(7):841-6.

Other supporting studies: Bowden et al (1994); Hirschfeld et al (1999); Zajecka et al (2002).