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.


METHODS
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.


CONCLUSIONS
Valproate can be safely administered by oral loading and may produce rapid onset of antimanic response in some patients.
Keck
P E
PE
Department of Psychiatry, University of Cincinnati College of Medicine, OH 45267-0559.
McElroy
S L
SL
Tugrul
K C
KC
Bennett
J A
JA
D000208:Acute Disease; D000284:Administration, Oral; D000328:Adult; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology; D004359:Drug Therapy, Combination; D005260:Female; D006760:Hospitalization; D006801:Humans; D008140:Lorazepam / Q000008:administration & dosage; D008297:Male; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D014635:Valproic Acid / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*
D014635:Valproic Acid; D008140:Lorazepam