Efficacy of divalproex vs lithium and placebo in the treatment of mania. The Depakote Mania Study Group.
OBJECTIVE
To compare the effectiveness of divalproex sodium with that of lithium and placebo in patients with acute mania.


METHODS
Randomized, double-blind, parallel-group study of treatment outcomes in patients with manic-depressive illness.


METHODS
A total of 179 hospitalized, acutely manic patients meeting the Research Diagnostic Criteria for manic disorder, approximately half of whom had been nonresponsive to lithium previously, were studied at nine university-affiliated hospitals.


METHODS
After a minimum 3-day washout period, random assignment for 21 days to divalproex, lithium, or placebo in a 2:1:2 ratio. Dosage of divalproex and lithium was increased if tolerated to a target concentration of 1041 mumol/L (150 micrograms/mL) or 1.5 mmol/L (conventionally expressed as milliequivalents per liter), respectively.


METHODS
Primary outcome measures were changes in the Mania Rating scale derived from the Schedule for Affective Disorders and Schizophrenia.


RESULTS
Intent-to-treat analysis for efficacy was based on data from 68, 35, and 73 patients in the divalproex, lithium, and placebo groups, respectively. Groups were initially comparable except that all eight patients with four or more manic episodes in the previous year were in the divalproex group. In 30%, 33%, and 51% of the above groups, treatment was prematurely terminated due to lack of efficacy, with fewer premature terminations from divalproex than placebo (P = .017). The proportions of patients improving at least 50% were higher for divalproex and lithium groups than for the placebo group: 48% for divalproex (P = .004) and 49% for lithium (P = .025) vs 25% for placebo. Divalproex was as effective in rapid-cycling manic patients as in other patients.


CONCLUSIONS
Both divalproex and lithium were significantly more effective than placebo in reducing the symptoms of acute mania. The efficacy of divalproex appears to be independent of prior responsiveness to lithium.
Bowden
C L
CL
Department of Psychiatry, University of Texas Health Science Center, San Antonio.
Brugger
A M
AM
Swann
A C
AC
Calabrese
J R
JR
Janicak
P G
PG
Petty
F
F
Dilsaver
S C
SC
Davis
J M
JM
Rush
A J
AJ
Small
J G
JG
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006760:Hospitalization; D006801:Humans; D008094:Lithium / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage / Q000627:therapeutic use*
D010919:Placebos; D014635:Valproic Acid; D008094:Lithium