Divalproex extended-release in acute bipolar II depression.
BACKGROUND
Divalproex extended-release (divalproex-ER) is effective in acute mania, and limited data suggest divalproex may have efficacy in acute bipolar depression.


METHODS
A 7-week, open-label trial of divalproex-ER monotherapy or adjunctive therapy was conducted in 28 outpatients (15 female, mean age 36.7+/-9.1, and mean duration of illness 22.1+/-11.1 years) with bipolar II depression (39% with rapid cycling course of illness within the prior year). Divalproex-ER was generally given as a single dose at bedtime, starting at 250mg and increased by 250mg every 4 days to symptom relief or adverse effects. Efficacy was assessed using weekly prospective Montgomery Asberg Depression Rating Scale (MADRS) scores.


RESULTS
Overall, mean divalproex-ER final doses and serum concentrations were 1469mg/day and 80.1microg/mL, respectively. Mean MADRS scores (last observation carried forward) decreased significantly from baseline in patients in the overall group (from 30.1 to 15.2, p<.00001). The overall response rate was 54%. Divalproex-ER therapy was generally well tolerated, with no early discontinuations due to adverse events.


CONCLUSIONS
This study is limited by a small sample size and an open-label study design with no placebo control.


CONCLUSIONS
Divalproex-ER as monotherapy and adjunctive therapy was well tolerated and yielded an overall response rate of 54% in bipolar II depression. Based on the results of this pilot study, randomized, double-blind, placebo-controlled studies of divalproex-ER in bipolar II depression are warranted.
Wang
P W
PW
Stanford University School of Medicine, Stanford, CA, USA. wangp0@stanford.edu
Nowakowska
C
C
Chandler
R A
RA
Hill
S J
SJ
Nam
J Y
JY
Culver
J L
JL
Keller
K L
KL
Ketter
T A
TA
D000208:Acute Disease; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001714:Bipolar Disorder / Q000097:blood / Q000188:drug therapy*; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D014635:Valproic Acid