Divalproex therapy in medication-naive and mood-stabilizer-naive bipolar II depression

There have been few systematic studies of the treatment of bipolar II depression. While divalproex sodium (DVPX) is effective in acute mania, there are few data on the antidepressant effects of DVPX. Similarly, little is known regarding the use of DVPX administered in a single daily dose.

We performed a 12-week open trial of DVPX monotherapy (mean dose 882 mg qhs, mean level 80.7 mug/ml) in nineteen (thirteen women, six men, mean age 29) bipolar II depressed outpatients. Eleven patients (six women, five men) were medication-naive (MN) and eight (seven women, one man) were mood stabilizer-naive (MSN), having had prior trials of antidepressants or stimulants. Mean illness and current depressive episode duration were 15.4 years and 11.8 weeks, respectively. DVPX was given as a single dose each evening starting with 250 mg at bedtime and increased by 250 mg at bedtime every 4 days until symptom relief or adverse effects were noted. Weekly prospective Hamilton Depression, Young Mania and Clinical Global Impression ratings were obtained.

DVPX therapy was generally well tolerated. Twelve of nineteen patients (63%) responded (>50% decrease in Hamilton Depression ratings). MN patients compared to MSN patients tended to have a higher response rate (9/11 versus 3/8, P<0.08). Mean Hamilton scores decreased from 22.2 to 9.6 (P<0.0001) in the entire group, from 20.6 to 6.6 (P<0.0003) in MN patients, and from 24.2 to 14.7 (P=0.008) in MSN patients.

Single daily dose DVPX monotherapy appeared to be well tolerated and substantially benefited 63% of patients with bipolar II depression. The trend towards a higher rate of antidepressant response to DVPX in MN patients (82%) compared to MSN patients (38%) could be due to a milder form or earlier phase of illness and the lack of prior medication exposure or failures. This uncontrolled open pilot study must be viewed with caution, and randomized double-blind placebo controlled studies of DVPX in bipolar II depression are warranted to confirm the possibility that single daily dose DVPX is an effective, well-tolerated, first-line monotherapy in this population.