0+/-26.8 ug/mL). After 12 weeks, 78% of subjects were considered responders, having general improvement in mood and functioning, with the majority showing improvement by week 3. Both YMRS and HAM-D scores decreased significantly compared with baseline. Depressive symptoms appeared to resolve especially rapidly,

with mean HAM-D scores achieving the end point mean by week 1. This rate of response may have been due to placebo response, receiving support from an academic institution, being in a study, and having regular visits to a physician. However, this placebo response would have been carried throughout Inhibitors,research,lifescience,medical the 12 weeks of the study. Of note, 6 out of 7 (86%) of subjects with MDD or dysthymia were considered responders. Again, caution should be applied to these results given the small sample size and lack of a control arm. Despite these promising findings regarding divalproex,

Findling and colleagues found divalproex to Inhibitors,research,lifescience,medical be no more effective than placebo in preventing worsening of mood symptoms in youth with cyclothymia or bipolar disorder not otherwise specified who were bipolar offspring.51 In this study, 56 subjects 5 to 17 years old were randomized to divalproex or placebo and assessed over an acute 8week period, and then followed monthly for up to 5 years, until clinical intervention Inhibitors,research,lifescience,medical was needed for mood symptoms. There was no difference between the treatment arms in

time to discontinuation from the study. However, both groups did show significant improvement in depressive and manic symptoms over time. Notably, divalproex was superior to placebo in time to discontinuation in a subset Inhibitors,research,lifescience,medical of patients who had three or more firstor second-degree relatives with an emotional and/or behavioral problem.52,53 It should also be noted that subjects in this study differed from those in the study by Chang and colleagues in that they had not had a past full depressive episode, and they were required to have a past Inhibitors,research,lifescience,medical significant 4-hour period of elation, indicating that they may have had less symptoms of depression. Nonetheless, there was no difference between divalproex and placebo for efficacy regarding depressive symptoms. Ouetiapine would seem a good candidate for use in first-episode bipolar depression, given its efficacy in adult bipolar GSK-3 depression.54 DelBello and colleagues55 conducted a 12-week study of open quetiapine for bipolar offspring with mood disorders (mean age =14.7 years), that were considered subsyndromal to full BD (no subjects had a history of mania). 11 (55%) had BD-NOS.3 had bipolar II disorder, 3 (11%) had dysthymia, 2 cyclothymia, and 1 MDD. Thus, almost all subjects had a bipolar spectrum disorder, and as such these subjects were farther along the progression line for BD than the previously discussed studies involving valproate.

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