An older report found 3 out of 6 (50%) of manic children placed on lithium to have a significant worsening of depressive symptoms.37 In a more recent study of 100 manic adolescents treated prospectively with lithium, mean HAM-D scores decreased overall from 12.63 to 6.74 over 4 weeks.38 It is not reported how many subjects had significant residual depressive symptoms Inhibitors,research,lifescience,medical at the end of the study. However, having depressive symptoms at the start of the study did not predict whether or not the subject responded to lithium by mania criteria. In another open study, Kowatch and colleagues reported on the naturalistic prospective treatment

of 35 manic children and adolescents who had previously been treated with 6 weeks of monotherapy with either Inhibitors,research,lifescience,medical lithium, valproate, or carbamazepine.39 Two subjects (5.7%) had a depressive episode despite treatment with two concurrent mood BMS-345541 cost stabilizers (lithium, divalproex, or carbamazepine). Antidepressants were subsequently added to the medication regimens with reported good response. Of 90 children and adolescents with BD treated openly with divalproex and lithium combination therapy, none continued Inhibitors,research,lifescience,medical to have significant depressive symptoms requiring discontinuation from the study.40 More recent large placebo-controlled studies offer some insight into the natural course and treatment of depressive symptoms in youth with BD.

For example, olanzapine was compared with placebo in a 3-week study of 1 58 youth with acute manic or mixed episodes.41 Eight percent of subjects on olanzapine Inhibitors,research,lifescience,medical and 14% of subjects on placebo switched to a full depressive episode by the end of the study. This was not a significant difference between groups, and the change in depressive symptomatology, while not reported, was also not different between groups. Thus, it would appear that at least for the acute treatment of depressive symptoms in the context of pediatric manic or mixed episodes, olanzapine is not effective. Similarly, in a study of divalproex versus placebo Inhibitors,research,lifescience,medical in 150 youth (10 to 17 years old)

with manic or mixed episodes, there was no difference in the amount of change in CDRS-R scores between groups.42 In a study of 116 similarly diagnosed youth, oxcarbazepine resulted in a 7.9point decrease in CDRS-R score, versus 6.4 for placebo, a nonsignificant decrease.43 Thus, as yet it does not appear that these commonly used treatments for children with BD result Adenosine in effective changes in depressive symptoms. Due to the predominance of subsyndromal depressive symptoms in bipolar youth, it would be important to conduct studies specifically examining treatment of these symptoms versus placebo. First-episode bipolar depression In a questionnaire of adults with BD, depressed mood was the most common presenting symptom before the onset of a full mood épisode.44 The initial episode is commonly (>50%) depressive.