Abstract

The presence of mixed (subsyndromal hypomanic) symptoms may influence treatment outcomes in pediatric bipolar depression. This post-hoc analysis investigated "bridge" symptoms that have cross-sectional and predictive associations with depressive and manic symptom clusters. The effects of these bridge symptoms on the response to lurasidone 20-80 mg/d compared to placebo treatment was analyzed in children and adolescents with bipolar I depression in a six-week, placebo-controlled, double-blind study followed by a 2-year, open- label extension study of lurasidone. Sleep disturbances, assessed by "difficulty with sleep" Children's Depression Rating Scale, Revised (CDRS-R) item-4 and "decreased need for sleep" Young Mania Rating Scale (YMRS) item-4, and "irritability" (CDRS-R item-8, YMRS item-5) were identified as "bridge" symptoms and found to have replicable causal associations with depressive (CDRS-R total) and manic symptom clusters (YMRS total) at baseline and week-6. A Ggreater improvement in overall depression severity at week 6 with lurasidone (vs. placebo) treatment was observed in the presence (vs. absence) of a"decreased need for sleep" at the baseline, mediated in part by significant reductions from study baseline in a"decreased need for sleep" and manic symptom severity. The absence of sleep disturbance and irritability in patients at open-label extension study baseline was associated with higher rates of sustained recovery (symptomatic and functional remission) for 6 months compared to patients with those symptoms at baseline (68% vs. 50%, Number Needed to Treat=6). Our findings suggest that sleep disturbance and irritability are cardinal symptoms that "bridge" between depressive and manic symptom clusters and influence treatment outcomes in youth with bipolar depression.

View details for DOI 10.2174/1570159X20666220927112625

View details for PubMedID 36173066