TY - JOUR
T1 - C-reactive protein and response to lurasidone treatment in children and adolescents with bipolar I depression
T2 - Results from a placebo-controlled trial
AU - Raison, Charles L.
AU - Siu, Cynthia
AU - Pikalov, Andrei
AU - Tocco, Michael
AU - Loebel, Antony
N1 - Funding Information:
Presented in part at the American College of Neuropsychopharmacology December 9-13, 2018; Hollywood, Florida; The 21st Annual ISBD Conference March 20-29, 2019; Sydney, Australia; and American Society of Clinical Psychopharmacology Annual Meeting May 28 - May 31, 2019, Scottsdale, Arizona. This study was sponsored and funded by Sunovion Pharmaceuticals Inc. The sponsor was involved in the design and collection of data. This publication is the work of authors. All authors contributed to the analysis and interpretation of data, and gave final approval for the manuscript. Dr. Raison reports that in the prior 12 months he has served as a consultant for Usona Institute, Emory Healthcare, Sage Pharmaceuticals and North American Center for Continuing Medical Education. Dr. Siu reports having received consulting fees from Sunovion, the Chinese University of Hong Kong, and the Centre for Addiction and Mental Health, Toronto. Drs. Loebel, Pikalov, and Tocco are employees of Sunovion Pharmaceuticals Inc.
Funding Information:
This study was sponsored and funded by Sunovion Pharmaceuticals Inc. The sponsor was involved in the design and collection of data. This publication is the work of authors. All authors contributed to the analysis and interpretation of data, and gave final approval for the manuscript.
Publisher Copyright:
© 2019 The Authors
PY - 2020/2
Y1 - 2020/2
N2 - This study sought to investigate associations between levels of high-sensitivity c-reactive protein (hsCRP) prior to treatment and change in depressive symptoms and cognition in a short-term, double-blind, placebo-controlled study of lurasidone in children and adolescents with bipolar I depression. Patients 10–17 years of age with a DSM-5 diagnosis of bipolar I depression were randomized to 6 weeks of double-blind treatment with flexibly dosed lurasidone (20–80 mg/day) (n = 173) or placebo (n = 170). The primary efficacy measure was change from baseline to week 6 in the Children's Depression Rating Scale, Revised (CDRS-R). Treatment response was defined as 50% or greater improvement on the CDRS-R from baseline to week 6. Cognitive function was evaluated with the computerized Brief Cogstate Battery at baseline and week 6. Analyses were adjusted for baseline BMI, as well as age. HsCRP was evaluated as a logarithmically transformed continuous variable and as a categorical variable dichotomized into lower (<1 mg/L) and higher (≥1 mg/L) subgroups. A significant interaction was found between baseline hsCRP and treatment group for change in CDRS-R score at study endpoint, with larger placebo-corrected effect sizes for lurasidone in the higher baseline hsCRP group (≥1 mg/L). A significant BMI-by-hsCRP-by-treatment interaction was found for response rate with higher baseline hsCRP levels associated with greater antidepressant response to lurasidone (vs. placebo) in the normal BMI range subgroup (NNT = 2 in higher hsCRP vs. NNT = 5 in lower hsCRP groups) but not in the overweight/obese patients (NNT = 6 in higher hsCRP vs. NNT = 5 in lower hsCRP). Similarly, a significant interaction effect was observed for the combination of hsCRP and BMI on the procognitive effect of lurasidone, with higher baseline hsCRP levels being associated with improvement in cognitive function for lurasidone (vs placebo) in the normal BMI range subgroup but not in overweight/obese patients. These results suggest that young patients with bipolar depression with normal weight and higher levels of pre-treatment CRP may show a greater placebo-adjusted improvement in depressive symptoms and cognitive performance when treated with lurasidone. If these findings are confirmed in future prospective studies, CRP and BMI may prove to be useful diagnostic and predictive biomarkers in the treatment with lurasidone of children and adolescents with bipolar depression.
AB - This study sought to investigate associations between levels of high-sensitivity c-reactive protein (hsCRP) prior to treatment and change in depressive symptoms and cognition in a short-term, double-blind, placebo-controlled study of lurasidone in children and adolescents with bipolar I depression. Patients 10–17 years of age with a DSM-5 diagnosis of bipolar I depression were randomized to 6 weeks of double-blind treatment with flexibly dosed lurasidone (20–80 mg/day) (n = 173) or placebo (n = 170). The primary efficacy measure was change from baseline to week 6 in the Children's Depression Rating Scale, Revised (CDRS-R). Treatment response was defined as 50% or greater improvement on the CDRS-R from baseline to week 6. Cognitive function was evaluated with the computerized Brief Cogstate Battery at baseline and week 6. Analyses were adjusted for baseline BMI, as well as age. HsCRP was evaluated as a logarithmically transformed continuous variable and as a categorical variable dichotomized into lower (<1 mg/L) and higher (≥1 mg/L) subgroups. A significant interaction was found between baseline hsCRP and treatment group for change in CDRS-R score at study endpoint, with larger placebo-corrected effect sizes for lurasidone in the higher baseline hsCRP group (≥1 mg/L). A significant BMI-by-hsCRP-by-treatment interaction was found for response rate with higher baseline hsCRP levels associated with greater antidepressant response to lurasidone (vs. placebo) in the normal BMI range subgroup (NNT = 2 in higher hsCRP vs. NNT = 5 in lower hsCRP groups) but not in the overweight/obese patients (NNT = 6 in higher hsCRP vs. NNT = 5 in lower hsCRP). Similarly, a significant interaction effect was observed for the combination of hsCRP and BMI on the procognitive effect of lurasidone, with higher baseline hsCRP levels being associated with improvement in cognitive function for lurasidone (vs placebo) in the normal BMI range subgroup but not in overweight/obese patients. These results suggest that young patients with bipolar depression with normal weight and higher levels of pre-treatment CRP may show a greater placebo-adjusted improvement in depressive symptoms and cognitive performance when treated with lurasidone. If these findings are confirmed in future prospective studies, CRP and BMI may prove to be useful diagnostic and predictive biomarkers in the treatment with lurasidone of children and adolescents with bipolar depression.
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U2 - 10.1016/j.bbi.2019.12.010
DO - 10.1016/j.bbi.2019.12.010
M3 - Article
C2 - 31857217
AN - SCOPUS:85076846465
SN - 0889-1591
VL - 84
SP - 269
EP - 274
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -