Summary: Younger people with bipolar disorder responded better to the antidepressant Latuda when they had increased inflammation biomarkers in their blood. Findings suggest C-reactive protein could be a predictive biomarker to identify which patients will respond to the antidepressant.
Source: University of Wisconsin Madison
Children and teens with bipolar depression responded better to an antipsychotic medicine if they had increased markers of inflammation in their blood, a new University of Wisconsin–Madison study shows.
The study suggests that C-reactive protein, a sign of systemic inflammation in the body that shows up in a readily available blood test, could be a predictive biomarker for identifying which patients with depression in the context of pediatric bipolar disorder will respond to medication.
“Inflammation is known to be associated with mood disorders in adults, but this is one of the first findings to show that it can also predict antidepressant response in teens and children,’’ says lead author Charles Raison, professor of human development and family studies in the UW–Madison School of Human Ecology and a member of the psychiatry faculty at the UW School of Medicine and Public Health. “The meeting point of inflammation and predictive biomarkers for antidepressant response is emerging as an important area of research.”
The findings were presented in December at the American College of Neuropsychopharmacology and published in the journal Brain, Behavior and Immunity. The research was sponsored and funded by Sunovion Pharmaceuticals, which makes Latuda, a version of the antipsychotic medication lurasidone, which was recently approved for use in pediatric patients.
The study looked at 347 children and teens ages 10 to 17 with pediatric bipolar disorder who were experiencing a depressive episode. About half were given lurasidone and the other half were given a placebo. Antipsychotics are a class of drugs used to manage bipolar disorder.
After six weeks, those who received the drug and showed the greatest improvement in depression symptoms as defined by the Children’s Depression Rating Scale also had the highest levels of C-reactive protein in their blood at the beginning.
However, the relationship only held for patients who were normal weight or underweight. Those with a body mass index (BMI) in the overweight or obese range with higher levels of C-reactive protein showed little difference in response between the drug and the placebo.
The authors suggest that this finding might be explained by the fact that inflammation in obese and overweight children and teens is more closely related to their body mass and metabolism rather than specifically related to the types of inflammatory processes that are known to increase the risk for developing depression.
C-reactive protein and response to lurasidone treatment in children and adolescents with bipolar I depression: Results from a placebo-controlled trial
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.