Increased circulatory IL-6 during 8-week fluoxetine treatment is a risk factor for suicidal behaviors in youth

Objective: Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat anxiety and/or depression in pediatric populations. However, the response rates are low (approximately 50%). Moreover, SSRI use is frequently associated with adverse events (AE). Currently there are no available biomarkers for treatment response/AE. Identification of biomarkers predicting early response and/or AE could help maximize the benefitrisk ratio for the use of SSRIs, and accelerate matching of treatments to patients. Pro-inflammatory cytokines were proposed as potential biomarkers. Method: Ninety-two patients (35 boys and 57 girls) with major depressive disorder and/or anxiety disorders, aged 13.90 +/- 2.41 years, were treated with fluoxetine (FLX) for 8 weeks. Plasma concentrations of TNF alpha, IL-6, and IL-1 beta were measured by enzyme linked immunosorbent assays before and after FLX treatment. Clinical response and AE were measured using several clinical scales, including the Clinical Global Impression - improvement, Children's Depression Rating Scale-Revised, the Beck Depression Inventory, the Screen for Child Anxiety Related Emotional Disorders, the Columbia suicide severity rating scale, and the Suicide Ideation Questionnaire. Results: IL-6 levels increased after treatment only in the group of children who developed FLX-associated suicidality. Conclusion: An increase in IL-6 levels during treatment may be a risk factor for the emergence of FLX-associated suicidality (OR= 1.70). Further studies are necessary to clarify the role and mechanism(s) of this cytokine in the pathogenesis of this life-threatening AE.