An increase in IL-6 levels at 6-month follow-up visit is associated with SSRI-emergent suicidality in high-risk children and adolescents treated with fluoxetine.

Major depressive disorder (MDD) is associated with alterations in circulatory cytokines, in adults as well as in children and adolescents. Administration of selective serotonin reuptake inhibitors (SSRIs) to MDD pediatric patients modifies cytokine levels. However, most studies only assessed changes over a short time period. In this study, we evaluated long-term effects of the SSRI fluoxetine (FLX) in children and adolescents treated for anxiety and/or MDD, including a high-risk group with pre-treatment suicidality. The study group included ninety-two patients (35 boys and 57 girls) with MDD and/or anxiety disorders, aged 13.90 ± 2.41 years. All patients were treated with FLX and followed for 6 months. The study group included children with pretreatment suicidality (high-risk group;N = 62) and without pretreatment suicidality (N = 30) according to the Columbia Suicide Severity Rating Scale. Plasma concentrations of TNFα, IL-6, and IL-1ß were measured by enzyme linked immunosorbent assays before and after six months of treatment. IL-6 and IL-1ß significantly increased as a factor of time after 6 months of treatment. The elevation was statistically significant confined to children with pretreatment suicidality. Within the children with pretreatment suicidality, IL-6 levels increased significantly after 6 months only in the children who developed SSRI-associated suicidality. To summarize, an increase in IL-6 levels after 6 months of treatment may be associated with SSRI-emergent suicidality in children with pretreatment suicidality. Further studies are needed to clarify the role and mechanism(s) of IL-6 in the pathogenesis of this life-threatening adverse event.

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 benefit-risk 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 ±â€¯2.41 years, were treated with fluoxetine (FLX) for 8 weeks. Plasma concentrations of TNFα, IL-6, and IL-1ß 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.

Predictors of Suicidal Behaviors during Hospitalization among Adolescents Admitted Due to Suicidal Behaviors: A 10-Year Retrospective Naturalistic Study.

Objectives: Suicidality during hospitalization is a common phenomenon with potential devastating consequences. We attempted to identify risk factors for in-hospital suicidality in a high risk group of adolescent inpatients hospitalized for suicidal behaviors (SB). Methods: The database of a tertiary adolescent psychiatric ward was screened for patients hospitalized consecutively for SB during 2001-2010. Data on documented demographic, clinical, and behavioral risk factors were collected. Suicidal events during hospitalization were classified according to the Columbia Classification Algorithm of Suicide Assessment. Results: The sample included 122 inpatients (53% female) aged 10-19 (Mean=15.77, Standard Deviation=2.89) years admitted for SB. Thirty-seven youth (30%) exhibited SB during the hospitalization period (the "suicidal group"), ten of which attempted suicide while hospitalized. There were no significant differences in demographic and clinical parameters between the suicidal and the non-suicidal groups. Younger age, history of drug use and a history of non-suicidal self-injury (NSSI) were independent predictors of a SA during hospitalization. A previous SA added significant risk to SA during hospitalization only in the group that had a history of NSSI. Conclusions: A high risk of SB exists among adolescents hospitalized for suicidality. The risk assessment for SA during hospitalization should include age, history of drug use and previous SA combined with a history of NSSI. Future studies should expand the efforts to identify potential risk factors of SB during hospitalization in this unique high-risk group.

Effects of long-term valproic acid treatment on hematological and biochemical parameters in adolescent psychiatric inpatients: a retrospective naturalistic study.

The objective of this study was to determine the long-term hematological and biochemical side effects of valproic acid (VPA) in psychiatric adolescent inpatients. A retrospective naturalistic study design was used. Participants were psychiatric inpatients treated with VPA, alone or in combination with other medications. Electronic medical files were reviewed for changes in hematological and biochemical parameters following a course of VPA treatment. One hundred and four adolescents aged 12-18 (mean 15.76±1.58) years fulfilled the study criteria. The mean blood level and duration of VPA treatment were 65.81±22.18 mcg/ml and 98.57±135.94 days, respectively. The mean levels of thyroid-stimulating hormones and triglyceride levels increased significantly from the first to the last measurement. Platelet count decreased significantly following VPA treatment. No correlation was observed between these parameters and age, duration of treatment, or VPA levels. No serious adverse events were reported. Long-term VPA treatment in adolescents with psychiatric disorders is associated with significant increases in triglyceride levels. Moreover, VPA-treated adolescent psychiatric inpatients may be at risk of developing pituitary-thyroid axis dysregulation and decreased platelet count. Therefore, baseline measurement of thyroid functions and metabolic and hematological parameters and monitoring throughout the treatment are recommended.