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

Maya Amitai*, Michal Taler, Reut Ben-Baruch, Maya Lebow, Ron Rotkopf, Alan Apter, Silvana Fennig, Avraham Weizman, Alon Chen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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 ± 2.41 years, were treated with fluoxetine (FLX) for 8 weeks. Plasma concentrations of TNFα, IL-6, and IL-1β 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.

Original languageEnglish
Pages (from-to)301-308
Number of pages8
JournalBrain, Behavior, and Immunity
StatePublished - Jul 2020


  • Adolescents
  • Children
  • IL-6
  • SSRI
  • Suicidality


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