Mood and anxiety disorders are common among children and adolescents, with depression affecting up to 3% and 12% of individuals in this age group, respectively. Up to 40% of such patients do not respond to the standard SSRI treatment approach, and there is no way to distinguish patients who will respond to SSRIs from those who will not. As a result, many patients are being needlessly given a drug that is ineffective and possibly harmful due to the risk of adverse effects, note the authors of a new study published in the Journal of Child and Adolescent Psychopharmacology.  

Previous findings from studies of adults with major depressive disorder (MDD) suggest that the disease may be linked with immune dysregulation, and that treatment with antidepressants “may influence the production of pro-and anti-inflammatory cytokines” and lead to “attenuation/normalization of overactive inflammatory processes,” wrote the authors of the present study, which is the first to investigate the effect of SSRIs on cytokines in children and adolescents.

The researchers, representing several Israeli universities, sought to determine whether proinflammatory cytokine levels could predict treatment response to fluoxetine in this age range. They hypothesized that fluoxetine would decrease cytokine levels and that patients with increased levels at baseline would be treatment-resistant.

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Participants included 41 patients with MDD or anxiety disorders per DSM-IV criteria, ranging in age from 9 to 18. Nine participants had both MDD and an anxiety disorder. Before and after receiving treatment with fluoxetine, they underwent blood testing for the assessment of their tumor necrosis factor (TNF)-a, interleukin (IL)-6, and IL-1b levels. At 2, 4, 6, and 8 weeks, participants were evaluated with various measures of mental health such as the Children’s Depression Rating Scale–Revised (CDRS-R), the Beck Depression Inventory(BDI), and the Screen for Child Anxiety Related Emotional Disorders (SCARED).

According to the results, 56% of patients demonstrated a response to treatment. After treatment, mean assessment scores changed as follows:

  • CDRS decreased from 59.17 (SD=20.63) to 34.93 (SD=14.34) (paired t=7.07, df=40, p<0.0001)
  • BDI decreased from 18.50 (SD=9.85) to 10.10 (SD=10.42) (paired t=6.10, df=40, p<0.0001)
  • SCARED decreased from 29.83 (SD=12.50) to 21.49 (SD=15.61) (paired t=4.07, df=40, p<0.0001)

Though there were no significant changes in IL-6 or IL-1b levels, treatment with fluoxetine led to a significant reduction in TNF-a. SSRI-refractory patients had higher levels of all 3 cytokines compared to SSRI-responsive ones, suggesting that these elevated levels could help to identify children who are unlikely to respond to treatment with fluoxetine.

Though more research should be conducted to clarify differences between youth and adults in terms of the immune-depression connection, these findings point to a suppressive action of fluoxetine on proinflammatory cytokine expression in children and adolescents. These results align with earlier findings in studies of adult patients.


1. National Institute of Mental Health. Any Disorder Among Children. Retrieved 10/24/16 from

2. National Institute of Mental Health. Retrieved 10/24/16 from

3. Amitai M, Taler M, Carmel M, et al. The relationship between plasma cytokine levels and response to selective serotonin reuptake inhibitor treatment in children and adolescents with depression and/or anxiety disorders. J Child Adolesc Psychopharmacol. 2016; 26(8):727-732.