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IL-17A Can Predict Antidepressant Resistance in MDD

Key clinical point: The pro-inflammatory cytokine interleukin-17A could serve as a potential marker of treatment resistance to antidepressants in patients with major depressive disorder (MDD).

Major finding: The mean levels of IL-17A remained stable in patients responding to treatment but increased sharply in nonresponders at week 6.

Study details: The plasma levels of various cytokines were compared in 48 patients with MDD at baseline and weeks 1 and 6 of antidepressant treatment in relation to therapy response.

Disclosures: The study was supported by the German Federal Ministry of Education and Research. The authors reported no financial interests or potential conflicts of interest.


Nothdurfter et al examined the trajectory of change in levels of eight different cytokines during treatment of major depression (MDD). The study examined 48 patients on no psychotropics (except hypnotics) at baseline. Psychiatrists individualized antidepressants for each patient. Blood was drawn before starting antidepressants, then 1 and 6 weeks afterwards.

Only one cytokine had a different trajectory in nonresponders: Mean levels of IL-17A were stable among patients whose depression responded to treatment but increased sharply in nonresponders at week 6. The finding appears statistically valid (interaction coefficient Time x Response = -0.518; p = 0.005).

Results of this study are consistent with the strong evidence of the “inflammatory hypothesis” of MDD—that increased proinflammatory cytokines play an important role in the pathogenesis of MDD1.

As noted by the researchers, IL-17A levels shows promise as a marker of MDD nonresponse to antidepressants. IL-17a did not differ between responders and nonresponders at week 1. IL-17A’s utility as a marker will require evidence that its levels early in treatment (e.g. at week 2) differentiates between responders and nonresponders.

Some experts posit that inflammation is primarily linked to early life adversity and to a subgroup of treatment-refractory MDD2. It would be worthwhile to examine whether early life adversity affects the trajectory of cytokines during MDD treatment.

Gita Ramamurthy, MD, FRCP (C)

Director - Psychiatric Consultation-Liaison Service

SUNY Upstate Medical University

1. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctot KL. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010;67:446-457.

2. Raison CL. Inflammatory depression: a trifecta of trouble. J Clin Psychiatry. 2014;75:663-664.


Nothdurfter C et al. Eur J Neurosci. 2019 Dec 2. doi: 10.1111/ejn.14636.