Cytokines and ECT: a New Meta-Analysis

Out on PubMed, from investigators in France, is this review:

Cytokines changes associated with electroconvulsive therapy in patients with treatment-resistant depression: a Meta-analysis.

Gay F, Romeo B, Martelli C, Benyamina A, Hamdani N.Psychiatry Res. 2021 Jan 16;297:113735. doi: 10.1016/j.psychres.2021.113735. Online ahead of print.PMID: 33497973 Review.

The abstract is copied below:

One third of depressive patients do not achieve remission after several steps of treatment and are considered as treatment resistant. Electroconvulsive therapy (ECT) improves symptoms in 70 to 90% of such cases. Resistant depression is associated with a dysregulation of the immune system with a dysbalance between the pro- and the anti-inflammatory cytokines. Therefore, we aimed to measure the kinetic of cytokines levels before, during and at the end of ECT. To test this hypothesis, we performed a meta-analysis assessing cytokines plasma levels before, during and after ECT in patients with major depressive disorders. After a systematic database search, means and standard deviations were extracted to calculate standardized mean differences. We found that IL-6 levels increased after 1 or 2 ECT session (p = 0.01) then decrease after 4 ECT sessions (p < 0.01) with no difference at the end of ECT (p = 0.94). A small number of studies were included and there was heterogeneity across them. The present meta-analysis reveals that ECT induces an initial increase of IL-6 levels and a potential decrease of TNF-α levels. No changes on IL-4 and IL-10 levels were found. Further work is necessary to clarify the impact of ECT on peripheral cytokines.

Keywords: Cytokines; Electroconvulsive Therapy; Inflammation; Major depressive disorders.

The conclusion:

Our work indicates that during ECT treatment, there is a proinflammatory response with an increased secretion of IL-6 levels, then an anti-inflammatory response with a decrease of IL-6 and TNF-α levels and in the end a trend decrease of TNF-α levels with a normalization of IL-6 levels. ECT may exert its effects in non-responsive pharmacotherapy patients by reducing inflammatory markers. Research and further studies are needed to better understand the therapeutic mechanisms of ECT and its impact on peripheral cytokines notably in non- responsive treatment patients.

This meta-analysis of plasma cytokines before, during, and after ECT included 9 articles and 198 patients. Because of many methodological differences between the studies (from collection times to analytic technique) the conclusions are quite "soft." The discussion has lots of contorted reasoning in an attempt to put together a coherent explanation of what depression and depression treatment (ECT) do to the immune system and inflammatory responses. Regulating a dysregulated system, "modulation, and "biphasic" or "multiphasic" are about as good as it gets. This is not the authors' fault, merely the primitive state of the evidence. 

For those of you with enhanced interest in the complex interaction of mood disorders and the immune system, a full read (~30 minutes) is definitely in order; for the rest of us, reading the abstract, conclusion paragraph and a look at the Forest plot should suffice (~8 minutes).