March 2, 2026
“A meta-analysis of 7 studies (N=1,493) found that higher baseline CRP predicts antidepressant non-response with a small but highly consistent effect (ES=-0.18, p=0.0006, I²=0%). IL-8 similarly predicted non-response. Notably, TNF-α, IL-10, and other widely studied cytokines did not show consistent meta-analytic associations — narrowing the inflammation signal to CRP and IL-8 as the clinically relevant markers to measure.”
“The ELEKT-D RCT (N=403) showed ketamine is non-inferior to ECT for treatment response (55% vs 41%) but inferior for remission (29% vs 47%). The two are not equivalent alternatives — they are different tools for different outcome goals. ECT for full remission in severe presentations. Ketamine for rapid response with a more favorable cognitive profile.”
“Zuranolone (Zurzuvae) — the first oral antidepressant with a genuinely novel mechanism (GABA-A positive allosteric modulator) in decades — was FDA-approved in August 2023. The clinical evidence supports it, particularly for postpartum depression where speed of onset matters. The access story is different: $15,900 list price, aggressive step therapy prior authorizations, and specialty tier placement are limiting real-world adoption more than clinical efficacy ever has.”
“TMS has been FDA-cleared for treatment-resistant depression since 2008 and has substantial meta-analytic evidence (50–60% response, 30–35% remission). CMS updated coverage criteria in 2024, reducing the failed-trial threshold and expanding deep TMS coverage. But bipolar depression, accelerated protocols (SAINT), and inadequate documentation of prior trials still block many of the patients with the highest disease burden.”