Effect of continuous esketamine infusion on brain white matter microstructure in patients with major depression: A...

Esketamine has demonstrated acute antidepressant effects in patients with major depressive disorder (MDD). This study investigated whether these effects associate with reversible white matter fiber integrity recovery using diffusion imaging.

Twenty patients with MDD and 20 healthy controls received 2-week esketamine treatment. Patients received 0.25 mg/kg intravenous esketamine. Emotional and cognitive recovery were assessed. Diffusion tensor imaging and tract-based spatial statistics evaluated white matter fiber integrity pre/post-treatment. Correlation analyses examined associations between white matter changes and clinical scales.

Compared to controls, patients with MDD exhibited decreased fractional anisotropy (FA) values of cerebral white matter fibers involving the association fibers, the commissural fibers and projection fibers. Esketamine effectively reduced depression, anxiety, and suicidal ideation scores while improving cognitive function. However, no reversible recovery of compromised white matter integrity was observed after 2 weeks of esketamine treatment. FA reductions in projection fibers correlated with anxiety and suicidal ideation severity.

Concurrent sertraline use and lack of placebo control limited our ability to isolate esketamine's effects. The wide age range may have introduced response variability. We used minimal effective dosages based on previous research. The small sample size limited statistical power. Larger, more controlled studies are needed to validate these preliminary findings.

This study enhances MDD neuropathological understanding, with widespread white matter impairment and associations between projection fibers and symptom severity. While producing significant antidepressant effects, short-term esketamine did not recover compromised white matter microstructure.