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T33

METABOLIC BURDEN, INFLAMMATION, AND ESKETAMINE EFFICACY IN TREATMENT-RESISTANT MAJOR DEPRESSIVE EPISODES

Favour Olaoluwa — Suzannah Wojcik2, Edward Horn3, Stefan Trivunovic4, Jessica Clausen4, Kelly Mascioli4, Richard Kohl2, Areebah Ahmed2, Glenda O’Hara4, Jess G. Fiedorowicz5, Pierre Blier2, Jeanne Talbot2, Jennifer L. Phillips2 1University of Toronto Scarborough, 2University of Ottawa Institute of Mental Health Research, 3University of Ottawa, 4Royal Ottawa Mental Health Centre, 5Ottawa Hospital Research Institute

2026 ASCP Annual Meeting

Background

Esketamine, a rapid-acting glutamatergic agent, has demonstrated clinical promise in treatment-resistant depression (TRD). Recent evidence has linked metabolic and inflammatory markers and response to antidepressant treatment. This study examined change in clinical symptoms and peripheral blood-based biomarkers in individuals with TRD receiving repeated esketamine treatments in a Canadian psychiatric hospital.

Methods

Data was derived from 25 participants with primary diagnosis of major depressive disorder or bipolar disorder receiving twice-weekly intranasal esketamine treatments over four weeks. Depressive symptoms were measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) and Patient Health Questionnaire-9 (PHQ-9). Metabolic syndrome criteria and high-sensitivity C-reactive protein (CRP) were assessed at baseline and after 4 weeks of treatment.

Results

Esketamine treatment was associated with significant decrease in both rateradministered and self-reported depressive symptom severity (MADRS, mean decrease 7.8 points, p < .001; PHQ-9, p < .001). Pre-treatment, 84% of patients had at least 1 metabolic dysregulation (most commonly elevated blood pressure or increased waist circumference), and 28% had elevated CRP. A higher number of pre-treatment metabolic abnormalities predicted greater decrease in depressive symptoms post-treatment (p=.037). Following 4 weeks of treatment, participants had a significant decrease in mean fasting glucose (p < .001), and systolic blood pressure (p=.01).

Conclusions

In this preliminary analysis, improvement in symptoms of depression was observed over 4 weeks of esketamine treatment. Further, we report evidence of associations between metabolic burden and treatment response to esketamine. These findings support the therapeutic effects of esketamine and emphasize the need for further investigation into its broader clinical and biological impacts.