Metabolic Burden and Response to Repeated Intranasal Esketamine in Treatment-Resistant Depression: A Longitudinal Multidomain Biomarker Study
Abstract
<title>Abstract</title> <p>Metabolic, inflammatory, and neurotrophic measures may provide complementary insight into biological heterogeneity underlying treatment-resistant depression and response to ketamine-based treatments. However, biomarker studies of ketamine treatment have focused on individual markers or biological domains, most commonly inflammatory or neurotrophic, while metabolic measures remain comparatively understudied. All three domains were examined in 30 individuals with treatment-resistant depression receiving eight intranasal esketamine treatments in a real-world clinical setting. Depressive symptoms, metabolic, inflammatory, and neurotrophic biomarkers were assessed before and after treatment. Esketamine treatment was associated with a reduction in Montgomery Åsberg Depression Rating Scale scores (mean decrease 7.7 points, p < 0.001; Cohen’s d = -0.90). Greater metabolic burden, quantified using a composite based on metabolic syndrome criteria and comprising waist circumference, triglycerides, HDL cholesterol, blood pressure, and fasting glucose, was associated with greater reductions in depressive symptoms following treatment, after adjustment for baseline depressive symptom severity (p = 0.032). Fasting glucose decreased following esketamine treatment (mean decrease 1.58 mmol/L, pFDR < 0.001; Cohen’s d = −1.61), without significant changes in body weight. In contrast, baseline inflammatory and neurotrophic composites were not associated with changes in depressive symptoms, and no inflammatory or neurotrophic biomarkers showed significant longitudinal changes. In sensitivity analyses excluding participants with diabetes or prescribed glucose-altering medications, higher baseline serum vascular endothelial growth factor (VEGF) was associated with greater reductions in depressive symptoms (pFDR = 0.043). These findings highlight the value of a multidomain approach and identify metabolic measures as an important domain for understanding heterogeneity in response to esketamine.</p>
Topics & conditions
Detected automatically by Psychedelic Commons from the title and abstract, not labels from the source. They may be incomplete.
Psychedelic Commons aggregates metadata from open sources and links back to the original. Rights remain with the authors and publishers. Something wrong with this record? Report a problem.