Multimodal predictors of response to intravenous ketamine in treatment-resistant depression: toward personalized treatment in major depressive and bipolar disorders
- 1Adult Psychiatry, Poznan University of Medical Sciences, Poland
- 2Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland
Abstract
Intravenous ketamine is a rapid-acting intervention for treatment-resistant depression (TRD) in adults with major depressive disorder and bipolar disorder (BD). While efficacy is established, a comprehensive integration of clinical, neurophysiological, biomarker, metabolic, and cognitive predictors remains lacking, limiting precision CNS-targeted therapy. To synthesize recent evidence on multimodal predictors of intravenous ketamine response in TRD and propose a preliminary clinical framework to guide personalized treatment. Following PRISMA guidelines, Scopus, PubMed, EMBASE, and MEDLINE were searched for English-language, peer-reviewed studies published within the last 5 years. Eligible studies included adults receiving intravenous ketamine for depressive disorders. Data were descriptively synthesized to identify consistent predictors, evidence clusters, and research gaps. The review included 150 studies. Key predictors of ketamine response included baseline depressive severity, comorbid anxiety, atypical depression and sleep phenotypes, inflammatory and neuroplastic biomarkers (eg, monocyte count, BDNF), metabolic factors (BMI, vitamin B12), genetic/epigenetic variants, neurophysiological signatures (EEG, TMS, fMRI connectivity), cognitive performance, and early symptomatic improvement. Integrative analysis suggests that glutamatergic, circadian, and inflammatory mechanisms interact to shape interindividual variability. Limitations include methodological heterogeneity and scarce long-term outcome data. Intravenous ketamine response in TRD is multifactorial, reflecting clinical phenotype, CNS biomarkers, neurophysiology, metabolism, and genetics. This review proposes a preliminary research framework and pilot clinical questionnaire intended to facilitate future investigation of individualized treatment approaches. However, most proposed predictors remain exploratory and require prospective validation before clinical implementation.
Related
- Optimizing the Therapeutic Index: Sequential Intraarterial–Intravenous PRRT with Personalized Volumetric-Adjusted Dosing
- Genetic Predictors of Curve Progression and Brace Treatment Response in Adolescent Idiopathic Scoliosis: Toward Personalized Management
- Combined Pectoral Nerve Block and Intravenous Dexmedetomidine in Contemporary Multimodal Breast Cancer Analgesia: A Real-World Cohort Study
- Generative AI-powered multimodal physiological sensors for personalized edge health monitoring
- Intravenous Ketamine or Esketamine in Adolescents With Major Depressive Disorder: A Systematic Review
BibTeX
@article{malewskakasprzak2026multimodal,
title = {{Multimodal predictors of response to intravenous ketamine in treatment-resistant depression: toward personalized treatment in major depressive and bipolar disorders}},
author = {Magda Malewska-Kasprzak and Filip Rybakowski and Monika Dmitrzak-Weglarz},
journal = {CNS Spectrums},
year = {2026},
month = sep,
doi = {10.1017/s1092852926101187},
url = {https://doi.org/10.1017/s1092852926101187},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Multimodal predictors of response to intravenous ketamine in treatment-resistant depression: toward personalized treatment in major depressive and bipolar disorders
AU - Magda Malewska-Kasprzak
AU - Filip Rybakowski
AU - Monika Dmitrzak-Weglarz
PY - 2026
DA - 2026/09/28
JO - CNS Spectrums
DO - 10.1017/s1092852926101187
UR - https://doi.org/10.1017/s1092852926101187
AB - Intravenous ketamine is a rapid-acting intervention for treatment-resistant depression (TRD) in adults with major depressive disorder and bipolar disorder (BD). While efficacy is established, a comprehensive integration of clinical, neurophysiological, biomarker, metabolic, and cognitive predictors remains lacking, limiting precision CNS-targeted therapy. To synthesize recent evidence on multimodal predictors of intravenous ketamine response in TRD and propose a preliminary clinical framework to guide personalized treatment. Following PRISMA guidelines, Scopus, PubMed, EMBASE, and MEDLINE were searched for English-language, peer-reviewed studies published within the last 5 years. Eligible studies included adults receiving intravenous ketamine for depressive disorders. Data were descriptively synthesized to identify consistent predictors, evidence clusters, and research gaps. The review included 150 studies. Key predictors of ketamine response included baseline depressive severity, comorbid anxiety, atypical depression and sleep phenotypes, inflammatory and neuroplastic biomarkers (eg, monocyte count, BDNF), metabolic factors (BMI, vitamin B12), genetic/epigenetic variants, neurophysiological signatures (EEG, TMS, fMRI connectivity), cognitive performance, and early symptomatic improvement. Integrative analysis suggests that glutamatergic, circadian, and inflammatory mechanisms interact to shape interindividual variability. Limitations include methodological heterogeneity and scarce long-term outcome data. Intravenous ketamine response in TRD is multifactorial, reflecting clinical phenotype, CNS biomarkers, neurophysiology, metabolism, and genetics. This review proposes a preliminary research framework and pilot clinical questionnaire intended to facilitate future investigation of individualized treatment approaches. However, most proposed predictors remain exploratory and require prospective validation before clinical implementation.
SN - 1092-8529
SN - 2165-6509
ER -