METABOLOMIC SIGNATURES AND THERAPEUTIC DRUG MONITORING IN SCHIZOPHRENIA: A SCOPING REVIEW OF ANTIPSYCHOTIC TREATMENT OUTCOMES
Author(s)
mariyam Afeeza, BPH1, ABDUL MANNAN FARUK AHMED, MPh2, Ganesan Rajalekshmi Saraswathy, PhD3, Juno J. Joel, PhD4.
1Department of Pharmacy Practice, NGSM Institute of Pharmaceutical Sciences, Nitte (Deemed to be University), Mangalore, India, 2Department of Pharmacy Practice, M S Ramaiah University Of Applied Sciences, bengaluru, India, 3Department of Pharmacy Practice, M S Ramaiah University Of Applied Sciences, Bangalore, India, 4Department of Pharmacy Practice, NGSM Institute of Pharmaceutical Sciences, Mangalore, India.
1Department of Pharmacy Practice, NGSM Institute of Pharmaceutical Sciences, Nitte (Deemed to be University), Mangalore, India, 2Department of Pharmacy Practice, M S Ramaiah University Of Applied Sciences, bengaluru, India, 3Department of Pharmacy Practice, M S Ramaiah University Of Applied Sciences, Bangalore, India, 4Department of Pharmacy Practice, NGSM Institute of Pharmaceutical Sciences, Mangalore, India.
OBJECTIVES: Antipsychotic response in schizophrenia is highly variable, lacking robust biomarkers to guide drug selection and identify early non-response. Metabolomics captures the downstream biochemical effects of antipsychotics, complementing therapeutic drug monitoring (TDM) by reflecting pharmacodynamic consequences rather than drug levels alone. This review mapped human metabolomic and lipidomic studies linking quantitative metabolite profiles to antipsychotic treatment outcomes (response, relapse, treatment resistance) to examine their relevance for TDM-oriented precision psychiatry.
METHODS: A scoping review was conducted following the Arksey and O’Malley framework, Joanna Briggs Institute guidance, and PRISMA-ScR guidelines. PubMed, Embase, and Scopus were systematically searched from inception. Eligible studies included original human research quantifying metabolomic or lipidomic profiles in plasma, serum, or cerebrospinal fluid (CSF) explicitly related to antipsychotic outcomes.
RESULTS: Eleven studies were included. In acute and first-episode cohorts, baseline or early-treatment metabolomic signatures predicted short-term response (AUCs ~0.80-0.94). Convergent findings implicated phosphatidylcholines, phosphatidylethanolamines, sphingomyelins, ceramides, and shorter-chain triglycerides as correlates of efficacy. Relapse-focused studies highlighted creatine, inosine, neurosteroids (progesterone, allopregnanolone), and cortisol. CSF profiling identified a glucoregulatory disease signature normalized only with early atypical antipsychotic intervention. Pilot data in treatment-resistant schizophrenia revealed distinct serum signatures involving the serine-glycine and kynurenine pathways, linked to cognition, disorganization, and drug-specific response.
CONCLUSIONS: Metabolomic signatures within glycerophospholipid, sphingolipid, amino acid, and neurosteroid pathways successfully track antipsychotic efficacy, relapse, and resistance. Integrating longitudinal metabolomic profiles with plasma drug concentrations could enhance TDM frameworks for stratified prescribing and early switching. However, external validation in harmonized, large-scale longitudinal studies is required.
METHODS: A scoping review was conducted following the Arksey and O’Malley framework, Joanna Briggs Institute guidance, and PRISMA-ScR guidelines. PubMed, Embase, and Scopus were systematically searched from inception. Eligible studies included original human research quantifying metabolomic or lipidomic profiles in plasma, serum, or cerebrospinal fluid (CSF) explicitly related to antipsychotic outcomes.
RESULTS: Eleven studies were included. In acute and first-episode cohorts, baseline or early-treatment metabolomic signatures predicted short-term response (AUCs ~0.80-0.94). Convergent findings implicated phosphatidylcholines, phosphatidylethanolamines, sphingomyelins, ceramides, and shorter-chain triglycerides as correlates of efficacy. Relapse-focused studies highlighted creatine, inosine, neurosteroids (progesterone, allopregnanolone), and cortisol. CSF profiling identified a glucoregulatory disease signature normalized only with early atypical antipsychotic intervention. Pilot data in treatment-resistant schizophrenia revealed distinct serum signatures involving the serine-glycine and kynurenine pathways, linked to cognition, disorganization, and drug-specific response.
CONCLUSIONS: Metabolomic signatures within glycerophospholipid, sphingolipid, amino acid, and neurosteroid pathways successfully track antipsychotic efficacy, relapse, and resistance. Integrating longitudinal metabolomic profiles with plasma drug concentrations could enhance TDM frameworks for stratified prescribing and early switching. However, external validation in harmonized, large-scale longitudinal studies is required.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
CO216
Topic
Clinical Outcomes, Health Service Delivery & Process of Care, Study Approaches
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Mental Health (including addiction), Personalized & Precision Medicine