Pathway     Sample Size     Concentration   Metabolite Platform Tissue N SZ Controls Antipsychotic Length of treatment relative to pre-treatment Reference Lipid class                   free fatty acids HPLC plasma 43 27 16 olanzapine 2-3 weeks ↓ [13] phosphatidylcholine HPLC plasma 43 27 16 olanzapine 2-3 weeks ↑ [13]   HPLC plasma 43 27 16 risperidone 2-3 weeks ↑ [13] phosphatidylethanolamine HPLC plasma 43 27 16 olanzapine 2-3 weeks ↑ [13]   HPLC plasma 43 27 16 risperidone 2-3 weeks ↑ [13]   HPLC plasma 43 27 16 aripriprazole 2-3 weeks ↑ [13]   HPLC plasma 43 27 16 olanzapine 2-3 weeks ↑ [13] lysophosphatidylcholine UPLC-MS/MS plasma 22 11 11 risperidone 6 weeks ↑* [12] phosphatidylcholine UPLC-MS/MS plasma 22 11 11 risperidone 6 weeks ↓* [12] Glycolysis                   glucose GC-MS serum 36 18 18 risperidone 8 weeks ↑ [11]   NMR urine 22 11 11 risperidone 6 weeks ↑* [12]   NMR plasma 22 11 11 risperidone 6 weeks ↑* [12] lactate GC-MS serum 36 18 18 risperidone 8 weeks ↑ [11]   NMR plasma 22 11 11 risperidone 6 weeks ↑* [12] Purine metabolism                   uric acid GC-MS serum 36 18 18 risperidone 8 weeks ↑ [11]   UPLC-MS/MS plasma 22 11 11 risperidone 6 weeks ↓* [12]   UPLC-MS/MS urine 22 11 11 risperidone 6 weeks ↑* [12] Vitamin E metabolism                   γ-Tocopherol GC-MS serum 36 18 18 risperidone 8 weeks ↑ [11] Alanine, aspartate and glutamate metabolism                   aspartate GC-MS serum 36 18 18 risperidone 8 weeks ↓ [11] Tryptophan metabolism                   tryptophan GC-MS serum 36 18 18 risperidone 8 weeks ↑ [11] Fatty acid metabolism                   linoleic acid GC-MS serum 36 18 18 risperidone 8 weeks ↑ [11] oleic acid GC-MS serum 36 18 18 risperidone 8 weeks ↑ [11] stearic acid GC-MS serum 36 18 18 risperidone 8 weeks ↓ [11] Steroid biosynthesis                   cholesterol GC-MS serum 36 18 18 risperidone 8 weeks ↑ [11] Tyrosine metabolism                   tyrosine GC-MS serum 36 18 18 risperidone 8 weeks ↑ [11] phenylalanine GC-MS serum 36 18 18 risperidone 8 weeks ↑ [11] Carbohydate metabolism                   erythrose GC-MS serum 36 18 18 risperidone 8 weeks ↓ [11] Glycine, serine and threonine metabolism                   glycine NMR plasma 22 11 11 risperidone 6 weeks ↑* [12] Lipoproteins                   lipoprotein NMR plasma 22 11 11 risperidone 6 weeks ↑* [12] low-density lipoprotein NMR plasma 22 11 11 risperidone 6 weeks ↑* [12] very low-density lipoprotein NMR plasma 22 11 11 risperidone 6 weeks ↑* [12] very low-density lipoprotein/low density lipid protein NMR plasma 22 11 11 risperidone 6 weeks ↑* [12] high density lipid protein NMR plasma 22 11 11 risperidone 6 weeks ↑* [12] lipid NMR plasma 22 11 11 risperidone 6 weeks ↓* [12] unsaturated fatty acids NMR plasma 22 11 11 risperidone 6 weeks ↑* [12] Antioxidants                   taurine NMR urine 22 11 11 risperidone 6 weeks ↓* [12] Amino-acid metabolism                   trimethylamine-N-oxide NMR urine 22 11 11 risperidone 6 weeks ↓* [12] Other pathways                   3-indolebutyrate fragments UPLC-MS/MS plasma 22 11 11 risperidone 6 weeks ↑* [12] creatine NMR urine 22 11 11 risperidone 6 weeks ↓* [12] creatinine UPLC-MS/MS urine 22 11 11 risperidone 6 weeks ↓* [12]   NMR urine 22 11 11 risperidone 6 weeks ↓* [12] pregnanediol UPLC-MS/MS urine 22 11 11 risperidone 6 weeks ↑* [12] 3-hydroxybutyrate NMR plasma 22 11 11 risperidone 6 weeks ↓* [12] acetoacetate NMR plasma 22 11 11 risperidone 6 weeks ↓* [12] *did not survive Bonferroni correction. GC-MS; gas chromatography-mass spectrometry , HPLC; high performace liquid chromatography, NMR; nuclear magnetic resonance spectroscopy, SZ; schizophrenia, UPLC-MS/MS; ultra-performance liquid chromatography−tandem mass spectrometry

Table 2: Effect of antipsychotic medications on metabolic markers.