Pharmacometabolomics of Response to Sertraline and to Placebo in Major Depressive Disorder – Possible Role for Methoxyindole Pathway
Pharmacometabolomics of Response to Sertraline and to Placebo in Major Depressive Disorder – Possible Role for Methoxyindole Pathway Hongjie Zhu1., Mikhail B. Bogdanov2., Stephen H. Boyle1, Wayne Matson3, Swati Sharma3, Samantha Matson3,4, Erik Churchill1, Oliver Fiehn5, John A. Rush6, Ranga R. Krishnan1,6, Eve Pickering7, Marielle Delnomdedieu8, Rima Kaddurah-Daouk1*, Pharmacometabolomics Research Network 1 Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina, United States of America, 2 Department of Neurology and Neuroscience Weill Cornell Medical College, New York, New York, United States of America, 3 Department of Systems Biochemistry, Bedford VA Medical Center, Bedford, Massachusetts, United States of America, 4 Massachusetts General Hospital, Boston, Massachusetts, United States of America, 5 Genome Center, University of California Davis, Davis, California, United States of America, 6 Duke-NUS Graduate Medical School, Singapore, Singapore, 7 Pfizer Global R&D, Clinical Research Statistics, Groton, Connecticut, United States of America, 8 Pfizer Global R&D, Neuroscience Clinical Research, Groton, Connecticut, United States of America Abstract Therapeutic response to selective serotonin (5-HT) reuptake inhibitors in Major Depressive Disorder (MDD) varies considerably among patients, and the onset of antidepressant therapeutic action is delayed until after 2 to 4 weeks of treatment. The objective of this study was to analyze changes within methoxyindole and kynurenine (KYN) branches of tryptophan pathway to determine whether differential regulation within these branches may contribute to mechanism of variation in response to treatment. Metabolomics approach was used to characterize early biochemical changes in tryptophan pathway and correlated biochemical changes with treatment outcome. Outpatients with MDD were randomly assigned to sertraline (n = 35) or placebo (n = 40) in a double-blind 4-week trial; response to treatment was measured using the 17-item Hamilton Rating Scale for Depression (HAMD17).
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