title: Early response to antipsychotic drug therapy as a clinical marker of subsequent response in the treatment of schizophrenia.
abstract: Our objective was to prospectively assess whether early (ie, 2 weeks) response to an antipsychotic predicts later (12-week) response and whether 'switching' early non-responders to another antipsychotic is a better strategy than 'staying'. This randomized, double-blind, flexible-dosed, 12-week study enrolled 628 patients diagnosed with schizophrenia or schizoaffective disorder. All initiated treatment with risperidone. Early response was defined as > or =20% improvement on the Positive and Negative Syndrome Scale (PANSS) total score following 2 weeks of treatment. Early responders (ERs) continued on risperidone, whereas early non-responders (ENRs) were randomized (1 : 1) to continue on risperidone 2-6 mg/day or switch to olanzapine 10-20 mg/day for 10 additional weeks. Compared with ENRs, risperidone ERs showed significantly greater reduction in PANSS total score (end point; p<001). Early response/non-response was highly predictive of subsequent clinical outcomes. Switching risperidone ENRs to olanzapine at week 2 resulted in a small but significantly greater reduction in PANSS total score (end point; p=0.020) and in depressive symptoms (end point; p=0.004); the reduction in PANSS was greater among those who were still moderately ill at 2 weeks. Switching risperidone ENRs to olanzapine also resulted in significantly greater increases in triglycerides, a significantly greater decrease in prolactin, and significantly less treatment-emergent dyskinesia. This is the first study to prospectively show that early response/non-response to an antipsychotic (risperidone) is a reliable clinical marker of subsequent clinical outcomes and that a 'switching' strategy based on this information may lead to greater clinical improvement than staying on a drug for a longer period in some patients.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. Kinon_Bruce@Lilly.com
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Kinon
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Haya
authors.initials: H
authors.lastname: Ascher-Svanum
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Stauffer
authors.forename: Sara
authors.initials: S
authors.lastname: Kollack-Walker
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Shitij
authors.initials: S
authors.lastname: Kapur
authors.forename: John M
authors.initials: JM
authors.lastname: Kane
mesh_terms: D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D000077152:Olanzapine; D011388:Prolactin / Q000378:metabolism; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000378:metabolism; D018967:Risperidone / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D014280:Triglycerides / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D014280:Triglycerides; D001569:Benzodiazepines; D011388:Prolactin; D018967:Risperidone; D000077152:Olanzapine