EARLY RESPONSE TO ANTIPSYCHOTICS – WHAT CHANGES EARLY AND HOW?

Abstract

score reduction) at week 1, 2 and 3 for UR (>30% total PANSS score) or remission (no more than mild symptoms) at endpoint. Results: In 127 adolescents (15.5 years) with schizophrenia (n=54) or psychosis NOS (n=73) treated openly for 3 months, CGI-S and CGAS score reductions were significantly more pronounced in the first 4 weeks vs. the following 8 weeks. CGI-I defined ER at 4 weeks predicted UR with a high sensitivity (83%), moderate specificity (69%) and good Positive Predictive Value (PPV: 78%), and Negative Predictive Value (NPV: 76%). ER patients had significantly greater improvements on the CGI-S and GAF score at 4, 8 and 12 weeks than early non-responders. Early nonresponders had significantly more parkinsonism (44.4% vs. 16.7%, p< .05). In the RCT, 293 adolescents (15.5 years) were randomized to aripiprazole 10 mg (N=99) or 30 mg (N=97), or placebo (N=98). Nearly 50% of the aripiprazole PANSS Total reduction was achieved by week 2; up to 75% by week 3. ER at week 3 had better predictive values than ER at week 2. At week 3, ER predicted UR at 6 week with high sensitivity (88%), specificity (83%), PPV (84%), and NPV (87%). Similarly good predictive values were found for remission: sensitivity=71%, specificity=76.2%, PPV=83%, NPV=62%. Patients achieving ER at week 2 and week 3 had significantly greater reductions in PANSS total, positive and negative scores, CGI-S, CGI-I, and CGAS scores (all p-values<0.001). The incidence of adverse events between ER and ENR patients was not different. Conclusions: Data in adolescents with schizophrenia-spectrum disorders confirm that most of the treatment response occurs early. Early non-response was a better predictor of later non-response in the RCT than in the naturalistic study that used more global outcome measures. Further studies in adolescents and in real-world settings are needed. In addition, the predictive value of early changes in the CGI-I score need to be examined in youth and adults to test if this more easily implementable scale could serve as a reliable, clinical indicator or early and ultimate response.