title: Early nonresponse determined by the clinical global impressions scale predicts poorer outcomes in youth with schizophrenia spectrum disorders naturalistically treated with second-generation antipsychotics.
abstract: OBJECTIVE
  The use of early response/nonresponse (ER/ENR) to antipsychotics as a predictor for ultimate response/nonresponse (UR/UNR) may help decrease inefficacious treatment continuation. However, data have been limited to adults, and ER/ENR has only been determined using time-consuming psychopathology rating scales. In the current study, we assessed if early improvement on the Clinical Global Impressions-Improvement (CGI-I) scale predicted UR/UNR in psychiatrically ill youth started on antipsychotic treatment.
  
  
  METHODS
  Seventy-nine youth aged 6-19 years, with schizophrenia spectrum disorders, treated naturalistically with aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone and evaluated monthly, were divided into ER/ENR groups at week 4, using at least "minimally improved" on the CGI-I scale. Prediction using week 4 ER/ENR status for UR (CGI-I=at least "much improved"), effectiveness and adverse effect outcomes at 8-12 weeks were assessed.
  
  
  RESULTS
  At 4 weeks, 45.6% of subjects were ER and 54.4% were ENR without differences regarding baseline demographic, illness, and treatment variables, except for higher age (p=0.034) and maximum risperidone dose (p=0.0043) in ENR. ER/ENR status at 4 weeks predicted UR/UNR at week 12 significantly (p<0.0001): Sensitivity=68.9%, specificity=85.3%, positive predictive value=86.1%, negative predictive value=67.4%. At weeks 4, 8, and 12, ER patients improved significantly more on the CGI-I, CGI-Severity, and Children's Global Assessment of Functioning scales, and more ER patients reached UR compared with ENR patients (83.3% vs. 34.9%, all p<0.0001). ENR patients had more extrapyramidal side effects (EPS) at weeks 4, 8, and 12 (p=0.0019-0.0079). UR was independently associated with ER (odds ratio [OR]=18.09; 95% confidence interval [CI]=4.71-91.68, p<0.0001) and psychosis not otherwise specified (NOS) (OR=4.82 [CI: 1.31-21.41], p=0.017) (r(2)=0.273, p<0.0001).
  
  
  CONCLUSIONS
  Older age and EPS were associated with ENR; ENR and schizophrenia were associated with UNR in naturalistically treated youth with schizophrenia spectrum disorders. Early CGI-I-based treatment decisions require further consideration and study.
authors.affiliation: 1 Mental Health Centre for Child and Adolescent Psychiatry , Glostrup, Denmark .
authors.forename: Marie
authors.initials: M
authors.lastname: Stentebjerg-Olesen
authors.forename: Pia
authors.initials: P
authors.lastname: Jeppesen
authors.forename: Anne K
authors.initials: AK
authors.lastname: Pagsberg
authors.forename: Anders
authors.initials: A
authors.lastname: Fink-Jensen
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kapoor
authors.forename: Raja
authors.initials: R
authors.lastname: Chekuri
authors.forename: Maren
authors.initials: M
authors.lastname: Carbon
authors.forename: Aseel
authors.initials: A
authors.lastname: Al-Jadiri
authors.forename: Taishiro
authors.initials: T
authors.lastname: Kishimoto
authors.forename: John M
authors.initials: JM
authors.lastname: Kane
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D011237:Predictive Value of Tests; D012559:Schizophrenia / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents