Early nonresponse determined by the clinical global impressions scale predicts poorer outcomes in youth with schizophrenia spectrum disorders naturalistically treated with second-generation antipsychotics

Marie Stentebjerg-Olesen, Pia Jeppesen, Anne K. Pagsberg, Anders Fink-Jensen, Sandeep Kapoor, Raja Chekuri, Maren Carbon, Aseel Al-Jadiri, Taishiro Kishimoto, John M. Kane, Christoph U. Correll

Research output: Contribution to journalArticle

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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) (r2=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.

Original languageEnglish
Pages (from-to)665-675
Number of pages11
JournalJournal of Child and Adolescent Psychopharmacology
Volume23
Issue number10
DOIs
Publication statusPublished - 2013 Dec 1
Externally publishedYes

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Antipsychotic Agents
Schizophrenia
Risperidone
olanzapine
Odds Ratio
Confidence Intervals
Therapeutics
Psychopathology
Psychotic Disorders
Demography
Sensitivity and Specificity

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pediatrics, Perinatology, and Child Health
  • Psychiatry and Mental health

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Early nonresponse determined by the clinical global impressions scale predicts poorer outcomes in youth with schizophrenia spectrum disorders naturalistically treated with second-generation antipsychotics. / Stentebjerg-Olesen, Marie; Jeppesen, Pia; Pagsberg, Anne K.; Fink-Jensen, Anders; Kapoor, Sandeep; Chekuri, Raja; Carbon, Maren; Al-Jadiri, Aseel; Kishimoto, Taishiro; Kane, John M.; Correll, Christoph U.

In: Journal of Child and Adolescent Psychopharmacology, Vol. 23, No. 10, 01.12.2013, p. 665-675.

Research output: Contribution to journalArticle

Stentebjerg-Olesen, Marie ; Jeppesen, Pia ; Pagsberg, Anne K. ; Fink-Jensen, Anders ; Kapoor, Sandeep ; Chekuri, Raja ; Carbon, Maren ; Al-Jadiri, Aseel ; Kishimoto, Taishiro ; Kane, John M. ; Correll, Christoph U. / Early nonresponse determined by the clinical global impressions scale predicts poorer outcomes in youth with schizophrenia spectrum disorders naturalistically treated with second-generation antipsychotics. In: Journal of Child and Adolescent Psychopharmacology. 2013 ; Vol. 23, No. 10. pp. 665-675.
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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) (r2=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.",
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T1 - Early nonresponse determined by the clinical global impressions scale predicts poorer outcomes in youth with schizophrenia spectrum disorders naturalistically treated with second-generation antipsychotics

AU - Stentebjerg-Olesen, Marie

AU - Jeppesen, Pia

AU - Pagsberg, Anne K.

AU - Fink-Jensen, Anders

AU - Kapoor, Sandeep

AU - Chekuri, Raja

AU - Carbon, Maren

AU - Al-Jadiri, Aseel

AU - Kishimoto, Taishiro

AU - Kane, John M.

AU - Correll, Christoph U.

PY - 2013/12/1

Y1 - 2013/12/1

N2 - 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) (r2=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.

AB - 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) (r2=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.

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