Baseline characteristics and early response at week 1 predict treatment outcome in adolescents with bipolar manic or mixed episode treated with olanzapine: Results from a 3-week, randomized, placebo-controlled trial

Le Xiao, Stephen J. Ganocy, Robert L Findling, Kiki Chang, Melissa P. DelBello, John M. Kane, Mauricio Tohen, Yu Tao Xiang, Christoph U. Correll

Research output: Contribution to journalReview article

Abstract

Background: Early predictors of response and remission in pediatric mania are lacking, requiring further study. Methods: This was a post hoc analysis of a 3-week, randomized, placebo-controlled trial of olanzapine conducted between November 2002 and May 2005 in 161 adolescents aged 13–17 years who were diagnosed with a DSM-IV acute manic or mixed episode of bipolar I disorder. Data from the olanzapine arm were analyzed to investigate the predictive power of early response or early nonresponse (≥25% or < 25% reduction in Young Mania Rating Scale [YMRS] score, respectively) at week 1 for ultimate response or nonresponse (≥ 50% or < 50% reduction in YMRS score, respectively) and for remission (YMRS total score ≤ 12 [standard definition] or ≤ 8 [stringent definition]) at week 3. Correlates of early response and ultimate response were examined in multivariable regression models. Results: By week 1, 69.2% of olanzapine-treated adolescents (n = 104, 2.5–20.0 mg/d) achieved early response, and 49.0% reached ultimate response at week 3. Patients with early response and early nonresponse were similar regarding baseline variables except higher scores for sleep and thought content were found with early response (P< .05) and higher olanzapine doses with early nonresponse (P< .01). At week 3, early response was associated with significantly greater improvements in YMRS, Clinical Global Impressions–Severity of Illness scale (both P< .001), and Overt Aggression Scale scores (P= .024). Adverse events were similar in patients with early response and early nonresponse, except for higher AIMS scores for patients with early nonresponse (P= .036). Early response significantly predicted ultimate response (OR = 5.61, P< .001; sensitivity = 86.3, specificity = 47.2, positive predictive value = 61.1, negative predictive value = 78.1). Significantly more early response than early nonresponse patients achieved ultimate response (61.1% vs 21.9%, P< .001) and remission defined by YMRS score ≤ 12 (45.8% vs 12.5%, P< .001) and YMRS score ≤ 8 (33.3% vs 3.1%, P< .001). In multivariable analyses, among other variables, early response remained an independent correlate of ultimate response and remission. Conclusions: In acute pediatric manic or mixed episodes, early response to olanzapine at week 1 was strongly associated with ultimate response and remission at week 3, while absence of early response predicted the unlikely success of further treatment.

Original languageEnglish (US)
Pages (from-to)e1158-e116
JournalJournal of Clinical Psychiatry
Volume78
Issue number9
DOIs
StatePublished - Nov 1 2017

Fingerprint

olanzapine
Bipolar Disorder
Randomized Controlled Trials
Placebos
Pediatrics
Aggression
Diagnostic and Statistical Manual of Mental Disorders

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Baseline characteristics and early response at week 1 predict treatment outcome in adolescents with bipolar manic or mixed episode treated with olanzapine : Results from a 3-week, randomized, placebo-controlled trial. / Xiao, Le; Ganocy, Stephen J.; Findling, Robert L; Chang, Kiki; DelBello, Melissa P.; Kane, John M.; Tohen, Mauricio; Xiang, Yu Tao; Correll, Christoph U.

In: Journal of Clinical Psychiatry, Vol. 78, No. 9, 01.11.2017, p. e1158-e116.

Research output: Contribution to journalReview article

Xiao, Le ; Ganocy, Stephen J. ; Findling, Robert L ; Chang, Kiki ; DelBello, Melissa P. ; Kane, John M. ; Tohen, Mauricio ; Xiang, Yu Tao ; Correll, Christoph U. / Baseline characteristics and early response at week 1 predict treatment outcome in adolescents with bipolar manic or mixed episode treated with olanzapine : Results from a 3-week, randomized, placebo-controlled trial. In: Journal of Clinical Psychiatry. 2017 ; Vol. 78, No. 9. pp. e1158-e116.
@article{9103ab591c6f43f09dea5303a9a9ae6f,
title = "Baseline characteristics and early response at week 1 predict treatment outcome in adolescents with bipolar manic or mixed episode treated with olanzapine: Results from a 3-week, randomized, placebo-controlled trial",
abstract = "Background: Early predictors of response and remission in pediatric mania are lacking, requiring further study. Methods: This was a post hoc analysis of a 3-week, randomized, placebo-controlled trial of olanzapine conducted between November 2002 and May 2005 in 161 adolescents aged 13–17 years who were diagnosed with a DSM-IV acute manic or mixed episode of bipolar I disorder. Data from the olanzapine arm were analyzed to investigate the predictive power of early response or early nonresponse (≥25{\%} or < 25{\%} reduction in Young Mania Rating Scale [YMRS] score, respectively) at week 1 for ultimate response or nonresponse (≥ 50{\%} or < 50{\%} reduction in YMRS score, respectively) and for remission (YMRS total score ≤ 12 [standard definition] or ≤ 8 [stringent definition]) at week 3. Correlates of early response and ultimate response were examined in multivariable regression models. Results: By week 1, 69.2{\%} of olanzapine-treated adolescents (n = 104, 2.5–20.0 mg/d) achieved early response, and 49.0{\%} reached ultimate response at week 3. Patients with early response and early nonresponse were similar regarding baseline variables except higher scores for sleep and thought content were found with early response (P< .05) and higher olanzapine doses with early nonresponse (P< .01). At week 3, early response was associated with significantly greater improvements in YMRS, Clinical Global Impressions–Severity of Illness scale (both P< .001), and Overt Aggression Scale scores (P= .024). Adverse events were similar in patients with early response and early nonresponse, except for higher AIMS scores for patients with early nonresponse (P= .036). Early response significantly predicted ultimate response (OR = 5.61, P< .001; sensitivity = 86.3, specificity = 47.2, positive predictive value = 61.1, negative predictive value = 78.1). Significantly more early response than early nonresponse patients achieved ultimate response (61.1{\%} vs 21.9{\%}, P< .001) and remission defined by YMRS score ≤ 12 (45.8{\%} vs 12.5{\%}, P< .001) and YMRS score ≤ 8 (33.3{\%} vs 3.1{\%}, P< .001). In multivariable analyses, among other variables, early response remained an independent correlate of ultimate response and remission. Conclusions: In acute pediatric manic or mixed episodes, early response to olanzapine at week 1 was strongly associated with ultimate response and remission at week 3, while absence of early response predicted the unlikely success of further treatment.",
author = "Le Xiao and Ganocy, {Stephen J.} and Findling, {Robert L} and Kiki Chang and DelBello, {Melissa P.} and Kane, {John M.} and Mauricio Tohen and Xiang, {Yu Tao} and Correll, {Christoph U.}",
year = "2017",
month = "11",
day = "1",
doi = "10.4088/JCP.16m10923",
language = "English (US)",
volume = "78",
pages = "e1158--e116",
journal = "Journal of Clinical Psychiatry",
issn = "0160-6689",
publisher = "Physicians Postgraduate Press Inc.",
number = "9",

}

TY - JOUR

T1 - Baseline characteristics and early response at week 1 predict treatment outcome in adolescents with bipolar manic or mixed episode treated with olanzapine

T2 - Results from a 3-week, randomized, placebo-controlled trial

AU - Xiao, Le

AU - Ganocy, Stephen J.

AU - Findling, Robert L

AU - Chang, Kiki

AU - DelBello, Melissa P.

AU - Kane, John M.

AU - Tohen, Mauricio

AU - Xiang, Yu Tao

AU - Correll, Christoph U.

PY - 2017/11/1

Y1 - 2017/11/1

N2 - Background: Early predictors of response and remission in pediatric mania are lacking, requiring further study. Methods: This was a post hoc analysis of a 3-week, randomized, placebo-controlled trial of olanzapine conducted between November 2002 and May 2005 in 161 adolescents aged 13–17 years who were diagnosed with a DSM-IV acute manic or mixed episode of bipolar I disorder. Data from the olanzapine arm were analyzed to investigate the predictive power of early response or early nonresponse (≥25% or < 25% reduction in Young Mania Rating Scale [YMRS] score, respectively) at week 1 for ultimate response or nonresponse (≥ 50% or < 50% reduction in YMRS score, respectively) and for remission (YMRS total score ≤ 12 [standard definition] or ≤ 8 [stringent definition]) at week 3. Correlates of early response and ultimate response were examined in multivariable regression models. Results: By week 1, 69.2% of olanzapine-treated adolescents (n = 104, 2.5–20.0 mg/d) achieved early response, and 49.0% reached ultimate response at week 3. Patients with early response and early nonresponse were similar regarding baseline variables except higher scores for sleep and thought content were found with early response (P< .05) and higher olanzapine doses with early nonresponse (P< .01). At week 3, early response was associated with significantly greater improvements in YMRS, Clinical Global Impressions–Severity of Illness scale (both P< .001), and Overt Aggression Scale scores (P= .024). Adverse events were similar in patients with early response and early nonresponse, except for higher AIMS scores for patients with early nonresponse (P= .036). Early response significantly predicted ultimate response (OR = 5.61, P< .001; sensitivity = 86.3, specificity = 47.2, positive predictive value = 61.1, negative predictive value = 78.1). Significantly more early response than early nonresponse patients achieved ultimate response (61.1% vs 21.9%, P< .001) and remission defined by YMRS score ≤ 12 (45.8% vs 12.5%, P< .001) and YMRS score ≤ 8 (33.3% vs 3.1%, P< .001). In multivariable analyses, among other variables, early response remained an independent correlate of ultimate response and remission. Conclusions: In acute pediatric manic or mixed episodes, early response to olanzapine at week 1 was strongly associated with ultimate response and remission at week 3, while absence of early response predicted the unlikely success of further treatment.

AB - Background: Early predictors of response and remission in pediatric mania are lacking, requiring further study. Methods: This was a post hoc analysis of a 3-week, randomized, placebo-controlled trial of olanzapine conducted between November 2002 and May 2005 in 161 adolescents aged 13–17 years who were diagnosed with a DSM-IV acute manic or mixed episode of bipolar I disorder. Data from the olanzapine arm were analyzed to investigate the predictive power of early response or early nonresponse (≥25% or < 25% reduction in Young Mania Rating Scale [YMRS] score, respectively) at week 1 for ultimate response or nonresponse (≥ 50% or < 50% reduction in YMRS score, respectively) and for remission (YMRS total score ≤ 12 [standard definition] or ≤ 8 [stringent definition]) at week 3. Correlates of early response and ultimate response were examined in multivariable regression models. Results: By week 1, 69.2% of olanzapine-treated adolescents (n = 104, 2.5–20.0 mg/d) achieved early response, and 49.0% reached ultimate response at week 3. Patients with early response and early nonresponse were similar regarding baseline variables except higher scores for sleep and thought content were found with early response (P< .05) and higher olanzapine doses with early nonresponse (P< .01). At week 3, early response was associated with significantly greater improvements in YMRS, Clinical Global Impressions–Severity of Illness scale (both P< .001), and Overt Aggression Scale scores (P= .024). Adverse events were similar in patients with early response and early nonresponse, except for higher AIMS scores for patients with early nonresponse (P= .036). Early response significantly predicted ultimate response (OR = 5.61, P< .001; sensitivity = 86.3, specificity = 47.2, positive predictive value = 61.1, negative predictive value = 78.1). Significantly more early response than early nonresponse patients achieved ultimate response (61.1% vs 21.9%, P< .001) and remission defined by YMRS score ≤ 12 (45.8% vs 12.5%, P< .001) and YMRS score ≤ 8 (33.3% vs 3.1%, P< .001). In multivariable analyses, among other variables, early response remained an independent correlate of ultimate response and remission. Conclusions: In acute pediatric manic or mixed episodes, early response to olanzapine at week 1 was strongly associated with ultimate response and remission at week 3, while absence of early response predicted the unlikely success of further treatment.

UR - http://www.scopus.com/inward/record.url?scp=85040027287&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85040027287&partnerID=8YFLogxK

U2 - 10.4088/JCP.16m10923

DO - 10.4088/JCP.16m10923

M3 - Review article

C2 - 28922591

AN - SCOPUS:85040027287

VL - 78

SP - e1158-e116

JO - Journal of Clinical Psychiatry

JF - Journal of Clinical Psychiatry

SN - 0160-6689

IS - 9

ER -