TY - JOUR
T1 - Early response or nonresponse at week 2 and week 3 predict ultimate response or nonresponse in adolescents with schizophrenia treated with olanzapine
T2 - results from a 6-week randomized, placebo-controlled trial
AU - Stentebjerg-Olesen, Marie
AU - Ganocy, Stephen J.
AU - Findling, Robert L.
AU - Chang, Kiki
AU - DelBello, Melissa P.
AU - Kane, John M.
AU - Tohen, Mauricio
AU - Jeppesen, Pia
AU - Correll, Christoph U.
N1 - Funding Information:
Drs. Stentebjerg-Olesen and Jeppesen report no conflicts of interest. Dr. Ganocy has received salary support from AstraZeneca and Eli Lilly. Dr. Chang is an unpaid consultant for GlaxoSmithKline, Merck, Bristol-Myers Squibb; has received research funding from GlaxoSmithKline and Merck and is on the DSMB for Sunovion. Dr. DelBello reports the following: Research Support from Eli Lilly Otsuka GlaxoSmithKline Merck Martek Novartis Lundbeck Shire Purdue Amylin Sunovion Pfizer, lecture bureau membership for Otsuka, Bristol-Myers Squibb, and consulting/Advisory Board/Honoraria/Travel with Pfizer, Dey, Lundbeck, Sunovian, Otsuka, Supernus, Dr. Findling receives or has received research support, acted as a consultant and/or served on a speaker’s bureau for Alexza Pharmaceuticals, American Academy of Child & Adolescent Psychiatry, American Physician Institute, American Psychiatric Press, AstraZeneca, Bracket, Bristol-Myers Squibb, Clinsys, CogCubed, Cognition Group, Coronado Biosciences, Dana Foundation, Forest, GlaxoSmithKline, Guilford Press, Johns Hopkins University Press, Johnson & Johnson, KemPharm, Lilly, Lundbeck, Merck, NIH, Novartis, Noven, Otsuka, Oxford University Press, Pfizer, Physicians Postgraduate Press, Rhodes Pharmaceuticals, Roche, Sage, Seaside Pharmaceuticals, Shire, Stanley Medical Research Institute, Sunovion, Supernus Pharmaceuticals, Transcept Pharmaceuticals, Validus, and WebMD. Dr. Kane has been a consultant and/or received honoraria from Amgen, Alkermes, Bristol-Myers Squibb, Eli Lilly, Forrest Labs, Genentech, IntraCellular Therapies. Janssen, Johnson and Johnson, Lundbeck, MedAvante, Novartis, Otsuka, Roche, Reviva, Sunovion,. He is a shareholder of MedAvante. Dr. Tohen was an Eli Lilly full time employee when the study was conducted (until 2008) and has received honoraria or consulted for AstraZeneca, Bristol-Myers Squibb, Glaxo-SmithKline, Forest, Eli Lilly, Johnson & Johnson, Merck, Otsuka, Sepracor, Sunovion, Lundbeck and Wyeth Corporations; his spouse was a fully time employee at Eli Lilly (until 2013). Dr. Correll has been a consultant and/or advisor to or has received honoraria from: AbbVie, Actavis, Alkermes, Bristol-Myers Squibb, Eli Lilly, Genentech, Gerson Lehrman Group, IntraCellular Therapies, Janssen/J&J, Lundbeck, MedAvante, Medscape, Otsuka, Pfizer, ProPhase, Roche, Sunovion, Supernus, and Takeda. He has received grant support from the American Academy of Child and Adolescent Psychiatry BMS, Janssen/J&J, National Institute of Mental Health (NIMH), Novo Nordisk A/S, Otsuka, Takeda and the Thrasher Foundation.
Publisher Copyright:
© 2015, Springer-Verlag Berlin Heidelberg.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - In adults with schizophrenia, early response/non-response (ER/ENR) to antipsychotics at 2 weeks robustly predicts ultimate response/non-response (UR/UNR). However, less data about the predictive value of ER/ENR exist in adolescents with schizophrenia. Post hoc analysis of a 6-week trial in adolescents aged 13–17 with schizophrenia were randomized 2:1 to olanzapine or placebo. ER was defined as ≥20 % reduction in Brief Psychiatric Rating Scale-children (BPRS-C) total score at week 2 (ER2) or 3 (ER3); UR was defined with increasing stringency as total BPRS-C score reduction ≥20, ≥30, ≥40 or ≥50 %; remission was defined cross-sectionally using Andreasen et al. (2005) criteria. By week 2 (n = 69) and 3 (n = 66), olanzapine-treated youth achieved 73.3 and 85.5 % of their overall BPRS-C score reduction at 6 weeks last observation carried forward. ER and ENR patients did not differ significantly regarding baseline demographic, illness and treatment variables. ER 2 (frequency = 68.1 %) and ER 3 (frequency = 65.2 %) significantly predicted UR and remission (p = 0.0044–p < 0.0001), with ER3 having more predictive power. A ≥ 20 % BPRS-C reduction threshold for ER had best predictive validity (area under the curve = 0.88–0.92). At 6 weeks, patients with ER had significantly greater improvements in BPRS-C, Clinical Global Impressions Improvement and Severity scores, greater cross-sectional remission and less all-cause discontinuation (p = 0.047–p < 0.0001). Adverse event profiles were similar in the ER and ENR groups. Adolescents with schizophrenia experienced the majority of symptomatic improvement early during olanzapine treatment. ER predicted UR and remission, with ER3 having best predictive power. A ≥ 20 % improvement threshold for defining ER was confirmed as a robust outcome indicator.
AB - In adults with schizophrenia, early response/non-response (ER/ENR) to antipsychotics at 2 weeks robustly predicts ultimate response/non-response (UR/UNR). However, less data about the predictive value of ER/ENR exist in adolescents with schizophrenia. Post hoc analysis of a 6-week trial in adolescents aged 13–17 with schizophrenia were randomized 2:1 to olanzapine or placebo. ER was defined as ≥20 % reduction in Brief Psychiatric Rating Scale-children (BPRS-C) total score at week 2 (ER2) or 3 (ER3); UR was defined with increasing stringency as total BPRS-C score reduction ≥20, ≥30, ≥40 or ≥50 %; remission was defined cross-sectionally using Andreasen et al. (2005) criteria. By week 2 (n = 69) and 3 (n = 66), olanzapine-treated youth achieved 73.3 and 85.5 % of their overall BPRS-C score reduction at 6 weeks last observation carried forward. ER and ENR patients did not differ significantly regarding baseline demographic, illness and treatment variables. ER 2 (frequency = 68.1 %) and ER 3 (frequency = 65.2 %) significantly predicted UR and remission (p = 0.0044–p < 0.0001), with ER3 having more predictive power. A ≥ 20 % BPRS-C reduction threshold for ER had best predictive validity (area under the curve = 0.88–0.92). At 6 weeks, patients with ER had significantly greater improvements in BPRS-C, Clinical Global Impressions Improvement and Severity scores, greater cross-sectional remission and less all-cause discontinuation (p = 0.047–p < 0.0001). Adverse event profiles were similar in the ER and ENR groups. Adolescents with schizophrenia experienced the majority of symptomatic improvement early during olanzapine treatment. ER predicted UR and remission, with ER3 having best predictive power. A ≥ 20 % improvement threshold for defining ER was confirmed as a robust outcome indicator.
KW - Adolescents
KW - Prediction
KW - Remission
KW - Response
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=84947490176&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84947490176&partnerID=8YFLogxK
U2 - 10.1007/s00787-015-0725-1
DO - 10.1007/s00787-015-0725-1
M3 - Article
C2 - 26032132
AN - SCOPUS:84947490176
SN - 1018-8827
VL - 24
SP - 1485
EP - 1496
JO - European Child and Adolescent Psychiatry
JF - European Child and Adolescent Psychiatry
IS - 12
ER -