TY - JOUR
T1 - Early Antipsychotic Non-response as a Predictor of Non-response and Non-remission in Adolescents With Psychosis Treated With Aripiprazole or Quetiapine
T2 - Results From the TEA Trial
AU - Pagsberg, Anne Katrine
AU - Krogmann, Amanda
AU - Jeppesen, Pia
AU - von Hardenberg, Laura
AU - Klauber, Dea G
AU - Jensen, Karsten Gjessing
AU - Rudå, Ditte
AU - Decara, Marie Stentebjerg
AU - Jepsen, Jens Richardt Møllegaard
AU - Fagerlund, Birgitte
AU - Fink-Jensen, Anders
AU - Correll, Christoph U
AU - Galling, Britta
N1 - Copyright © 2022. Published by Elsevier Inc.
PY - 2022/8/1
Y1 - 2022/8/1
N2 - OBJECTIVE: To evaluate 1) whether early nonresponse to antipsychotics predicts nonresponse and nonremission, 2) patient and illness characteristics as outcome predictors, and 3) response prediction of 30-item Positive and Negative Syndrome Scale (PANSS-30) compared with 6-item PANSS (PANSS-6) and Clinical Global Impressions-Improvement Scale (CGI-I) in youths with first-episode psychosis.METHOD: Post hoc analysis from a 12-week, double-blinded, randomized trial of aripiprazole vs extended-release quetiapine in adolescents (age 12-17 years) with first-episode psychosis was performed. Early nonresponse (week 2 or week 4) was defined as <20% symptom reduction (PANSS-30) (or <20% symptom reduction [PANSS-6] or CGI-I score 4-7 [less than "minimally improved"]). Nonresponse (week 12) was defined as <50% symptom reduction (PANSS-30). Nonremission (week 12) was defined as a score of >3 on 8 selected PANSS-items. Positive/negative predictive values (PPV/NPV) and receiver operating characteristics, binary logistic regression models, and PPV/NPV using PANSS-6 and CGI-I were analyzed.RESULTS: Of 113 randomized patients, 84 were included in post hoc analysis (mean [SD] age = 15.7 [1.3] years; 28.6% male). The 12-week symptom decrease was 31.9% [27.9%], most pronounced within the first 2 weeks (61.1% of total PANSS reduction). Response (27.4%) and remission (22.6%) rates were low. Results indicated that early nonresponse reliably predicted 12-week nonresponse (PPV: week 2, 82.2%; week 4, 90.0%) and nonremission (PPV: week 2, 80.0%; week 4, 90.0%); early nonresponse at week 4 was a statistically significant baseline predictor for 12-week nonresponse; and PANSS-6 had similar predictive significance as PANSS-30. However, outcomes were heterogeneous using CGI-I.CONCLUSION: In youths with first-episode psychosis showing early nonresponse to aripiprazole or extended-release quetiapine, switching antipsychotic drug should be considered. PANSS-6 is a feasible and clinically relevant alternative to PANSS-30 to predict 12-week nonresponse/nonremission.CLINICAL TRIAL REGISTRATION INFORMATION: Tolerance and Effect of Antipsychotics in Children and Adolescents With Psychosis; https://www.CLINICALTRIALS: gov/; NCT01119014.
AB - OBJECTIVE: To evaluate 1) whether early nonresponse to antipsychotics predicts nonresponse and nonremission, 2) patient and illness characteristics as outcome predictors, and 3) response prediction of 30-item Positive and Negative Syndrome Scale (PANSS-30) compared with 6-item PANSS (PANSS-6) and Clinical Global Impressions-Improvement Scale (CGI-I) in youths with first-episode psychosis.METHOD: Post hoc analysis from a 12-week, double-blinded, randomized trial of aripiprazole vs extended-release quetiapine in adolescents (age 12-17 years) with first-episode psychosis was performed. Early nonresponse (week 2 or week 4) was defined as <20% symptom reduction (PANSS-30) (or <20% symptom reduction [PANSS-6] or CGI-I score 4-7 [less than "minimally improved"]). Nonresponse (week 12) was defined as <50% symptom reduction (PANSS-30). Nonremission (week 12) was defined as a score of >3 on 8 selected PANSS-items. Positive/negative predictive values (PPV/NPV) and receiver operating characteristics, binary logistic regression models, and PPV/NPV using PANSS-6 and CGI-I were analyzed.RESULTS: Of 113 randomized patients, 84 were included in post hoc analysis (mean [SD] age = 15.7 [1.3] years; 28.6% male). The 12-week symptom decrease was 31.9% [27.9%], most pronounced within the first 2 weeks (61.1% of total PANSS reduction). Response (27.4%) and remission (22.6%) rates were low. Results indicated that early nonresponse reliably predicted 12-week nonresponse (PPV: week 2, 82.2%; week 4, 90.0%) and nonremission (PPV: week 2, 80.0%; week 4, 90.0%); early nonresponse at week 4 was a statistically significant baseline predictor for 12-week nonresponse; and PANSS-6 had similar predictive significance as PANSS-30. However, outcomes were heterogeneous using CGI-I.CONCLUSION: In youths with first-episode psychosis showing early nonresponse to aripiprazole or extended-release quetiapine, switching antipsychotic drug should be considered. PANSS-6 is a feasible and clinically relevant alternative to PANSS-30 to predict 12-week nonresponse/nonremission.CLINICAL TRIAL REGISTRATION INFORMATION: Tolerance and Effect of Antipsychotics in Children and Adolescents With Psychosis; https://www.CLINICALTRIALS: gov/; NCT01119014.
KW - adolescents
KW - early response
KW - PANSS-6
KW - psychopharmacology
KW - psychosis
KW - Predictive Value of Tests
KW - Double-Blind Method
KW - Antipsychotic Agents/pharmacology
KW - Humans
KW - Male
KW - Treatment Outcome
KW - Aripiprazole/pharmacology
KW - Adolescent
KW - Psychotic Disorders/drug therapy
KW - Female
KW - Quetiapine Fumarate/therapeutic use
KW - Child
UR - http://www.scopus.com/inward/record.url?scp=85126013868&partnerID=8YFLogxK
U2 - 10.1016/j.jaac.2021.11.032
DO - 10.1016/j.jaac.2021.11.032
M3 - Journal article
C2 - 35026408
VL - 61
SP - 997
EP - 1009
JO - Journal of the American Academy of Child and Adolescent Psychiatry
JF - Journal of the American Academy of Child and Adolescent Psychiatry
SN - 0890-8567
IS - 8
ER -