Myrto T Samara1, Claudia Leucht1, Mariska M Leeflang1, Ion-George Anghelescu1, Young-Chul Chung1, Benedicto Crespo-Facorro1, Helio Elkis1, Kotaro Hatta1, Ina Giegling1, John M Kane1, Monica Kayo1, Martin Lambert1, Ching-Hua Lin1, Hans-Jürgen Möller1, José María Pelayo-Terán1, Michael Riedel1, Dan Rujescu1, Benno G Schimmelmann1, Alessandro Serretti1, Christoph U Correll1, Stefan Leucht1. 1. From the Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, the Netherlands; Dr. Kurt Fontheim's Hospital for Mental Health, Liebenburg, Germany; Chonbuk National University Medical School, Jeonju, Korea; the Department of Psychiatry, Marqués de Valdecilla University Hospital-IDIVAL, School of Medicine, University of Cantabria, Santander, Spain; CIBERSAM (Centro Investigación Biomédica en Red Salud Mental), Madrid; the Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; the Department of Psychiatry, Juntendo University Nerima Hospital, Tokyo; the Department of Psychiatry, Ludwig-Maximilians University, Munich; the Department of Psychiatry, University of Halle-Wittenberg, Halle, Germany; Hofstra North Shore Long Island Jewish School of Medicine, Hempstead, N.Y.; the Zucker Hillside Hospital, Glen Oaks, N.Y.; the Department of Psychiatry and Psychotherapy, Centre of Psychosocial Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung, Taiwan; the Department of Psychiatry, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; University Hospital of Child and Adolescent Psychiatry, University of Bern, Bern, Switzerland; and the Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy.
Abstract
OBJECTIVE: How long clinicians should wait before considering an antipsychotic ineffective and changing treatment in schizophrenia is an unresolved clinical question. Guidelines differ substantially in this regard. The authors conducted a diagnostic test meta-analysis using mostly individual patient data to assess whether lack of improvement at week 2 predicts later nonresponse. METHOD: The search included EMBASE, MEDLINE, BIOSIS, PsycINFO, Cochrane Library, CINAHL, and reference lists of relevant articles, supplemented by requests to authors of all relevant studies. The main outcome was prediction of nonresponse, defined as <50% reduction in total score on either the Positive and Negative Syndrome Scale (PANSS) or Brief Psychiatric Rating Scale (BPRS) (corresponding to at least much improved) from baseline to endpoint (4-12 weeks), by <20% PANSS or BPRS improvement (corresponding to less than minimally improved) at week 2. Secondary outcomes were absent cross-sectional symptomatic remission and <20% PANSS or BPRS reduction at endpoint. Potential moderator variables were examined by meta-regression. RESULTS: In 34 studies (N=9,460) a <20% PANSS or BPRS reduction at week 2 predicted nonresponse at endpoint with a specificity of 86% and a positive predictive value (PPV) of 90%. Using data for observed cases (specificity=86%, PPV=85%) or lack of remission (specificity=77%, PPV=88%) yielded similar results. Conversely, using the definition of <20% reduction at endpoint yielded worse results (specificity=70%, PPV=55%). The test specificity was significantly moderated by a trial duration of <6 weeks, higher baseline illness severity, and shorter illness duration. CONCLUSIONS: Patients not even minimally improved by week 2 of antipsychotic treatment are unlikely to respond later and may benefit from a treatment change.
OBJECTIVE: How long clinicians should wait before considering an antipsychotic ineffective and changing treatment in schizophrenia is an unresolved clinical question. Guidelines differ substantially in this regard. The authors conducted a diagnostic test meta-analysis using mostly individual patient data to assess whether lack of improvement at week 2 predicts later nonresponse. METHOD: The search included EMBASE, MEDLINE, BIOSIS, PsycINFO, Cochrane Library, CINAHL, and reference lists of relevant articles, supplemented by requests to authors of all relevant studies. The main outcome was prediction of nonresponse, defined as <50% reduction in total score on either the Positive and Negative Syndrome Scale (PANSS) or Brief Psychiatric Rating Scale (BPRS) (corresponding to at least much improved) from baseline to endpoint (4-12 weeks), by <20% PANSS or BPRS improvement (corresponding to less than minimally improved) at week 2. Secondary outcomes were absent cross-sectional symptomatic remission and <20% PANSS or BPRS reduction at endpoint. Potential moderator variables were examined by meta-regression. RESULTS: In 34 studies (N=9,460) a <20% PANSS or BPRS reduction at week 2 predicted nonresponse at endpoint with a specificity of 86% and a positive predictive value (PPV) of 90%. Using data for observed cases (specificity=86%, PPV=85%) or lack of remission (specificity=77%, PPV=88%) yielded similar results. Conversely, using the definition of <20% reduction at endpoint yielded worse results (specificity=70%, PPV=55%). The test specificity was significantly moderated by a trial duration of <6 weeks, higher baseline illness severity, and shorter illness duration. CONCLUSIONS:Patients not even minimally improved by week 2 of antipsychotic treatment are unlikely to respond later and may benefit from a treatment change.
Authors: Marie Stentebjerg-Olesen; Stephen J Ganocy; Robert L Findling; Kiki Chang; Melissa P DelBello; John M Kane; Mauricio Tohen; Pia Jeppesen; Christoph U Correll Journal: Eur Child Adolesc Psychiatry Date: 2015-06-02 Impact factor: 4.785