Early Improvement As a Predictor of Later Response to Antipsychotics in Schizophrenia: A Diagnostic Test Review

Samara, Myrto T; Leucht, Claudia; Leeflang, Mariska M; Anghelescu, Ion-George; Chung, Young-Chul; Crespo-Facorro, Benedicto; Elkis, Helio; Hatta, Kotaro; Giegling, Ina; Kane, John M; Kayo, Monica; Lambert, Martin; Lin, Ching-Hua; Möller, Hans-Jürgen; Pelayo-Terán, José María; Riedel, Michael; Rujescu, Dan; Schimmelmann, Benno Karl Edgar; Serretti, Alessandro; Correll, Christoph U; ... (2015). Early Improvement As a Predictor of Later Response to Antipsychotics in Schizophrenia: A Diagnostic Test Review. American journal of psychiatry, 172(7), pp. 617-629. American Psychiatric Association 10.1176/appi.ajp.2015.14101329

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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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > University Psychiatric Services > University Hospital of Child and Adolescent Psychiatry and Psychotherapy

UniBE Contributor:

Schimmelmann, Benno Karl Edgar


600 Technology > 610 Medicine & health




American Psychiatric Association




Nicole Jansen

Date Deposited:

07 Jul 2015 13:36

Last Modified:

11 Nov 2015 11:37

Publisher DOI:


PubMed ID:






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