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

Text appi.ajp.2015.pdf - Published Version Restricted to registered users only Available under License Publisher holds Copyright. Download (844kB) | Request a copy

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.

Interest & Impact

Downloads

1 since deposited on 07 Jul 2015
0 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item