Early Prediction of Antipsychotic Nonresponse Among Patients With Schizophrenia

Stefan Leucht, M.D.; Raymonde Busch, Dipl. Math.; Werner Kissling, M.D.; and John M. Kane, M.D.

Objective: Schizophrenia guidelines recommend waiting several weeks before major changes in antipsychotic treatment are implemented. If, however, nonresponders could be identified shortly after treatment initiation, considerable time could be saved by rapidly switching such patients to potentially more effective alternatives. We therefore attempted to identify what degree of nonresponse shortly after initiation of antipsychotic drug treatment predicts nonresponse at 4 weeks.

Method: Individual patient data from 7 randomized, controlled antipsychotic drug trials including 1708 patients with schizophrenia or schizophreniform disorder according to DSM-III-R or DSM-IV criteria and positive symptoms (mean ± SD age of 36.0 ± 10.9 years; 1054 men and 654 women) were pooled. Receiver-operator curves and logistic regression analyses were used to predict nonresponse at week 4 from the percentage Brief Psychiatric Rating Scale (BPRS) score change at weeks 1 and 2. Three criteria for nonresponse at week 4 were examined: less than 25% BPRS score reduction, less than 50% BPRS score reduction, and "no remission."

Results: Cutoffs predicting nonresponse at 4 weeks with 90% specificity were virtually no response at week 1 (less than 3%-7% BPRS score reduction) and less than 15%, 25%, and 20% at week 2 for the 3 nonresponse criteria described above, respectively. However, to predict less than 25% BPRS score reduction with a positive predictive value of 80%, the cutoff needed was 0% BPRS score reduction at week 2. When the cutoffs identified were entered in logistic regression analyses together with other parameters, they remained the strongest predictors of nonresponse.

Conclusions: Patients with no improvement of symptoms during the first 2 weeks of treatment are unlikely to respond at week 4 and may benefit from a change of treatment.

(J Clin Psychiatry 2007;68:352-360)

Received May 29, 2006; accepted Aug, 18, 2006. From the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München (Drs. Leucht and Kissling); and Institute of Medical Statistics and Epidemiology, Technische Universität München (Ms. Busch), Munich, Germany; and The Zucker Hillside Hospital, Glen Oaks, N.Y. (Drs. Leucht and Kane).

Supported by the American Psychiatric Association/AstraZeneca Young Minds in Psychiatry Award 2004. The study received no other funding.

Presented at the 13th Biennial Schizophrenia Winter Workshop, Feb. 4-10, 2006, Davos, Switzerland.

The authors wish to thank SanofiAventis for allowing use of their original patient data.

Financial disclosure appears at the end of the article.

Corresponding author and reprints: Stefan Leucht, M.D., Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München, Ismaningerstr. 22, 81675 München, Germany (e-mail: Stefan.Leucht@lrz.tum.de).