Schizophrenia Bulletin Advance Access originally published online on August 11, 2006
Schizophrenia Bulletin 2007 33(1):183-191; doi:10.1093/schbul/sbl025
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Is the Superior Efficacy of New Generation Antipsychotics an Artifact of LOCF?
2 Klinik für Psychiatrie und Psychotherapie der TU-München, Klinikum rechts der Isar, Ismaningerstr. 22, 81675 München, Germany
3 Psychiatrische Klinik der Ludwig-Maximilians-Universität München
4 Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago and Maryland Psychiatric Research Center, University of Maryland School of Medicine
1 To whom correspondence should be addressed; tel: +49-89-4140-4249, fax: +49-89-4140-4888, e-mail: stefan.leucht{at}lrz.tum.de.
It has been argued that the efficacy superiority found in meta-analyses for some of the atypical antipsychotics is an artifact of higher dropout rates due to side effects in the haloperidol group combined with last-observation-carried-forward (LOCF) analyses. We therefore reanalyzed a number of pivotal studies comparing new generation antipsychotics (NGAs) and conventional antipsychotics (CAs). A total of 5 studies (n = 1271) comparing amisulpride and 3 studies (n = 2454) comparing olanzapine with CAs were reanalyzed using original patient data. We applied 4 different models: LOCF, completer analysis, LOCF but excluding dropouts due to adverse events, and LOCF but excluding all dropouts with the exception of dropouts related to efficacy. Effect sizes expressed as standardized mean differences between NGAs and CAs based on the 4 different analysis models were compared. The overall results were not different irrespective of the model used. Single studies, however, showed higher effect sizes when LOCF instead of other models was used. Overall, it does not seem that higher dropout rates due to side effects in the haloperidol groups together with LOCF analyses consistently biased the results in favor of amisulpride and olanzapine. Because the results of the single studies, however, showed that this may occasionally be the case, future studies should look at the data from different angles applying sensitivity analyses, and they may use alternative statistics such as mixed models, which need to be developed further. Ultimately, strategies to reduce dropout rates are needed.
Keywords: schizophrenia / olanzapine / amisulpride / bias / atypical antipsychotics
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Rabinowitz and O. Davidov The Association of Dropout and Outcome in Trials of Antipsychotic Medication and Its Implications for Dealing With Missing Data Schizophr Bull, March 1, 2008; 34(2): 286 - 291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Adams, E. S. F. Coutinho, J. Davis, L. Duggan, S. Leucht, C. Li, and P. Tharyan Cochrane Schizophrenia Group Schizophr Bull, March 1, 2008; 34(2): 259 - 265. [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Owens How CATIE brought us back to Kansas: a critical re-evaluation of the concept of atypical antipsychotics and their place in the treatment of schizophrenia Advan. Psychiatr. Treat., January 1, 2008; 14(1): 17 - 28. [Abstract] [Full Text] [PDF]
|
|