CoChat
Sign Up
Cited by 193Schizophrenia research and treatmentStatistical Methods in Clinical TrialsMeta-analysis and systematic reviews

Is the superior efficacy of new generation antipsychotics an artifact of LOCF?

Open access
Leucht, S., Engel, R. R., Bauml, J., Davis, J. M.·2006·Schizophrenia Bulletin
DOI 10.1093/schbul/sbl025PMC PMC2632292
Open this paper in CoChat — free account

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1093/schbul/sbl025

Cites

29 of 29 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

1 of the 30 references couldn’t be matched to a known paper.

Research works printed but not linked: 7

  1. [17]Pichot P, Boyer P. Etude multicentrique controlée en double insu: amisulpride (Solian 200) versus halopéridol à forte dose dans les états psychotiques aigus. Ann Psychiatr. 1988;3(3):326–332. [Google Scholar]
  2. [18]Pichot P, Boyer P. Amisulpride. Paris, France: Expansion scientifique francaise; 1989. Controlled double-blind multi-centre trial of low dose amisulpride versus fluphenazine in the treatment of the negative syndrome of chronic schizophrenia; pp. 125–137. [Google Scholar]
  3. [19]Costa e Silva JA . Amisulpride. Paris, France: Expansion scientifique francaise; 1989. Comparative double-blind study of amisulpride versus haloperidol in the treatment of acute psychotic states; pp. 93–104. [Google Scholar]
  4. [21]Ziegler B. Amisulpride. Paris, France: Expansion scientifique francaise; 1989. Study of the efficacy of a substituted benzamide amisulpride, versus haloperidol, in productive schizophrenia; pp. 73–81. [Google Scholar]
  5. [22]American Psychiatric Association. Diagnostic and Statistical Manual for Mental Disorders. third revision, revised (DSM-III-R) Washington, DC: American Psychiatric Association; 1987. [Google Scholar]
  6. [23]American Psychiatric Association. Diagnostic and Statistical Manual for Mental Disorders, 4th ed. Washington, DC: American Psychiatric Association; 1994. [Google Scholar]
  7. [27]Kinon BJ, Liu-Seifert H, Adams DH. Predominance of psychiatric-based reasons for antipsychotic treatment discontinuation. Biol Psychiatry. 2005;57:105S–106S. [Google Scholar]

Cited by

Sorted by citations

Related

Authors
Leucht, S., Engel, R. R., Bauml, J., & Davis, J. M.
Affiliations
  • TUM Klinikum (DE)
  • Ludwig-Maximilians-Universität München (DE)
  • University of Illinois Chicago (US)
ORCID
Venue
Schizophrenia Bulletin
Publisher
Oxford University Press (OUP)
Published
2006-12-07
Volume
33
Issue
1
Pages
183-191
ISSN
  • 0586-7614 (ISSN-L)
  • 1745-1701
DOI
10.1093/schbul/sbl025
PMC
PMC2632292
OpenAlex
W2127313266
Cited by
193
References
30
Citations by year
2026: 1 · 2025: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 5 · 2018: 7 · 2017: 9 · 2016: 12 · 2015: 22 · 2014: 27 · 2013: 34 · 2012: 41
FWCI
3.18
Type
journal article
Language
en
Open access
Locations
  • Schizophrenia Bulletin (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
  • Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
Keywords
last observation carried forward, missing data
MeSH terms
Olanzapine, Amisulpride, Benzodiazepines, Flupenthixol, Haloperidol, Humans, Patient Dropouts, Psychiatric Status Rating Scales, Psychotropic Drugs, Schizophrenia, Schizophrenic Psychology, Sulpiride, Bias, Randomized Controlled Trials as Topic, Artifacts, Treatment Outcome

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review