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Annotation

Rosenheck RA. Pharmacotherapy of first-episode schizophrenia. Lancet . 2008 Mar 29 ; 371(9618):1048-9. PubMed Abstract

Comments on Paper and Primary News
Primary News: Study Questions Advantages of Newer Antipsychotics for Early Schizophrenia

Comment by:  Jan Volavka
Submitted 2 April 2008 Posted 3 April 2008
  I recommend this paper

The EUFEST study found that haloperidol, in comparison with several SGAs, was associated with a higher rate of overall treatment discontinuation, a higher rate of discontinuation because of lack of efficacy, a higher rate of discontinuation because of side effects, and worse outcome on the CGI and the GAF. Surprisingly, the authors’ last sentence reads: “It cannot be concluded that SGAs are more efficacious than is haloperidol….” Although restraint in scientific conclusions is generally admirable, I think that these authors are being too conservative in the interpretation of their important findings.

The reason for their hesitancy, it appears, is that the PANSS and the rehospitalization rates have not shown significant differences among drugs. Furthermore, they are concerned about the possibility of provider expectation biasing the results against haloperidol: if the psychiatrists expected haloperidol to do poorly, perhaps they were more likely to discontinue it than another treatment in which they believed. But the lack of difference on the PANSS total can have many...  Read more


View all comments by Jan Volavka

Primary News: Study Questions Advantages of Newer Antipsychotics for Early Schizophrenia

Comment by:  Peter F. Buckley
Submitted 11 April 2008 Posted 11 April 2008

This timely study, conducted by a stellar group of European investigators, adds to the continued debate about choice of medications for schizophrenia, informed by other similarly impressive pragmatic trials such as CATIE and CUTlass. Unlike the other recently published first-episode treatment study—the CAFE study (McEvoy et al., 2007)—which was double blind and compared SGAs only (risperidone versus olanzapine versus quetiapine), EUFEST better fits the model of a pragmatic trial and also included a FGA comparator. Although readers, particularly policy makers, will inevitably be drawn to the “Should I choose an FGA or SGA” content of this study, it seems to me that the most striking finding is (yet again) how frequently patients stop their medications. The 72 percent overall “All Cause” Discontinuation rate bears an uncanny resemblance to the 74 percent in CATIE and to the similar rate in the one-year CAFE first-episode study. Thus, medication non-adherence is a major treatment...  Read more


View all comments by Peter F. Buckley

Primary News: Study Questions Advantages of Newer Antipsychotics for Early Schizophrenia

Comment by:  Leslie Citrome
Submitted 18 April 2008 Posted 19 April 2008
  I recommend this paper

Although in EUFEST, psychopathology improved to a similar extent among the different groups, durability of the medication was quite different. This is of the utmost importance when it comes to treating patients—no one would disagree that continuation on medication is crucial in the successful treatment of patients with schizophrenia. If my goal is to pick the antipsychotic that my first-episode patient will stick with the longest, olanzapine or amisulpride appears to be what the data recommend. The alternative is to prescribe something else and then switch if necessary. Curiously, amisulpride and olanzapine (and risperidone) appeared to perform better than haloperidol in the Davis meta-analysis published when EUFEST was being launched (Davis et al., 2003).

As an exercise in looking at EUFEST through the lens of evidence-based medicine, I calculated the number needed to treat (NNT) for all-cause discontinuation (Citrome, 2008). NNT yields statistically significant pair-wise...  Read more


View all comments by Leslie Citrome

Primary News: Study Questions Advantages of Newer Antipsychotics for Early Schizophrenia

Comment by:  Herbert Meltzer (Disclosure)
Submitted 29 April 2008 Posted 29 April 2008

EUFEST, CATIE, and CUtLASS: Should Atypical Antipsychotic Drugs Remain the Most Prescribed Treatment for Schizophrenia?
The EUFEST (Kahn et al., 2008) study is the third major effectiveness-style study published in the last three years whose goal has been to compare typical and atypical antipsychotic drugs in the treatment of specified subgroups of patients with schizophrenia, the others being CATIE (Lieberman et al., 2005) and CUtLASS (Jones et al., 2006). The authors of EUFEST close their report with: “…it cannot be concluded that second-generation antipsychotic drugs are more efficacious than is haloperidol in the treatment of these (first-episode schizophrenia) patients” despite the fact that the discontinuation rate was the primary endpoint, and there was a significantly lower rate of discontinuation of the atypical drugs: 40 percent for amisulpride, 33 percent for olanzapine, 53 percent for quetiapine, and 45 percent for...  Read more


View all comments by Herbert Meltzer

Primary News: Study Questions Advantages of Newer Antipsychotics for Early Schizophrenia

Comment by:  Erik JohnsenHugo A. Jorgensen
Submitted 12 May 2008 Posted 14 May 2008

In our recently published systematic review of randomized effectiveness trials on SGAs (Johnsen and Jorgensen, 2008), the main findings were that chronically ill patients treated with olanzapine had longer time until treatment discontinuation and/or better drug compliance compared to those treated with the other SGAs, as well as the FGAs in those studies that had an FGA arm. The SGAs and FGAs did not differ on efficacy measures, and there were surprisingly few differences among SGAs on tolerability outcomes. The most consistent tolerability difference among the SGAs was in the area of metabolic adverse effects, where olanzapine-treated patients had more weight gain and adverse influence on cholesterol and triglyceride levels. The most pronounced difference between FGAs and SGAs on tolerability outcomes was that the FGAs were associated with significantly more extrapyramidal side effects (EPS) or discontinuation owing to EPS in the majority of studies. We noticed that this finding was also replicated in the EUFEST.

In summary,...  Read more


View all comments by Erik Johnsen
View all comments by Hugo A. Jorgensen
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