All meta-analyses – JNK inhibitor in vitro analyzing similar data sets – found that amisulpride, clozapine, olanzapine, and risperidone were significantly more efficacious than FGAs. When Leucht and colleagues14 reviewed the head-tohead comparisons of SGAs they reported a similar pattern. Regarding total PANSS score change, olanzapine was

more efficacious than aripiprazole, quetiapine, risperidone, and ziprasidone; risperidone Inhibitors,research,lifescience,medical was more efficacious than quetiapine and ziprasidone, and amisulpride was not statistically different from olanzapine or risperidone. However, regarding dropouts due to inefficacy, olanzapine was only superior to quetiapine and ziprasidone, two Inhibitors,research,lifescience,medical SGAs often dosed inappropriately low in schizophrenia, and amisulpride was more efficacious than ziprasidone. Surprisingly, clozapine only proved to be superior to zotepine and to

risperidone in dropouts due to inefficacy. As the authors suggest, possibly inadequate doses of clozapine used in some studies might have contributed to these findings, which are inconsistent with most of the large individual studies. In comparing Inhibitors,research,lifescience,medical these analyses to the results of CATIE and CUtLASS, there are some consistencies. In CATIE,17 olanzapine was superior in dropout rates due to inefficacy and time on effective treatment (at least when including the 23% of patients who were rerandomized to olanzapine), and clozapine (though given openly) was superior to all other studied SGAs in phase 2.28 In CUtLASS,24

clozapine was superior to other SGAs as well, but in this study, quality of life, and not all-cause discontinuation, was the primary Inhibitors,research,lifescience,medical outcome measure. This difference highlights the importance of the choice of the primary outcome measure, particularly in effectiveness studies, where the outcome is supposed to address elements of efficacy, tolerability, patient acceptability, and functioning. Although the meta-analyses Inhibitors,research,lifescience,medical tended to find more support for risperidone’s superiority than CATIE did, the dose equivalences used in CATIE have been challenged where the modal dose of risperidone was only 3.9 mg/day. However, there were no differences between the individually studied SGAs and the FGA comparator perphenazine in CATIE,17 Tryptophan synthase as well as between the class of clinician’s choice SGAs and FGAs (mainly consisting of sulpiride, which some consider to be an SGA) in CUtLASS.23 The large effectiveness trials have been discussed in great detail elsewhere. Despite the rigorousness with which we try to design trials, there are always compromises in both design and execution that are unavoidable, particularly when multiple outcome measures are included and multiple questions are addressed simultaneously. A particularly important issue which impacts all of the effectiveness trials was stressed by Kraemer et al.