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The usefulness and use of second-generation - page 12 / 81





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Critical Review and summary of information about the effects and safety of second-generation antipsychotic medications

Clinical Data1

For this Update to the WPA Technical Review of Evidence and Recommendations on the Use and Usefulness of Second-Generation Antipsychotic Medications, the scientific literature from January 2000 to  March 2002 was searched for clinical studies of antipsychotic drug treatment. As mentioned earlier, suggestions concerning papers to reviewed, in both 2001/2002 and previous years, were also received from the institutions and experts consulted individually and through the mechanisms of national review meetings.  Reports that were found to be relevant to the scope of this review and of sufficient methodological rigour were selected for inclusion in this Update.


As a follow-up to a pivotal clozapine and chlorpromazine comparison (‘Study 30'), Kane; et al. [2,3] compared clozapine and haloperidol treatment used for 29 weeks in 71 community-based partially responsive but residually symptomatic patients with schizophrenia. Those treated with clozapine had a significantly lower dropout rate than those given haloperidol (35% versus 67%), and a higher rate of response (57% versus 25%). Clozapine-treated patients had more side-effects including salivation, dizziness, sweating and decreased appetite.

In a series of articles, Volavka et al. [4]2 reported the results of a 14-week randomised double-blind trial comparing clozapine, olanzapine, risperidone and haloperidol in 157 partially responsive but residually symptomatic patients with schizophrenia. They found that the three SGAMs produced statistically significant reductions in symptoms from baseline, while haloperidol did not, but only clozapine and olanzapine were significantly better than haloperidol. However, the doses of olanzapine and risperidone were higher than usual (olanzapine mean, 30.4 mg/day; risperidmean, 11.4 mg/day). Although the greater efficacy of the SGAMs was statistically significant, it was clinically modest. EPSs were more common in patients treated with haloperidol and risperidone, and weight gain was greater with clozapine and olanzapine treatment.  Using data from the same study, Citrome et al. [5] examined the treatment effects on aggressive behavior. They found that clozapine was significantly more effective in reducing hostility and aggression than haloperidol, while olanzapine and risperidone were not.

In a novel study to evaluate the effects of treatment on suicidal behavior, Meltzer [6] randomized 980 patients with schizophrenia or schizoaffective disorder at

1 The references to studies used in the review of evidence are listed in Table 1 on pages 22-28.

2 This paragraph is reprinted on pages 14 (for olanzapine) and 17 (for risperidone) since the Volavka et al. study compared these three drugs and the chapters dealing with these drugs may be cited separately.

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