Double-Blind Comparison of Olanzapine Versus Risperidone in the Treatment of Schizophrenia and Other Psychotic Disorders

Abstract

Olanzapine and risperidone, both second-generation antipsychotic agents, represent two different pharmacologic strategies. Although they share some in vitro properties, they differ by virtue of their chemical structure, spectrum of receptor binding affinities, animal neuropharmacology, pharmacokinetics, and in vivo neuroimaging profile. Based on such differences, it was hypothesized that the two compounds would show distinct safety and/or efficacy characteristics. To test this hypothesis, an international, multicenter, double-blind, parallel-group, 28-week prospective study was conducted with 339 patients who met DSM-IV criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. Results of the study indicated that both olanzapine and risperidone were safe and effective in the management of psychotic symptoms. However, olanzapine demonstrated significantly greater efficacy in negative symptoms (Scale for Assessment of Negative Symptoms summary score), as well as overall response rate (> or = 40% decrease in the Positive and Negative Syndrome Scale total score). Furthermore, a statistically significantly greater proportion of the olanzapine-treated than risperidone-treated patients maintained their response at 28 weeks based on Kaplan-Meier survival curves. The incidence of extrapyramidal side effects, hyperprolactinemia, and sexual dysfunction was statistically significantly lower in olanzapine-treated than risperidone-treated patients. In addition, statistically significantly fewer adverse events were reported by olanzapine-treated patients than by their risperidone-treated counterparts. Thus, the differential preclinical profiles of these two drugs were also evident in a controlled, clinical investigation. Olanzapine seemed to have a risk-versus-benefit advantage.

S100B Serum Levels and Long-Term Improvement of Negative Symptoms in Patients with Schizophrenia

“…The improvement of psychopathology, especially the PANSS negative score during the trial, is remarkable but not completely unusual. Similar longitudinal investigations reported comparable findings (Tran et al, 1997;Peuskens et al, 1999). Others, however, showed much smaller changes in stable outpatients or first-episode patients (eg Hirsch et al, 2002;Lieberman et al, 2003).…”

“…The dropout rates of patients during the study of 25% (T12) or 40% (T24), respectively, were within the expected range of such longterm trials. In two double-blind multicenter studies with schizophrenic patients over 28 weeks dropout rates of 40 or 55%, respectively, were reported (Tran et al, 1997;Hirsch et al, 2002). The improvement of psychopathology, especially the PANSS negative score during the trial, is remarkable but not completely unusual.…”

A systematic review of atypical antipsychotic drugs in schizophrenia

“…There were 14 trials in which olanzapine was compared with atypical antipsychotic treatments: Beasley 1999, 176,177 Fleming 1998, 70 Oliemeulen 2000, 109 HGCF 2001 (Eli Lilly), Bitter 1999 (clozapine), 74 Jones 1998, 180 Littrell 1999, 154 Tran 1997, 171 Kolff 2000, 152 Malyarov 1999, 153 Conley 2001, 161 Gureje 1998 (risperidone), 186 Lecrubier 1999 (amisulpride), 42 Study R-0548 (ziprasidone: Pfizer, commercial-inconfidence).…”

“…In the original review, 23 studies were identified for inclusion: Blin 1996, 251 Borison 1991, 252 Bouchard 1998, 253 Ceskova 1993, 254 Chouinard 1993, 255 Claus 1991, 256 Emsley 1995, 257 Hoyberg 1993, 258 Huttunen 1995, 259 Mahmoud 1998, 260 Marder 1994, 116 Mesotten 1991, 261 Min 1993, 262 Peuskens 1995, 263 Fleurot 1997, 62 Bondolfi 1998, 110 Anand 1998, 111 Breier 1999, 112 Wahlbeck 2000, 113 Tran 1997, 171 Klieser 1996, 264 Jones 1998, 193 Gureje 1998. 186 Data extraction sheets for these studies are presented in appendix 3.…”

Comparison of Rapidly Acting Intramuscular Olanzapine, Lorazepam, and Placebo A Double-blind, Randomized Study in Acutely Agitated Patients with Dementia

“…To assess treatment-emergent parkinsonism, the proportion of patients with a Simpson-Angus total score Ͼ 3 during the 24-h study period was calculated from among those with a total score р 3 at baseline. This definition was established a priori and has been used in previous olanzapine studies (Sanger et al 1999;Tran et al 1997). Kaplan-Meier estimates of time to response on the PANSS-EC during the 2 h post first injection were compared among treatment groups using a logrank test.…”