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| |  Study Compares Two Main Schizophrenia Drugs SCARBOROUGH, Ont., May 21, 1997 -- An international study comparing antipsychotic drugs found Zyprexa(TM) (olanzapine) to be more effective in treating several key outcomes of schizophrenia than risperidone. The findings of the first double-blind, head-to-head study were announced yesterday at the American Psychiatric Association annual meeting in San Diego. The study was conducted by Eli Lilly and Company. "The fact that patients receiving Zyprexa reported statistically significant differences on several key outcomes including "negative'' symptoms, incidences of relapse and interpersonal relations is instructive to medical professionals treating patients with schizophrenia,'' said Dr. Barry Jones, associate director, clinical research Eli Lilly Canada Inc. Schizophrenia is a devastating disease afflicting 1 per cent of the world's population. Symptoms of the disease include "positive'' symptoms, such as hallucinations, delusions and hearing voices, and "negative'' symptoms such as social withdrawal and little or inappropriate emotional response. Study design The double-blind study, conducted in nine countries with 41 investigators, enrolled a total of 339 patients randomized to either Zyprexa or risperidone. The study lasted 28 weeks. Patients met the DSM-IV criteria for schizophrenia, schizophreniform disorder or schizoaffective disorder and were required to have a minimum score of 24 on the Brief Psychiatric Rating Scale (BPRS). Dosing ranges were 10-20 mg/day for Zyprexa and 4-12 mg/day for risperidone. Dosing was flexible within each range, and investigators were instructed to adjust the dose to optimize patient outcome. At study end, the average modal dose for Zyprexa was 17.2 mg/day, and the average modal dose for risperidone was 7.2 mg/day. Study results Interim results of this study, involving the first 297 patients who completed the eight-week, acute phase of treatment, were presented at a major scientific meeting in December 1996. Final results include all 339 patients who had the opportunity to complete the 28 week trial. Of the 339 randomized patients, 178 patients (olanzapine n equals 99, risperidone n equals 79) completed 28 weeks of double-blind therapy. Patients were evaluated on the Positive and Negative Symptom Scale (PANSS), which measures the severity of the symptoms of schizophrenia. At 28 weeks, Zyprexa and risperidone exhibited comparable improvement on the PANSS positive score; the Clinical Global Impression (CGI) scale, which measures the overall severity of the illness; and the BPRS total. However, an alternative measure of efficacy was comparative rates of response. Zyprexa and risperidone demonstrated comparable effectiveness in reducing the severity of positive and negative symptoms on the PANSS score by 20 of 30 per cent. However, a statistically significantly greater number of Zyprexa patients showed at least a 40 per cent improvement (36.8 per cent of Zyprexa patients vs. 26.7 per cent of risperidone patients) and 50 per cent improvement (21.7 per cent of Zyprexa patients vs. 12.1 per cent of risperidone patients) after 28 weeks. Negative symptoms: Zyprexa patients reported statistically significantly greater improvements on the Scale of the Assessment of Negative Symptoms, or SANS score. At week 28, Zyprexa patients reported a mean decrease of 4.3 with a standard deviation of 5.3 on the SANS summary score. Risperidone patients reported a mean decrease of 2.9 with a standard deviation of 3.8 on the SANS summary score. Depressive symptoms: At 28 weeks, the Zyprexa treatment group showed statistically significantly greater improvement than the risperidone group in the depressive symptoms as indicated by change in the PANSS depressive score. Relapse rates: Relapse was defined as a return of psychotic symptoms. Relapse rates were studied by looking at those who reported at least a 20 per cent decrease on the PANSS total score after eight weeks of theapy. If those patients experienced a 20 per cent increase in the PANNS total score and a CGI severity score of at least 3 in the next 20 weeks, they were deemed to have experienced a relapse. Kaplan-Meier estimated survival curves revealed that statistically significantly fewer Zyprexa patients experienced a relapse by 28 weeks. The estimated rate of relapse at 28 weeks was 12 per cent for Zyprexa, vs. 32 per cent for risperidone. EPS: Extrapyramidal side Effects (EPS), are Parkinsonian-like movement disorders associated with most antipsychotics. After 28 weeks, patients treated with risperidone were statistically significantly more likely to report any EPS events than Zyprexa-treated patients (31.1 per cent of risperidone patients vs. 18.6 per cent of Zyprexa patients). In addition, risperidone-treated patients reported statistically significantly more dystonic events at 28 weeks (6.0 per cent of risperidone vs. 1.7 per cent of Zyprexa patients). Statistically significantly more risperidone-treated patients reported Parkinsonian events at 28 weeks as well (18.6 per cent of risperidone patients vs. 9.9 per cent of Zyprexa patients at 28 weeks). At week 28, Zyprexa-treated patients had statistically significantly less incidence of treatment-emergent EPS based on the Barnes Akathisia scale, a measurement of akathisia-type EPS, and the Simpson-Angus Scale, a scale that measures Parkinsonian-like EPS. At week 28, the percentage of Zyprexa patients experiencing treatment-emergent akathisia was 15.9 per cent compared with 27.3 per cent of risperidone-treated patients. Treatment-emergent Parkinsonism was experienced by 12.5 per cent of the Zyprexa patients and 22.3 per cent of the risperidone patients at week 28. The rate of treatment-emergent dyskinetic symptoms at week 28 was statistically significantly higher for the risperidone-treated group than the Zyprexa treatment group (10.7 per cent of risperidone patients vs. 4.6 per cent of Zyprexa patients). Prolactin elevations: Statistically significantly fewer Zyprexa patients reported high prolactin elevations above standard reference ranges at any time during the study compared with risperidone-treated patients (51.2 per cent vs. 94.4 per cent). Interpersonal relations: At 28 weeks, both groups reported comparable improvements in their total Heinrichs-Carpenter Quality of Life Scale (QLS) score, which measures such factors as interpersonal relations and productivity in occupational roles. However, the Zyprexa group demonstrated a statistically significantly greater long-term improvement in inter-personal relations (p equals .011), a subset of the QLS. Other safety information After 28 weeks of therapy, one event, weight gain was reported statistically significantly more often among the Zyprexa-treated patients (16.3 per cent of Zyprexa patients vs. 7.8 per cent of risperidone patients). Between treatment groups, Zyprexa-treated patients experienced significantly greater weight gain (4.1 (plus sign or minus sign) 5.9 kg) than risperidone-treated patients (2.3 (plus sign or minus sign) 4.8 kg). In contrast, nausea, amblyopia, extrapyramidal syndrome, increased salivation, suicide attempts, abnormal ejaculation, back pain, creatine phosphokinase increases and urinary tract infections were reported statistically significantly more often among risperidone-treated patients.
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