Ziprasidone 40 and 120 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 4-week placebo-controlled trial. An exploratory haloperidol-controlled dose-finding study of ziprasidone in hospitalized patients with schizophrenia or schizoaffective disorder. Ziprasidone 80 mg/day and 160 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 6-week placebo-controlled trial. Ziprasidone Study Group.
A double-blind, placebo-controlled, multicenter study, was performed to evaluate the efficacy and safety of ziprasidone in 139 patients with an acute exacerbation of schizophrenia or schizoaffective disorder. Patients were randomized to receive ziprasidone 40 mg/day, 120 mg/day or placebo for 28 days. Ziprasidone 120 mg/day was significantly more effective than placebo in improving the BPRS total, CGI-S. BPRS depression cluster and BPRS anergia cluster scores (all P < 0.05). Similarly, the percentages of patients classified as responders on the BPRS (> or = 30% reduction) and the CGI improvement (score < or = 2) were significantly greater with ziprasidone 120 mg/day compared with placebo (P < 0.05). The number of patients who experienced an adverse event was similar in all three treatment groups, and discontinuation due to adverse events was rare (five of 91 ziprasidone-treated patients). The most frequently reported adverse events, that were more common in either ziprasidone group than in the placebo group, were dyspepsia, constipation, nausea and abdominal pain. There was a notably low incidence extrapyramidal side-effects (including akathisia) and postural hypotension and no pattern of laboratory abnormalities or apparent weight gain. Ziprasidone-treated patients were not clinically different from placebo-treated patients on the Simpson-Angus Rating scale, Barnes Akathisia scale and AIMS assessments. These results indicate that ziprasidone 120 mg/day is effective in the treatment of the positive, negative and affective symptoms of schizophrenia and schizoaffective disorder with a very low side-effect burden. Ninety patients with schizophrenia or schizoaffective disorder according to DSM-III-R criteria participated in this double-blind, exploratory, dose-ranging trial. After a single-blind washout period of 4 to 7 days, patients were randomly assigned to receive one of four fixed doses of the new antipsychotic, ziprasidone 4 (N = 19), 10 (N = 17), 40 (N = 17), or 160 (N = 20) mg/day or haloperidol 15 mg/day (N = 17) for 4 weeks. A dose-response relationship among ziprasidone groups was established for improvements in Clinical Global Impression Severity (CGI-S) score (p = 0.002) but not in Brief Psychiatric Rating Scale (BPRS) total score (p = 0.08). The intent-to-treat analysis of mean changes from baseline in the BPRS total, BPRS Psychosis core, and CGI-S scores demonstrated that ziprasidone 160 mg/day was comparable with haloperidol in reducing overall psychopathology and positive symptoms and was superior to ziprasidone 4 mg/day. Despite the small sample size and short duration of the trial, the improvement in CGI-S with both ziprasidone 160 mg/day and haloperidol 15 mg/day was statistically significantly greater than with ziprasidone 4 mg/day (p = 0.001 andp = 0.005, respectively). The percentage of patients classified as responders on both the BPRS total (> or = 30% improvement) and CGI-Improvement (score of 1 or 2) scales in the ziprasidone 160 mg/day group was similar to that in the haloperidol group and nonsignificantly greater than that in the ziprasidone 4 mg/day group. On all assessments of clinical efficacy, the improvements associated with ziprasidone 4 mg/day, 10 mg/day, and 40 mg/day were similar. Concomitant benztropine use at any time during the study was less frequent with ziprasidone 160 mg/day (15%) than with haloperidol (53%). Haloperidol was associated with a sustained hyperprolactinemia, unlike ziprasidone, where only transient elevations in prolactin that returned to normal within the dosing interval were observed. Ziprasidone was well tolerated, and the incidence of adverse events was similar in all groups. The results of this study suggest that ziprasidone 160 mg/day is as effective as haloperidol 15 mg/day in reducing overall psychopathology and positive symptoms of an acute exacerbation of schizophrenia or schizoaffective disorder but has a lower potential to induce extrapyramidal symptoms. In this double-blind study, patients with an acute exacerbation of schizophrenia or schizoaffective disorder were randomized to receive either ziprasidone 80 mg/day (n = 106) or 160 mg/day (n = 104) or placebo (n = 92), for 6 weeks. Both doses of ziprasidone were statistically significantly more effective than placebo in improving the PANSS total, BPRS total, BPRS core items, CGI-S, and PANSS negative subscale scores (p < .05). Ziprasidone 160 mg/day significantly improved depressive symptoms in patients with clinically significant depression at baseline (MADRS > or = 14, over-all mean 23.5) (p < .05) as compared with placebo. The percentage of patients experiencing adverse events was similar in each treatment group, and resultant discontinuation was rare. The most frequent adverse events associated with ziprasidone were generally mild dyspepsia, nausea, dizziness, and transient somnolence. Ziprasidone was shown to have a very low liability for inducing movement disorders and weight gain. The results indicate that ziprasidone is effective and well tolerated in the treatment of the positive, negative, and depressive symptoms of an acute exacerbation of schizophrenia or schizoaffective disorder.
Currently data are limited. Ziprasidone may be an effective antipsychotic with less extrapyramidal effects than haloperidol. It also, however, causes more nausea and vomiting than the typical drugs, and, at present, there is no data suggesting that it is different to other atypical compounds. Well planned, conducted and reported long term randomised trials are needed if ziprasidone is to be accepted into everyday use.