Intramuscular ziprasidone, 2 mg versus 10 mg, in the short-term management of agitated psychotic patients.

BACKGROUND: There is a clear need for effective, well-tolerated intramuscular (i.m.) agents for the acute control of agitated psychotic patients. Currently used agents, including conventional antipsychotics and/or benzodiazepines, may be associated with distressing side effects such as extrapyramidal side effects and excessive sedation. OBJECTIVE: The objective of this study was to evaluate the efficacy and tolerability of the rapid-acting i.m. formulation of the novel antipsychotic ziprasidone in the treatment of inpatients with psychosis and acute agitation (DSM-IV diagnoses). METHOD: In a 24-hour, double-blind, fixed-dose clinical trial, patients were randomly assigned to receive up to 4 injections (every 2 hours p.r.n.) of 2 mg (N = 54) or 10 mg (N = 63) of ziprasidone i.m. The Behavioral Activity Rating Scale measured behavioral symptoms at baseline and the response to treatment up to 4 hours after the first i.m. injection. RESULTS: Ziprasidone i.m., 10 mg, rapidly reduced symptoms of acute agitation and was significantly more effective (p < .01) than the 2-mg dose up to 4 hours after the first injection. Patients were calmed but not excessively sedated, and over half were classed as responders 2 hours after the 10-mg dose. No acute dystonia or behavioral disinhibition was reported. One patient who received the 10-mg dose experienced the extrapyramidal side effect akathisia. CONCLUSION: Ziprasidone i.m., 10 mg, is rapidly effective and well tolerated in the short-term management of the agitated psychotic patient. Comparison with a study of identical design comparing 2-mg with 20-mg doses in patients with similar levels of psychopathology suggests that efficacy with 10 mg or 20 mg of ziprasidone i.m. is significant and dose related.

Intramuscular (IM) ziprasidone 20 mg is effective in reducing acute agitation associated with psychosis: a double-blind, randomized trial.

RATIONALE: Intramuscular (IM) conventional antipsychotics and/or benzodiazepines are effective in the short-term treatment of acutely agitated psychotic patients but may be associated with adverse effects. A short-acting IM formulation of the novel antipsychotic, ziprasidone, which may offer advantages over conventional agents, has been developed. OBJECTIVE: To compare ziprasidone IM 2 mg (n=38) and 20 mg (n=41) in the acute control and short-term management of agitated psychotic patients. METHODS: A prospective, randomized, double-blind, 24-h study assessed efficacy using the Behavioral Activity Rating Scale (BARS) and the PANSS. The BARS is a validated rating scale for the assessment of treatment response in acute agitation associated with psychosis. Following the initial dose, three more doses could be given 4 h apart if needed during the 24-h period. RESULTS: The mean BARS score had decreased 15 min after the first 20 mg IM dose and was statistically significantly lower than the 2 mg group at 30 min post-dose. The improvement with the 20 mg dose increased until 2 h, and was maintained until at least 4 h post-dose (P<0.001). Two hours after the first injection, almost all of the patients receiving ziprasidone 20 mg were BARS responders compared with just one-third of those receiving 2 mg ziprasidone (P<0.001). The calming effect of ziprasidone was also evident by the significant reduction in PANSS agitation items (P<0.05) and CGI-severity at 4 h (P=0.008). Both ziprasidone doses were very well tolerated. Ziprasidone IM 20 mg was not associated with EPS, dystonia, akathisia, respiratory depression or with excessive sedation. CONCLUSIONS: Ziprasidone IM 20 mg substantially and significantly reduced the symptoms of acute agitation in patients with psychotic disorders. Ziprasidone 20 mg IM was very well tolerated and produced no dystonia or akathisia.

Validation of the behavioural activity rating scale (BARS): a novel measure of activity in agitated patients.

We report psychometric results of the Behavioural Activity Rating Scale (BARS) using data from three Phase III clinical trials of intramuscular ziprasidone in acutely agitated patients with psychosis (Studies 1 and 2) or in stable psychotic patients (Study 3). Convergent validity and divergent validity were assessed with baseline data from Studies 1 and 2 in subjects with acute agitation. To investigate convergent validity, we sought Pearson and Spearman correlation of BARS scores with scores on the Clinical Global Impression of Severity (CGI-S) Scale and a predefined cluster of agitation-related items from the Positive and Negative Syndrome Scale (PANSS). For divergent validity, we sought Pearson and Spearman correlation between BARS scores and a predefined cluster of PANSS items measuring negative symptoms. Discriminant validity was investigated with the help of subjects with moderate psychopathology (Study 3). Wilcoxon rank-sum and two-sample t tests determined whether mean (or median) BARS scores differed between subjects with acute agitation (Studies 1 and 2) and moderate psychopathology (Study 3). Responsiveness to treatment effect and rater reliability were also evaluated. In Study 2, Pearson correlation coefficients of BARS scores with PANSS agitation items and CGI-S were moderate (convergent validity) and statistically significant (P<0.005). The correlation between BARS scores and PANSS negative component scores was low (divergent validity). Treatment effect size was larger for BARS than for PANSS agitation items and CGI-S (responsive to treatment differences). Virtually perfect inter- and intra-rater reliability was achieved. Study 1 produced similar results. BARS showed psychometrically valid properties for measurement of behavioral activity in acutely agitated patients with psychosis.