A randomized, double-blind, placebo-controlled study of rapid-acting intramuscular olanzapine in Japanese patients for schizophrenia with acute agitation

Abstract

BackgroundOlanzapine rapid-acting intramuscular (IM) injection is an atypical antipsychotic drug already used overseas and recently approved in Japan. The objective of this study was to confirm the efficacy of rapid-acting IM olanzapine 10 mg was greater than IM placebo in patients with exacerbation of schizophrenia with acute psychotic agitation by comparing changes from baseline to 2 hours after the first IM injection, as measured by the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) total score.MethodsWe conducted a placebo-controlled, randomized, double-blind, parallel-group study in Japanese patients diagnosed with schizophrenia according to the diagnostic criteria specified in the DSM-IV-TR. Patients were randomized to 2 treatment groups: IM olanzapine (10 mg) or IM placebo. The primary efficacy outcome was the change in PANSS-EC from baseline to 2 hours after the first IM injection. Treatment groups were compared with an analysis of variance model which included treatment and site as factors. During the 24-hour treatment period, safety was assessed by clinical examination and laboratory investigations, electrocardiograms, extrapyramidal symptoms scales, and recording spontaneously reported adverse events.ResultsOf the 91 randomized patients, 90 patients (45 IM olanzapine-group; 45 IM placebo-group) were in the full analysis set. The mean change of PANSS-EC total score from baseline to 2 hours after the first IM injection (mean±standard deviation) was −9.2±4.5 for the IM olanzapine group and −2.8±5.6 for the IM placebo group. The difference between treatment groups was statistically significant (p<.001). There were no deaths, serious adverse events, treatment-emergent adverse events (TEAEs) leading to discontinuation, severe TEAEs, or instances of oversedation in this study. There were no statistically significant differences between treatment groups in the proportion of patients with potentially clinically significant changes in laboratory tests, vital signs (blood pressure and pulse rate), electrocardiograms, and treatment-emergent extrapyramidal symptoms.ConclusionThe efficacy of IM olanzapine 10 mg in patients with exacerbation of schizophrenia with acute psychotic agitation was greater than IM placebo in the primary efficacy measure, PANSS-EC. Intramuscular olanzapine 10 mg was shown to be generally safe and tolerable, and could be a new option for treatment of schizophrenia in Japan.Trial RegistrationNCT00970281

Intramuscular olanzapine for agitated patients: A systematic review and meta-analysis of randomized controlled trials

“…We excluded a further 43 studies following a review of the titles and abstract, and 5 additional articles after full-text review (these were review articles). Two additional studies (Katagiri et al, 2012;Ono et al, 2009) were identified from the Katagiri et al (2013) paper (Fig. 1).…”

“…1). In total, we identified 13 studies, as follows: 7 comparisons with 1059 patients for OLA-IM versus placebo: (Breier et al, 2002;Katagiri et al, 2013;Katagiri et al, 2012;Meehan et al, 2001Meehan et al, , 2002Ono et al, 2009;Wright et al, 2001); 5 comparisons with 613 patients for OLA-IM versus HAL-IM (Baldacara et al, 2011;Breier et al, 2002;Chan et al, 2014;Hsu et al, 2010;Wright et al, 2001); 2 comparisons with 108 patients for OLA-IM versus ZIP-IM (Baldacara et al, 2011;Mantovani et al, 2013); 2 comparisons with 110 patients for OLA-IM versus HAL-IM plus midazolam (Baldacara et al, 2011;Mantovani et al, 2013); 3 comparisons with 412 patients for OLA-IM versus HAL-IM plus promethazine (Baldacara et al, 2011;Mantovani et al, 2013;Raveendran et al, 2007); 2 comparisons with 355 patients for OLA-IM versus LOR-IM Meehan et al, 2002); and 1 comparison with 67 patients for OLA-IM versus HAL-IM plus LOR-IM (Huang et al, 2015).…”

Pharmacological treatment of acute agitation associated with psychotic and bipolar disorder: a systematic review and meta-analysis

“…The most frequently investigated treatment was haloperidol monotherapy (Wright et al ., ; Breier et al ., ; Kinon et al ., ; Andrezina et al ., ; Tran‐Johnson et al ., ; Lim et al ., ; Fang et al ., ; Zhang et al ., ). Olanzapine was used in six trials (Meehan et al ., ; Wright et al ., ; Breier et al ., ; Kinon et al ., ; Hsu et al ., ; Katagiri et al ., ), aripiprazole featured in three trials (Andrezina et al ., ; Tran‐Johnson et al ., ; Zimbroff et al ., ), loxapine in three trials (Allen et al ., ; Lesem et al ., ; Kwentus et al ., ), risperidone monotherapy was utilised in two trials (Hsu et al ., ; Lim et al ., ) and lorazepam monotherapy in two trials. (Meehan et al ., ; Zimbroff et al ., ).…”

“…One trial reported assessing the blinding procedures (Lesem et al ., ). In 11 trials, the participants were reported to be blinded to their treatment assignment (Meehan et al ., ; Wright et al ., ; Breier et al ., ; Kinon et al ., ; Andrezina et al ., ; Tran‐Johnson et al ., ; Zimbroff et al ., ; Allen et al ., ; Lesem et al ., ; Kwentus et al ., ; Katagiri et al ., ) All trials appeared to include at least 80% of participants in the final analyses. In all cases where appropriate, the last observation carried forward method was used to compensate for patient losses.…”

“…Nine of the included trials (Meehan et al ., ; Wright et al ., ; Breier et al ., ; Andrezina et al ., ; Tran‐Johnson et al ., ; Allen et al ., ; Lesem et al ., ; Kwentus et al ., ; Katagiri et al ., ) compared interventions to a placebo arm.…”