Safety and effectiveness of rapid-acting intramuscular olanzapine for agitation associated with schizophrenia – Japan postmarketing surveillance study

Abstract

ObjectiveThe objective of this study was to evaluate the safety and effectiveness of rapid-acting intramuscular (IM) olanzapine in the treatment of acute agitation associated with schizophrenia in real-world clinical settings in Japan.MethodsIn this multicenter, postmarketing surveillance (PMS) study, patients with acute agitation associated with schizophrenia were treated with IM olanzapine daily in a daily clinical setting. The observational period ranged from 1 to 7 days, including the day of initial administration. Safety was assessed by reporting treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs). The Positive and Negative Syndrome Scale – Excited Component (PANSS-EC) score was used to evaluate effectiveness at baseline and at 2 hours (after each administration), 2 days, and 3 days (end of the observational period) from the last administration of the IM olanzapine injection.ResultsThe safety analysis set included 999 patients, and the initial dose of 10 mg was administered to 955 patients. TEAEs were reported in 28 patients (36 events), the most common of which were dyslalia (5 patients), akathisia and somno lence (4 patients each), hepatic function abnormal (3 patients), and constipation and dehydration (2 patients each). One serious adverse event of akathisia occurred during the observation period. The PANSS-EC score (mean ± standard deviation) was 23.3±6.4 (n=625) at baseline, 16.9±7.0 (n=522) at 2 hours after initial injection, and 14.9±6.5 (n=650) at the last observation carried forward.ConclusionThe results of this Japanese PMS study demonstrated that IM olanzapine is safe and has a favorable effectiveness profile in the treatment of schizophrenia patients with acute agitation.

Effectiveness and safety of oral olanzapine treatment transitioned from rapid-acting intramuscular olanzapine for agitation associated with schizophrenia

“…We have previously reported the results of the observational postmarketing surveillance (PMS) study conducted in Japan to evaluate the safety and effectiveness of rapid-acting intramuscular olanzapine (RAIM) for agitation associated with schizophrenia. 14 A significant improvement in the total PANSS-EC score compared with the baseline score was seen at 2 hours after initial administration of RAIM, and this reduction in agitation was maintained for 3 days since the last RAIM administration, regardless of the treatment following RAIM. There were no new safety concerns identified in the original PMS study.…”

“…The original PMS study had a 3-day observational period after the last administration of RAIM, including the initial day of administration. 14 In order to observe the effectiveness and safety for the acute and maintenance treatment phases in patients who transitioned from RAIM to oral olanzapine treatment during the original PMS study, we added an additional observational period as the extension study. These patients were monitored for 7 days from the initial RAIM administration.…”

“…The participants in the original PMS were patients with schizophrenia who had psychomotor agitation associated with schizophrenia and had been administered RAIM, as described in detail by Katagiri et al 14 The participants who entered to the extension study were decided at physicians’ discretion among patients who received oral olanzapine after RAIM administration during the original study period.…”

“…Patients were excluded from enrollment if they had contraindications to intramuscular olanzapine in the Japanese package insert, 15 were specifically in a comatose state, were under the effect of central nervous system depressants, such as barbiturate derivatives, had a medical history of hypersensitivity to any ingredients of intramuscular olanzapine, for example, adrenaline currently used. 14 In addition to those criteria, oral olanzapine has contraindication to diabetes and history of diabetes in Japan, so patients with them were also excluded from the extension study. 16…”

“…Therefore, here we evaluate the effectiveness and safety profiles of patients who transitioned from RAIM to oral olanzapine treatment in a real-world clinical setting, which was longer than in the previous report that only included the acute period. 14 …”