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

Abstract

Objective

To assess the effectiveness and safety of oral olanzapine treatment transitioned from rapid-acting intramuscular olanzapine (RAIM) in patients with acute agitation associated with schizophrenia in a real-world clinical setting.

Methods

The postmarketing surveillance study with a 3-day observational period after the last RAIM administration was conducted (original study). Following this, an extended study was added for patients who received oral olanzapine after RAIM administration during the original study period, in order to additionally observe them for 7 days after initial RAIM administration. Effectiveness and safety from initial RAIM administration were evaluated using the Positive and Negative Syndrome Scale-Excited Component score and treatment-emergent adverse events (TEAEs), respectively.

Results

The effectiveness and safety analysis set included a total of 521 and 522 patients, respectively. A majority of patients received 10 mg of RAIM (475/522 patients, 91.0%). The mean ± SD total Positive and Negative Syndrome Scale-Excited Component score was 23.6±6.2 (n=318) at baseline (before initial RAIM administration), 17.4±6.8 (n=280) at 2 hours after initial administration, 16.2±6.8 (n=246) 2 days after final administration, 14.9±6.2 (n=248) 3 days after final administration, 13.8±5.9 (n=242) 4 days after final administration, 13.2±5.8 (n=221) 7 days after initial administration, and 13.4±6.2 (n=351) at final observation (with the last observation carried forward approach), showing that reduction in agitation seen with RAIM was sustained with oral dose of olanzapine. The most common TEAEs were dyslalia and somnolence (each event occurred in four patients), and abnormal hepatic function and constipation (occurred in three patients). One serious adverse event of sudden cardiac death occurred after transitioned to oral olanzapine with many other antipsychotic drugs.

Conclusion

In the treatment of acute agitation associated with schizophrenia, RAIM could be generally transitioned to oral olanzapine without exacerbating adverse events or losing treatment effect.

Keywords:

• agitation
• schizophrenia
• rapid-acting intramuscular olanzapine
• Japan postmarketing surveillance study
• PANSS-EC

Supplementary material

Table S1 Oral olanzapine dose after administration of 5 and 20 mg on the last day of rapid-acting intramuscular olanzapine

Acknowledgments

The authors are very grateful to all the physicians of the study sites, the patients and their family members, and other persons who were involved in these studies. Medical writing assistance was provided by Deborah D’Souza, PhD, of inVentiv Health Clinical, LLC, funded by Eli Lilly Japan K.K. These studies were sponsored by Eli Lilly Japan K.K.

Disclosure

Masanori Taketsuna contributed to this work as a former full-time employee of Eli Lilly Japan K.K. The opinions expressed in this work are solely his own and do not represent his current affiliation (Division of Medical Statistics, Translational Research Informatics Center, Foundation for Biomedical Research and Innovation). All the other authors are employees of Eli Lilly Japan K.K. The authors report no other conflicts of interest in this work.