Long-Term Safety and Tolerability of Open-Label Olanzapine Long-Acting Injection in the Treatment of Schizophrenia: 190-Week Interim Results

The primary objective of this ongoing study is to examine the long-term safety and tolerability of olanzapine long-acting injection (LAI). Current results are from a 190-week interim analysis. Patients were 18–75 years of age with schizophrenia (N = 909) or schizoaffective disorder (N = 22) previously enrolled in 1 of 3 randomized clinical trials of olanzapine LAI. In this open-label extension study, all patients received flexibly-dosed olanzapine LAI every 2–4 weeks. At time of analysis, rate of study discontinuation was 46.3%. The 18-month discontinuation rate was 34.2%. Adverse events in $5% of patients were increased weight, insomnia, anxiety, somnolence, headache, and nasopharyngitis. There were 26 occurrences of post-injection delirium/sedation syndrome which all fully resolved within 72 hours. Mean weight change was +1.81 kg, with 32.1% of patients experiencing $7% weight gain. Mean Clinical Global Impressions-Severity scores remained stable throughout (2.9 at baseline to 2.8 at endpoint). Pharmacokinetic analyses indicated consistent olanzapine plasma concentrations over time, with no evidence of long-term accumulation. Safety profile was consistent with that of oral olanzapine, with the exception of findings specific to intramuscular injection. During the study period, there were 16 (1.7%) occurrences of treatment-emergent diabetes and 1 occurrence of treatment-emergent diabetic ketoacidosis. Percentages of patients with EPS scale-defined treatment-emergent akathisia, parkinsonism, and dyskinesia were 3.3%, 6.6%, and 3.0%, respectively.