An 8-Week, Double-Blind, Randomized, Placebo-Controlled Study of Olanzapine Long-Acting Injection in Acutely Ill Patients With Schizophrenia

Objective: To examine the efficacy and tolerability of a new injectable formulation of olanzapine, olanzapine long-acting injection (LAI), relative to placebo for treatment of acutely ill patients with schizophrenia.

Method: Patients with DSM-IV or DSM-IV-TR schizophrenia in this 8-week, double-blind study were randomly assigned to receive 210 mg/2 weeks, 300 mg/2 weeks, or 405 mg/4 weeks of olanzapine LAI or placebo/2 weeks. No oral antipsychotic supplementation was permitted. The primary efficacy measure was mean baseline-to-end point change in Positive and Negative Syndrome Scale (PANSS) total score. The study was conducted from June 2004 to April 2005.

Results: Mean baseline-to-end point decreases in PANSS total scores were significantly greater for all olanzapine LAI regimens relative to placebo (all p values < .001). The 300 mg/2 weeks and 405 mg/4 weeks olanzapine LAI groups separated from placebo on the PANSS total at 3 days after starting treatment, and all olanzapine LAI groups separated from placebo by 7 days. Rates of clinical improvement (end point Clinical Global Impressions-Improvement scale score <= 3) were significantly higher for all olanzapine LAI groups relative to placebo (p < .001). Incidences of sedation and increased appetite were significantly higher for 300 mg/2 weeks olanzapine LAI relative to placebo (p < .05). Mean weight gain (3.2-4.8 vs. 0.3 kg, p = 7% of baseline (23.6-35.4% vs. 12.4%, p <= .046) were significantly greater for olanzapine LAI relative to placebo. Significant differences between all olanzapine LAI groups and placebo were observed regarding mean baseline-to-end point changes in fasting total cholesterol (5.5-10.4 vs. -7.0 mg/dL; p <= .015) and between the 210 mg/2 weeks and 405 mg/4 weeks groups (26.3-30.3 vs. -9.4 mg/dL; p <= .016), but not the 300 mg/2 weeks group (17.6 mg/dL; p = .055), and placebo for fasting triglycerides.

Conclusions: In this 8-week study, olanzapine LAI administered at 2- or 4-week injection intervals was significantly more efficacious than placebo for the treatment of acutely ill patients with schizophrenia despite no use of supplemental oral antipsychotics. Consistent with changes previously observed with oral olanzapine, clinically significant weight gain and changes in some lipid parameters were observed in patients treated with olanzapine LAI.

Trial Registration:clinicaltrials.gov Identifier: NCT00088478