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BMC Psychiatry. 2011; 11: 28.
Published online Feb 15, 2011. doi:  10.1186/1471-244X-11-28
PMCID: PMC3048520
Dose-associated changes in safety and efficacy parameters observed in a 24-week maintenance trial of olanzapine long-acting injection in patients with schizophrenia
Angela L Hill,corresponding author1 Bin Sun,1 Jamie L Karagianis,2 Susan B Watson,1 and David P McDonnell1
1Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, 46285, USA
2Eli Lilly Canada Inc., 3650 Danforth Avenue, Toronto, Ontario M1N 2E8, Canada
corresponding authorCorresponding author.
Angela L Hill: ahill/at/lilly.com; Bin Sun: bin.sun/at/i3statprobe.com; Jamie L Karagianis: karagianisja/at/lilly.com; Susan B Watson: s.watson/at/lilly.com; David P McDonnell: mcdonnelldp/at/lilly.com
Received June 28, 2010; Accepted February 15, 2011.
Abstract
Background
In a recently published 24-week maintenance study of olanzapine long-acting injection (LAI) in schizophrenia (Kane et al., 2010), apparent dose-associated changes were noted in both efficacy and safety parameters. To help clinicians balance safety and efficacy when choosing a dose of olanzapine LAI, we further studied these changes.
Methods
Outpatients with schizophrenia who had maintained stability on open-label oral olanzapine for 4 to 8 weeks were randomly assigned to "low" (150 mg/2 weeks; N = 140), "medium" (405 mg/4 weeks; N = 318), or "high" (300 mg/2 weeks; N = 141) dosages of olanzapine LAI for 24 weeks. Potential relationships between dose and several safety or efficacy measures were examined via regression analysis, the Jonckheere-Terpstra test (continuous data), or the Cochran-Armitage test (categorical data).
Results
Safety parameters statistically significantly related to dose were mean weight change (low: +0.67 [SD = 4.38], medium: +0.89 [SD = 3.87], high: +1.70 [SD = 4.14] kg, p = .024; effect size [ES] = 0.264 high vs. low dose), mean change in prolactin (low: -5.61 [SD = 12.49], medium: -2.76 [SD = 19.02]), high: +3.58 [SD = 33.78] μg/L, p = .001; ES = 0.410 high vs. low dose), fasting triglycerides change from normal at baseline to high (low: 3.2%, medium: 6.0%, high: 18.9%, p = .001; NNT = 7 high vs. low dose) and fasting high-density lipoprotein cholesterol change from normal at baseline to low (low: 13.8%, medium: 19.6%, high: 30.7%, p = .019; NNT = 6 high vs. low dose). Efficacy measures significantly related to dose included Positive and Negative Syndrome Scale total score mean change (low: +2.66 [SD = 14.95], medium: -0.09 [SD = 13.47], high: -2.19 [SD = 13.11], p <.01; ES = 0.356 high vs. low dose), relapse rate (low: 16%, medium: 10%, high: 5%, p = .003; NNT = 9 high vs. low dose), all-cause discontinuation rate (low: 36%, medium: 30%, high: 24%, p = .037; NNT = 9 high vs. low dose), and rate of discontinuation due to efficacy-related reasons (low: 20%, medium: 14%, high: 6%, p <.001). Time to all-cause discontinuation (p = .035) and time to relapse (p = .005) were also significantly related to dose.
Conclusions
Analyses of several safety and efficacy parameters revealed significant associations with dose of olanzapine LAI, with the highest dose generally showing greater efficacy as well as greater adverse changes in metabolic safety measures. When considering olanzapine LAI, as with all antipsychotics, it is important to carefully consider the potential benefits and risks for an individual patient.
Trial Registration
ClinicalTrials.gov: NCT00088491
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